Evidence for motivational effects elicited by activation of GABA-A or dopamine receptors in the nucleus accumbens shell

PubMed Central

Wirtshafter, David; Stratford, Thomas R.

2011-01-01

Microinjections of the inhibitory GABA-A receptor agonist muscimol into the shell region of the nucleus accumbens (AcbSh) have been reported to induce large increases in food intake, but the effect of these injections on motivational processes is less clear. In the current study, bilateral injections of saline, muscimol (50 ng/side) or D-amphetamine (10 μg/side) were made into the AcbSh of rats trained to lever press on a progressive ratio schedule for food reward. Injections of both muscimol and amphetamine were found to produce a large increase in the breaking point relative to saline injections. This result suggests that inactivation of the AcbSh does not simply drive ingestive behavior, but also affects motivational processes assessed by the progressive ratio schedule. Breaking points were also increased by injections of amphetamine into the AcbSh. PMID:20598739

Aerobic exercise decreases the positive-reinforcing effects of cocaine.

PubMed

Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L

2008-11-01

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

A quantitative analysis of the effects of qualitatively different reinforcers on fixed ratio responding in inbred strains of mice

PubMed Central

Hutsell, Blake A.; Newland, M. Christopher

2013-01-01

Previous studies of inbred mouse strains have shown reinforcer-strain interactions that may potentially mask differences among strains in memory performance. The present research examined the effects of two qualitatively different reinforcers (heterogeneous mix of flavored pellets and sweetened-condensed milk) on responding maintained by fixed-ratio schedules of reinforcement in three inbred strains of mice (BALB/c, C57BL/6, & DBA/2). Responses rates for all strains were a bitonic (inverted U) function of the size of the fixed-ratio schedule and were generally higher when responding was maintained by milk. For the DBA/2 and C57BL/6 and to a lesser extent the BALB/c, milk primarily increased response rates at moderate fixed ratios, but not at the largest fixed ratios tested. A formal model of ratio-schedule performance, Mathematical Principles of Reinforcement (MPR), was applied to the response rate functions of individual mice. According to MPR, the differences in response rates maintained by pellets and milk were mostly due to changes in motoric processes as indicated by changes in the minimum response time (δ) produced by each reinforcer type and not specific activation (a), a model term that represents value and is correlated with reinforcer magnitude and the break point obtained under progressive ratio schedules. In addition, MPR also revealed that, although affected by reinforcer type, a parameter interpreted as the rate of saturation of working memory (λ), differed among the strains. PMID:23357283

High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

PubMed

Cornish, Jennifer L; Clemens, Kelly J; Thompson, Murray R; Callaghan, Paul D; Dawson, Bronwyn; McGregor, Iain S

2008-01-01

Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

NASA Astrophysics Data System (ADS)

Waller, J. M.; Andrade, E.; Saulsberry, R. L.

2010-02-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

PubMed

Olarte-Sánchez, C M; Valencia-Torres, L; Cassaday, H J; Bradshaw, C M; Szabadi, E

2013-12-01

Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

Evaluation of a Postoperative Pain-Like State on Motivated Behavior in Rats: Effects of Plantar Incision on Progressive-Ratio Food-Maintained Responding.

PubMed

Warner, Emily; Krivitsky, Rebecca; Cone, Katherine; Atherton, Phillip; Pitre, Travis; Lanpher, Janell; Giuvelis, Denise; Bergquist, Ivy; King, Tamara; Bilsky, Edward J; Stevenson, Glenn W

2015-12-01

There has been recent interest in characterizing the effects of pain-like states on motivated behaviors in order to quantify how pain modulates goal-directed behavior and the persistence of that behavior. The current set of experiments assessed the effects of an incisional postoperative pain manipulation on food-maintained responding under a progressive-ratio (PR) operant schedule. Independent variables included injury state (plantar incision or anesthesia control) and reinforcer type (grain pellet or sugar pellet); dependent variables were tactile sensory thresholds and response breakpoint. Once responding stabilized on the PR schedule, separate groups of rats received a single ventral hind paw incision or anesthesia (control condition). Incision significantly reduced breakpoints in rats responding for grain, but not sugar. In rats responding for sugar, tactile hypersensitivity recovered within 24 hr, indicating a faster recovery of incision-induced tactile hypersensitivity compared to rats responding for grain, which demonstrated recovery at PD2. The NSAID analgesic, diclofenac (5.6 mg/kg) completely restored incision-depressed PR operant responding and tactile sensitivity at 3 hr following incision. The PR schedule differentiated between sucrose and grain, suggesting that relative reinforcing efficacy may be an important determinant in detecting pain-induced changes in motivated behavior. © 2015 Wiley Periodicals, Inc.

Evaluation of a post-operative pain-like state on motivated behavior in rats: Effects of plantar incision on progressive-ratio food-maintained responding

PubMed Central

Warner, Emily; Krivitsky, Rebecca; Cone, Katherine; Atherton, Phillip; Pitre, Travis; Lanpher, Janell; Giuvelis, Denise; Bergquist, Ivy; King, Tamara; Bilsky, Edward J.; Stevenson, Glenn W.

2015-01-01

There has been recent interest in characterizing the effects of pain-like states on motivated behaviors in order to quantify how pain modulates goal-directed behavior and the persistence of that behavior. The current set of experiments assessed the effects of an incisional post-operative pain manipulation on food-maintained responding under a progressive-ratio (PR) operant schedule. Independent variables included injury state (plantar incision or anesthesia control) and reinforcer type (grain pellet or sugar pellet); dependent variables were tactile sensory thresholds and response breakpoint. Once responding stabilized on the PR schedule, separate groups of rats received a single ventral hind paw incision or anesthesia (control condition). Incision significantly reduced breakpoints in rats responding for grain, but not sugar. In rats responding for sugar, tactile hypersensitivity recovered within 24 hrs, indicating a faster recovery of incision-induced tactile hypersensitivity compared to rats responding for grain, which demonstrated recovery at PD2. The NSAID analgesic, diclofenac (5.6 mg/kg) completely restored incision-depressed PR operant responding and tactile sensitivity at 3 hr following incision. The PR schedule differentiated between sucrose and grain, suggesting that relative reinforcing efficacy may be an important determinant in detecting pain-induced changes in motivated behavior. PMID:26494422

Human's choices in situations of time-based diminishing returns.

PubMed Central

Hackenberg, T D; Axtell, S A

1993-01-01

Three experiments examined adult humans' choices in situations with contrasting short-term and long-term consequences. Subjects were given repeated choices between two time-based schedules of points exchangeable for money: a fixed schedule and a progressive schedule that began at 0 s and increased by 5 s with each point delivered by that schedule. Under "reset" conditions, choosing the fixed schedule not only produced a point but it also reset the requirements of the progressive schedule to 0 s. In the first two experiments, reset conditions alternated with "no-reset" conditions, in which progressive-schedule requirements were independent of fixed-schedule choices. Experiment 1 entailed choices between a progressive-interval schedule and a fixed-interval schedule, the duration of which varied across conditions. Switching from the progressive- to the fixed-interval schedule was systematically related to fixed-interval size in 4 of 8 subjects, and in all subjects occurred consistently sooner in the progressive-schedule sequence under reset than under no-reset procedures. The latter result was replicated in a second experiment, in which choices between progressive- and fixed-interval schedules were compared with choices between progressive- and fixed-time schedules. In Experiment 3, switching patterns under reset conditions were unrelated to variations in intertrial interval. In none of the experiments did orderly choice patterns depend on verbal descriptions of the contingencies or on schedule-controlled response patterns in the presence of the chosen schedules. The overall pattern of results indicates control of choices by temporarily remote consequences, and is consistent with versions of optimality theory that address performance in situations of diminishing returns. PMID:8315364

Second-order schedules of token reinforcement with pigeons: effects of fixed- and variable-ratio exchange schedules.

PubMed

Foster, T A; Hackenberg, T D; Vaidya, M

2001-09-01

Pigeons' key pecks produced food under second-order schedules of token reinforcement, with light-emitting diodes serving as token reinforcers. In Experiment 1, tokens were earned according to a fixed-ratio 50 schedule and were exchanged for food according to either fixed-ratio or variable-ratio exchange schedules, with schedule type varied across conditions. In Experiment 2, schedule type was varied within sessions using a multiple schedule. In one component, tokens were earned according to a fixed-ratio 50 schedule and exchanged according to a variable-ratio schedule. In the other component, tokens were earned according to a variable-ratio 50 schedule and exchanged according to a fixed-ratio schedule. In both experiments, the number of responses per exchange was varied parametrically across conditions, ranging from 50 to 400 responses. Response rates decreased systematically with increases in the fixed-ratio exchange schedules, but were much less affected by changes in the variable-ratio exchange schedules. Response rates were consistently higher under variable-ratio exchange schedules than tinder comparable fixed-ratio exchange schedules, especially at higher exchange ratios. These response-rate differences were due both to greater pre-ratio pausing and to lower local rates tinder the fixed-ratio exchange schedules. Local response rates increased with proximity to food under the higher fixed-ratio exchange schedules, indicative of discriminative control by the tokens.

Deciphering the Adaptive Immune Response to Ovarian Cancer

DTIC Science & Technology

2014-10-01

of 10 mg/mL. Wells containing anti-CD3/ anti-CD28 coated beads (bead-to-cell ratio of 1:1) or human cytomegalovirus, Epstein - Barr virus , and...Waldenstrom’s Macroglobulinemia (MYD88L265P). CONCLUSION: Overall, this study is progressing on schedule and on budget. We have developed the...apart from T-cell–medi- ated control of virus -induced cancers (3). More obvious in humans is the influence of the immune system on cancer progression and

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

2009-01-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

48 CFR 852.236-84 - Schedule of work progress.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Schedule of work progress... Schedule of work progress. As prescribed in 836.575, insert the following clause: Schedule of Work Progress... indicates the anticipated installation of work versus the elapsed contract time, for the approval of the...

Correspondence between Single versus Daily Preference Assessment Outcomes and Reinforcer Efficacy under Progressive-Ratio Schedules

ERIC Educational Resources Information Center

Call, Nathan A.; Trosclair-Lasserre, Nicole M.; Findley, Addie J.; Reavis, Andrea R.; Shillingsburg, M. Alice

2012-01-01

Research has suggested that a daily multiple-stimulus-without-replacement (MSWO) preference assessment may be more sensitive to changes in preference than other assessment formats, thereby resulting in greater correspondence with reinforcer efficacy over time (DeLeon et al., 2001). However, most prior studies have measured reinforcer efficacy…

Correspondence between Preference Assessment Outcomes and Stimulus Reinforcer Value for Social Interactions

ERIC Educational Resources Information Center

Davis, Tonya N.; Hodges, Abby; Weston, Regan; Hogan, Emily; Padilla-Mainor, Kristen

2017-01-01

Preferred forms of social interaction were identified using a paired-stimulus format in which two 3-5 s videos of the experimenter providing the social interaction to the participant were presented. Reinforcer efficacy of the high-, medium-, and low-preferred interactions was evaluated using a progressive-ratio schedule to determine the amount of…

Hypocretin/orexin antagonists decrease cocaine self-administration by female rhesus monkeys.

PubMed

Foltin, Richard W; Evans, Suzette M

2018-07-01

The hypocretin/orexin system is involved in regulating arousal, and much recent work demonstrates that decreasing hypocretin receptor-1 (HCRTr1) activity using antagonists decreases appetitive behavior, including stimulant drug self-administration and reinstatement. The present study determined the effects of hypocretin-1 and HCRTr1 antagonists on responding reinforced by intravenous (i.v.) cocaine self-administration (0.0125 - 0.05 mg/kg/infusion) in 5 female rhesus monkeys. Responding was examined using 3 schedules of reinforcement: 1) a Fixed interval 1 min, Fixed ratio 10 Chain schedule [FI 1-min (FR10:S)], 2) a Progressive Ratio (PR) schedule, and 3) a cocaine vs. candy. Choice schedule: the HCRTr1 antagonist SB-334867 (8-24 mg/kg, i.m.) decreased cocaine taking under the Chain schedule and PR schedule in all 5 monkeys and in 4 of the 5 monkeys under the Choice schedule. d- Amphetamine (0.06 - 0.25 mg/kg, i.m.), tested as a control manipulation, decreased cocaine taking in all 5 monkeys under the Chain schedule. The peptide hypocretin-1 (0.072 mg/kg, i.v.) increased cocaine taking in the monkeys with low rates of cocaine taking under the Chain (3/4) and Choice (4/5) schedules. Reinstatement of extinguished cocaine responding following response-independent delivery of a large dose of cocaine (0.3 mg/kg) was attenuated in 3 of the 5 monkeys by the HCRTr1 antagonist SB-334867. These data expand upon work accomplished in predominantly male rodents suggesting that the hypocretin system modulates the response to appetitive stimuli. A better understanding of this system offers promise as a novel approach in medication development for appetitive disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

48 CFR 836.575 - Schedule of work progress.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Schedule of work progress. 836.575 Section 836.575 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SPECIAL... work progress. The contracting officer shall insert the clause at 852.236-84, Schedule of work progress...

Choice in situations of time-based diminishing returns: immediate versus delayed consequences of action.

PubMed Central

Hackenberg, T D; Hineline, P N

1992-01-01

Pigeons chose between two schedules of food presentation, a fixed-interval schedule and a progressive-interval schedule that began at 0 s and increased by 20 s with each food delivery provided by that schedule. Choosing one schedule disabled the alternate schedule and stimuli until the requirements of the chosen schedule were satisfied, at which point both schedules were again made available. Fixed-interval duration remained constant within individual sessions but varied across conditions. Under reset conditions, completing the fixed-interval schedule not only produced food but also reset the progressive interval to its minimum. Blocks of sessions under the reset procedure were interspersed with sessions under a no-reset procedure, in which the progressive schedule value increased independent of fixed-interval choices. Median points of switching from the progressive to the fixed schedule varied systematically with fixed-interval value, and were consistently lower during reset than during no-reset conditions. Under the latter, each subject's choices of the progressive-interval schedule persisted beyond the point at which its requirements equaled those of the fixed-interval schedule at all but the highest fixed-interval value. Under the reset procedure, switching occurred at or prior to that equality point. These results qualitatively confirm molar analyses of schedule preference and some versions of optimality theory, but they are more adequately characterized by a model of schedule preference based on the cumulated values of multiple reinforcers, weighted in inverse proportion to the delay between the choice and each successive reinforcer. PMID:1548449

GABA(A) and dopamine receptors in the nucleus accumbens shell differentially influence performance of a water-reinforced progressive ratio task.

PubMed

Covelo, Ignacio R; Wirtshafter, David; Stratford, Thomas R

2012-03-01

Several authors have shown that injections of the GABA(A) agonist muscimol into the medial shell region of the nucleus accumbens (AcbSh) result in large increases in food, but not water, intake. In previous studies we demonstrated that intra-AcbSh injections of either muscimol or of the indirect dopamine agonist amphetamine increase response output on a food-reinforced progressive ratio schedule. In the current experiment we extended these observations by examining the effects of muscimol and amphetamine injections on the performance of a water-reinforced progressive ratio task in mildly deprived animals. We found that muscimol did not affect the number of responses made in the water-reinforced task, even though a marked increase in responding was observed after amphetamine. Muscimol did, however, significantly increase food intake in the same animals. The results suggest that the enhancing effects of intra-AcbSh muscimol differ from those of amphetamine in that they are selective for food-reinforced behaviors. Copyright © 2011. Published by Elsevier Inc.

Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

PubMed

Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

2013-03-01

Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats

PubMed Central

Besheer, Joyce; Faccidomo, Sara; Grondin, Julie J. M.; Hodge, Clyde W.

2008-01-01

Background Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self-administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement. Methods Alcohol-preferring (P) rats were trained to self-administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self-administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance. Results The mGluR1 antagonist, 3,4-dihydro-2H-pyrano[2,3]b quinolin-7-yl (cis-4-methoxy-cyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6-methyl-2-(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose-dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity. Conclusions Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self-administer ethanol. PMID:18162077

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans.

PubMed

Stoops, William W; Vansickel, Andrea R; Lile, Joshua A; Rush, Craig R

2007-05-01

Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified progressive-ratio procedure in two sessions in which they received pretreatment with either 0 or 15 mg oral d-amphetamine 2 h prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

Reinforcing and discriminative stimulus effects of RTI 111, a 3-phenyltropane analog, in rhesus monkeys: interaction with methamphetamine.

PubMed

Ranaldi, R; Anderson, K G; Carroll, F I; Woolverton, W L

2000-12-01

The neuronal actions of methamphetamine (MA) include an increase in extracellular levels of monoamines, presumably via reverse transport involving the monoamine transporters. This action is thought to play an important role in the effects of MA. Therefore, in the present experiment, it was hypothesized that a monoamine uptake blocker would block behavioral effects of MA related to its abuse. RTI 111, a newly synthesized 3-phenyltropane analog with high affinity for the dopamine, norepinephrine, and serotonin transporters, was evaluated alone and in combination with MA for its ability to block the reinforcing and discriminative stimulus effects of MA in rhesus monkeys. RTI 111 (0.0003-0.03 mg/kg, i.v.) was made available to four rhesus monkeys for self-administration under a fixed-ratio 25 (FR 25) schedule of reinforcement. RTI 111 (0.01-0.1 mg/kg, i.m.) was also administered as a pretreatment (15 min prior) to four monkeys self-administering MA (0.0-0.3 mg/kg per injection, i.v.) on a progressive-ratio schedule of reinforcement. MA (0.01-1.0 mg/kg, i.m.), RTI 111 (0.001-0.1 mg/kg, i.m.), or the combination of MA and RTI 111 were administered to four monkeys trained to discriminate (+)-amphetamine (AMPH; 1.0 or 1.7 mg/kg, intragastric) from saline. When RTI 111 was made available for self-administration under an FR 25 schedule it functioned as a positive reinforcer in all four monkeys tested. When RTI 111 was given as a pretreatment to monkeys self-administering MA under a progressive-ratio schedule, the MA dose-response function shifted to the left and down. When RTI 111 or MA were given to monkeys trained to discriminate AMPH from saline, full AMPH-like responding was observed for both drugs. Given in combination, RTI 111 shifted the MA dose-response function to the left. These data suggest that RTI 111 is behaviorally similar to traditional psychomotor stimulants that act at the DA transporter and that it increases, rather than blocks, the behavioral potency of MA.

The Peroxisome Proliferator-Activated Receptor Alpha Agonist Fenofibrate Attenuates Alcohol Self-administration in Rats

PubMed Central

Haile, Colin N.; Kosten, Therese A.

2017-01-01

Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment. Results showed fenofibrate dose-dependently decreased EtOH self-administration under both schedules of reinforcement with the greatest effects seen after four to five days of treatment. Fenofibrate decreased responding for sucrose only under the PR schedule of reinforcement and this effect was not dose-dependent. These findings provide further evidence for fenofibrate as a potential treatment for alcohol use disorder in humans. PMID:28088358

Contextual Interference in Complex Bimanual Skill Learning Leads to Better Skill Persistence

PubMed Central

Pauwels, Lisa; Swinnen, Stephan P.; Beets, Iseult A. M.

2014-01-01

The contextual interference (CI) effect is a robust phenomenon in the (motor) skill learning literature. However, CI has yielded mixed results in complex task learning. The current study addressed whether the CI effect is generalizable to bimanual skill learning, with a focus on the temporal evolution of memory processes. In contrast to previous studies, an extensive training schedule, distributed across multiple days of practice, was provided. Participants practiced three frequency ratios across three practice days following either a blocked or random practice schedule. During the acquisition phase, better overall performance for the blocked practice group was observed, but this difference diminished as practice progressed. At immediate and delayed retention, the random practice group outperformed the blocked practice group, except for the most difficult frequency ratio. Our main finding is that the random practice group showed superior performance persistence over a one week time interval in all three frequency ratios compared to the blocked practice group. This study contributes to our understanding of learning, consolidation and memory of complex motor skills, which helps optimizing training protocols in future studies and rehabilitation settings. PMID:24960171

Combating Drug Abuse by Targeting Toll-Like Receptor 4 (TLR)

DTIC Science & Technology

2015-12-01

animals continued with cocaine self-administration for an additional 4 days. The animals then underwent six days of extinction training followed by cue... extinction conditions to identify the indirect effects of (+)- naltrexone administration on cocaine seeking. Animals administered (+)-naltrexone during...sterile water and implanted after the last day of self-administration on FR5 (one day prior to the start of the progressive ratio schedule). The animals

Disrupted social development enhances the motivation for cocaine in rats.

PubMed

Baarendse, Petra J J; Limpens, Jules H W; Vanderschuren, Louk J M J

2014-04-01

Early social experiences are of major importance for behavioural development. In particular, social play behaviour during post-weaning development is thought to facilitate the attainment of social, emotional and cognitive capacities. Conversely, social insults during development can cause long-lasting behavioural impairments and increase the vulnerability for psychiatric disorders, such as drug addiction. The aim of this study was to investigate whether a lack of social experiences during the juvenile and early adolescent stage, when social play behaviour is highly abundant, alters cocaine self-administration in rats. Rats were socially isolated from postnatal days 21 to 42 followed by re-socialization until adulthood. Cocaine self-administration was then assessed under a fixed ratio and progressive ratio schedule of reinforcement. Next, cue, cocaine and stress-induced reinstatement of cocaine seeking was determined following extinction of self-administration. Early social isolation resulted in an enhanced acquisition of self-administration of a low dose (0.083 mg/infusion) of cocaine, but the sensitivity to cocaine reinforcement, assessed using a dose-response analysis, was not altered in isolated rats. Moreover, isolated rats displayed an increased motivation for cocaine under a progressive ratio schedule of reinforcement. Extinction and reinstatement of cocaine seeking was not affected by early social isolation. Early social isolation causes a long-lasting increase in the motivation to self-administer cocaine. Thus, aberrations in post-weaning social development, such as the absence of social play, enhance the vulnerability for drug addiction later in life.

Nucleus accumbens opioid, GABaergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat.

PubMed

Zhang, Min; Balmadrid, Christian; Kelley, Ann E

2003-04-01

The current studies were designed to evaluate whether incentive motivation for palatable food is altered after manipulations of opioid, GABAergic, and dopaminergic transmission within the nucleus accumbens. A progressive ratio schedule was used to measure lever-pressing for sugar pellets after microinfusion of drugs into the nucleus accumbens in non-food-deprived rats. The mu opioid agonist D-Ala2, NMe-Phe4, Glyo15-enkephalin and the indirect dopamine agonist amphetamine induced a marked increase in break point and correct lever-presses; the GABA(A) agonist muscimol did not affect breakpoint or lever-presses. The data suggest that opioid, dopaminergic, and GABAergic systems within the accumbens differentially modulate food-seeking behavior through mechanisms related to hedonic evaluation of food, incentive salience, and control of motor feeding circuits, respectively.

What 50 Years of Research Tell Us About Pausing Under Ratio Schedules of Reinforcement

PubMed Central

Schlinger, Henry D; Derenne, Adam; Baron, Alan

2008-01-01

Textbooks in learning and behavior commonly describe performance on fixed-ratio schedules as “break and run,” indicating that after reinforcement subjects typically pause and then respond quickly to the next reinforcement. Performance on variable-ratio schedules, on the other hand, is described as steady and fast, with few long pauses. Beginning with Ferster and Skinner's magnum opus, Schedules of Reinforcement (1957), the literature on pausing under ratio schedules has identified the influences on pausing of numerous important variables, in particular ratio size and reinforcement magnitude. As a result, some previously held assumptions have been called into question. For example, research has shown that the length of the pause is controlled not only by the preceding ratio, as Ferster and Skinner and others had assumed (and as implied by the phrase postreinforcement pause), but by the upcoming ratio as well. Similarly, despite the commonly held belief that ratio pausing is unique to the fixed-ratio schedule, there is evidence that pausing also occurs under variable-ratio schedules. If such widely held beliefs are incorrect, then what about other assumptions? This article selectively examines the literature on pausing under ratio schedules over the past 50 years and concludes that although there may indeed be some common patterns, there are also inconsistencies that await future resolution. Several accounts of pausing under ratio schedules are discussed along with the implications of the literature for human performances, most notably the behaviors termed procrastination. PMID:22478501

Instructional versus schedule control of humans' choices in situations of diminishing returns

PubMed Central

Hackenberg, Timothy D.; Joker, Veronica R.

1994-01-01

Four adult humans chose repeatedly between a fixed-time schedule (of points later exchangeable for money) and a progressive-time schedule that began at 0 s and increased by a fixed number of seconds with each point delivered by that schedule. Each point delivered by the fixed-time schedule reset the requirements of the progressive-time schedule to its minimum value. Subjects were provided with instructions that specified a particular sequence of choices. Under the initial conditions, the instructions accurately specified the optimal choice sequence. Thus, control by instructions and optimal control by the programmed contingencies both supported the same performance. To distinguish the effects of instructions from schedule sensitivity, the correspondence between the instructed and optimal choice patterns was gradually altered across conditions by varying the step size of the progressive-time schedule while maintaining the same instructions. Step size was manipulated, typically in 1-s units, first in an ascending and then in a descending sequence of conditions. Instructions quickly established control in all 4 subjects but, by narrowing the range of choice patterns, they reduced subsequent sensitivity to schedule changes. Instructional control was maintained across the ascending sequence of progressive-time values for each subject, but eventually diminished, giving way to more schedule-appropriate patterns. The transition from instruction-appropriate to schedule-appropriate behavior was characterized by an increase in the variability of choice patterns and local increases in point density. On the descending sequence of progressive-time values, behavior appeared to be schedule sensitive, sometimes even optimally sensitive, but it did not always change systematically with the contingencies, suggesting the involvement of other factors. PMID:16812747

A Model of Alcohol Drinking under an Intermittent Access Schedule Using Group-Housed Mice

PubMed Central

Smutek, Magdalena; Turbasa, Mateusz; Sikora, Magdalena; Piechota, Marcin; Zajdel, Joanna; Przewlocki, Ryszard; Parkitna, Jan Rodriguez

2014-01-01

Here, we describe a new model of voluntary alcohol drinking by group-housed mice. The model employs sensor-equipped cages that track the behaviors of the individual animals via implanted radio chips. After the animals were allowed intermittent access to alcohol (three 24 h intervals every week) for 4 weeks, the proportions of licks directed toward bottles containing alcohol were 50.9% and 39.6% for the male and female mice, respectively. We used three approaches (i.e., quinine adulteration, a progressive ratio schedule and a schedule involving a risk of punishment) to test for symptoms of compulsive alcohol drinking. The addition of 0.01% quinine to the alcohol solution did not significantly affect intake, but 0.03% quinine induced a greater than 5-fold reduction in the number of licks on the alcohol bottles. When the animals were required to perform increasing numbers of instrumental responses to obtain access to the bottle with alcohol (i.e., a progressive ratio schedule), they frequently reached a maximum of 21 responses irrespective of the available reward. Although the mice rarely achieved higher response criteria, the number of attempts was ∼10 times greater in case of alcohol than water. We have developed an approach for mapping social interactions among animals that is based on analysis of the sequences of entries into the cage corners. This approach allowed us to identify the mice that followed other animals in non-random fashions. Approximately half of the mice displayed at least one interaction of this type. We have not yet found a clear correlation between imitative behavior and relative alcohol preference. In conclusion, the model we describe avoids the limitations associated with testing isolated animals and reliably leads to stable alcohol drinking. Therefore, this model may be well suited to screening for the effects of genetic mutations or pharmacological treatments on alcohol-induced behaviors. PMID:24804807

Distinct Contributions of Dopamine in the Dorsolateral Striatum and Nucleus Accumbens Shell to the Reinforcing Properties of Cocaine

PubMed Central

Veeneman, Maartje M J; Broekhoven, Mark H; Damsteegt, Ruth; Vanderschuren, Louk J M J

2012-01-01

Dopaminergic neurotransmission in the dorsal and ventral striatum is thought to be involved in distinct aspects of cocaine addiction. Ventral striatal dopamine mediates the acute reinforcing properties of cocaine, whereas dopamine in the dorsolateral striatum (DLS) is thought to become involved in later stages of the addiction process to mediate well-established cue-controlled drug seeking. However, it is unclear whether the DLS also has a role in the reinforcing properties of cocaine itself. Therefore, we systematically investigated the involvement of dopamine in dorsal and ventral striatal regions in cocaine self-administration, using various schedules of reinforcement in animals with limited drug taking experience. Intra-DLS infusion of the dopamine receptor antagonist α-flupenthixol did not affect the acquisition of cocaine self-administration, increased cocaine self-administration under a fixed ratio-1 (FR-1) schedule of reinforcement, caused a rightward and downward shift of the dose–response curve of cocaine under an FR-1 schedule of reinforcement and decreased responding for cocaine under a progressive ratio (PR) schedule of reinforcement. Infusion of α-flupenthixol into the ventral nucleus accumbens (NAcc) shell inhibited the acquisition of cocaine self-administration, reduced responding for the drug under FR-1 and PR schedules of reinforcement, and caused a downward shift of the dose–response curve of cocaine self-administration under an FR-1 schedule of reinforcement. These data show that dopamine in both the DLS and NAcc shell is involved in cocaine reinforcement. We suggest that the DLS and the NAcc shell mediate somewhat distinct facets of the reinforcing properties of cocaine, related to its rewarding and motivational aspects, respectively. PMID:21918505

Generating variable and random schedules of reinforcement using Microsoft Excel macros.

PubMed

Bancroft, Stacie L; Bourret, Jason C

2008-01-01

Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time. Generating schedule values for variable and random reinforcement schedules can be difficult. The present article describes the steps necessary to write macros in Microsoft Excel that will generate variable-ratio, variable-interval, variable-time, random-ratio, random-interval, and random-time reinforcement schedule values.

Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55,940 on morphine self-administration behaviour and the endogenous opioid system.

PubMed

Biscaia, Miguel; Fernández, Beatriz; Higuera-Matas, Alejandro; Miguéns, Miguel; Viveros, Maria-Paz; García-Lecumberri, Carmen; Ambrosio, Emilio

2008-04-01

Early cannabinoid consumption may predispose individuals to the misuse of addictive drugs later in life. However, there is a lack of experimental evidence as to whether cannabinoid exposure during adolescence might differently affect opiate reinforcing efficacy and the opioid system in adults of both sexes. Our aim was to examine whether periadolescent chronic exposure to the cannabinoid agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and the opioid system in adulthood. Morphine reinforcing was studied under a progressive ratio (PR) reinforcement schedule in adult male and female rats that previously acquired morphine self-administration under a fixed ratio 1 (FR1) schedule. Binding levels and functionality of mu-opioid receptors were also evaluated. Periadolescent cannabinoid exposure altered morphine self-administration and the opioid system in adult rats in a sex-dependent manner. CP-55,940-exposed males exhibited higher self-administration rates under a FR1, but not under a PR schedule. In females, CP-55,940 did not modify morphine self-administration under either schedule. Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-shell observed in these animals.

Comparing fixed-amount and progressive-amount DRO Schedules for tic suppression in youth with chronic tic disorders.

PubMed

Capriotti, Matthew R; Turkel, Jennifer E; Johnson, Rachel A; Espil, Flint M; Woods, Douglas W

2017-01-01

Chronic tic disorders (CTDs) involve motor and/or vocal tics that often cause substantial distress and impairment. Differential reinforcement of other behavior (DRO) schedules of reinforcement produce robust, but incomplete, reductions in tic frequency in youth with CTDs; however, a more robust reduction may be needed to affect durable clinical change. Standard, fixed-amount DRO schedules have not commonly yielded such reductions, so we evaluated a novel, progressive-amount DRO schedule, based on its ability to facilitate sustained abstinence from functionally similar behaviors. Five youth with CTDs were exposed to periods of baseline, fixed-amount DRO (DRO-F), and progressive-amount DRO (DRO-P). Both DRO schedules produced decreases in tic rate and increases in intertic interval duration, but no systematic differences were seen between the two schedules on any dimension of tic occurrence. The DRO-F schedule was generally preferred to the DRO-P schedule. Possible procedural improvements and other future directions are discussed. © 2016 Society for the Experimental Analysis of Behavior.

Generating Variable and Random Schedules of Reinforcement Using Microsoft Excel Macros

PubMed Central

Bancroft, Stacie L; Bourret, Jason C

2008-01-01

Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time. Generating schedule values for variable and random reinforcement schedules can be difficult. The present article describes the steps necessary to write macros in Microsoft Excel that will generate variable-ratio, variable-interval, variable-time, random-ratio, random-interval, and random-time reinforcement schedule values. PMID:18595286

A hybrid online scheduling mechanism with revision and progressive techniques for autonomous Earth observation satellite

NASA Astrophysics Data System (ADS)

Li, Guoliang; Xing, Lining; Chen, Yingwu

2017-11-01

The autonomicity of self-scheduling on Earth observation satellite and the increasing scale of satellite network attract much attention from researchers in the last decades. In reality, the limited onboard computational resource presents challenge for the online scheduling algorithm. This study considered online scheduling problem for a single autonomous Earth observation satellite within satellite network environment. It especially addressed that the urgent tasks arrive stochastically during the scheduling horizon. We described the problem and proposed a hybrid online scheduling mechanism with revision and progressive techniques to solve this problem. The mechanism includes two decision policies, a when-to-schedule policy combining periodic scheduling and critical cumulative number-based event-driven rescheduling, and a how-to-schedule policy combining progressive and revision approaches to accommodate two categories of task: normal tasks and urgent tasks. Thus, we developed two heuristic (re)scheduling algorithms and compared them with other generally used techniques. Computational experiments indicated that the into-scheduling percentage of urgent tasks in the proposed mechanism is much higher than that in periodic scheduling mechanism, and the specific performance is highly dependent on some mechanism-relevant and task-relevant factors. For the online scheduling, the modified weighted shortest imaging time first and dynamic profit system benefit heuristics outperformed the others on total profit and the percentage of successfully scheduled urgent tasks.

Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement

PubMed Central

Sharf, Ruth; Sarhan, Maysa; Brayton, Catherine E.; Guarnieri, Douglas J.; Taylor, Jane R.; DiLeone, Ralph J.

2010-01-01

Background Orexin (hypocretin) signaling is implicated in drug addiction and reward, but its role in feeding and food-motivated behavior remains unclear. Methods We investigated orexin’s contribution to food-reinforced instrumental responding using an orexin 1 receptor (Ox1r) antagonist, orexin −/− (OKO) and littermate wild-type (WT) mice, and RNAi-mediated knockdown of orexin. C57BL/6J (n=76) and OKO (n=39) mice were trained to nose poke for food under a variable ratio (VR) schedule of reinforcement. Once responding stabilized, a progressive ratio (PR) schedule was initiated to evaluate motivation to obtain food reinforcement. Results Blockade of Ox1r in C57BL/6J mice impaired performance under both the VR and PR schedules of reinforcement, indicating impaired motivational processes. In contrast, OKO mice initially demonstrated a delay in acquisition, but eventually achieved levels of responding similar to those observed in WT animals. Moreover, OKO mice did not differ from WT mice under a PR schedule, indicating delayed learning processes but no motivational impairments. Considering the differences between pharmacological blockade of Ox1r and the OKO mice, animals with RNAi mediated knockdown of orexin were then generated and analyzed to eliminate possible developmental effects of missing orexin. Orexin gene knockdown in the lateral hypothalamus (LH) in C57BL/6J mice resulted in blunted performance under both the VR and PR schedules, resembling data obtained following Ox1r antagonism. Conclusions The behavior seen in OKO mice likely reflects developmental compensation often seen in mutant animals. These data suggest that activation of the Ox1r is a necessary component of food-reinforced responding and/or motivation in normal mice. PMID:20189166

Lack of effect of habenula lesion on heroin self-administration in rats.

PubMed

Wang, Yuhong; Zhang, Fuqiang; Tang, Shuaien; Lai, Miaojun; Hao, Wei; Zhang, Yong; Yang, Jianli; Zhou, Wenhua

2009-09-18

We examined the effects of bilateral electric lesion of the habenula (Hb) on the acquisition and maintenance of heroin self-administration. The rats were trained to self-administer heroin (0.05 mg/kg/infusion) under FR1 schedule in daily 4h sessions. A progressive ratio schedule (PR3-4) was used to evaluate the relative motivational value of heroin reinforcement. Compared with the controls, neither pre-training nor post-training of Hb lesions had any effects on the total amount of infusions and motivational value of heroin reward. However, pre-training Hb lesion caused transient active and inactive nose-poke responding in the early phase of training, suggesting increased locomotor exploration. The results suggest that Hb might not play an important role in mediating the acute reinforcing effect of heroin.

Effects of Cocaine on Performance under Fixed-Interval Schedules with a Small Tandem Ratio Requirement

ERIC Educational Resources Information Center

Pinkston, Jonathan W.; Branch, Marc N.

2004-01-01

Daily administration of cocaine often results in the development of tolerance to its effects on responding maintained by fixed-ratio schedules. Such effects have been observed to be greater when the ratio value is small, whereas less or no tolerance has been observed at large ratio values. Similar schedule-parameter-dependent tolerance, however,…

Interresponse Time Structures in Variable-Ratio and Variable-Interval Schedules

ERIC Educational Resources Information Center

Bowers, Matthew T.; Hill, Jade; Palya, William L.

2008-01-01

The interresponse-time structures of pigeon key pecking were examined under variable-ratio, variable-interval, and variable-interval plus linear feedback schedules. Whereas the variable-ratio and variable-interval plus linear feedback schedules generally resulted in a distinct group of short interresponse times and a broad distribution of longer…

Consumption-leisure tradeoffs in pigeons: Effects of changing marginal wage rates by varying amount of reinforcement.

PubMed

Green, L; Kagel, J H; Battalio, R C

1987-01-01

Pigeons' rates of responding and food reinforcement under simple random-ratio schedules were compared with those obtained under comparable ratio schedules in which free food deliveries were added, but the duration of each food delivery was halved. These ratio-with-free-food schedules were constructed so that, were the pigeon to maintain the same rate of responding as it had under the simple ratio schedule, total food obtained (earned plus free) would remain unchanged. However, any reduction in responding would reduce total food consumption below that under the simple ratio schedule. These "compensated wage decreases" led to decreases in responding and decreases in food consumption, as predicted by an economic model of labor supply. Moreover, the reductions in responding increased as the ratio value increased (i.e., as wage rates decreased). Pigeons, therefore, substituted leisure for consumption. The relationship between these procedures and negative-income-tax programs is noted.

The GLP-1 agonist exendin-4 attenuates self-administration of sweetened fat on fixed and progressive ratio schedules of reinforcement

PubMed Central

Bernosky-Smith, Kimberly A.; Stanger, David B.; Trujillo, Alexandria J.; Mitchell, Luke R.; Espana, Rodrigo A.; Bass, Caroline E.

2016-01-01

GLP-1 agonists such as exendin-4 (EX4) are used in the treatment of type 2 diabetes and have the additional benefit of promoting weight loss. GLP-1 agonists decrease feeding through peripheral affects, but recent evidence suggests they may also influence sweet or high fat preference, as well as the motivation to obtain these tastants. Yet it remains unclear how GLP-1 induced alterations in food preference influences the decrease in overall feeding. The current study sought to determine if EX4 affects the reinforcing strength and consumption of a highly palatable sweet/fat reinforcer. Rats were trained to self-administer sweetened vegetable shortening (SVS) under fixed (FR) and progressive ratio (PR) schedules of reinforcement. EX4 (0.3 - 2.4 μg/kg, IP) administered one hour prior to operant sessions significantly reduced responding for SVS under both FR and PR schedules (e.g. total reinforcers and breakpoints, respectively), although the lowest active dose (0.6 μg/kg) significantly suppressed FR responding only. EX4 also dose dependently decreased locomotor activity (0.6-2.4 μg/kg doses), but did not enhance acute kaolin intake, indicating that EX4-induced nausea did not influence the self-administration results. Analysis of ED50 values show that EX4 is more effective at inhibiting FR responding versus PR, indicating that EX4 may have more potent effects on consummatory versus appetitive feeding behaviors. Although EX4 caused generalized behavioral suppression, these results cannot fully explain the decreases in operant responding. For example, the 0.6 μg/kg dose inhibited only FR responding, even though the rats were physically capable of responding at a higher rate during PR sessions. In addition, the rate of intake was constant at the beginning of the sessions in both PR and FR schedules, regardless of the dose. Together these data suggest that EX4 inhibits consumption of a palatable high sweet/high fat reinforcer potentially through altering satiety. PMID:26701752

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

Spike: AI scheduling for Hubble Space Telescope after 18 months of orbital operations

NASA Technical Reports Server (NTRS)

Johnston, Mark D.

1992-01-01

This paper is a progress report on the Spike scheduling system, developed by the Space Telescope Science Institute for long-term scheduling of Hubble Space Telescope (HST) observations. Spike is an activity-based scheduler which exploits artificial intelligence (AI) techniques for constraint representation and for scheduling search. The system has been in operational use since shortly after HST launch in April 1990. Spike was adopted for several other satellite scheduling problems; of particular interest was the demonstration that the Spike framework is sufficiently flexible to handle both long-term and short-term scheduling, on timescales of years down to minutes or less. We describe the recent progress made in scheduling search techniques, the lessons learned from early HST operations, and the application of Spike to other problem domains. We also describe plans for the future evolution of the system.

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys.

PubMed

Gerak, Lisa R; Collins, Gregory T; France, Charles P

2016-12-01

Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin 2C [5-hydroxytryptamine 2C (5-HT 2C )] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1-1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32-100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10-17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys

PubMed Central

Gerak, Lisa R.; Collins, Gregory T.

2016-01-01

Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C [5-hydroxytryptamine2C (5-HT2C)] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32–320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1–1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32–100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10–17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. PMID:27650954

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Genetic differences in NMDA and D1 receptor levels, and operant responding for food and morphine in Lewis and Fischer 344 rats.

PubMed

Martín, Sonsoles; Lyupina, Yulia; Crespo, José Antonio; González, Begoña; García-Lecumberri, Carmen; Ambrosio, Emilio

2003-05-30

Previously, we have shown that Lewis (LEW) rats acquire faster than Fischer 344 (F344) rats operant food- and morphine-reinforced tasks under fixed-ratio schedules of reinforcement. The first purpose of the present work has been to study if differences in operant responding behavior may participate in the reported differences in morphine self-administration behavior between both inbred rat strains. To this end, we have analyzed the microstructure of responding obtained under a variable-interval (VI) of food reinforcement by calculating the inter-response time (IRT) for each rat strain. LEW rats exhibited shorter IRTs than F344 rats, suggesting that LEW rats may have an inherent high or compulsive operant responding activity. When subjects of both inbred rat strains were submitted to a schedule of morphine reinforcement of high responding requirements such as progressive ratio schedules, LEW rats also reached significantly higher breaking points and final response ratio than F344 rats for i.v. morphine self-administration. Given that there are neurochemical differences between both rat strains and that glutamatergic N-methyl-D-aspartate (NMDA) and dopaminergic D(1) receptors have been involved in operant responding behavior, a second purpose of this work has been to measure basal NMDA and D(1) receptor levels in these rat strains by quantitative receptor autoradiography. Compared to F344 rats, LEW rats showed higher basal NMDA receptor levels in frontal and cingulate cortex, caudate putamen, central amygdaloid nuclei, and intermediate white layer of superior colliculus, and higher basal D(1) receptor levels in several areas of hippocampus and thalamus, and substantia nigra pars reticulata. Taken together, these results suggest that an inherent high operant responding activity of LEW rats may have a role in the previous reported faster acquisition of opiate-reinforced behavior in operant self-administration paradigms under fixed-ratio schedules of reinforcement. In addition, a basal higher NMDA and D(1) receptor levels of LEW rats compared to F344 rats may participate in the neurochemical background that mediates the behavioral differences between both inbred rat strains.

Reinforcer devaluation as a consequence of acute nicotine exposure and withdrawal

PubMed Central

Kirshenbaum, Ari; Green, John; Fay, Michael; Parks, Angelique; Phillips, Jesse; Stone, Jason; Roy, Tessa

2014-01-01

RATIONALE Nicotine discontinuation produces behaviors in rats that are congruent with anhedonia, and these symptoms may be related to the devaluation of non-nicotine reinforcers. OBJECTIVE Four separate experiments were performed to explore the parameters surrounding nicotine-induced reinforcer devaluation. METHODS In Experiments 1 and 2, nicotine (0.1 or 0.3 mg/kg) or 0.3 mg/kg nicotine plus 1.0 mg/kg mecamylamine was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. In order to (a) evaluate reinforcer enhancement by nicotine, and (b) reinforcer devaluation in the absence of nicotine, all rats experienced two PR schedule sessions per day for 10 days. Experiment 3 involved nicotine (0.3 mg/kg) and a visual stimulus in place of sucrose reinforcement. In Experiment 4, rats received nicotine (0.3 mg/kg) either before or after a single PR-schedule session for 10 days. RESULTS Experiments 1 and 2 demonstrate that reinforcer devaluation is related to the occupation of nicotinic-acetylcholine receptors. Results from Experiment 3 provide some evidence that devaluation occurs with either sucrose or visual-stimulus reinforcement. Experiment 4 demonstrates that a necessary condition for reinforcer devaluation to occur is the concurrent exposure to the reinforcer and nicotine. CONCLUSIONS Reinforcer devaluation in rats emerges rapidly in a progressive, orderly fashion that coincides with accumulated exposure to nicotine. These results suggest that reinforcer devaluation may be a feature of nicotine that contributes to the abuse liability of tobacco products. PMID:25401169

The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats.

PubMed

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

2016-09-01

Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads. Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule. Cocaine-maintained breakpoints increased by ∼17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ∼70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner.

The Effects of Sex, Estrous Cycle, and Social Contact on Cocaine and Heroin Self-Administration in Rats

PubMed Central

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

2017-01-01

Rationale Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. Objective Examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads. Methods Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive-ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed-ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed-ratio schedule. Results Cocaine-maintained breakpoints increased by ~17% in females during estrus but remained consistent in males. Heroin self-administration decreased by ~70% during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. Conclusions Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner. PMID:27370020

Evaluating The Influence of Postsession Reinforcement on Choice of Reinforcers

PubMed Central

Kodak, Tiffany; Lerman, Dorothea C; Call, Nathan

2007-01-01

Factors that influence reinforcer choice have been examined in a number of applied studies (e.g., Neef, Mace, Shea, & Shade, 1992; Shore, Iwata, DeLeon, Kahng, & Smith, 1997; Tustin, 1994). However, no applied studies have evaluated the effects of postsession reinforcement on choice between concurrently available reinforcers, even though basic findings indicate that this is an important factor to consider (Hursh, 1978; Zeiler, 1999). In this bridge investigation, we evaluated the influence of postsession reinforcement on choice of two food items when task responding was reinforced on progressive-ratio schedules. Participants were 3 children who had been diagnosed with developmental disabilities. Results indicated that response allocation shifted from one food item to the other food item under thinner schedules of reinforcement when no postsession reinforcement was provided. These findings suggest that the efficacy of instructional programs or treatments for problem behavior may be improved by restricting reinforcers outside treatment sessions. PMID:17970264

Evaluating the influence of postsession reinforcement on choice of reinforcers.

PubMed

Kodak, Tiffany; Lerman, Dorothea C; Call, Nathan

2007-01-01

Factors that influence reinforcer choice have been examined in a number of applied studies (e.g., Neef, Mace, Shea, & Shade, 1992; Shore, Iwata, DeLeon, Kahng, & Smith, 1997; Tustin, 1994). However, no applied studies have evaluated the effects of postsession reinforcement on choice between concurrently available reinforcers, even though basic findings indicate that this is an important factor to consider (Hursh, 1978; Zeiler, 1999). In this bridge investigation, we evaluated the influence of postsession reinforcement on choice of two food items when task responding was reinforced on progressive-ratio schedules. Participants were 3 children who had been diagnosed with developmental disabilities. Results indicated that response allocation shifted from one food item to the other food item under thinner schedules of reinforcement when no postsession reinforcement was provided. These findings suggest that the efficacy of instructional programs or treatments for problem behavior may be improved by restricting reinforcers outside treatment sessions.

The Isolation of Motivational, Motoric, and Schedule Effects on Operant Performance: A Modeling Approach

PubMed Central

Brackney, Ryan J; Cheung, Timothy H. C; Neisewander, Janet L; Sanabria, Federico

2011-01-01

Dissociating motoric and motivational effects of pharmacological manipulations on operant behavior is a substantial challenge. To address this problem, we applied a response-bout analysis to data from rats trained to lever press for sucrose on variable-interval (VI) schedules of reinforcement. Motoric, motivational, and schedule factors (effort requirement, deprivation level, and schedule requirements, respectively) were manipulated. Bout analysis found that interresponse times (IRTs) were described by a mixture of two exponential distributions, one characterizing IRTs within response bouts, another characterizing intervals between bouts. Increasing effort requirement lengthened the shortest IRT (the refractory period between responses). Adding a ratio requirement increased the length and density of response bouts. Both manipulations also decreased the bout-initiation rate. In contrast, food deprivation only increased the bout-initiation rate. Changes in the distribution of IRTs over time showed that responses during extinction were also emitted in bouts, and that the decrease in response rate was primarily due to progressively longer intervals between bouts. Taken together, these results suggest that changes in the refractory period indicate motoric effects, whereas selective alterations in bout initiation rate indicate incentive-motivational effects. These findings support the use of response-bout analyses to identify the influence of pharmacological manipulations on processes underlying operant performance. PMID:21765544

Developmental and familial predictors of adult cognitive traits in the European starling

PubMed Central

Nettle, Daniel; Andrews, Clare P.; Monaghan, Pat; Brilot, Ben O.; Bedford, Thomas; Gillespie, Robert; Bateson, Melissa

2015-01-01

In birds, there is evidence that adult cognitive traits can both run in families and be affected by early developmental influences. However, different studies use different cognitive tasks, which may not be measuring the same traits, and also focus on different developmental factors. We report results from a study in which we administered multiple cognitive tasks (autoshaping, discrimination learning, reversal learning, progressive ratio schedule, extinction learning and impulsivity) to a cohort of 34 European starlings, Sturnus vulgaris, for which several early developmental measures were available. The cohort consisted of siblings raised either apart or together, whose position in the size hierarchy of the rearing brood had been experimentally manipulated. We examined how the different cognitive measures covaried, the extent to which they ran in families, and which of the developmental factors predicted which of the cognitive outcomes. We found that discrimination and reversal learning speeds were positively correlated, as were breakpoint on the progressive ratio schedule and resistance to extinction. Otherwise, the cognitive measures were uncorrelated, suggesting that they reflected different underlying traits. All traits except discrimination and reversal learning speed ran in families to a substantial extent. Using a model selection approach, we found evidence that natal brood size and developmental telomere attrition (the extent to which the birds' erythrocyte telomeres shortened in early life, an integrative measure of developmental stress) were related to several adult cognitive measures. Results are discussed with respect to the best way of measuring avian cognitive abilities, and the utility of developmental telomere attrition as a predictor of adult outcomes. PMID:26405302

Caffeine increases the motivation to obtain non-drug reinforcers in rats

PubMed Central

Sheppard, A. Brianna; Gross, Skyler C.; Pavelka, Sarah A.; Hall, Melanie J.; Palmatier, Matthew I.

2012-01-01

BACKGROUND Caffeine is widely considered to be a reinforcer in humans, but this effect is difficult to measure in non-human animals. We hypothesized that caffeine may have dual reinforcing effects comparable to nicotine - limited primary reinforcing effects, but potent reinforcement enhancing effects. The present studies tested this hypothesis by investigating the effect of caffeine on responding for non-drug rewards. METHODS In two experiments, rats were shaped to respond on a progressive ratio (PR) schedule for sucrose solution (20% w/v; Experiment 1) or a fixed ratio 2 (FR2) schedule for a moderately reinforcing visual stimulus (VS; Experiment 2). Pretreatment with various doses of caffeine (0–50 mg/kg, intraperitoneal injection) were administered prior to tests over successive week days (M-F). In Experiment 1, acute administration of low-moderate caffeine doses (6.25–25 mg/kg) increased responding for sucrose under the PR schedule. This effect of caffeine declined over the initial 15 test days. In Experiment 2, only acute pretreatment with 12.5 mg/kg caffeine increased responding for the visual stimulus and complete tolerance to this effect of caffeine was observed over the 15 days of testing. In follow up tests we found that abstinence periods of 4 and 8 days resulted in incomplete recovery of the enhancing effects of caffeine. CONCLUSION The findings suggest that caffeine enhances the reinforcing effects of non-drug stimuli, but that the pharmacological profile of these effects may differ from other psychomotor stimulants. PMID:22336397

Effects of a Signaled Delay to Reinforcement in the Previous and Upcoming Ratios on Between-Ratio Pausing in Fixed-Ratio Schedules

ERIC Educational Resources Information Center

Harris, Aimee; Foster, T. Mary; Levine, Joshua; Temple, William

2012-01-01

Domestic hens responded under multiple fixed-ratio fixed-ratio schedules with equal fixed ratios. One component provided immediate reinforcement and the other provided reinforcement after a delay, signaled by the offset of the key light. The components were presented quasi-randomly so that all four possible transitions occurred in each session.…

Curriculum-Based Measurement of Reading Growth: Weekly versus Intermittent Progress Monitoring

ERIC Educational Resources Information Center

Jenkins, Joseph; Schulze, Margaret; Marti, Allison; Harbaugh, Allen G.

2017-01-01

We examined the idea that leaner schedules of progress monitoring (PM) can lighten assessment demands without undermining decision-making accuracy. Using curriculum-based measurement of reading, we compared effects on decision accuracy of 5 intermittent PM schedules relative to that of every-week PM. For participating students with high-incidence…

National Research Council Dialogue to Assess Progress on NASA's Title of CRM Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Crooke, Julie A.

2005-01-01

Contents include the following: General Background and Introduction of Capability Roadmaps "Title." Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

77 FR 53948 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-04

... proposes to amend the current fee schedule that applies to CME's OTC Interest Rate Swap (``IRS'') clearing offering. Specifically, CME will be adding; (i) An optional alternative fee schedule, (ii) progressive fee... changes relates to new progressive fee tiers. Under these changes, each calendar quarter, firms may...

National Research Council Dialogue to Assess Progress on NASA's Human Health & Support Systems Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Aikins, Jan

2005-01-01

Contents include the following: General Background and Introduction of Capability Roadmaps. Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

Suppression by the cannabinoid CB1 receptor antagonist, rimonabant, of the reinforcing and motivational properties of a chocolate-flavoured beverage in rats.

PubMed

Maccioni, Paola; Pes, Daniela; Carai, Mauro A M; Gessa, Gian Luigi; Colombo, Giancarlo

2008-05-01

Pharmacological blockade of the cannabinoid CB1 receptor has been repeatedly reported to suppress intake of food, including highly palatable foods, in laboratory animals. This study was designed to investigate whether treatment with the cannabinoid CB1 receptor antagonist, rimonabant, would reduce the reinforcing and motivational properties of a chocolate-flavoured beverage [containing 5% (w/v) chocolate powder] in nonfood-deprived and nonwater-deprived Wistar rats trained to self-administer this beverage under an operant conditioning procedure. This study was also aimed at assessing to what degree self-administration behaviour could be manipulated environmentally. After a period of training and maintenance of the self-administration behaviour, separate groups of rats were exposed to different experimental conditions [session length varying from 20 to 120 min; fixed ratio (FR) schedule of reinforcement varying from FR10 to FR40; reinforcer presentation varying from 2.5 to 10 s; concentration of the chocolate powder varying from 5% (w/v) to 0%]; other rat groups were used to test the effect of acute and repeated treatment with rimonabant (1-5.6 mg/kg, intraperitoneally) on two schedules of reinforcement (FR10 and progressive ratio) and extinction responding. All rats rapidly acquired and steadily maintained high levels of self-administration of the chocolate-flavoured beverage. Changes in experimental conditions modified the rats' self-administration behaviour; these changes seemed to be the result of the rats' attempt to adjust their behaviour so as to consume as much of the chocolate-flavoured beverage as possible when it was presented at its most palatable 5% concentration. Treatment with rimonabant dose-dependently suppressed self-administration of the chocolate-flavoured beverage. When rimonabant was administered repeatedly, only a modest degree of tolerance developed to its reducing effect. Finally, treatment with rimonabant resulted in a dose-dependent reduction of the motivational properties of the chocolate-flavoured beverage, measured by the progressive ratio schedule of reinforcement and extinction-responding procedure. These results suggest that self-administration of a chocolate-flavoured beverage can be rapidly and reliably established in rats and that this behaviour is environmentally manipulable. These results also suggest that the cannabinoid CB1 receptor is a crucial component of the neural substrate mediating the reinforcing and motivational properties of a highly palatable food such as a chocolate-flavoured beverage.

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

PubMed

Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

Second-Order Schedules of Token Reinforcement with Pigeons: Implications for Unit Price

ERIC Educational Resources Information Center

Bullock, Christopher E.; Hackenberg, Timothy D.

2006-01-01

Four pigeons were exposed to second-order schedules of token reinforcement, with stimulus lights serving as token reinforcers. Tokens were earned according to a fixed-ratio (token-production) schedule, with the opportunity to exchange tokens for food (exchange period) occurring after a fixed number had been produced (exchange-production ratio).…

Human instrumental performance in ratio and interval contingencies: A challenge for associative theory.

PubMed

Pérez, Omar D; Aitken, Michael R F; Zhukovsky, Peter; Soto, Fabián A; Urcelay, Gonzalo P; Dickinson, Anthony

2016-12-15

Associative learning theories regard the probability of reinforcement as the critical factor determining responding. However, the role of this factor in instrumental conditioning is not completely clear. In fact, free-operant experiments show that participants respond at a higher rate on variable ratio than on variable interval schedules even though the reinforcement probability is matched between the schedules. This difference has been attributed to the differential reinforcement of long inter-response times (IRTs) by interval schedules, which acts to slow responding. In the present study, we used a novel experimental design to investigate human responding under random ratio (RR) and regulated probability interval (RPI) schedules, a type of interval schedule that sets a reinforcement probability independently of the IRT duration. Participants responded on each type of schedule before a final choice test in which they distributed responding between two schedules similar to those experienced during training. Although response rates did not differ during training, the participants responded at a lower rate on the RPI schedule than on the matched RR schedule during the choice test. This preference cannot be attributed to a higher probability of reinforcement for long IRTs and questions the idea that similar associative processes underlie classical and instrumental conditioning.

Artificial intelligence approaches to astronomical observation scheduling

NASA Technical Reports Server (NTRS)

Johnston, Mark D.; Miller, Glenn

1988-01-01

Automated scheduling will play an increasing role in future ground- and space-based observatory operations. Due to the complexity of the problem, artificial intelligence technology currently offers the greatest potential for the development of scheduling tools with sufficient power and flexibility to handle realistic scheduling situations. Summarized here are the main features of the observatory scheduling problem, how artificial intelligence (AI) techniques can be applied, and recent progress in AI scheduling for Hubble Space Telescope.

40 CFR Table 5 to Subpart Fff of... - Generic Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Generic Compliance Schedules and Increments of Progress 5 Table 5 to Subpart FFF of Part 62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan...

40 CFR Table 5 to Subpart Fff of... - Generic Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Generic Compliance Schedules and Increments of Progress 5 Table 5 to Subpart FFF of Part 62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan...

40 CFR Table 5 to Subpart Fff of... - Generic Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 9 2012-07-01 2012-07-01 false Generic Compliance Schedules and Increments of Progress 5 Table 5 to Subpart FFF of Part 62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan...

40 CFR Table 5 to Subpart Fff of... - Generic Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 9 2014-07-01 2014-07-01 false Generic Compliance Schedules and Increments of Progress 5 Table 5 to Subpart FFF of Part 62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan...

40 CFR Table 5 to Subpart Fff of... - Generic Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 9 2013-07-01 2013-07-01 false Generic Compliance Schedules and Increments of Progress 5 Table 5 to Subpart FFF of Part 62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan...

National Research Council Dialogue to Assess Progress on NASA's Advanced Modeling, Simulation and Analysis Capability and Systems Engineering Capability Roadmap Development

NASA Technical Reports Server (NTRS)

Aikins, Jan

2005-01-01

Contents include the following: General Background and Introduction of Capability Roadmaps. Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

Tolerance to Effects of Cocaine on Behavior under a Response-Initiated Fixed-Interval Schedule

ERIC Educational Resources Information Center

Weaver, Matthew T.; Branch, Marc N.

2008-01-01

Tolerance to effects of cocaine can be modulated by schedules of reinforcement. With multiple ratio schedules, research has shown an inverse relationship between ratio requirement and amount of tolerance that resulted from daily administration of the drug. In contrast, tolerance to the effects of cocaine on behavior under multiple interval…

Contingency discriminability and the generalized matching law describe choice on concurrent ratio schedules of wheel-running reinforcement.

PubMed

Belke, Terry W

2012-07-01

Belke (2010) showed that on concurrent ratio schedules, the difference in ratio requirements required to produce near exclusive preference for the lower ratio alternative was substantively greater when the reinforcer was wheel running than when it was sucrose. The current study replicated this finding and showed that this choice behavior can be described by the matching law and the contingency discriminability model. Eight female Long Evans rats were exposed to concurrent VR schedules of wheel-running reinforcement (30s) and the schedule value of the initially preferred alternative was systematically increased. Two rats rapidly developed exclusive preference for the lower ratio alternative, but the majority did not - even when ratios differed by 20:1. Analysis showed that estimates of slopes from the matching law and the proportion of reinforcers misattributed from the contingency discriminability model were related to the ratios at which near exclusive preference developed. The fit of these models would be consistent with misattribution of reinforcers or poor discrimination between alternatives due to the long duration of wheel running. Copyright © 2012 Elsevier B.V. All rights reserved.

Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?

ERIC Educational Resources Information Center

Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.

2005-01-01

Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…

Response Strength in Extreme Multiple Schedules

PubMed Central

McLean, Anthony P; Grace, Randolph C; Nevin, John A

2012-01-01

Four pigeons were trained in a series of two-component multiple schedules. Reinforcers were scheduled with random-interval schedules. The ratio of arranged reinforcer rates in the two components was varied over 4 log units, a much wider range than previously studied. When performance appeared stable, prefeeding tests were conducted to assess resistance to change. Contrary to the generalized matching law, logarithms of response ratios in the two components were not a linear function of log reinforcer ratios, implying a failure of parameter invariance. Over a 2 log unit range, the function appeared linear and indicated undermatching, but in conditions with more extreme reinforcer ratios, approximate matching was observed. A model suggested by McLean (1991), originally for local contrast, predicts these changes in sensitivity to reinforcer ratios somewhat better than models by Herrnstein (1970) and by Williams and Wixted (1986). Prefeeding tests of resistance to change were conducted at each reinforcer ratio, and relative resistance to change was also a nonlinear function of log reinforcer ratios, again contrary to conclusions from previous work. Instead, the function suggests that resistance to change in a component may be determined partly by the rate of reinforcement and partly by the ratio of reinforcers to responses. PMID:22287804

Constraint-Based Scheduling System

NASA Technical Reports Server (NTRS)

Zweben, Monte; Eskey, Megan; Stock, Todd; Taylor, Will; Kanefsky, Bob; Drascher, Ellen; Deale, Michael; Daun, Brian; Davis, Gene

1995-01-01

Report describes continuing development of software for constraint-based scheduling system implemented eventually on massively parallel computer. Based on machine learning as means of improving scheduling. Designed to learn when to change search strategy by analyzing search progress and learning general conditions under which resource bottleneck occurs.

Extended Pausing by Humans on Multiple Fixed-Ratio Schedules with Varied Reinforcer Magnitude and Response Requirements

ERIC Educational Resources Information Center

Williams, Dean C.; Saunders, Kathryn J.; Perone, Michael

2011-01-01

We conducted three experiments to reproduce and extend Perone and Courtney's (1992) study of pausing at the beginning of fixed-ratio schedules. In a multiple schedule with unequal amounts of food across two components, they found that pigeons paused longest in the component associated with the smaller amount of food (the lean component), but only…

Demand Equations for Qualitatively Different Foods under Fixed-Ratio Schedules: A Comparison of Three Data Conversions

ERIC Educational Resources Information Center

Foster, T. Mary; Sumpter, Catherine E.; Temple, William; Flevill, Amanda; Poling, Alan

2009-01-01

Concurrent schedules were used to establish 6 hens' preferences for three foods. The resulting biases suggested wheat was preferred over honey-puffed and puffed wheat, and puffed wheat was the least preferred food. The hens then responded under fixed-ratio schedules for each food in 40-min (excluding reinforcer time) sessions, with the response…

Research, Development and Validation of the Daily Demand Computer Schedule 360/50. Final Report.

ERIC Educational Resources Information Center

Ovard, Glen F.; Rowley, Vernon C.

A study was designed to further the research, development and validation of the Daily Demand Computer Schedule (DDCS), a system by which students can be rescheduled daily for facilitating their individual continuous progress through the curriculum. It will allow teachers to regroup students as needed based upon that progress, and will make time a…

Scheduling Earth Observing Fleets Using Evolutionary Algorithms: Problem Description and Approach

NASA Technical Reports Server (NTRS)

Globus, Al; Crawford, James; Lohn, Jason; Morris, Robert; Clancy, Daniel (Technical Monitor)

2002-01-01

We describe work in progress concerning multi-instrument, multi-satellite scheduling. Most, although not all, Earth observing instruments currently in orbit are unique. In the relatively near future, however, we expect to see fleets of Earth observing spacecraft, many carrying nearly identical instruments. This presents a substantially new scheduling challenge. Inspired by successful commercial applications of evolutionary algorithms in scheduling domains, this paper presents work in progress regarding the use of evolutionary algorithms to solve a set of Earth observing related model problems. Both the model problems and the software are described. Since the larger problems will require substantial computation and evolutionary algorithms are embarrassingly parallel, we discuss our parallelization techniques using dedicated and cycle-scavenged workstations.

High and escalating levels of cocaine intake are dissociable from subsequent incentive motivation for the drug in rats.

PubMed

Allain, Florence; Bouayad-Gervais, Karim; Samaha, Anne-Noël

2018-01-01

Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, human cocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels. Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement. First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement. Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern-even in small amounts-is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.

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.

Extended Pausing by Humans on Multiple Fixed-Ratio Schedules with Varied Reinforcer Magnitude and Response Requirements

PubMed Central

Williams, Dean C; Saunders, Kathryn J; Perone, Michael

2011-01-01

We conducted three experiments to reproduce and extend Perone and Courtney's (1992) study of pausing at the beginning of fixed-ratio schedules. In a multiple schedule with unequal amounts of food across two components, they found that pigeons paused longest in the component associated with the smaller amount of food (the lean component), but only when it was preceded by the rich component. In our studies, adults with mild intellectual disabilities responded on a touch-sensitive computer monitor to produce money. In Experiment 1, the multiple-schedule components differed in both response requirement and reinforcer magnitude (i.e., the rich component required fewer responses and produced more money than the lean component). Effects shown with pigeons were reproduced in all 7 participants. In Experiment 2, we removed the stimuli that signaled the two schedule components, and participants' extended pausing was eliminated. In Experiment 3, to assess sensitivity to reinforcer magnitude versus fixed-ratio size, we presented conditions with equal ratio sizes but disparate magnitudes and conditions with equal magnitudes but disparate ratio sizes. Sensitivity to these manipulations was idiosyncratic. The present experiments obtained schedule control in verbally competent human participants and, despite procedural differences, we reproduced findings with animal participants. We showed that pausing is jointly determined by past conditions of reinforcement and stimuli correlated with upcoming conditions. PMID:21541121

Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength.

PubMed

Phillips, Benjamin U; Heath, Christopher J; Ossowska, Zofia; Bussey, Timothy J; Saksida, Lisa M

2017-09-01

Operant testing is a widely used and highly effective method of studying cognition in rodents. Performance on such tasks is sensitive to reinforcer strength. It is therefore advantageous to select effective reinforcers to minimize training times and maximize experimental throughput. To quantitatively investigate the control of behavior by different reinforcers, performance of mice was tested with either strawberry milkshake or a known powerful reinforcer, super saccharin (1.5% or 2% (w/v) saccharin/1.5% (w/v) glucose/water mixture). Mice were tested on fixed (FR)- and progressive-ratio (PR) schedules in the touchscreen-operant testing system. Under an FR schedule, both the rate of responding and number of trials completed were higher in animals responding for strawberry milkshake versus super saccharin. Under a PR schedule, mice were willing to emit similar numbers of responses for strawberry milkshake and super saccharin; however, analysis of the rate of responding revealed a significantly higher rate of responding by animals reinforced with milkshake versus super saccharin. To determine the impact of reinforcer strength on cognitive performance, strawberry milkshake and super saccharin-reinforced animals were compared on a touchscreen visual discrimination task. Animals reinforced by strawberry milkshake were significantly faster to acquire the discrimination than animals reinforced by super saccharin. Taken together, these results suggest that strawberry milkshake is superior to super saccharin for operant behavioral testing and further confirms that the application of response rate analysis to multiple ratio tasks is a highly sensitive method for the detection of behavioral differences relevant to learning and motivation.

48 CFR 36.515 - Schedules for construction contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contemplated, the contract amount is expected to exceed the simplified acquisition threshold, and the period of... covering other management approaches for ensuring that a contractor makes adequate progress. [48 FR 42356... Schedules for construction contracts. The contracting officer may insert the clause at 52.236-15, Schedules...

Wheel running exercise attenuates vulnerability to self-administer nicotine in rats.

PubMed

Sanchez, Victoria; Lycas, Matthew D; Lynch, Wendy J; Brunzell, Darlene H

2015-11-01

Preventing or postponing tobacco use initiation could greatly reduce the number of tobacco-related deaths. While evidence suggests that exercise is a promising treatment for tobacco addiction, it is not clear whether exercise could prevent initial vulnerability to tobacco use. Thus, using an animal model, we examined whether exercise attenuates vulnerability to the use and reinforcing effects of nicotine, the primary addictive chemical in tobacco. Initial vulnerability was assessed using an acquisition procedure wherein exercising (unlocked running wheel, n=10) and sedentary (locked or no wheel, n=12) male adolescent rats had access to nicotine infusions (0.01-mg/kg) during daily 21.5-h sessions beginning on postnatal day 30. Exercise/sedentary sessions (2-h/day) were conducted prior to each of the acquisition sessions. The effects of exercise on nicotine's reinforcing effects were further assessed in separate groups of exercising (unlocked wheel, n=7) and sedentary (no wheel, n=5) rats responding for nicotine under a progressive-ratio schedule with exercise/sedentary sessions (2-h/day) conducted before the daily progressive-ratio sessions. While high rates of acquisition of nicotine self-administration were observed among both groups of sedentary controls, acquisition was robustly attenuated in the exercise group with only 20% of exercising rats meeting the acquisition criterion within the 16-day testing period as compared to 67% of the sedentary controls. Exercise also decreased progressive-ratio responding for nicotine as compared to baseline and to sedentary controls. Exercise may effectively prevent the initiation of nicotine use in adolescents by reducing the reinforcing effects of nicotine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats.

PubMed

Gellner, Candice A; Belluzzi, James D; Leslie, Frances M

2016-10-01

Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents. Published by Elsevier Ltd.

Discordance between 'actual' and 'scheduled' check-in times at a heart failure clinic.

PubMed

Gorodeski, Eiran Z; Joyce, Emer; Gandesbery, Benjamin T; Blackstone, Eugene H; Taylor, David O; Tang, W H Wilson; Starling, Randall C; Hachamovitch, Rory

2017-01-01

A 2015 Institute Of Medicine statement "Transforming Health Care Scheduling and Access: Getting to Now", has increased concerns regarding patient wait times. Although waiting times have been widely studied, little attention has been paid to the role of patient arrival times as a component of this phenomenon. To this end, we investigated patterns of patient arrival at scheduled ambulatory heart failure (HF) clinic appointments and studied its predictors. We hypothesized that patients are more likely to arrive later than scheduled, with progressively later arrivals later in the day. Using a business intelligence database we identified 6,194 unique patients that visited the Cleveland Clinic Main Campus HF clinic between January, 2015 and January, 2017. This clinic served both as a tertiary referral center and a community HF clinic. Transplant and left ventricular assist device (LVAD) visits were excluded. Punctuality was defined as the difference between 'actual' and 'scheduled' check-in times, whereby negative values (i.e., early punctuality) were patients who checked-in early. Contrary to our hypothesis, we found that patients checked-in late only a minority of the time (38% of visits). Additionally, examining punctuality by appointment hour slot we found that patients scheduled after 8AM had progressively earlier check-in times as the day progressed (P < .001 for trend). In both a Random Forest-Regression framework and linear regression models the most important risk-adjusted predictors of early punctuality were: later in the day appointment hour slot, patient having previously been to the hospital, age in the early 70s, and white race. Patients attending a mixed population ambulatory HF clinic check-in earlier than scheduled times, with progressive discrepant intervals throughout the day. This finding may have significant implications for provider utilization and resource planning in order to maximize clinic efficiency. The impact of elective early arrival on patient's perceived wait times requires further study.

Exclusive Preference Develops Less Readily on Concurrent Ratio Schedules with Wheel-Running than with Sucrose Reinforcement

PubMed Central

Belke, Terry W

2010-01-01

Previous research suggested that allocation of responses on concurrent schedules of wheel-running reinforcement was less sensitive to schedule differences than typically observed with more conventional reinforcers. To assess this possibility, 16 female Long Evans rats were exposed to concurrent FR FR schedules of reinforcement and the schedule value on one alternative was systematically increased. In one condition, the reinforcer on both alternatives was .1 ml of 7.5% sucrose solution; in the other, it was a 30-s opportunity to run in a wheel. Results showed that the average ratio at which greater than 90% of responses were allocated to the unchanged alternative was higher with wheel-running reinforcement. As the ratio requirement was initially increased, responding strongly shifted toward the unchanged alternative with sucrose, but not with wheel running. Instead, responding initially increased on both alternatives, then subsequently shifted toward the unchanged alternative. Furthermore, changeover responses as a percentage of total responses decreased with sucrose, but not wheel-running reinforcement. Finally, for some animals, responding on the increasing ratio alternative decreased as the ratio requirement increased, but then stopped and did not decline with further increments. The implications of these results for theories of choice are discussed. PMID:21451744

Exclusive preference develops less readily on concurrent ratio schedules with wheel-running than with sucrose reinforcement.

PubMed

Belke, Terry W

2010-09-01

Previous research suggested that allocation of responses on concurrent schedules of wheel-running reinforcement was less sensitive to schedule differences than typically observed with more conventional reinforcers. To assess this possibility, 16 female Long Evans rats were exposed to concurrent FR FR schedules of reinforcement and the schedule value on one alternative was systematically increased. In one condition, the reinforcer on both alternatives was .1 ml of 7.5% sucrose solution; in the other, it was a 30-s opportunity to run in a wheel. Results showed that the average ratio at which greater than 90% of responses were allocated to the unchanged alternative was higher with wheel-running reinforcement. As the ratio requirement was initially increased, responding strongly shifted toward the unchanged alternative with sucrose, but not with wheel running. Instead, responding initially increased on both alternatives, then subsequently shifted toward the unchanged alternative. Furthermore, changeover responses as a percentage of total responses decreased with sucrose, but not wheel-running reinforcement. Finally, for some animals, responding on the increasing ratio alternative decreased as the ratio requirement increased, but then stopped and did not decline with further increments. The implications of these results for theories of choice are discussed.

Error Argumentation Enhance Adaptability in Adults With Low Motor Ability.

PubMed

Lee, Chi-Mei; Bo, Jin

2016-01-01

The authors focused on young adults with varying degrees of motor difficulties and examined their adaptability in a visuomotor adaptation task where the visual feedback of participants' movement error was presented with either 1:1 ratio (i.e., regular feedback schedule) or 1:2 ratio (i.e., enhanced feedback schedule). Within-subject design was used with two feedback schedules counter-balanced and separated for 10 days. Results revealed that participants with greater motor difficulties showed less adaptability than those with normal motor abilities in the regular feedback schedule; however, all participants demonstrated similar level of adaptability in the enhanced feedback schedule. The results suggest that error argumentation enhances adaptability in adults with low motor ability.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

PubMed

Jiménez Fonseca, Paula; Carmona-Bayonas, Alberto; Hernández, Raquel; Custodio, Ana; Cano, Juana Maria; Lacalle, Alejandra; Echavarria, Isabel; Macias, Ismael; Mangas, Monserrat; Visa, Laura; Buxo, Elvira; Álvarez Manceñido, Felipe; Viudez, Antonio; Pericay, Carles; Azkarate, Aitor; Ramchandani, Avinash; López, Carlos; Martinez de Castro, Eva; Fernández Montes, Ana; Longo, Federico; Sánchez Bayona, Rodrigo; Limón, Maria Luisa; Diaz-Serrano, Asun; Martin Carnicero, Alfonso; Arias, David; Cerdà, Paula; Rivera, Fernando; Vieitez, Jose Maria; Sánchez Cánovas, Manuel; Garrido, M; Gallego, J

2017-09-05

The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Influences on Cocaine Tolerance Assessed under a Multiple Conjunctive Schedule of Reinforcement

ERIC Educational Resources Information Center

Yoon, Jin Ho; Branch, Marc N.

2009-01-01

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the…

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,…

Cost-effectiveness of treating normal tension glaucoma.

PubMed

Li, Emmy Y; Tham, Clement C; Chi, Stanley C; Lam, Dennis S

2013-05-13

To assess the long-term cost-effectiveness of treating normal tension glaucoma (NTG). A Markov decision-analytic health model was developed to determine the cost-effectiveness of treating NTG with IOP lowering therapy to prevent progressive visual field loss. Transitional probabilities were derived from the Collaborative Normal Tension Glaucoma Study and cost data obtained from the literature and the Medicare fee schedule. Incremental cost-effectiveness ratios (ICER) of treating all patients with NTG and treating selected individuals with risk factors for disease progression were determined using Monte Carlo simulation. Sensitivity analyses were performed by varying the cost of consultations, medications, laser/surgery, and adjusting utility loss from progressed states. The ICER of treating all patients with NTG over a 10-year period was United States (US) $34,225 per quality-adjusted life year (QALY). The ICER would be reduced when treatment was offered selectively to those with risk factors for disease progression. The ICER for treating NTG patients with disc hemorrhage, migraine, and those who were female were US $24,350, US $25,533, and US $27,000 per QALY, respectively. The cost-effectiveness of treating all NTG patients in this model was sensitive to cost fluctuation of medications, choice of utility score associated with disease progression, and insensitive to cost of consultations and laser/surgery. It is cost-effective, in the long-term, to offer IOP lowering therapy, aiming for a 30% reduction from the baseline, to all NTG patients. The incremental cost-effectiveness ratio of treating all patients with normal tension glaucoma over a 10-year period was $34,225 per quality-adjusted life year and should be offered to individuals in need.

Effects of Escalating and Descending Schedules of Incentives on Cigarette Smoking in Smokers without Plans to Quit

ERIC Educational Resources Information Center

Romanowich, Paul; Lamb, R. J.

2010-01-01

Contingent incentives can reduce substance abuse. Escalating payment schedules, which begin with a small incentive magnitude and progressively increase with meeting the contingency, increase smoking abstinence. Likewise, descending payment schedules can increase cocaine abstinence. The current experiment enrolled smokers without plans to quit in…

Randomized trial of HPV4 vaccine assessing the response to HPV4 vaccine in two schedules among Peruvian female sex workers.

PubMed

Brown, Brandon; Blas, Magaly; Cabral, Alejandra; Carcamo, Cesar; Gravitt, Patti; Halsey, Neal

2012-03-16

Two hundred female sex workers (FSWs) in Lima, Peru were randomized to receive HPV4 vaccine in the standard (0, 2, 6 months) or a modified schedule (0, 3, 6 months). One hundred and eighty four (92%) participants completed 3 doses of vaccine. Baseline seropositive rates were 58% for HPV6, 22.5% for HPV11, 41.5% for HPV16, and 13% for HPV18. The final geometric mean antibody titer (GMT) following vaccination was significantly greater for women who were seropositive at baseline compared to seronegative women: HPV6 (GMT ratio=2.3, p<0.01), HPV11 (GMT ratio=2.7, p<0.01), HPV16 (GMT ratio=1.3, p=0.04), and HPV18 (GMT ratio=2.4, p<0.01). Antibody titers in the modified schedule were not inferior to those in the standard schedule, suggesting the modified schedule may be paired with required STD visits. Although all women benefit from vaccination, administration at a younger age and before sexual debut is needed to achieve maximum protection from vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

ROBucket: A low cost operant chamber based on the Arduino microcontroller.

PubMed

Devarakonda, Kavya; Nguyen, Katrina P; Kravitz, Alexxai V

2016-06-01

The operant conditioning chamber is a cornerstone of animal behavioral research. Operant boxes are used to assess learning and motivational behavior in animals, particularly for food and drug reinforcers. However, commercial operant chambers cost several thousands of dollars. We have constructed the Rodent Operant Bucket (ROBucket), an inexpensive and easily assembled open-source operant chamber based on the Arduino microcontroller platform, which can be used to train mice to respond for sucrose solution or other liquid reinforcers. The apparatus contains two nose pokes, a drinking well, and a solenoid-controlled liquid delivery system. ROBucket can run fixed ratio and progressive ratio training schedules, and can be programmed to run more complicated behavioral paradigms. Additional features such as motion sensing and video tracking can be added to the operant chamber through the array of widely available Arduino-compatible sensors. The design files and programming code are open source and available online for others to use.

Progress and Compliance in Alcohol Abuse Treatment*

PubMed Central

Lien, Hsien-Ming; Lu, Mingshan; Ma, Ching-To Albert; McGuire, Thomas G.

2009-01-01

Improving patient compliance with physicians’ treatment or prescription recommendations is an important goal in medical practice. We examine the relationship between treatment progress and patient compliance. We hypothesize that patients balance expected benefits and costs during a treatment episode when deciding on compliance; a patient is more likely to comply if doing so results in an expected gain in health benefit. We use a unique data set of outpatient alcohol abuse treatment to identify a relationship between treatment progress and compliance. Treatment progress is measured by the clinician’s comments after each attended visit. Compliance is measured by a client attending a scheduled appointment, and continuing with treatment. We find that a patient who is making progress is less likely to drop out of treatment. We find no evidence that treatment progress raises the likelihood of a patient attending the next scheduled visit. Our results are robust to unobserved patient heterogeneity. PMID:20031241

External incentives and internal states guide goal-directed behavior via the differential recruitment of the nucleus accumbens and the medial prefrontal cortex.

PubMed

Moscarello, J M; Ben-Shahar, O; Ettenberg, A

2010-10-13

Goal-directed behavior is governed by internal physiological states and external incentives present in the environment (e.g. hunger and food). While the role of the mesocorticolimbic dopamine (DA) system in behavior guided by environmental incentives has been well studied, the effect of relevant physiological states on the function of this system is less understood. The current study examined the role of the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) in the kind of food-reinforced behaviors known to be sensitive to the internal state produced by food deprivation conditions. Operant lever-press reinforced on fixed ratio 1 (FR1) and progressive ratio (PR) schedules was tested after temporary inactivation of, or DA receptor blockade in, the prelimbic mPFC or NAcc core of rats with differing levels of food deprivation (0, 12 and 36-h). Food deprivation increased PR breakpoints, as well as the number of lever-presses emitted on the FR1 schedule. Both temporary inactivation and DA blockade of NAcc reduced breakpoints across deprivation conditions, while temporary inactivation and DA blockade of mPFC reduced breakpoints only in food-deprived rats. Neither manipulation of mPFC and NAcc had any effect on behavior reinforced on the FR1 schedule. Thus, mPFC and NAcc were differentially relevant to the behaviors tested-NAcc was recruited when the behavioral cost per reinforcer was rising or high regardless of food deprivation conditions, while mPFC was recruited when food-deprived animals behaved through periods of sparse reinforcement density in order to maximize available gain. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Effect of (L)-cysteine on acetaldehyde self-administration.

PubMed

Peana, Alessandra T; Muggironi, Giulia; Fois, Giulia R; Zinellu, Manuel; Sirca, Donatella; Diana, Marco

2012-08-01

Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered. This study examined the effects of l-cysteine pre-treatment during the acquisition and maintenance phases of ACD (0.2%) self-administration as well as on the deprivation effect after ACD extinction and on a progressive ratio (PR) schedule of reinforcement. In a separate PR schedule of reinforcement, the effect of l-cysteine was assessed on the break-point produced by ethanol (10%). Furthermore, we tested the effect of l-cysteine on saccharin (0.2%) reinforcement. Wistar rats were trained to self-administer ACD by nose poking on a fixed ratio (FR1) schedule in 30-min daily sessions. Responses on an active nose-poke caused delivery of ACD solution, whereas responses on an inactive nose-poke had no consequences. l-cysteine reduced the acquisition (40 mg/kg), the maintenance and the deprivation effect (100 mg/kg) of ACD self-administration. Furthermore, at the same dose, l-cysteine (120 mg/kg) decreased both ACD and ethanol break point. In addition, l-cysteine was unable to suppress the different responses for saccharin, suggesting that its effect did not relate to an unspecific decrease in a general motivational state. Compared to saline, l-cysteine did not modify responses on inactive nose-pokes, suggesting an absence of a non-specific behavioural activation. Taken together, these results could support the hypotheses that ACD possesses reinforcing properties and l-cysteine reduces motivation to self-administer ACD. Copyright © 2012 Elsevier Inc. All rights reserved.

Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys

PubMed Central

Newman, Jennifer L.; Perry, Jennifer L.; Carroll, Marilyn E.

2007-01-01

Environmental factors, including social interaction, can alter the effects of drugs of abuse on behavior. The present study was conducted to examine the effects of social stimuli on oral phencyclidine (PCP) self-administration by rhesus monkeys. Ten adult rhesus monkeys (M. mulatta) were housed side by side in modular cages that could be configured to provide visual, auditory, and olfactory stimuli provided by another monkey located in the other side of the paired unit. During the first experiment, monkeys self-administered PCP (0.25 mg/ml) and water under concurrent fixed ratio (FR) 16 schedules of reinforcement with either a solid or a grid (social) partition separating each pair of monkeys. In the second experiment, a PCP concentration-response relationship was determined under concurrent progressive ratio (PR) schedules of reinforcement under the solid and grid partition conditions. Under the concurrent FR 16 schedules, PCP and water self-administration was significantly higher during exposure to a cage mate through a grid partition than when a solid partition separated the monkeys. The relative reinforcing strength of PCP, as measured by PR break points, was greater during the grid partition condition compared to the solid partition condition indicated by an upward shift in the concentration-response curve. To determine whether the social stimuli provided by another monkey led to activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may have evoked the increase of PCP self-administration during the grid partition condition, a third experiment was conducted to examine cortisol levels under the two housing conditions. A modest, but nonsignificant increase in cortisol levels was found upon switching from the solid to the grid partition condition. The results suggest that social stimulation among monkeys in adjoining cages leads to enhanced reinforcing strength of PCP. PMID:17560636

Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism.

PubMed

Li, Zhimin; Zharikova, Alevtina; Vaughan, Cheryl H; Bastian, Jaime; Zandy, Shannon; Esperon, Leonardo; Axman, Elyssia; Rowland, Neil E; Peris, Joanna

2010-01-15

We investigated the neurochemical mechanism of how high-dose ethanol exposure may increase motivation for ethanol consumption. First, we developed an animal model of increased motivation for ethanol using a progressive ratio (PR) schedule. Sprague-Dawley rats were trained to administer 10% ethanol-containing gelatin or plain gelatin (on alternate weeks) in daily 30-min sessions under different fixed ratio (FR) and PR schedules. During FR schedules, rats self-administered about 1 g/kg ethanol, which was decreased to 0.4+/-0.03 g/kg under PR10. Rats then received four pairs of either 3 g/kg ethanol or saline injections during the weeks when the reinforcer was plain gelatin. During subsequent ethanol gel sessions, breakpoints and ethanol consumption rose 40% in the high-dose ethanol group by the fourth set of injections with no change in plain gel responding. Alterations in amino acids in the ventral striatum (VS) during PR10 responding for 10% ethanol gelatin and plain gelatin were measured using microdialysis sampling coupled with capillary electrophoresis and laser-induced fluorescence detection. There was greater release of taurine, glycine and glutamate in the NAC of the high-dose ethanol rats during 10% ethanol-containing gelatin responding, compared to the control rats or during plain gel responding. An increase in the release of glycine in this same brain region has recently been shown to be involved with anticipation of a reward. Thus, it appears that intermittent high-dose ethanol exposure not only increases motivation for ethanol responding but may also change neurotransmitter release that mediates anticipation of reinforcement, which may play a key role in the development of alcoholism. Copyright 2009 Elsevier B.V. All rights reserved.

EMG biofeedback: the effects of CRF, FR, VR, FI, and VI schedules of reinforcement on the acquisition and extinction of increases in forearm muscle tension.

PubMed

Cohen, S L; Richardson, J; Klebez, J; Febbo, S; Tucker, D

2001-09-01

Biofeedback was used to increase forearm-muscle tension. Feedback was delivered under continuous reinforcement (CRF), variable interval (VI), fixed interval (FI), variable ratio (VR), and fixed ratio (FR) schedules of reinforcement when college students increased their muscle tension (electromyograph, EMG) above a high threshold. There were three daily sessions of feedback, and Session 3 was immediately followed by a session without feedback (extinction). The CRF schedule resulted in the highest EMG, closely followed by the FR and VR schedules, and the lowest EMG scores were produced by the FI and VI schedules. Similarly, the CRF schedule resulted in the greatest amount of time-above-threshold and the VI and FI schedules produced the lowest time-above-threshold. The highest response rates were generated by the FR schedule, followed by the VR schedule. The CRF schedule produced relatively low response rates, comparable to the rates under the VI and FI schedules. Some of the data are consistent with the partial-reinforcement-extinction effect. The present data suggest that different schedules of feedback should be considered in muscle-strengthening-contexts such as during the rehabilitation of muscles following brain damage or peripheral nervous-system injury.

Response Strength in Extreme Multiple Schedules

ERIC Educational Resources Information Center

McLean, Anthony P.; Grace, Randolph C.; Nevin, John A.

2012-01-01

Four pigeons were trained in a series of two-component multiple schedules. Reinforcers were scheduled with random-interval schedules. The ratio of arranged reinforcer rates in the two components was varied over 4 log units, a much wider range than previously studied. When performance appeared stable, prefeeding tests were conducted to assess…

Coordination of appointments for anesthesia care outside of operating rooms using an enterprise-wide scheduling system.

PubMed

Dexter, Franklin; Xiao, Yan; Dow, Angella J; Strader, Melissa M; Ho, Danny; Wachtel, Ruth E

2007-12-01

An anesthesia department implemented scheduling of anesthetics outside of operating rooms (non-OR) by clerks and nurses from other departments using its hospital's enterprise-wide scheduling system. Observational studies chronicled the change over 2 yr as non-OR time was allocated by specialty, and nonanesthesia clerks and nurses scheduled anesthesia teams. Experimental studies investigated how tabular and graphical displays affected the scheduling of milestones (e.g., NPO times) and appointments before anesthetics. Anesthetics performed in allocated time increased progressively from 0% to 75%. Scheduling of anesthetics by nonanesthesia clerks and nurses increased progressively from 0% to 77%. Consistency of patient instructions was improved. The quality of resulting schedules was good. Implementation was not associated with worsening of multiple operational measures of performance such as cancellation rates, turnover times, or complaints. However, schedulers struggled to understand fasting and arrival times of patients, despite using a web site with statistically generated values in tabular formats. Experiments revealed that people ignored their knowledge that anesthetics can start earlier than scheduled. Participants made good decisions with both tabular and graphical displays when scheduling appointments preceding anesthesia. Enterprise-wide scheduling can coordinate anesthetics with other appointments on the same date and improve consistency and accuracy of patient instructions customized to the probability of an anesthetic starting early. The usefulness of implementation depends on the value in having more patient-centered care and/or in having patients arrive just in time for non-OR anesthesia, surgery, or regional block placement (e.g., at facilities with limited physical space).

Comparison of the effects of antipsychotic drugs on the schedule-controlled behavior of squirrel monkeys and pigeons.

PubMed

Barrett, J E

1983-04-01

Lever pressing by squirrel monkeys and key pecking by pigeons were maintained under a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule by the presentation of food. These responses, which differed under the two schedules, but were similar for both species, were used to compare the effects of antipsychotic compounds from different pharmacological classes. Except for differences in potency levels, the effects of intermediate doses of haloperidol and molindone were similar in monkeys and pigeons; these compounds decreased responding under the fixed-interval schedule at doses that did not affect fixed-ratio responding. Similar effects also occurred with chlorpromazine, promazine and thiothixene in pigeons. With monkeys, however, intermediate doses of promazine decreased fixed-ratio responding more than responding maintained under the fixed-interval schedule, while chlorpromazine and thiothixene produced similar effects on responding under both schedules. The effects of novel antipsychotic, clozapine, differed from those of the other agents in both monkeys and pigeons. With both species clozapine increased fixed interval responding at doses that did not affect responding under the fixed-ratio schedule. Doses required to reduce responding at least 50% were approximately 5 to 160 times greater for pigeons than for monkeys for all drugs except clozapine which was equipotent in both species. In monkeys the order of potency was haloperidol greater than molindone = thiothixene greater than chlorpromazine greater than clozapine greater than promazine, whereas in pigeons the order was haloperidol greater than thiothixene greater than clozapine greater than molindone greater than promazine greater than chlorpromazine.

Choice with frequently changing food rates and food ratios.

PubMed

Baum, William M; Davison, Michael

2014-03-01

In studies of operant choice, when one schedule of a concurrent pair is varied while the other is held constant, the constancy of the constant schedule may exert discriminative control over performance. In our earlier experiments, schedules varied reciprocally across components within sessions, so that while food ratio varied food rate remained constant. In the present experiment, we held one variable-interval (VI) schedule constant while varying the concurrent VI schedule within sessions. We studied five conditions, each with a different constant left VI schedule. On the right key, seven different VI schedules were presented in seven different unsignaled components. We analyzed performances at several different time scales. At the longest time scale, across conditions, behavior ratios varied with food ratios as would be expected from the generalized matching law. At shorter time scales, effects due to holding the left VI constant became more and more apparent, the shorter the time scale. In choice relations across components, preference for the left key leveled off as the right key became leaner. Interfood choice approximated strict matching for the varied right key, whereas interfood choice hardly varied at all for the constant left key. At the shortest time scale, visit patterns differed for the left and right keys. Much evidence indicated the development of a fix-and-sample pattern. In sum, the procedural difference made a large difference to performance, except for choice at the longest time scale and the fix-and-sample pattern at the shortest time scale. © Society for the Experimental Analysis of Behavior.

Scheduling time-critical graphics on multiple processors

NASA Technical Reports Server (NTRS)

Meyer, Tom W.; Hughes, John F.

1995-01-01

This paper describes an algorithm for the scheduling of time-critical rendering and computation tasks on single- and multiple-processor architectures, with minimal pipelining. It was developed to manage scientific visualization scenes consisting of hundreds of objects, each of which can be computed and displayed at thousands of possible resolution levels. The algorithm generates the time-critical schedule using progressive-refinement techniques; it always returns a feasible schedule and, when allowed to run to completion, produces a near-optimal schedule which takes advantage of almost the entire multiple-processor system.

Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion.

PubMed

Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

2017-01-01

Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion. Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding. Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine. Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.

High Energy Power and Propulsion Capability Roadmap: General Background and Introduction

NASA Technical Reports Server (NTRS)

Bankston, Perry

2005-01-01

Agency objective are: Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

Distribution of a Generic Mission Planning and Scheduling Toolkit for Astronomical Spacecraft

NASA Technical Reports Server (NTRS)

Kleiner, Steven C.

1998-01-01

This 2-year report describes the progress made to date on the project to package and distribute the planning and scheduling toolkit for the SWAS astronomical spacecraft. SWAS was scheduled to be launched on a Pegasus XL vehicle in fall 1995. Three separate failures in the launch vehicle have delayed the SWAS launch. The researchers have used this time to continue developing scheduling algorithms and GUI design. SWAS is expected to be launched this year.

Comparing self-guided learning and educator-guided learning formats for simulation-based clinical training.

PubMed

Brydges, Ryan; Carnahan, Heather; Rose, Don; Dubrowski, Adam

2010-08-01

In this paper, we tested the over-arching hypothesis that progressive self-guided learning offers equivalent learning benefit vs. proficiency-based training while limiting the need to set proficiency standards. We have shown that self-guided learning is enhanced when students learn on simulators that progressively increase in fidelity during practice. Proficiency-based training, a current gold-standard training approach, requires achievement of a criterion score before students advance to the next learning level. Baccalaureate nursing students (n = 15/group) practised intravenous catheterization using simulators that differed in fidelity (i.e. students' perceived realism). Data were collected in 2008. Proficiency-based students advanced from low- to mid- to high-fidelity after achieving a proficiency criterion at each level. Progressive students self-guided their progression from low- to mid- to high-fidelity. Yoked control students followed an experimenter-defined progressive practice schedule. Open-ended students moved freely between the simulators. One week after practice, blinded experts evaluated students' skill transfer on a standardized patient simulation. Group differences were examined using analyses of variance. Proficiency-based students scored highest on the high-fidelity post-test (effect size = 1.22). An interaction effect showed that the Progressive and Open-ended groups maintained their performance from post-test to transfer test, whereas the Proficiency-based and Yoked control groups experienced a significant decrease (P < 0.05). Surprisingly, most Open-ended students (73%) chose the progressive practice schedule. Progressive training and proficiency-based training resulted in equivalent transfer test performance, suggesting that progressive students effectively self-guided when to transition between simulators. Students' preference for the progressive practice schedule indicates that educators should consider this sequence for simulation-based training.

Generating Variable and Random Schedules of Reinforcement Using Microsoft Excel Macros

ERIC Educational Resources Information Center

Bancroft, Stacie L.; Bourret, Jason C.

2008-01-01

Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time.…

Discordance between 'actual' and 'scheduled' check-in times at a heart failure clinic

PubMed Central

Joyce, Emer; Gandesbery, Benjamin T.; Blackstone, Eugene H.; Taylor, David O.; Tang, W. H. Wilson; Starling, Randall C.; Hachamovitch, Rory

2017-01-01

Introduction A 2015 Institute Of Medicine statement “Transforming Health Care Scheduling and Access: Getting to Now”, has increased concerns regarding patient wait times. Although waiting times have been widely studied, little attention has been paid to the role of patient arrival times as a component of this phenomenon. To this end, we investigated patterns of patient arrival at scheduled ambulatory heart failure (HF) clinic appointments and studied its predictors. We hypothesized that patients are more likely to arrive later than scheduled, with progressively later arrivals later in the day. Methods and results Using a business intelligence database we identified 6,194 unique patients that visited the Cleveland Clinic Main Campus HF clinic between January, 2015 and January, 2017. This clinic served both as a tertiary referral center and a community HF clinic. Transplant and left ventricular assist device (LVAD) visits were excluded. Punctuality was defined as the difference between ‘actual’ and ‘scheduled’ check-in times, whereby negative values (i.e., early punctuality) were patients who checked-in early. Contrary to our hypothesis, we found that patients checked-in late only a minority of the time (38% of visits). Additionally, examining punctuality by appointment hour slot we found that patients scheduled after 8AM had progressively earlier check-in times as the day progressed (P < .001 for trend). In both a Random Forest-Regression framework and linear regression models the most important risk-adjusted predictors of early punctuality were: later in the day appointment hour slot, patient having previously been to the hospital, age in the early 70s, and white race. Conclusions Patients attending a mixed population ambulatory HF clinic check-in earlier than scheduled times, with progressive discrepant intervals throughout the day. This finding may have significant implications for provider utilization and resource planning in order to maximize clinic efficiency. The impact of elective early arrival on patient’s perceived wait times requires further study. PMID:29136649

Some Determinants of Remote Behavioral History Effects in Humans

ERIC Educational Resources Information Center

Hirai, Mariko; Okouchi, Hiroto; Matsumoto, Akio; Lattal, Kennon A.

2011-01-01

Undergraduates were exposed to a series of reinforcement schedules: first, to a fixed-ratio (FR) schedule in the presence of one stimulus and to a differential-reinforcement-of-low-rate (DRL) schedule in the presence of another (multiple FR DRL training), then to a fixed-interval (FI) schedule in the presence of a third stimulus (FI baseline),…

Exclusive Preference Develops Less Readily on Concurrent Ratio Schedules with Wheel-Running than with Sucrose Reinforcement

ERIC Educational Resources Information Center

Belke, Terry W.

2010-01-01

Previous research suggested that allocation of responses on concurrent schedules of wheel-running reinforcement was less sensitive to schedule differences than typically observed with more conventional reinforcers. To assess this possibility, 16 female Long Evans rats were exposed to concurrent FR FR schedules of reinforcement and the schedule…

An open source device for operant licking in rats.

PubMed

Longley, Matthew; Willis, Ethan L; Tay, Cindy X; Chen, Hao

2017-01-01

We created an easy-to-use device for operant licking experiments and another device that records environmental variables. Both devices use the Raspberry Pi computer to obtain data from multiple input devices (e.g., radio frequency identification tag readers, touch and motion sensors, environmental sensors) and activate output devices (e.g., LED lights, syringe pumps) as needed. Data gathered from these devices are stored locally on the computer but can be automatically transferred to a remote server via a wireless network. We tested the operant device by training rats to obtain either sucrose or water under the control of a fixed ratio, a variable ratio, or a progressive ratio reinforcement schedule. The lick data demonstrated that the device has sufficient precision and time resolution to record the fast licking behavior of rats. Data from the environment monitoring device also showed reliable measurements. By providing the source code and 3D design under an open source license, we believe these examples will stimulate innovation in behavioral studies. The source code can be found at http://github.com/chen42/openbehavior.

An open source device for operant licking in rats

PubMed Central

Longley, Matthew; Willis, Ethan L.; Tay, Cindy X.

2017-01-01

We created an easy-to-use device for operant licking experiments and another device that records environmental variables. Both devices use the Raspberry Pi computer to obtain data from multiple input devices (e.g., radio frequency identification tag readers, touch and motion sensors, environmental sensors) and activate output devices (e.g., LED lights, syringe pumps) as needed. Data gathered from these devices are stored locally on the computer but can be automatically transferred to a remote server via a wireless network. We tested the operant device by training rats to obtain either sucrose or water under the control of a fixed ratio, a variable ratio, or a progressive ratio reinforcement schedule. The lick data demonstrated that the device has sufficient precision and time resolution to record the fast licking behavior of rats. Data from the environment monitoring device also showed reliable measurements. By providing the source code and 3D design under an open source license, we believe these examples will stimulate innovation in behavioral studies. The source code can be found at http://github.com/chen42/openbehavior. PMID:28229020

Advanced Telescopes and Observatories and Scientific Instruments and Sensors Capability Roadmaps: General Background and Introduction

NASA Technical Reports Server (NTRS)

Coulter, Dan; Bankston, Perry

2005-01-01

Agency objective are: Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior

PubMed Central

Poland, Ryan S.; Bull, Cecilia; Syed, Wahab A.; Bowers, M. Scott

2015-01-01

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule. PMID:26437131

Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

PubMed Central

Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

2013-01-01

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

NASA's Human Planetary Landing Systems Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Mueller, Rob

2005-01-01

General Background and Introduction of Capability Roadmaps Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date)

The relative effects on math performance of single- versus multiple-ratio schedules: a case study1

PubMed Central

Lovitt, Tom C.; Esveldt, Karen A.

1970-01-01

This series of four experiments sought to assess the comparative effects of multiple- versus single-ratio schedules on a pupil's responding to mathematics materials. Experiment I, which alternated between single- and multiple-ratio contingencies, revealed that during the latter phase the subject responded at a higher rate. Similar findings were revealed by Exp. II. The third experiment, which manipulated frequency of reinforcement rather than multiple ratios, revealed that the alteration had a minimal effect on the subject's response rate. A final experiment, conducted to assess further the effects of multiple ratios, provided data similar to those of Exp. I and II. PMID:16795267

Some effects of overall rate of earning reinforcers on run lengths and visit durations.

PubMed

Macdonall, James S

2006-07-01

In a concurrent schedule, responding at each alternative is controlled by a pair of schedules that arrange reinforcers for staying at that alternative and reinforcers for switching to the other alternative. Each pair of schedules operates only while at the associated alternative. When only one pair of stay and switch schedules is presented, the rates of earning reinforcers for staying divided by the rates of earning reinforcers for switching controls the mean number responses in a visit and the mean duration of visits. The purpose of the present experiment was to see whether the sum of the rates of earning stay and switch reinforcers changed the way that run length and visit duration were affected by the ratio of the rates of stay to switch reinforcers. Rats were exposed to pairs of stay and switch schedules that varied both the ratio of the rates of earning stay and switch reinforcers and the sum of the rates of earning stay and switch reinforcers. Run lengths and visit durations were joint functions of the ratio of the rates of earning stay and switch reinforcers and the sum of the rates of earning stay and switch reinforcers. These results shows that the effect of the ratio of the sum of the rates of earning stay and switch reinforcers results from processes operating at the alternative, rather than from processes operating at both alternatives.

40 CFR 62.14540 - When must I complete each increment of progress?

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and Increments of Progress § 62...

40 CFR 62.14540 - When must I complete each increment of progress?

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and Increments of Progress § 62...

Influences on cocaine tolerance assessed under a multiple conjunctive schedule of reinforcement.

PubMed

Yoon, Jin Ho; Branch, Marc N

2009-11-01

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key-pecking responses of White Carneau pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose-effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.

Resurgence in Siamese fighting fish, Betta splendens.

PubMed

da Silva, Stephanie P; Cançado, Carlos R X; Lattal, Kennon A

2014-03-01

Resurgence of previously reinforced responding was investigated in male Siamese fighting fish (Betta splendens). Swimming through a ring produced 15-s mirror presentations according to, with different fish, either a fixed-ratio 1 or a variable-interval 60-s schedule of reinforcement. When responding was stable, a differential-reinforcement-of-other-behavior schedule was substituted for the mirror-presentation schedule. Following this, mirror presentations were discontinued (extinction). During this latter phase, there were transient increases in the ring-swim response relative to the frequency of such responding during the differential-reinforcement-of-other behavior schedule. Resurgence was similar for the fish exposed previously to the fixed-ratio or to the variable-interval schedule. These results extend to Siamese fighting fish a well-established behavioral phenomenon previously not observed in this species or with this response topography, and only rarely reported following the removal of a non-consumable reinforcer. Copyright © 2014 Elsevier B.V. All rights reserved.

Schedule and status of irradiation experiments

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

Rowcliffe, A.F.; Grossbeck, M.L.; Robertson, J.P.

1998-09-01

The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has one irradiation experiment in reactor and five experiments in the design or construction stages. Postirradiation examination and testing is in progress on ten experiments.

Constraint-based integration of planning and scheduling for space-based observatory management

NASA Technical Reports Server (NTRS)

Muscettola, Nicola; Smith, Steven F.

1994-01-01

Progress toward the development of effective, practical solutions to space-based observatory scheduling problems within the HSTS scheduling framework is reported. HSTS was developed and originally applied in the context of the Hubble Space Telescope (HST) short-term observation scheduling problem. The work was motivated by the limitations of the current solution and, more generally, by the insufficiency of classical planning and scheduling approaches in this problem context. HSTS has subsequently been used to develop improved heuristic solution techniques in related scheduling domains and is currently being applied to develop a scheduling tool for the upcoming Submillimeter Wave Astronomy Satellite (SWAS) mission. The salient architectural characteristics of HSTS and their relationship to previous scheduling and AI planning research are summarized. Then, some key problem decomposition techniques underlying the integrated planning and scheduling approach to the HST problem are described; research results indicate that these techniques provide leverage in solving space-based observatory scheduling problems. Finally, more recently developed constraint-posting scheduling procedures and the current SWAS application focus are summarized.

Pre-emphasis determination for an S-band constant bandwidth FM/FM station

NASA Technical Reports Server (NTRS)

Wallace, G. R.; Salter, W. E.

1972-01-01

Pre-emphasis schedules are given for 11 constant-bandwidth FM subcarriers modulating an S band transmitter at three receiver signal to noise ratios (i.e., 9, 15, and 25 dB). The criterion for establishing these pre-emphasis curves is the achievement, at various receiver intermediate frequency signal to noise ratios, of equal receiver output signal to noise ratios for all channels. It is realized that these curves may not be the optimum pre-emphasis curves based on overall efficiency or maximum utilization of the allotted spectrum, but they are near-optimum for data with channels which require equal output signal to noise ratios, such as spectral densities. The empirically derived results are compared with a simplified, analytically derived schedule and the primary differences are explained. The S band pre-emphasis schedule differs from the lower frequency VHF case. Since most proportional bandwidth and constant bandwidth systems use ground based recorders and some use flight recorders (as the Saturn systems did on VHF proportional bandwidth telemetry), the effects of these recorders are discussed and a modified pre-emphasis schedule is presented showing the results of this study phase.

40 CFR 62.14555 - What if I do not meet an increment of progress?

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and Increments of Progress § 62...

40 CFR 62.14555 - What if I do not meet an increment of progress?

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and Increments of Progress § 62...

Unit Price and Choice in a Token-Reinforcement Context

ERIC Educational Resources Information Center

Foster, Theresa A.; Hackenberg, Timothy D.

2004-01-01

Pigeons were exposed to multiple and concurrent second-order schedules of token reinforcement, with stimulus lights serving as token reinforcers. Tokens were produced and exchanged for food according to various fixed-ratio schedules, yielding equal and unequal unit prices (responses per unit food delivery). On one schedule (termed the "standard…

Immunogenicity and reactogenicity of alternative schedules of HPV vaccine in Vietnam: a cluster randomized noninferiority trial.

PubMed

Neuzil, Kathleen M; Canh, Do Gia; Thiem, Vu Dinh; Janmohamed, Amynah; Huong, Vu Minh; Tang, Yuxiao; Diep, Nguyen Thi Ngoc; Tsu, Vivien; LaMontagne, D Scott

2011-04-13

Human papillomavirus (HPV) vaccine programs may decrease the morbidity and mortality due to cervical cancer seen among women in low-resource countries. However, the 3-dose schedule over a 6-month period is a potential barrier to vaccine introduction in such settings. To determine the immunogenicity and reactogenicity of different dosing schedules of quadrivalent HPV vaccine in adolescent girls in Vietnam. Open-label, cluster randomized, noninferiority study (conducted between October 2007 and January 2010) assessing 4 schedules of an HPV vaccine delivered in 21 schools to 903 adolescent girls (aged 11-13 years at enrollment) living in northwestern Vietnam. Intramuscular injection of 3 doses of quadrivalent HPV vaccine delivered on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months). Serum anti-HPV geometric mean titers (GMT) measured 1 month after the third dose of the HPV vaccine was administered; GMT was determined by type-specific competitive immunoassay. Noninferiority of each alternative vaccination dosing schedule was achieved if the lower bound of the multiplicity-adjusted confidence interval (CI) of the type-specific GMT ratio for HPV-16 and HPV-18 was greater than 0.5 (primary outcome). Safety outcomes were immediate reactions, local reactions, fever within 7 days after each dose, and serious adverse events up to 30 days following the last dose. In the intention-to-treat analysis, 809 girls who received at least 1 HPV vaccine dose had valid serum measurements 1 month after the third dose. After the third dose, the GMTs for those in the standard schedule group who received doses at 0, 2, and 6 months were 5808.0 (95% CI, 4961.4-6799.0) for HPV-16 and 1729.9 (95% CI, 1504.0-1989.7) for HPV-18; 5368.5 (95% CI, 4632.4-6221.5) and 1502.3 (95% CI, 1302.1-1733.2), respectively, for those whose received doses at 0, 3, and 9 months; 5716.4 (95% CI, 4876.7-6700.6) and 1581.5 (95% CI, 1363.4-1834.6), respectively, for those who received doses at 0, 6, and 12 months; and 3692.5 (95% CI, 3145.3-4334.9) and 1335.7 (95% CI, 1191.6-1497.3), respectively, for those who received doses at 0, 12, and 24 months. Noninferiority criteria were met for the alternative schedule groups that received doses at 0, 3, and 9 months (HPV-16 GMT ratio: 0.92 [95% CI, 0.71-1.20]; HPV-18 GMT ratio: 0.87 [95% CI, 0.68-1.11]) and at 0, 6, and 12 months (HPV-16 GMT ratio: 0.98 [95% CI, 0.75-1.29]; HPV-18 GMT ratio: 0.91 [95% CI, 0.71-1.17]). Prespecified noninferiority criteria were not met for the alternative schedule group that received doses at 0, 12, and 24 months (HPV-16 GMT ratio: 0.64 [95% CI, 0.48-0.84]; HPV-18 GMT ratio: 0.77 [95% CI, 0.62-0.96]). Pain at the injection site was the most common adverse event. Among adolescent girls in Vietnam, administration of the HPV vaccine on standard and alternative schedules was immunogenic and well tolerated. The use of 2 alternative dosing schedules (at 0, 3, and 9 months and at 0, 6, and 12 months) compared with a standard schedule (at 0, 2, and 6 months) did not result in inferior antibody concentrations. clinicaltrials.gov Identifier: NCT00524745.

National Research Council Dialogue to Assess Progress on NASA's Transformational Spaceport and Range Technologies Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Skelly, Darin M.

2005-01-01

Viewgraphs on the National Research Council's diaglog to assess progress on NASA's transformational spaceport and range technologies capability roadmap development is presented. The topics include: 1) Agency Goals and Objectives; 2) Strategic Planning Transformation; 3) Advanced Planning Organizational Roles; 4) Public Involvement in Strategic Planning; 5) Strategic Roadmaps; 6) Strategic Roadmaps Schedule; 7) Capability Roadmaps; 8) Capability Charter; 9) Process for Team Selection; 10) Capability Roadmap Development Schedule Overview; 11) Purpose of NRC Review; 12) Technology Readiness Levels; 13) Capability Readiness Levels; 14) Crosswalk Matrix Trans Spaceport & Range; 15) Example linkage to other roadmaps; 16) Capability Readiness Levels Defined; and 17) Crosswalk Matrix Ratings Work In-progress.

Evidence of Self-correction of Child Sex Ratios in India: A District-Level Analysis of Child Sex Ratios From 1981 to 2011.

PubMed

Diamond-Smith, Nadia; Bishai, David

2015-04-01

Sex ratios in India have become increasingly imbalanced over the past decades. We hypothesize that when sex ratios become very uneven, the shortage of girls will increase girls' future value, leading sex ratios to self-correct. Using data on children under 5 from the last four Indian censuses, we examine the relationship between the sex ratio at one point in time and the change in sex ratio over the next 10 years by district. Fixed-effects models show that when accounting for unobserved district-level characteristics--including total fertility rate, infant mortality rate, percentage literate, percentage rural, percentage scheduled caste, percentage scheduled tribe, and a time trend variable--sex ratios are significantly negatively correlated with the change in sex ratio in the successive 10-year period. This suggests that self-corrective forces are at work on imbalanced sex ratios in India.

The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors

PubMed Central

Perry, Adam N.; Westenbroek, Christel; Becker, Jill B.

2013-01-01

Rationale Cocaine dependence is characterized by compulsive drug taking that supercedes other recreational, occupational or social pursuits. We hypothesized that rats vulnerable to addiction could be identified within the larger population based on their preference for cocaine over palatable food rewards. Objectives To validate the choice self-administration paradigm as a preclinical model of addiction, we examined changes in motivation for cocaine and recidivism to drug seeking in cocaine-preferring and pellet-preferring rats. We also examined behavior in males and females to identify sex differences in this “addicted” phenotype. Methods Preferences were identified during self-administration on a fixed-ratio schedule with cocaine-only, pellet-only and choice sessions. Motivation for each reward was probed early and late during self-administration using a progressive-ratio schedule. Reinstatement of cocaine- and pellet-seeking was examined following exposure to their cues and non-contingent delivery of each reward. Results Cocaine preferring rats increased their drug intake at the expense of pellets, displayed increased motivation for cocaine, attenuated motivation for pellets and greater cocaine and cue-induced reinstatement of drug seeking. Females were more likely to develop cocaine preferences and recidivism of cocaine- and pellet-seeking was sexually dimorphic. Conclusions The choice self-administration paradigm is a valid preclinical model of addiction. The unbiased selection criteria also revealed sex-specific vulnerability factors that could be differentiated from generalized sex differences in behavior, which has implications for the neurobiology of addiction and effective treatments in each sex. PMID:24260227

The development of a preference for cocaine over food identifies individual rats with addiction-like behaviors.

PubMed

Perry, Adam N; Westenbroek, Christel; Becker, Jill B

2013-01-01

Cocaine dependence is characterized by compulsive drug taking that supercedes other recreational, occupational or social pursuits. We hypothesized that rats vulnerable to addiction could be identified within the larger population based on their preference for cocaine over palatable food rewards. To validate the choice self-administration paradigm as a preclinical model of addiction, we examined changes in motivation for cocaine and recidivism to drug seeking in cocaine-preferring and pellet-preferring rats. We also examined behavior in males and females to identify sex differences in this "addicted" phenotype. Preferences were identified during self-administration on a fixed-ratio schedule with cocaine-only, pellet-only and choice sessions. Motivation for each reward was probed early and late during self-administration using a progressive-ratio schedule. Reinstatement of cocaine- and pellet-seeking was examined following exposure to their cues and non-contingent delivery of each reward. Cocaine preferring rats increased their drug intake at the expense of pellets, displayed increased motivation for cocaine, attenuated motivation for pellets and greater cocaine and cue-induced reinstatement of drug seeking. Females were more likely to develop cocaine preferences and recidivism of cocaine- and pellet-seeking was sexually dimorphic. The choice self-administration paradigm is a valid preclinical model of addiction. The unbiased selection criteria also revealed sex-specific vulnerability factors that could be differentiated from generalized sex differences in behavior, which has implications for the neurobiology of addiction and effective treatments in each sex.

Differential impact of response effort within a response chain on use of mands in a student with autism.

PubMed

Buckley, Scott D; Newchok, Debra K

2005-01-01

We investigated the effects of response effort on the use of mands during functional communication training (FCT) in a participant with autism. The number of links in a picture exchange response chain determined two levels of response effort. Each level was paired with a fixed ratio (FR3) schedule of reinforcement for aggression in a reversal design. Responding to either schedule produced access to a preferred item. The participant opted for the low effort mand while aggression decreased significantly. However, the high effort mand did not compete with the FR3 schedule for aggression. Results are discussed in terms of response effort within a response chain of a picture exchange system and competing ratio schedules for problem behavior during mand training.

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

Interaction of reinforcement schedules, a behavioral prosthesis, and work-related behavior in adults with mental retardation.

PubMed

Saunders, Richard R; McEntee, Julie E; Saunders, Muriel D

2005-01-01

The effects of variable-interval (VI) and fixed-ratio (FR) schedules of reinforcement for work-related behavior and an organizer for the work materials (behavioral prosthesis) were evaluated with 3 adults with severe or profound mental retardation. The participants had been recommended for study because of high rates of off-task and aberrant behavior in their daily vocational training programs. For 2 participants, VI and FR schedules resulted in the same outcome: more aberrant behavior than on-task and off-task behavior combined. The FR schedule nearly eliminated emission of aberrant and off-task behavior by the 3rd participant. Combining the behavioral prosthesis with FR reinforcement (FR+O) increased the proportion of time spent in on-task behavior by all participants under certain FR schedule parameters. Second-by-second analyses of the observation records revealed that FR schedules reduced off-task and aberrant behavior during work sequences (i.e., ratio runs), and FR+O led to a further reduction of these behaviors during postreinforcement pauses. Overall, the results show how organizer and schedule parameters can be adjusted to produce an optimized balance between productivity and reinforcement while undesirable behavior is minimized.

Evidence for positive, but not negative, behavioral contrast with wheel-running reinforcement on multiple variable-ratio schedules.

PubMed

Belke, Terry W; Pierce, W David

2016-12-01

Rats responded on a multiple variable-ratio (VR) 10 VR 10 schedule of reinforcement in which lever pressing was reinforced by the opportunity to run in a wheel for 30s in both the changed (manipulated) and unchanged components. To generate positive contrast, the schedule of reinforcement in the changed component was shifted to extinction; to generate negative contrast, the schedule was shifted to VR 3. With the shift to extinction in the changed component, wheel-running and local lever-pressing rates increased in the unchanged component, a result supporting positive contrast; however, the shift to a VR 3 schedule in the changed component showed no evidence of negative contrast in the unaltered setting, only wheel running decreased in the unchanged component. Changes in wheel-running rates across components were consistent in showing a compensation effect, depending on whether the schedule manipulation increased or decreased opportunities for wheel running in the changed component. These findings are the first to demonstrate positive behavioral contrast on a multiple schedule with wheel running as reinforcement in both components. Copyright © 2016 Elsevier B.V. All rights reserved.

Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Who Experienced Disease Progression During or After Trastuzumab-Based Therapy.

PubMed

Urruticoechea, Ander; Rizwanullah, Mohammed; Im, Seock-Ah; Ruiz, Antonio Carlos Sánchez; Láng, István; Tomasello, Gianluca; Douthwaite, Hannah; Badovinac Crnjevic, Tanja; Heeson, Sarah; Eng-Wong, Jennifer; Muñoz, Montserrat

2017-09-10

Purpose To assess the efficacy and safety of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy and received a prior taxane. Patients and Methods Patients were randomly assigned to arm A: trastuzumab 8 mg/kg → 6 mg/kg once every 3 weeks plus capecitabine 1,250 mg/m 2 twice a day (2 weeks on, 1 week off, every 3 weeks); or arm B: pertuzumab 840 mg → 420 mg once every 3 weeks plus trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m 2 on the same schedule as arm A. The primary end point was independent review facility-assessed progression-free survival (IRF PFS). Secondary end points included overall survival (OS) and safety. Hierarchical testing procedures were used to control type I error for statistical testing of IRF PFS, OS, and objective response rate. Results Randomly assigned (intent-to-treat) populations were 224 and 228 patients in arms A and B, respectively. Median IRF PFS at 28.6 and 25.3 months' median follow-up was 9.0 v 11.1 months (hazard ratio, 0.82; 95% CI, 0.65 to 1.02; P = .0731) and interim OS was 28.1 v 36.1 months (hazard ratio, 0.68; 95% CI, 0.51 to 0.90). The most common adverse events (all grades; incidence of ≥ 10% in either arm and ≥ 5% difference between arms) were hand-foot syndrome, nausea, and neutropenia in arm A, and diarrhea, rash, and nasopharyngitis in arm B. Conclusion The addition of pertuzumab to trastuzumab and capecitabine did not significantly improve IRF PFS. An 8-month increase in median OS to 36.1 months with pertuzumab was observed. Statistical significance for OS cannot be claimed because of the hierarchical testing of OS after the primary PFS end point; however, the magnitude of OS difference is in keeping with prior experience of pertuzumab in metastatic breast cancer. No new safety signals were identified.

Automated telescope scheduling

NASA Technical Reports Server (NTRS)

Johnston, Mark D.

1988-01-01

With the ever increasing level of automation of astronomical telescopes the benefits and feasibility of automated planning and scheduling are becoming more apparent. Improved efficiency and increased overall telescope utilization are the most obvious goals. Automated scheduling at some level has been done for several satellite observatories, but the requirements on these systems were much less stringent than on modern ground or satellite observatories. The scheduling problem is particularly acute for Hubble Space Telescope: virtually all observations must be planned in excruciating detail weeks to months in advance. Space Telescope Science Institute has recently made significant progress on the scheduling problem by exploiting state-of-the-art artificial intelligence software technology. What is especially interesting is that this effort has already yielded software that is well suited to scheduling groundbased telescopes, including the problem of optimizing the coordinated scheduling of more than one telescope.

An Exploration of Remote History Effects in Humans

ERIC Educational Resources Information Center

Okouchi, Hiroto

2007-01-01

One group of undergraduates responded under a fixed-ratio (FR) 25 schedule and a second group responded under a differential-reinforcement-of-low-rate (DRL) 5-s schedule (first history phase). Both groups of subjects were then exposed to a differential-reinforcement-of-other-behavior (DRO) 5-s schedule (second history phase), and finally to…

Power Management for Space Advanced Life Support

NASA Technical Reports Server (NTRS)

Jones, Harry

2001-01-01

Space power systems include the power source, storage, and management subsystems. In current crewed spacecraft, solar cells are the power source, batteries provide storage, and the crew performs any required load scheduling. For future crewed planetary surface systems using Advanced Life Support, we assume that plants will be grown to produce much of the crew's food and that nuclear power will be employed. Battery storage is much more costly than nuclear power capacity and so is not likely to be used. We investigate the scheduling of power demands by the crew or automatic control, to reduce the peak power load and the required generating capacity. The peak to average power ratio is a good measure of power use efficiency. We can easily schedule power demands to reduce the peak power from its maximum, but simple scheduling approaches may not find the lowest possible peak to average power ratio. An initial power scheduling example was simple enough for a human to solve, but a more complex example with many intermittent load demands required automatic scheduling. Excess power is a free resource and can be used even for minor benefits.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

PubMed Central

2011-01-01

Background To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Methods Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. Results From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. Conclusions In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. Trial registration ClinicalTrials.gov NCT00540800. PMID:21324184

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial.

PubMed

Nuzzo, Francesco; Morabito, Alessandro; Gravina, Adriano; Di Rella, Francesca; Landi, Gabriella; Pacilio, Carmen; Labonia, Vincenzo; Rossi, Emanuela; De Maio, Ermelinda; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; Thomas, Renato; Rinaldo, Massimo; Botti, Gerardo; Di Bonito, Maurizio; Di Maio, Massimo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2011-02-16

To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. ClinicalTrials.gov NCT00540800.

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.

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.

Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

PubMed

Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

2016-06-02

Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

PubMed Central

Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

2015-01-01

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between inflammatory pain and opioid abuse liability, and should help to facilitate the development of novel and safer opioid-based strategies for treating chronic pain. PMID:26338332

Role of mu, but not delta or kappa, opioid receptors in context-induced reinstatement of oxycodone seeking.

PubMed

Bossert, Jennifer M; Hoots, Jennifer K; Fredriksson, Ida; Adhikary, Sweta; Zhang, Michelle; Venniro, Marco; Shaham, Yavin

2018-05-19

Relapse to nonmedical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta, and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/d in Context A; lever pressing was paired with a discrete cue. Next, we extinguished the lever pressing in the presence of the discrete cue in Context B and then tested the rats for reinstatement of oxycodone seeking in both contexts. We retrained rats to self-administer oxycodone in Context A, re-extinguished their lever pressing in Context B, and retested them for reinstatement in both contexts. Prior to testing, we injected the rats with vehicle or antagonists of MOR (naltrexone; 0.5 or 1.0 mg/kg), DOR (naltrindole; 7.5 or 15 mg/kg), or KOR (LY2456302; 5 or 10 mg/kg). We also tested the effect of naltrexone, naltrindole, and LY2456302 on oxycodone self-administration under fixed-ratio-1 (FR1) and progressive-ratio (PR) reinforcement schedules. We observed context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction. Naltrexone, but not naltrindole or LY2456302, injections decreased this reinstatement. Additionally, naltrexone increased oxycodone self-administration under the FR1 schedule and decreased oxycodone self-administration under the PR schedule; naltrindole and LY2456302 were ineffective. Results demonstrate a critical role of MOR, but not DOR or KOR, in context-induced reinstatement of oxycodone seeking and oxycodone self-administration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cross-Layer Adaptive Feedback Scheduling of Wireless Control Systems

PubMed Central

Xia, Feng; Ma, Longhua; Peng, Chen; Sun, Youxian; Dong, Jinxiang

2008-01-01

There is a trend towards using wireless technologies in networked control systems. However, the adverse properties of the radio channels make it difficult to design and implement control systems in wireless environments. To attack the uncertainty in available communication resources in wireless control systems closed over WLAN, a cross-layer adaptive feedback scheduling (CLAFS) scheme is developed, which takes advantage of the co-design of control and wireless communications. By exploiting cross-layer design, CLAFS adjusts the sampling periods of control systems at the application layer based on information about deadline miss ratio and transmission rate from the physical layer. Within the framework of feedback scheduling, the control performance is maximized through controlling the deadline miss ratio. Key design parameters of the feedback scheduler are adapted to dynamic changes in the channel condition. An event-driven invocation mechanism for the feedback scheduler is also developed. Simulation results show that the proposed approach is efficient in dealing with channel capacity variations and noise interference, thus providing an enabling technology for control over WLAN. PMID:27879934

An examination of the effects of subthalamic nucleus inhibition or μ-opioid receptor stimulation on food-directed motivation in the non-deprived rat

PubMed Central

Pratt, Wayne E.; Choi, Eugene; Guy, Elizabeth G.

2012-01-01

The subthalamic nucleus (STN) serves important functions in regulating movement, cognition, and motivation and is connected with cortical and basal ganglia circuits that process reward and reinforcement. In order to further examine the role of the STN on motivation toward food in non-deprived rats, these experiments studied the effects of pharmacological inhibition or μ-opioid receptor stimulation of the STN on the 2-hr intake of a sweetened fat diet, the amount of work exerted to earn sucrose on a progressive ratio 2 (PR-2) schedule of reinforcement, and performance on a differential reinforcement of low-rate responding (DRL) schedule for sucrose reward. Separate behavioral groups (N = 6–9) were tested following bilateral inhibition of the STN with the GABAA receptor agonist muscimol (at 0–5 ng/0.5 μl/side) or following μ-opioid receptor stimulation with the agonist D-Ala2, N-MePhe4, Gly-ol-enkephalin (DAMGO; at 0, 0.025 or 0.25 μg/0.5 μl/side). Although STN inhibition increased ambulatory behavior during 2-hr feeding sessions, it did not significantly alter intake of the sweetened fat diet. STN inhibition also did not affect the breakpoint for sucrose pellets during a 1-hr PR-2 reinforcement schedule or impact the number of reinforcers earned on a 1-hr DRL-20 sec reinforcement schedule in non-deprived rats. In contrast, STN μ-opioid receptor stimulation significantly increased feeding on the palatable diet and reduced the reinforcers earned on a DRL-20 schedule, although DAMGO microinfusions had no effect on PR-2 performance. These data suggest that STN inhibition does not enhance incentive motivation for food in the absence of food restriction and that STN μ-opioid receptors play an important and unique role in motivational processes. PMID:22391117

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

PubMed Central

Levy, AnneMarie; Limebeer, Cheryl L.; Ferdinand, Justin; Shillingford, Ucal; Parker, Linda A.; Leri, Francesco

2014-01-01

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets. PMID:24561923

48 CFR 2452.216-70 - Estimated cost, base fee and award fee.

Code of Federal Regulations, 2010 CFR

2010-10-01

...] increments on the schedule set forth in the Performance Evaluation Plan established by the government. The amount payable shall be based on the progress toward completion of contract tasks as determined by the... payments of the award fee in accordance with the schedule established in the Performance Evaluation Plan...

Flexibility for Vocational Education through Computer Scheduling. Quarterly Report.

ERIC Educational Resources Information Center

Allen, Dwight W.

This progress report of a 2-year project (ending April 30, 1968) offers a random sampling of course schedule configurations and specific course performance criteria submitted to the Stanford project staff for evaluation and comment, and a brief statement of the project's data collection and data evaluation objectives. The project seeks to…

Changes in Blood Pressure and Heart Rate during Fixed-Interval Responding in Squirrel Monkeys

ERIC Educational Resources Information Center

DeWeese, Jo

2009-01-01

Episodic and sustained increases in heart rate and mean arterial blood pressure can occur with recurring patterns of schedule-controlled behavior. Most previous studies were conducted under fixed-ratio schedules, which maintained a consistent high rate of responding that alternated with periods of no responding during times when the schedule was…

Run Clever – No difference in risk of injury when comparing progression in running volume and running intensity in recreational runners: A randomised trial

PubMed Central

Rasmussen, Sten; Sørensen, Henrik; Parner, Erik Thorlund; Lind, Martin; Nielsen, Rasmus Oestergaard

2018-01-01

Background/aim The Run Clever trial investigated if there was a difference in injury occurrence across two running schedules, focusing on progression in volume of running intensity (Sch-I) or in total running volume (Sch-V). It was hypothesised that 15% more runners with a focus on progression in volume of running intensity would sustain an injury compared with runners with a focus on progression in total running volume. Methods Healthy recreational runners were included and randomly allocated to Sch-I or Sch-V. In the first eight weeks of the 24-week follow-up, all participants (n=839) followed the same running schedule (preconditioning). Participants (n=447) not censored during the first eight weeks entered the 16-week training period with a focus on either progression in intensity (Sch-I) or volume (Sch-V). A global positioning system collected all data on running. During running, all participants received real-time, individualised feedback on running intensity and running volume. The primary outcome was running-related injury (RRI). Results After preconditioning a total of 80 runners sustained an RRI (Sch-I n=36/Sch-V n=44). The cumulative incidence proportion (CIP) in Sch-V (reference group) were CIP2 weeks 4.6%; CIP4 weeks 8.2%; CIP8 weeks 13.2%; CIP16 weeks 28.0%. The risk differences (RD) and 95% CI between the two schedules were RD2 weeks=2.9%(−5.7% to 11.6%); RD4 weeks=1.8%(−9.1% to 12.8%); RD8 weeks=−4.7%(−17.5% to 8.1%); RD16 weeks=−14.0% (−36.9% to 8.9%). Conclusion A similar proportion of runners sustained injuries in the two running schedules. PMID:29527322

Tolerance to cocaine's effects on schedule-controlled behavior: role of delay between pause-ending responses and reinforcement.

PubMed

Macaskill, Anne C; Branch, Marc N

2012-01-01

The schedule of reinforcement under which behavior is maintained is an important contributor to whether tolerance to the behavioral effects of cocaine develops. Schedule parameter value (for example, fixed-ratio size) has been shown to affect the development of tolerance under some schedule types but not others, but the specific procedural variables causing this effect remain to be identified. To date, schedule-parameter-related tolerance has developed when a longer pause after reinforcement does not lead to a shorter delay between the response that ends the pause and reinforcement. The current study investigated the importance of this variable in pigeons using a multiple chained Fixed-Ratio 1, Fixed-Time x schedule, in which the first key peck in a trial produced a stimulus change and initiated a delay at the end of which food was presented regardless of whether or not additional pecks were made during the delay. Dose-response curves were assessed before, during and after chronic (daily) administration of cocaine. Tolerance to the pause-increasing effects of cocaine occurred to a similar degree regardless of the scheduled time between the end of the pause and reinforcement. Therefore, the relationship between pause length and delay to reinforcement does not provide an explanation for schedule-parameter-related tolerance. Copyright © 2011 Elsevier Inc. All rights reserved.

Visuomotor adaptability in older adults with mild cognitive decline.

PubMed

Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

2017-02-01

The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitization of salt appetite is associated with increased "wanting" but not "liking" of a salt reward in the sodium-deplete rat.

PubMed

Clark, Jeremy J; Bernstein, Ilene L

2006-02-01

To examine the role of incentive sensitization in the potentiation of salt appetite by prior depletions, the authors assessed the motivation to obtain salt ("wanting") and the palatability of salt ("liking") independently in salt-sensitized rats. Breakpoint on a progressive ratio reinforcement schedule was used to measure salt wanting and taste reactivity was used to measure salt liking in rats with and without a history of Na+ depletion. Salt-sensitized rats displayed higher breakpoints relative to controls. However, a history of Na+ depletion was not associated with a greater positive shift in taste reactivity measures. The data suggest that these components of reward are separable in this model and support the general proposition that sensitization may alter wanting but not liking.

29 CFR 1908.7 - Relationship to enforcement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... exemption program). (b) Effect upon scheduling. (1) An onsite consultative visit already in progress will.... The consultant and the employer shall notify the compliance officer of the visit in progress and...

29 CFR 1908.7 - Relationship to enforcement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... exemption program). (b) Effect upon scheduling. (1) An onsite consultative visit already in progress will.... The consultant and the employer shall notify the compliance officer of the visit in progress and...

29 CFR 1908.7 - Relationship to enforcement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... exemption program). (b) Effect upon scheduling. (1) An onsite consultative visit already in progress will.... The consultant and the employer shall notify the compliance officer of the visit in progress and...

29 CFR 1908.7 - Relationship to enforcement.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... exemption program). (b) Effect upon scheduling. (1) An onsite consultative visit already in progress will.... The consultant and the employer shall notify the compliance officer of the visit in progress and...

29 CFR 1908.7 - Relationship to enforcement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... exemption program). (b) Effect upon scheduling. (1) An onsite consultative visit already in progress will.... The consultant and the employer shall notify the compliance officer of the visit in progress and...

How should periods without social interaction be scheduled? Children's preference for practical schedules of positive reinforcement.

PubMed

Luczynski, Kevin C; Hanley, Gregory P

2014-01-01

Several studies have shown that children prefer contingent reinforcement (CR) rather than yoked noncontingent reinforcement (NCR) when continuous reinforcement is programmed in the CR schedule. Preference has not, however, been evaluated for practical schedules that involve CR. In Study 1, we assessed 5 children's preference for obtaining social interaction via a multiple schedule (periods of fixed-ratio 1 reinforcement alternating with periods of extinction), a briefly signaled delayed reinforcement schedule, and an NCR schedule. The multiple schedule promoted the most efficient level of responding. In general, children chose to experience the multiple schedule and avoided the delay and NCR schedules, indicating that they preferred multiple schedules as the means to arrange practical schedules of social interaction. In Study 2, we evaluated potential controlling variables that influenced 1 child's preference for the multiple schedule and found that the strong positive contingency was the primary variable. © Society for the Experimental Analysis of Behavior.

IOPS advisor: Research in progress on knowledge-intensive methods for irregular operations airline scheduling

NASA Technical Reports Server (NTRS)

Borse, John E.; Owens, Christopher C.

1992-01-01

Our research focuses on the problem of recovering from perturbations in large-scale schedules, specifically on the ability of a human-machine partnership to dynamically modify an airline schedule in response to unanticipated disruptions. This task is characterized by massive interdependencies and a large space of possible actions. Our approach is to apply the following: qualitative, knowledge-intensive techniques relying on a memory of stereotypical failures and appropriate recoveries; and quantitative techniques drawn from the Operations Research community's work on scheduling. Our main scientific challenge is to represent schedules, failures, and repairs so as to make both sets of techniques applicable to the same data. This paper outlines ongoing research in which we are cooperating with United Airlines to develop our understanding of the scientific issues underlying the practicalities of dynamic, real-time schedule repair.

Producing Satisfactory Solutions to Scheduling Problems: An Iterative Constraint Relaxation Approach

NASA Technical Reports Server (NTRS)

Chien, S.; Gratch, J.

1994-01-01

One drawback to using constraint-propagation in planning and scheduling systems is that when a problem has an unsatisfiable set of constraints such algorithms typically only show that no solution exists. While, technically correct, in practical situations, it is desirable in these cases to produce a satisficing solution that satisfies the most important constraints (typically defined in terms of maximizing a utility function). This paper describes an iterative constraint relaxation approach in which the scheduler uses heuristics to progressively relax problem constraints until the problem becomes satisfiable. We present empirical results of applying these techniques to the problem of scheduling spacecraft communications for JPL/NASA antenna resources.

Progressive content-based retrieval of image and video with adaptive and iterative refinement

NASA Technical Reports Server (NTRS)

Li, Chung-Sheng (Inventor); Turek, John Joseph Edward (Inventor); Castelli, Vittorio (Inventor); Chen, Ming-Syan (Inventor)

1998-01-01

A method and apparatus for minimizing the time required to obtain results for a content based query in a data base. More specifically, with this invention, the data base is partitioned into a plurality of groups. Then, a schedule or sequence of groups is assigned to each of the operations of the query, where the schedule represents the order in which an operation of the query will be applied to the groups in the schedule. Each schedule is arranged so that each application of the operation operates on the group which will yield intermediate results that are closest to final results.

Progression in Running Intensity or Running Volume and the Development of Specific Injuries in Recreational Runners: Run Clever, a Randomized Trial Using Competing Risks.

PubMed

Ramskov, Daniel; Rasmussen, Sten; Sørensen, Henrik; Parner, Erik Thorlund; Lind, Martin; Nielsen, Rasmus

2018-06-12

Study Design Randomized clinical trial, etiology. Background Training intensity and volume have been proposed to be associated with specific running-related injuries. If such an association exists, secondary preventive measures could be initiated by clinicians based on symptoms of a specific injury diagnosis. Objectives To test the following hypotheses: (i) A running schedule focusing on intensity will increase the risk of sustaining Achilles tendinopathy, gastrocnemius injuries and plantar fasciitis compared with hypothesized volume-related injuries. (ii) A running schedule focusing on running volume will increase the risk of sustaining patellofemoral pain syndrome, iliotibial band syndrome and patellar tendinopathy compared with hypothesized intensity-related injuries. Methods Healthy recreational runners were included in a 24-week follow-up, divided into 8-week preconditioning and 16-week specific focus-training. Participants were randomized to one of two running schedules: Schedule Intensity(Sch-I) or Schedule Volume(Sch-V). Sch-I progressed the amount of high intensity running (≥88% VO2max) each week. Sch-V progressed total weekly running volume. Global positioning system watch or smartphone collected data on running. Running-related injuries were diagnosed based on a clinical examination. Estimates were risk difference (RD) and 95%CI. Results Of 447 runners, a total of 80 sustained an injury (Sch-I n=36; Sch-V n=44). Risk of intensity injuries in Sch-I were: RD 2-weeks =-0.8%[-5.0;3.4]; RD 4-weeks =-0.8%[-6.7;5.1]; RD 8-weeks =-2.0%[-9.2;5.1]; RD 16-weeks =-5.1%[-16.5;6.3]. Risk of volume injuries in Sch-V were: RD 2-weeks =-0.9%[-5.0;3.2]; RD 4-weeks =-2.0%[-7.5;3.5]; RD 8-weeks =-3.2%[-9.1;2.7]; RD 16-weeks =-3.4%[-13.2;6.2]. Conclusion No difference in risk of hypothesized intensity and volume specific running-related injuries exist between running schedules focused on progression in either running intensity or volume. Level of Evidence Etiology, level 1b. J Orthop Sports Phys Ther, Epub 12 Jun 2018. doi:10.2519/jospt.2018.8062.

Curriculum-Based Measurement of Oral Reading: Multi-Study Evaluation of Schedule, Duration, and Dataset Quality on Progress Monitoring Outcomes

ERIC Educational Resources Information Center

Christ, Theodore J.; Zopluoglu, Cengiz; Monaghen, Barbara D.; Van Norman, Ethan R.

2013-01-01

Curriculum-Based Measurement of Oral Reading (CBM-R) is used to collect time series data, estimate the rate of student achievement, and evaluate program effectiveness. A series of 5 studies were carried out to evaluate the validity, reliability, precision, and diagnostic accuracy of progress monitoring across a variety of progress monitoring…

Progress Monitoring with Computer Adaptive Assessments: The Impact of Data Collection Schedule on Growth Estimates

ERIC Educational Resources Information Center

Nelson, Peter M.; Van Norman, Ethan R.; Klingbeil, Dave A.; Parker, David C.

2017-01-01

Although extensive research exists on the use of curriculum-based measures for progress monitoring, little is known about using computer adaptive tests (CATs) for progress-monitoring purposes. The purpose of this study was to evaluate the impact of the frequency of data collection on individual and group growth estimates using a CAT. Data were…

Daily sodium and potassium excretion can be estimated by scheduled spot urine collections.

PubMed

Doenyas-Barak, Keren; Beberashvili, Ilia; Bar-Chaim, Adina; Averbukh, Zhan; Vogel, Ofir; Efrati, Shai

2015-01-01

The evaluation of sodium and potassium intake is part of the optimal management of hypertension, metabolic syndrome, renal stones, and other conditions. To date, no convenient method for its evaluation exists, as the gold standard method of 24-hour urine collection is cumbersome and often incorrectly performed, and methods that use spot or shorter collections are not accurate enough to replace the gold standard. The aim of this study was to evaluate the correlation and agreement between a new method that uses multiple-scheduled spot urine collection and the gold standard method of 24-hour urine collection. The urine sodium or potassium to creatinine ratios were determined for four scheduled spot urine samples. The mean ratios of the four spot samples and the ratios of each of the single spot samples were corrected for estimated creatinine excretion and compared to the gold standard. A significant linear correlation was demonstrated between the 24-hour urinary solute excretions and estimated excretion evaluated by any of the scheduled spot urine samples. The correlation of the mean of the four spots was better than for any of the single spots. Bland-Altman plots showed that the differences between these measurements were within the limits of agreement. Four scheduled spot urine samples can be used as a convenient method for estimation of 24-hour sodium or potassium excretion. © 2015 S. Karger AG, Basel.

24 CFR 1006.430 - Corrective and remedial action.

Code of Federal Regulations, 2011 CFR

2011-04-01

... plan; (3) Made substantial progress in carrying out its program and achieving its quantifiable goals as... to submit progress schedules for completing activities or complying with the requirements of the Act... appropriate technical assistance using existing grant funds or other available resources to overcome the...

Mathematical modeling of prostate cancer progression in response to androgen ablation therapy.

PubMed

Jain, Harsh Vardhan; Clinton, Steven K; Bhinder, Arvinder; Friedman, Avner

2011-12-06

Prostate cancer progression depends in part on the complex interactions between testosterone, its active metabolite DHT, and androgen receptors. In a metastatic setting, the first line of treatment is the elimination of testosterone. However, such interventions are not curative because cancer cells evolve via multiple mechanisms to a castrate-resistant state, allowing progression to a lethal outcome. It is hypothesized that administration of antiandrogen therapy in an intermittent, as opposed to continuous, manner may bestow improved disease control with fewer treatment-related toxicities. The present study develops a biochemically motivated mathematical model of antiandrogen therapy that can be tested prospectively as a predictive tool. The model includes "personalized" parameters, which address the heterogeneity in the predicted course of the disease under various androgen-deprivation schedules. Model simulations are able to capture a variety of clinically observed outcomes for "average" patient data under different intermittent schedules. The model predicts that in the absence of a competitive advantage of androgen-dependent cancer cells over castration-resistant cancer cells, intermittent scheduling can lead to more rapid treatment failure as compared to continuous treatment. However, increasing a competitive advantage for hormone-sensitive cells swings the balance in favor of intermittent scheduling, delaying the acquisition of genetic or epigenetic alterations empowering androgen resistance. Given the near universal prevalence of antiandrogen treatment failure in the absence of competing mortality, such modeling has the potential of developing into a useful tool for incorporation into clinical research trials and ultimately as a prognostic tool for individual patients.

Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats.

PubMed

Schmeichel, Brooke E; Matzeu, Alessandra; Koebel, Pascale; Vendruscolo, Leandro F; Sidhu, Harpreet; Shahryari, Roxana; Kieffer, Brigitte L; Koob, George F; Martin-Fardon, Rémi; Contet, Candice

2018-04-06

The hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Chronic Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake under extended access conditions, a model that mimics key features of compulsive cocaine taking. In addition, Hcrt silencing decreased motivation for both cocaine and a highly palatable food reward (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence for general measures of arousal and stress reactivity. At the molecular level, chronic Hcrt knockdown reduced the number of neurons expressing dynorphin (DYN), and to a smaller extent melanin-concentrating hormone (MCH), in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.

Escape from rich-to-lean transitions: Stimulus change and timeout.

PubMed

Retzlaff, Billie J; Parthum, Elizabeth T P; Pitts, Raymond C; Hughes, Christine E

2017-01-01

Extended pausing during discriminable transitions from rich-to-lean conditions can be viewed as escape (i.e., rich-to-lean transitions function aversively). In the current experiments, pigeons' key pecking was maintained by a multiple fixed-ratio fixed-ratio schedule of rich or lean reinforcers. Pigeons then were provided with another, explicit, mechanism of escape by changing the stimulus from the transition-specific stimulus used in the multiple schedule to a mixed-schedule stimulus (Experiment 1) or by producing a period of timeout in which the stimulus was turned off and the schedule was suspended (Experiment 2). Overall, escape was under joint control of past and upcoming reinforcer magnitudes, such that responses on the escape key were most likely during rich-to-lean transitions, and second-most likely during lean-to-lean transitions. Even though pigeons pecked the escape key, they paused before doing so, and the latency to begin the fixed ratio (i.e., the pause) remained extended during rich-to-lean transitions. These findings suggest that although the stimulus associated with rich-to-lean transitions functioned aversively, pausing is more than simply escape responding from the stimulus. © 2017 Society for the Experimental Analysis of Behavior.

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

High Stakes Assessment: A Local District Perspective.

ERIC Educational Resources Information Center

Oldham, Ben R.

The Kentucky Education Reform Act legislated by the 1990 General Assembly created a high-stakes school performance accountability system to monitor the progress of implementation. One major component of the accountability system is a schedule of consequences designed to reward those schools making sufficient progress in improving student…

Using a Self-Control Training Procedure To Increase Appropriate Behavior.

ERIC Educational Resources Information Center

Dixon, Mark R.; Hayes, Linda J.; Binder, Lisa M.; Manthey, Sharon; Sigman, Connie; Zdanowski, Darlene M.

1998-01-01

A study evaluated teaching a technique for self-control to three adults with developmental disabilities. Concurrent fixed-duration/progressive-duration reinforcement schedules were introduced in which both smaller and larger reinforcers were available immediately. When progressively increasing delays were introduced for the larger reinforcer,…

National Research Council Dialogue to Assess Progesss on NASA's Human Exploration Systems and Mobility Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Inman, Thomas

2005-01-01

General Background and Introduction of Capability Roadmaps: Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Technology and Capability Readiness Levels. Relationships Between Roadmaps. Purpose of NRC Review. Capability Roadmap Development (Team Progress to Date).

Properties of behavior under different random ratio and random interval schedules: A parametric study.

PubMed

Dembo, M; De Penfold, J B; Ruiz, R; Casalta, H

1985-03-01

Four pigeons were trained to peck a key under different values of a temporally defined independent variable (T) and different probabilities of reinforcement (p). Parameter T is a fixed repeating time cycle and p the probability of reinforcement for the first response of each cycle T. Two dependent variables were used: mean response rate and mean postreinforcement pause. For all values of p a critical value for the independent variable T was found (T=1 sec) in which marked changes took place in response rate and postreinforcement pauses. Behavior typical of random ratio schedules was obtained at T 1 sec and behavior typical of random interval schedules at T 1 sec. Copyright © 1985. Published by Elsevier B.V.

Integrated planning and scheduling for Earth science data processing

NASA Technical Reports Server (NTRS)

Boddy, Mark; White, Jim; Goldman, Robert; Short, Nick, Jr.

1995-01-01

Several current NASA programs such as the EOSDIS Core System (ECS) have data processing and data management requirements that call for an integrated planning and scheduling capability. In this paper, we describe the experience of applying advanced scheduling technology operationally, in terms of what was accomplished, lessons learned, and what remains to be done in order to achieve similar successes in ECS and other programs. We discuss the importance and benefits of advanced scheduling tools, and our progress toward realizing them, through examples and illustrations based on ECS requirements. The first part of the paper focuses on the Data Archive and Distribution (DADS) V0 Scheduler. We then discuss system integration issues ranging from communication with the scheduler to the monitoring of system events and re-scheduling in response to them. The challenge of adapting the scheduler to domain-specific features and scheduling policies is also considered. Extrapolation to the ECS domain raises issues of integrating scheduling with a product-generation planner (such as PlaSTiC), and implementing conditional planning in an operational system. We conclude by briefly noting ongoing technology development and deployment projects being undertaken by HTC and the ISTB.

29 CFR 1903.19 - Abatement verification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... identify the violation and the steps to be taken to achieve abatement, including a schedule for completing..., the progress report must identify, in a single sentence if possible, the action taken to achieve abatement and the date the action was taken. Note to paragraph (f): Appendix B contains a Sample Progress...

75 FR 34705 - Information Collection; Submission for OMB Review, Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... respond, including the use of appropriate automated, electronic, mechanical, or other technological... Progress Report was published in the Federal Register on March 12, 2010. This comment period ended on May... encouraged the Corporation to retain the current Progress Report submission schedule of semi-annually to help...

Teaching Multi-Level Classes: A Lesson from the Past.

ERIC Educational Resources Information Center

Book, Leon C.

The laboratory school for Southeast Missouri State University offers individualized French and Spanish second language instruction to secondary students by scheduling them together in one multilevel class. Students progress individually and in small groups through planned, self-paced, continuous progress programs. Each student is given a checklist…

National Research Council Dialogue to Assess Progress on NASA's Systems Engineering Cost/Risk Analysis Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Regenie, Victoria

2005-01-01

Contents include the following: General Background and Introduction of Capability. Roadmaps for Systems Engineering Cost/Risk Analysis. Agency Objectives. Strategic Planning Transformation. Review Capability Roadmaps and Schedule. Review Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

76 FR 79754 - Twelfth Meeting: RTCA Special Committee 220, Automatic Flight Guidance and Control

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... technologies Administrative items (meeting schedule, location, and next meeting agenda) Any other business... 2 status--progress, issues and plan Review of WG 3 status--progress, issues and plans Review action.... Issued in Washington, DC, on December 15, 2011. Robert L. Bostiga, Manager, Business Operations Branch...

Techniques for cash management in scheduling manufacturing operations

NASA Astrophysics Data System (ADS)

Morady Gohareh, Mehdy; Shams Gharneh, Naser; Ghasemy Yaghin, Reza

2017-06-01

The objective in traditional scheduling is usually time based. Minimizing the makespan, total flow times, total tardi costs, etc. are instances of these objectives. In manufacturing, processing each job entails a cost paying and price receiving. Thus, the objective should include some notion of managing the flow of cash. We have defined two new objectives: maximization of average and minimum available cash. For single machine scheduling, it is demonstrated that scheduling jobs in decreasing order of profit ratios maximizes the former and improves productivity. Moreover, scheduling jobs in increasing order of costs and breaking ties in decreasing order of prices maximizes the latter and creates protection against financial instability.

Optimal Scheduling of Time-Shiftable Electric Loads in Expeditionary Power Grids

DTIC Science & Technology

2015-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS OPTIMAL SCHEDULING OF TIME-SHIFTABLE ELECTRIC LOADS IN EXPEDITIONARY POWER GRIDS by John G...to 09-25-2015 4. TITLE AND SUBTITLE OPTIMAL SCHEDULING OF TIME-SHIFTABLE ELECTRIC LOADS IN EXPEDI- TIONARY POWER GRIDS 5. FUNDING NUMBERS 6. AUTHOR(S...eliminate unmanaged peak demand, reduce generator peak-to-average power ratios, and facilitate a persistent shift to higher fuel efficiency. Using

Monitoring road safety development at regional level: A case study in the ASEAN region.

PubMed

Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher

2017-09-01

Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.

Countdown to 2015: comparing progress towards the achievement of the health Millennium Development Goals in Ethiopia and other sub-Saharan African countries.

PubMed

Accorsi, Sandro; Bilal, Nejmudin Kedir; Farese, Pasquale; Racalbuto, Vincenzo

2010-05-01

Mid-way 2007 reports indicate that many low-income countries, at current rates of progress, are unlikely to reach the Millennium Development Goals (MDG) by 2015. In Ethiopia, a decline was observed in under-five mortality rates from 204 to 123 per 1000 live births between 1990 and 2005, showing good progress towards the achievement of MDG4. A downward trend was observed in the maternal mortality ratio; however, because of the high degree of sampling variability, it is not possible to reach any firm conclusion about the possibility of achieving MDG5. Regarding MDG6, good progress was observed in controlling HIV/AIDS and malaria, whereas MDG indicators related to tuberculosis are still below international standards. Therefore, performance was not uniform across programmes. In general, interventions that can be routinely scheduled, such as immunisation, had much higher coverage than those that rely on functional health systems and clinical services proximate to households with 24h availability, such as skilled care at birth. These mixed results highlight that, although MDGs focus on specific diseases and conditions, targets cannot be achieved without strengthening health systems. It is for this reason that the strategic health plan in Ethiopia is focusing on high-impact and cost-effective health interventions and on health systems strengthening. Copyright 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

An Improved Scheduling Algorithm for Data Transmission in Ultrasonic Phased Arrays with Multi-Group Ultrasonic Sensors

PubMed Central

Tang, Wenming; Liu, Guixiong; Li, Yuzhong; Tan, Daji

2017-01-01

High data transmission efficiency is a key requirement for an ultrasonic phased array with multi-group ultrasonic sensors. Here, a novel FIFOs scheduling algorithm was proposed and the data transmission efficiency with hardware technology was improved. This algorithm includes FIFOs as caches for the ultrasonic scanning data obtained from the sensors with the output data in a bandwidth-sharing way, on the basis of which an optimal length ratio of all the FIFOs is achieved, allowing the reading operations to be switched among all the FIFOs without time slot waiting. Therefore, this algorithm enhances the utilization ratio of the reading bandwidth resources so as to obtain higher efficiency than the traditional scheduling algorithms. The reliability and validity of the algorithm are substantiated after its implementation in the field programmable gate array (FPGA) technology, and the bandwidth utilization ratio and the real-time performance of the ultrasonic phased array are enhanced. PMID:29035345

Idle efficiency and pollution results for two-row swirl-can combustors having 72 modules

NASA Technical Reports Server (NTRS)

Biaglow, J. A.; Trout, A. M.

1975-01-01

Two 72-swirl-can-module combustors were investigated in a full annular combustor test facility at engine idle conditions typical of a 30:1 pressure-ratio engine. The effects of radial and circumferential fuel scheduling on combustion efficiency and gaseous pollutants levels were determined. Test conditions were inlet-air temperature, 452 K; inlet total pressure, 34.45 newtons per square centimeter; and reference velocity, 19.5 meters per second. A maximum combustion efficiency of 98.1 percent was achieved by radial scheduling of fuel to the inner row of swirl-can modules. Emission index values were 6.9 for unburned hydrocarbons and 50.6 for carbon monoxide at a fuel-air ratio of 0.0119. Circumferential fuel scheduling of two 90 degree sectors of the swirl-can arrays produced a maximum combustion efficiency of 97.3 percent. The emission index values were 12.0 for unburned hydrocarbons and 69.2 for carbon monoxide at a fuel-air ratio of 0.0130.

Examining the reinforcing value of stimuli within social and non-social contexts in children with and without high-functioning autism

PubMed Central

Goldberg, Melissa C; Allman, Melissa J; Hagopian, Louis P; Triggs, Mandy M; Frank-Crawford, Michelle A; Mostofsky, Stewart H; Denckla, Martha B; DeLeon, Iser G

2018-01-01

One of the key diagnostic criteria for autism spectrum disorder includes impairments in social interactions. This study compared the extent to which boys with high-functioning autism and typically developing boys “value” engaging in activities with a parent or alone. Two different assessments that can empirically determine the relative reinforcing value of social and non-social stimuli were employed: paired-choice preference assessments and progressive-ratio schedules. There were no significant differences between boys with high-functioning autism and typically developing boys on either measure. Moreover, there was a strong correspondence in performance across these two measures for participants in each group. These results suggest that the relative reinforcing value of engaging in activities with a primary caregiver is not diminished for children with autism spectrum disorder. PMID:27368350

Examining the reinforcing value of stimuli within social and non-social contexts in children with and without high-functioning autism.

PubMed

Goldberg, Melissa C; Allman, Melissa J; Hagopian, Louis P; Triggs, Mandy M; Frank-Crawford, Michelle A; Mostofsky, Stewart H; Denckla, Martha B; DeLeon, Iser G

2017-10-01

One of the key diagnostic criteria for autism spectrum disorder includes impairments in social interactions. This study compared the extent to which boys with high-functioning autism and typically developing boys "value" engaging in activities with a parent or alone. Two different assessments that can empirically determine the relative reinforcing value of social and non-social stimuli were employed: paired-choice preference assessments and progressive-ratio schedules. There were no significant differences between boys with high-functioning autism and typically developing boys on either measure. Moreover, there was a strong correspondence in performance across these two measures for participants in each group. These results suggest that the relative reinforcing value of engaging in activities with a primary caregiver is not diminished for children with autism spectrum disorder.

High-sucrose diets in male rats disrupt aspects of decision making tasks, motivation and spatial memory, but not impulsivity measured by operant delay-discounting.

PubMed

Wong, Alanna; Dogra, Vimi R; Reichelt, Amy C

2017-06-01

Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus and prefrontal cortex, leading to perturbations in behavioural control. Impairments in behavioural control have been observed in obese people on tasks that involve making choices, including delay-discounting, indicative of increased impulsivity. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) in young male rats on behavioural tasks reliant on hippocampal function including delay-discounting, T-maze forced choice alternation and place recognition memory, as well as progressive ratio to measure motivation. We observed deficits in place recognition memory and T-maze forced choice alternation, indicative of hippocampal deficits in rats with a history of sucrose consumption. Moreover, rats with a history of sucrose consumption were less motivated to lever press for rewards on a progressive ratio schedule. However, rats with a history of sucrose consumption performed equally to control animals during the delay-discounting task, suggesting that they discounted for reward size over a delay in a manner comparable to control animals. These findings indicate that high-sucrose diets impact on spatial and working memory processes, but do not induce impulsive-like choice behaviours in rats, suggesting that unhealthy diet choices may not influence this aspect of decision-making behaviour. Copyright © 2017 Elsevier B.V. All rights reserved.

Further Evaluation of the Use of Multiple Schedules for Behavior Maintained by Negative Reinforcement.

PubMed

Campos, Claudia; Leon, Yanerys; Sleiman, Andressa; Urcuyo, Beatriz

2017-03-01

One potential limitation of functional communication training (FCT) is that after the functional communication response (FCR) is taught, the response may be emitted at high rates or inappropriate times. Thus, schedule thinning is often necessary. Previous research has demonstrated that multiple schedules can facilitate schedule thinning by establishing discriminative control of the communication response while maintaining low rates of problem behavior. To date, most applied research evaluating the clinical utility of multiple schedules has done so in the context of behavior maintained by positive reinforcement (e.g., attention or tangible items). This study examined the use of a multiple schedule with alternating Fixed Ratio (FR 1)/extinction (EXT) components for two individuals with developmental disabilities who emitted escape-maintained problem behavior. Although problem behavior remained low during all FCT and multiple schedule phases, the use of the multiple schedule alone did not result in discriminated manding.

Do Conditional Reinforcers Count?

PubMed Central

Davison, Michael; Baum, William M

2006-01-01

Six pigeons were trained on a procedure in which seven components arranged different food-delivery ratios on concurrent variable-interval schedules each session. The components were unsignaled, lasted for 10 food deliveries, and occurred in random order with a 60-s blackout between components. The schedules were arranged using a switching-key procedure in which two responses on a center key changed the schedules and associated stimuli on two side keys. In Experiment 1, over five conditions, an increasing proportion of food deliveries accompanied by a magazine light was replaced with the presentation of the magazine light only. Local analyses of preference showed preference pulses toward the alternative that had just produced either a food-plus-magazine-light or magazine-light-only presentation, but pulses after food deliveries were always greater than those after magazine lights. Increasing proportions of magazine lights did not change the size of preference pulses after food or magazine-light presentations. Experiment 2 investigated the effects of correlations between food ratios and magazine-light ratios: In Condition 6, magazine-light ratios in components were inversely correlated (−1.0) with food ratios, and in Condition 7, magazine-light ratios were uncorrelated with food ratios. In Conditions 8 and 9, pecks also produced occasional 2.5-s flashes of a green keylight. In Condition 8, food and magazine-light ratios were correlated 1.0 whereas food and green-key ratios were correlated −1.0. In Condition 9, food and green-key ratios were correlated 1.0 whereas food and magazine-light ratios were correlated −1.0. Preference pulses toward alternatives after magazine lights and green keys depended on the correlation between these event ratios and the food ratios: If the ratios were correlated +1.0, positive preference pulses resulted; if the correlation was −1.0, preference pulses were negative. These results suggest that the Law of Effect has more to do with events signaling consequences than with strengthening responses. PMID:17191753

Choice with a fixed requirement for food, and the generality of the matching relation

PubMed Central

Stubbs, D. Alan; Dreyfus, Leon R.; Fetterman, J. Gregor; Dorman, Lana G.

1986-01-01

Pigeons were trained on choice procedures in which responses on each of two keys were reinforced probabilistically, but only after a schedule requirement had been met. Under one arrangement, a fixed-interval choice procedure was used in which responses were not reinforced until the interval was over; then a response on one key would be reinforced, with the effective key changing irregularly from interval to interval. Under a second, fixed-ratio choice procedure, responses on either key counted towards completion of the ratio and then, once the ratio had been completed, a response on the probabilistically selected key would produce food. In one experiment, the schedule requirements were varied for both fixed-interval and fixed-ratio schedules. In the second experiment, relative reinforcement rate was varied. And in a third experiment, the duration of an intertrial interval separating choices was varied. The results for 11 pigeons across all three experiments indicate that there were often large deviations between relative response rates and relative reinforcement rates. Overall performance measures were characterized by a great deal of variability across conditions. More detailed measures of choice across the schedule requirement were also quite variable across conditions. In spite of this variability, performance was consistent across conditions in its efficiency of producing food. The absence of matching of behavior allocation to reinforcement rate indicates an important difference between the present procedures and other choice procedures; that difference raises questions about the specific conditions that lead to matching as an outcome. PMID:16812452

Separating the effects of interreinforcement time and number of interreinforcement responses1

PubMed Central

Neuringer, Allen J.; Schneider, Bruce A.

1968-01-01

The relative importance of interreinforcement time and interreinforcement responses was evaluated by varying each independently. To do this, a blackout was presented after each nonreinforced response under both fixed-ratio and fixed-interval schedules of reinforcement. Manipulating the blackout duration under the fixed-ratio schedule caused interreinforcement time to vary without affecting the number of interreinforcement responses. Pigeons' post-reinforcement and post-blackout response latencies were found to increase linearly with interreinforcement time. Under the fixed-interval schedule, the same blackout manipulations changed the number of interreinforcement responses without affecting interreinforcement time. Post-reinforcement and post-blackout response latencies under this condition were approximately constant. These results suggest that responding is controlled by interreinforcement time and is not influenced by the number of responses emitted between reinforcements. PMID:16811313

Optimal RTP Based Power Scheduling for Residential Load in Smart Grid

NASA Astrophysics Data System (ADS)

Joshi, Hemant I.; Pandya, Vivek J.

2015-12-01

To match supply and demand, shifting of load from peak period to off-peak period is one of the effective solutions. Presently flat rate tariff is used in major part of the world. This type of tariff doesn't give incentives to the customers if they use electrical energy during off-peak period. If real time pricing (RTP) tariff is used, consumers can be encouraged to use energy during off-peak period. Due to advancement in information and communication technology, two-way communications is possible between consumers and utility. To implement this technique in smart grid, home energy controller (HEC), smart meters, home area network (HAN) and communication link between consumers and utility are required. HEC interacts automatically by running an algorithm to find optimal energy consumption schedule for each consumer. However, all the consumers are not allowed to shift their load simultaneously during off-peak period to avoid rebound peak condition. Peak to average ratio (PAR) is considered while carrying out minimization problem. Linear programming problem (LPP) method is used for minimization. The simulation results of this work show the effectiveness of the minimization method adopted. The hardware work is in progress and the program based on the method described here will be made to solve real problem.

Pigeons' demand and preference for specific and generalized conditioned reinforcers in a token economy.

PubMed

Tan, Lavinia; Hackenberg, Timothy D

2015-11-01

Pigeons' demand and preference for specific and generalized tokens was examined in a token economy. Pigeons could produce and exchange different colored tokens for food, for water, or for food or water. Token production was measured across three phases, which examined: (1) across-session price increases (typical demand curve method); (2) within-session price increases (progressive-ratio, PR, schedule); and (3) concurrent pairwise choices between the token types. Exponential demand curves were fitted to the response data and accounted for over 90% total variance. Demand curve parameter values, Pmax , Omax and α showed that demand was ordered in the following way: food tokens, generalized tokens, water tokens, both in Phase 1 and in Phase 3. This suggests that the preferences were predictable on the basis of elasticity and response output from the demand analysis. Pmax and Omax values failed to consistently predict breakpoints and peak response rates in the PR schedules in Phase 2, however, suggesting limits on a unitary conception of reinforcer efficacy. The patterns of generalized token production and exchange in Phase 3 suggest that the generalized tokens served as substitutes for the specific food and water tokens. Taken together, the present findings demonstrate the utility of behavioral economic concepts in the analysis of generalized reinforcement. © Society for the Experimental Analysis of Behavior.

Canadian Environmental Concerns: Winnipeg, Manitoba. Progress Report. Project Canada West.

ERIC Educational Resources Information Center

Western Curriculum Project on Canada Studies, Edmonton (Alberta).

Part I of this progress report places emphasis on curriculum development from the standpoint of the teacher-developer. The role is defined and factors such as teacher selection, release time, administrative cooperation, work schedules, assigned work space, and benefits to the school division and to the teacher are discussed. Recommendations deal…

40 CFR 35.4170 - What kinds of reporting does EPA require?

Code of Federal Regulations, 2011 CFR

2011-07-01

... OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Technical Assistance Managing Your Tag... period which ends June 30 and December 31 of each year. (b) [Reserved] (c) Progress Report Full description in chart or narrative format of the progress your group made in relation to your approved schedule...

Continual planning and scheduling for managing patient tests in hospital laboratories.

PubMed

Marinagi, C C; Spyropoulos, C D; Papatheodorou, C; Kokkotos, S

2000-10-01

Hospital laboratories perform examination tests upon patients, in order to assist medical diagnosis or therapy progress. Planning and scheduling patient requests for examination tests is a complicated problem because it concerns both minimization of patient stay in hospital and maximization of laboratory resources utilization. In the present paper, we propose an integrated patient-wise planning and scheduling system which supports the dynamic and continual nature of the problem. The proposed combination of multiagent and blackboard architecture allows the dynamic creation of agents that share a set of knowledge sources and a knowledge base to service patient test requests.

Improving DOE Project Performance Using the DOD Integrated Master Plan - 12481

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

Alleman, Glen B.; Nosbisch, Michael R.

2012-07-01

DOE O 413 measures a project's progress to plan by the consumption of funding, the passage of time, and the meeting of milestones. In March of 2003, then Under Secretary, Energy, Science, Card received a memo directing the implementation of Project Management and the Project Management Manual, including the Integrated Master Plan and Integrated Master Schedule. This directive states 'the integrated master plan and schedule tie together all project tasks by showing their logical relationships and any constraints controlling the start or finish of each task. This process results in a hierarchy of related functional and layered schedules derived frommore » the Work Breakdown Structure that can be used for monitoring and controlling project progress'. This paper shows how restoring the IMP/IMS paradigm to DOE program management increases the probability of program success in ways not currently available using DOD O 413 processes alone. Using DOE O 413 series guidance, adding the Integrated Master Plan and Integrated Master Schedule paradigm would provide a hierarchical set of performance measures for each 'package of work,' that provides measurable visibility to the increasing maturity of the project. This measurable maturity provides the mechanism to forecast future performance of cost, schedule, and technical outcomes in ways not available using just the activities in DOE O 413. With this information project managers have another tool available to address the issues identified in GAO-07-336 and GAO-09-406. (authors)« less

Attenuated behavioural responses to acute and chronic cocaine in GASP-1-deficient mice.

PubMed

Boeuf, Julien; Trigo, José Manuel; Moreau, Pierre-Henri; Lecourtier, Lucas; Vogel, Elise; Cassel, Jean-Cristophe; Mathis, Chantal; Klosen, Paul; Maldonado, Rafael; Simonin, Frédéric

2009-09-01

G protein-coupled receptor (GPCR) associated sorting protein 1 (GASP-1) interacts with GPCRs and is implicated in their postendocytic sorting. Recently, GASP-1 has been shown to regulate dopamine (D(2)) and cannabinoid (CB1) receptor signalling, suggesting that preventing GASP-1 interaction with GPCRs might provide a means to limit the decrease in receptor signalling upon sustained agonist treatment. In order to test this hypothesis, we have generated and behaviourally characterized GASP-1 knockout (KO) mice and have examined the consequences of the absence of GASP-1 on chronic cocaine treatments. GASP-1 KO and wild-type (WT) mice were tested for sensitization to the locomotor effects of cocaine. Additional mice were trained to acquire intravenous self-administration of cocaine on a fixed ratio 1 schedule of reinforcement, and the motivational value of cocaine was then assessed using a progressive ratio schedule of reinforcement. The dopamine and muscarinic receptor densities were quantitatively evaluated in the striatum of WT and KO mice tested for sensitization and self-administration. Acute and sensitized cocaine-locomotor effects were attenuated in KO mice. A decrease in the percentage of animals that acquired cocaine self-administration was also observed in GASP-1-deficient mice, which was associated with pronounced down-regulation of dopamine and muscarinic receptors in the striatum. These data indicate that GASP-1 participates in acute and chronic behavioural responses induced by cocaine and are in agreement with a role of GASP-1 in postendocytic sorting of GPCRs. However, in contrast to previous studies, our data suggest that upon sustained receptor stimulation GASP-1 stimulates recycling rather than receptor degradation.

Chronic Cocaine-Induced H3 Acetylation and Transcriptional Activation of CaMKIIα in the Nucleus Accumbens Is Critical for Motivation for Drug Reinforcement

PubMed Central

Wang, Lei; Lv, Zhigang; Hu, Zhaoyang; Sheng, Jian; Hui, Bin; Sun, Jie; Ma, Lan

2010-01-01

The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription is mediated by epigenetic mechanisms that alter the chromatin structure at specific gene promoters. To better understand the involvement of epigenetic regulation in drug reinforcement properties, rats were subjected to cocaine self-administration paradigm. Daily histone deacetylase (HDAC) inhibitor infusions in the shell of the nucleus accumbens (NAc) caused an upward shift in the dose-response curve under fixed-ratio schedule and increased the break point under progressive-ratio schedule, indicating enhanced motivation for self-administered drug. The effect of the HDAC inhibitor is attributed to the increased elevation of histone acetylation induced by chronic, but not acute, cocaine experience. In contrast, neutralizing the chronic cocaine-induced increase in histone modification by the bilateral overexpression of HDAC4 in the NAc shell reduced drug motivation. The association between the motivation for cocaine and the transcriptional activation of addiction-related genes by H3 acetylation in the NAc shell was analyzed. Among the genes activated by chronic cocaine experiences, the expression of CaMKIIα, but not CaMKIIβ, correlated positively with motivation for the drug. Lentivirus-mediated shRNA knockdown experiments showed that CaMKIIα, but not CaMKIIβ, in the NAc shell is essential for the maintenance of motivation to self-administered cocaine. These findings suggest that chronic drug-use-induced transcriptional activation of genes, such as CaMKIIα, modulated by H3 acetylation in the NAc is a critical regulatory mechanism underlying motivation for drug reinforcement. PMID:20010550

75 FR 7580 - Proposed Rate Adjustment for Kerr-Philpott System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

..., CP&L-1-A, CP&L-2-A, CP&L-3-A, CP&L-4-A, AP-1-A, AP-2-A, AP-3-A, AP-4-A, NC-1-A, Replacement-2, and... transmission arrangement. Rate Schedule CP&L-1-B Available to public bodies and cooperatives in North Carolina... Carolina Power & Light (also known as Progress Energy Carolinas). Rate Schedule CP&L-2-B Available to...

Do scheduled caste and scheduled tribe women legislators mean lower gender-caste gaps in primary schooling in India?

PubMed

Halim, Nafisa; Yount, Kathryn M; Cunningham, Solveig

2016-07-01

Despite India's substantial investments in primary schooling, gaps in schooling persist across gender and caste-with scheduled caste and scheduled tribe (SC/ST) girls being particularly disadvantaged. The representation of SC/ST women in state legislatures may help to mitigate this disadvantage. Specifically, because of her intersecting gender and caste/tribe identities, a SC/ST woman legislator might maintain a strong sense of solidarity especially with SC/ST girls and women, and support legislative policies benefitting SC/ST girls. Consequently, for this reason, we expect that living in a district where SC/ST women represent in state legislatures in a higher proportion may increase SC/ST girls' primary school completion, progression and performance. We tested this hypothesis using district-level data between 2000 and 2004 from the Indian Election Commission, the 2004/5 India Human Development Survey, and the Indian Census of 2001. As expected, the representation of SC/ST women in state legislatures was positively associated with SC/ST girls' grade completion and age-appropriate grade progression but was apparent not SC/ST girls' primary-school performance. SC/ST women's representation in state legislatures may reduce gender-caste gaps in primary-school attainment in India. Copyright © 2016. Published by Elsevier Inc.

Do scheduled caste and scheduled tribe women legislators mean lower gender-caste gaps in primary schooling in India?

PubMed Central

Halim, Nafisa; Yount, Kathryn M.; Cunningham, Solveig

2017-01-01

Despite India’s substantial investments in primary schooling, gaps in schooling persist across gender and caste—with scheduled caste and scheduled tribe (SC/ST) girls being particularly disadvantaged. The representation of SC/ST women in state legislatures may help to mitigate this disadvantage. Specifically, because of her intersecting gender and caste/tribe identities, a SC/ST woman legislator might maintain a strong sense of solidarity especially with SC/ST girls and women, and support legislative policies benefitting SC/ST girls. Consequently, for this reason, we expect that living in a district where SC/ST women represent in state legislatures in a higher proportion may increase SC/ST girls’ primary school completion, progression and performance. We tested this hypothesis using district-level data between 2000 and 2004 from the Indian Election Commission, the 2004/5 India Human Development Survey, and the Indian Census of 2001. As expected, the representation of SC/ST women in state legislatures was positively associated with SC/ST girls’ grade completion and age-appropriate grade progression but was apparent not SC/ST girls’ primary-school performance. SC/ST women’s representation in state legislatures may reduce gender-caste gaps in primary-school attainment in India. PMID:27194655

5 CFR 340.101 - Principal statutory requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Findings and Purpose Sec. 2. (a) The Congress finds that— (1) many individuals in our society possess great... be equal to the percentage which bears the same ratio to the percentage determined under this... scheduled workweek bears to the average number of hours in the regularly scheduled workweek of an employee...

Do Conditional Reinforcers Count?

ERIC Educational Resources Information Center

Davison, Michael; Baum, William M.

2006-01-01

Six pigeons were trained on a procedure in which seven components arranged different food-delivery ratios on concurrent variable-interval schedules each session. The components were unsignaled, lasted for 10 food deliveries, and occurred in random order with a 60-s blackout between components. The schedules were arranged using a switching-key…

Effects of Behavioral History on Resistance to Change

ERIC Educational Resources Information Center

Doughty, Adam H.; Cirino, Sergio; Mayfield, Kristin H.; da Silva, Stephanie P.; Okouchi, Hiroto; Lattal, Kennon A.

2005-01-01

Two experiments examined whether differential resistance to change would occur under identical variable-interval schedules as a function of a differential behavioral history. In Experiment 1, each of 3 pigeons first pecked at different rates under a multiple variable-ratio differential-reinforcement-of-low-rate schedule. In a subsequent condition,…

Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: A real-world data, non-inferiority analysis.

PubMed

Visa, Laura; Jiménez-Fonseca, Paula; Martínez, Elena Asensio; Hernández, Raquel; Custodio, Ana; Garrido, Manuel; Viudez, Antonio; Buxo, Elvira; Echavarria, Ignacio; Cano, Juana María; Macias, Ismael; Mangas, Montserrat; de Castro, Eva Martínez; García, Teresa; Manceñido, Felipe Álvarez; Montes, Ana Fernández; Azkarate, Aitor; Longo, Federico; Serrano, Asunción Díaz; López, Carlos; Hurtado, Alicia; Cerdá, Paula; Serrano, Raquel; Gil-Negrete, Aitziber; Carnicero, Alfonso Martín; Pimentel, Paola; Ramchandani, Avinash; Carmona-Bayonas, Alberto

2018-05-01

Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.<70years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. 33% (n=489) of the cases analyzed were ≥70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3-4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91-1.14), P (non inferiority)=0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87-1.08), P(non-inferiority)=0.001. In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

A quantitative analysis of sensitivity to the conditioned reinforcing value of terminal-link stimuli in a concurrent-chains schedule.

PubMed Central

Omino, T

1993-01-01

Pigeons were exposed to a concurrent-chains schedule in which a single variable-interval 30-s schedule was used in the initial links and fixed-time schedules were used in the terminal links. Three types of keylight conditions were used in the terminal links. In the first condition, different delays were associated with different keylight stimuli (cued condition). In the second condition, different delays were associated with the same stimulus, either a blackout (uncued blackout condition) or a white key (uncued white condition). Paired values of terminal-link fixed-time schedules differed by a constant ratio of 3:1, while the absolute value of delays was varied from 3 s to 54 s. The results showed that choice proportions for the shorter of two delays increased when the absolute size of the delays was increased for all keylight conditions. Further, the choice proportions for the shorter delay increased from the uncued blackout condition, to the uncued white condition, to the cued condition. A modified version of Fantino's (1969) delay-reduction model (expressed as a function relating the response ratio to the delay-reduction ratio) can be applied to these data by showing that sensitivity to delay reduction increased from the uncued blackout condition, to the uncued white condition, to the cued condition. Thus, the present study demonstrated that a modified version of the delay-reduction model can be used to assess quantitative differences in the terminal-link keylight condition in terms of sensitivity to delay reduction (i.e., the conditioned reinforcing value of the terminal-link keylight stimuli). PMID:8283150

Phase II study of a novel taxane (Cabazitaxel-XRP 6258) in previously treated advanced non-small cell lung cancer (NSCLC) patients.

PubMed

Madan, Ankit; Jones, Benjamin S; Bordoni, Rodolfo; Saleh, Mansoor N; Jerome, Mary S; Miley, Deborah K; Jackson, Bradford E; Robert, Francisco

2016-09-01

Given the success of cabazitaxel in patients with prostate cancer who progressed after receiving prior chemotherapy, its preclinical efficacy in various cell lines and possible ability to cross blood-brain barrier, cabazitaxel was hypothesized to increase objective response rate (ORR) in second-line setting in non-small cell lung cancer (NSCLC). This was a phase II 2-stage trial in 28 patients using two different treatment schedules (A: 20 mg/m(2) every 3 weeks intravenously and B: 8.4 mg/m(2) intravenously weekly) to determine the ORR of cabazitaxel with secondary end points including progression-free survival (PFS), safety, and overall survival (OS). There was one objective response in schedule B. PFS and OS of schedule A was 3 and 6 months, respectively. PFS and OS of schedule B was 3 and 13 months, respectively. The stable disease rate was higher in schedule A (SD = 69.23 %; 95 % CL 38.57, 90.90) as compared to schedule B (SD = 38.46 %; 95 % CL 13.86, 68.42), but this difference was not statistically significant (P value = 0.1156). There were two grade 5 toxicities from sepsis. Hematuria of any grade developed in greater percentage of patients (35%) as compared to previous cabazitaxel phase 3 trial and led to change in our protocol. Response to cabazitaxel in NSCLC was not as robust as seen in prostate cancer and not superior to currently used agents such as docetaxel, pemetrexed, and erlotinib. In absence of significant objective responses, the second stage of the study was not undertaken.

[Intrathecal methotrexate in breast cancer meningeal carcinomatosis - Experience with a new administration schedule].

PubMed

Cochereau, Delphine; Da Costa, Sabrina; Le Maignan, Christine; Gauthier, Hélène; Cochereau, Jérôme; Espié, Marc; Giacchetti, Sylvie; Teixeira, Luis

2016-05-01

Methotrexate represents the standard intrathecal treatment of breast cancer meningeal carcinomatosis. However, its optimal schedule remains undefined. The aim of the present study was to evaluate results obtained with the methotrexate schedule used in Saint-Louis hospital (Paris). Patients followed in Saint-Louis hospital for breast cancer and who received intrathecal methotrexate were included in this retrospective monocentric study. Intrathecal treatment received contained methotrexate 12 mg/day (days: 1-5) and then 15 mg/week until progression or toxicity. Between 2003 and 2015, 41 patients were included. Primitive tumours were RH+/HER2-, HER2+ and triple-negative in respectively 66%, 14%, 5% and 15% of patients, 22% of them had meningeal carcinomatosis as metastatic disease initial manifestation. Objective response rate was 54%, median overall survival was 4.0 mois [CI 95%: 3-7.3] and 1-year survival rate was 15.2% (11.4%, 50% et 0% in RH+/HER2-, HER2+ and triple-negative subgroups; HR=0.45 [0.21-0.97] between HER2+ and RH+/HER2-). In univariate analysis, prognostic factors were brain involvement (p=0.049), initial cerebrospinal fluid protein level (p=0.0002) and concomitant systemic treatment received (p=0.049). This intrathecal methotrexate schedule demonstrates a similar median overall survival as the one obtained with a dose-dense schedule and an improved quality of life. Nevertheless, as the objective response and 1-year survival rates are slightly inferior, a dose-dense schedule remains still preferred in HER2+ patients or in those harboring a mainly meningeal progression. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Stimulus Effects on Local Preference: Stimulus-Response Contingencies, Stimulus-Food Pairing, and Stimulus-Food Correlation

ERIC Educational Resources Information Center

Davison, Michael; Baum, William M.

2010-01-01

Four pigeons were trained in a procedure in which concurrent-schedule food ratios changed unpredictably across seven unsignaled components after 10 food deliveries. Additional green-key stimulus presentations also occurred on the two alternatives, sometimes in the same ratio as the component food ratio, and sometimes in the inverse ratio. In eight…

Relative potency of varenicline or fluvoxamine to reduce responding for ethanol versus food depends on the presence or absence of concurrently earned food.

PubMed

Ginsburg, Brett C; Lamb, Richard J

2014-03-01

Varenicline, a nicotinic partial agonist, selectively reduces ethanol (EtOH)- versus sucrose-maintained behavior when tested in separate groups, yet like the indirect agonist fluvoxamine, this selectively inverts when EtOH and food are concurrently available. Here, we extend these findings by examining varenicline and fluvoxamine effects under a multiple concurrent schedule where food and EtOH are concurrently available in different components: Component 1 where the food fixed-ratio was 25 and Component 2 where the food fixed-ratio was 75. The EtOH fixed-ratio was always 5. Food-maintained responding predominated in Component 1, while EtOH-maintained responding predominated in Component 2. In a second experiment, varenicline effects were assessed under a multiple schedule where food, then EtOH, then again food were available in separate 5-minute components with fixed-ratios of 5 for each reinforcement. In the multiple concurrent schedule, varenicline was more potent at reducing food- versus EtOH-maintained responding in both components and reduced EtOH-maintained responding more potently during Component 1 (when food was almost never earned) than in Component 2 (where food was often earned). Fluvoxamine was similarly potent at reducing food- and EtOH-maintained responding. Under the multiple schedule, varenicline, like fluvoxamine, more potently decreases EtOH- versus food maintained responding when only food or EtOH is available in separate components. These results demonstrate that selective effects on drug- versus alternative-maintained behavior depend on the schedule arrangement, and assays in which EtOH or an alternative is the only programmed reinforcement may overestimate the selectivity of treatments to decrease EtOH self-administration. Thus selective effects obtained under one assay may not generalize to another. Better understanding the behavioral mechanisms responsible for these results may help to guide pharmaco-therapeutic development for substance use disorders.

Multiple determinants of transfer of evaluative function after conditioning with free-operant schedules of reinforcement.

PubMed

Dack, Charlotte; Reed, Phil; McHugh, Louise

2010-11-01

The aim of the four present experiments was to explore how different schedules of reinforcement influence schedule-induced behavior, their impact on evaluative ratings given to conditioned stimuli associated with each schedule through evaluative conditioning, and the transfer of these evaluations through derived stimulus networks. Experiment 1 compared two contrasting response reinforcement rules (variable ratio [VR], variable interval [VI]). Experiment 2 varied the response to reinforcement rule between two schedules but equated the outcome to response rate (differential reinforcement of high rate [DRH] vs. VR). Experiment 3 compared molar and molecular aspects of contingencies of reinforcement (tandem VIVR vs. tandem VRVI). Finally, Experiment 4 employed schedules that induced low rates of responding to determine whether, under these circumstances, responses were more sensitive to the molecular aspects of a schedule (differential reinforcement of low rate [DRL] vs. VI). The findings suggest that the transfer of evaluative functions is determined mainly by differences in response rate between the schedules and the molar aspects of the schedules. However, when neither schedule was based on a strong response reinforcement rule, the transfer of evaluative judgments came under the control of the molecular aspects of the schedule.

Time-based air traffic management using expert systems

NASA Technical Reports Server (NTRS)

Tobias, L.; Scoggins, J. L.

1986-01-01

A prototype expert system has been developed for the time scheduling of aircraft into the terminal area. The three functions of the air-traffic-control schedule advisor are as follows: (1) for each new arrival, it develops an admisible flight plan for that aircraft; (2) as the aircraft progresses through the terminal area, it monitors deviations from the aircraft's flight plan and provides advisories to return the aircraft to its assigned schedule; and (3) if major disruptions such as missed approaches occur, it develops a revised plan. The advisor is operational on a Symbolics 3600, and is programmed in MRS (a logic programming language), Lisp, and Fortran.

Time-based air traffic management using expert systems

NASA Technical Reports Server (NTRS)

Tobias, L.; Scoggins, J. L.

1986-01-01

A prototype expert system was developed for the time scheduling of aircraft into the terminal area. The three functions of the air traffic control schedule advisor are as follows: first, for each new arrival, it develops an admissible flight plan for that aircraft. Second, as the aircraft progresses through the terminal area, it monitors deviations from the flight plan and provides advisories to return the aircraft to its assigned schedule. Third, if major disruptions such as missed approaches occur, it develops a revised plan. The advisor is operational on a Symbolics 3600, and is programed in MRS (a logic programming language), Lisp, and FORTRAN.

Human Schedule Performance, Protocol Analysis, and the "Silent Dog" Methodology

ERIC Educational Resources Information Center

Cabello, Francisco; Luciano, Carmen; Gomez, Inmaculada; Barnes-Holmes, Dermot

2004-01-01

The purpose of the current experiment was to investigate the role of private verbal behavior on the operant performances of human adults, using a protocol analysis procedure with additional methodological controls (the "silent dog" method). Twelve subjects were exposed to fixed ratio 8 and differential reinforcement of low rate 3-s schedules. For…

Effects of Historical and Social Variables on Instruction Following

ERIC Educational Resources Information Center

Kroger-Costa, Andreia; Abreu-Rodrigues, Josele

2012-01-01

The present study investigated the effect of the presence of the experimenter on behavioral sensitivity to contingency change. In history training, college students were exposed to differential reinforcement of low rate (DRL) and fixed-ratio (FR) schedules, and in testing, to a fixed-interval (FI) schedule. For the control group, instructions were…

Stock optimizing in choice when a token deposit is the operant.

PubMed

Widholm, J J; Silberberg, A; Hursh, S R; Imam, A A; Warren-Boulton, F R

2001-11-01

Each of 2 monkeys typically earned their daily food ration by depositing tokens in one of two slots. Tokens deposited in one slot dropped into a bin where they were kept (token kept). Deposits to a second slot dropped into a bin where they could be obtained again (token returned). In Experiment 1, a fixed-ratio (FR) 5 schedule that provided two food pellets was associated with each slot. Both monkeys preferred the token-returned slot. In Experiment 2, both subjects chose between unequal FR schedules with the token-returned slot always associated with the leaner schedule. When the FRs were 2 versus 3 and 2 versus 6, preferences were maintained for the token-returned slot; however, when the ratios were 2 versus 12, preference shifted to the token-kept slot. In Experiment 3, both monkeys chose between equal-valued concurrent variable-interval variable-interval schedules. Both monkeys preferred the slot that returned tokens. In Experiment 4, both monkeys chose between FRs that typically differed in size by a factor of 10. Both monkeys preferred the FR schedule that provided more food per trial. These data show that monkeys will choose so as to increase the number of reinforcers earned (stock optimizing) even when this preference reduces the rate of reinforcement (all reinforcers divided by session time).

Techniques for establishing schedules with wheel running as reinforcement in rats.

PubMed

Iversen, I H

1993-07-01

In three experiments, access to wheel running was contingent on lever pressing. In each experiment, the duration of access to running was reduced gradually to 4, 5, or 6 s, and the schedule parameters were expanded gradually. The sessions lasted 2 hr. In Experiment 1, a fixed-ratio 20 schedule controlled a typical break-and-run pattern of lever pressing that was maintained throughout the session for 3 rats. In Experiment 2, a fixed-interval schedule of 6 min maintained lever pressing throughout the session for 3 rats, and for 1 rat, the rate of lever pressing was positively accelerated between reinforcements. In Experiment 3, a variable-ratio schedule of 20 or 35 was in effect and maintained lever pressing at a very stable pace throughout the session for 2 of 3 rats; for 1 rat, lever pressing was maintained at an irregular rate. When the session duration was extended to successive 24-hr periods, with food and water accessible in Experiment 3, lever pressing settled into a periodic pattern occurring at a high rate at approximately the same time each day. In each experiment, the rats that developed the highest local rates of running during wheel access also maintained the most stable and highest rates of lever pressing.

Blockade of α2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment.

PubMed

Baskin, Britahny M; Nic Dhonnchadha, Bríd Á; Dwoskin, Linda P; Kantak, Kathleen M

2017-10-01

Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. Following treatment from postnatal days 28-55 with atomoxetine (0.3 mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3 mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10-56 μg/side) directly into prelimbic cortex. Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.

High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

PubMed

Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

2013-09-01

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

PubMed

Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

2016-08-04

Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Hedonic and motivational responses to food reward are unchanged in rats with neuropathic pain

PubMed Central

Okun, Alec; McKinzie, David L.; Witkin, Jeffrey M.; Remeniuk, Bethany; Husein, Omar; Gleason, Scott D.; Oyarzo, Janice; Navratilova, Edita; McElroy, Brian; Cowen, Stephen; Kennedy, Jeffrey D.; Porreca, Frank

2016-01-01

Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. Here, we independently evaluated hedonic qualities of sweet or bitter tastants as well as motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation (SNL). Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions and “liking/disliking” responses were scored according to a facial reactivity scale. SNL rats did not differ from controls in either “liking” or “disliking” reactions to intraoral sucrose or quinine, respectively, at post-surgery day 21, suggesting no differences in perceived hedonic value of sweet or bitter tastants. To assess possible motivational deficits during acute and chronic pain, we employed fixed- and progressive-ratio response paradigms of sucrose pellet presentation in rats with transient inflammatory or chronic neuropathic pain. Assessment of response acquisition and break points under the progressive ratio schedule revealed no differences between sham and SNL rats for up to 120 days post-injury. However, rats with inflammation showed decrements in lever pressing and break points on post-CFA days 1 and 2 that normalized by day 4, consistent with transient ongoing pain. Thus, while acute, ongoing inflammatory pain may transiently reduce reward motivation, we did not detect influences of chronic neuropathic pain on hedonic or motivational responses to food rewards. Adaptations that allow normal reward responding to food regardless of chronic pain may be of evolutionary benefit to promote survival. PMID:27548047

Central melanocortins regulate the motivation for sucrose reward.

PubMed

Pandit, Rahul; van der Zwaal, Esther M; Luijendijk, Mieneke C M; Brans, Maike A D; van Rozen, Andrea J; Oude Ophuis, Ralph J A; Vanderschuren, Louk J M J; Adan, Roger A H; la Fleur, Susanne E

2015-01-01

The role of the melanocortin (MC) system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH), whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP) has the opposite effect. MC receptors are widely expressed in both hypothalamic and extra-hypothalamic brain regions, including nuclei involved in food reward and motivation, such as the nucleus accumbens (NAc) and the ventral tegmental area. This suggests that MCs modulate motivational aspects of food intake. To test this hypothesis, rats were injected intracerebroventricularly with α-MSH or AGRP and their motivation for sucrose was tested under a progressive ratio schedule of reinforcement. Food motivated behavior was dose-dependently decreased by α-MSH. Conversely, AGRP increased responding for sucrose, an effect that was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast to progressive ratio responding, free intake of sucrose remained unaltered upon α-MSH or AGRP infusion. In addition, we investigated whether the effects of α-MSH and AGRP on food motivation were mediated by the NAc shell. In situ hybridization of MC3 and MC4 receptor expression confirmed that the MC4 receptor was expressed throughout the NAc, and injection of α-MSH and AGRP into the NAc shell caused a decrease and an increase in motivation for sucrose, respectively. These data show that the motivation for palatable food is modulated by MC4 receptors in the NAc shell, and demonstrate cross-talk between the MC and dopamine system in the modulation of food motivation.

Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase.

PubMed

Vichaya, Elisabeth G; Laumet, Geoffroy; Christian, Diana L; Grossberg, Aaron J; Estrada, Darlene J; Heijnen, Cobi J; Kavelaars, Annemieke; Robert Dantzer

2018-04-27

Despite years of research, our understanding of the mechanisms by which inflammation induces depression is still limited. As clinical data points to a strong association between depression and motivational alterations, we sought to (1) characterize the motivational changes that are associated with inflammation in mice, and (2) determine if they depend on inflammation-induced activation of indoleamine 2,3 dioxygenase-1 (IDO1). Lipopolysaccharide (LPS)-treated or spared nerve injured (SNI) wild type (WT) and Ido1 -/- mice underwent behavioral tests of antidepressant activity (e.g., forced swim test) and motivated behavior, including assessment of (1) reward expectancy using a food-related anticipatory activity task, (2) willingness to work for reward using a progressive ratio schedule of food reinforcement, (3) effort allocation using a concurrent choice task, and (4) ability to associate environmental cues with reward using conditioned place preference. LPS- and SNI-induced deficits in behavioral tests of antidepressant activity in WT but not Ido1 -/- mice. Further, LPS decreased food related-anticipatory activity, reduced performance in the progressive ratio task, and shifted effort toward the preferred reward in the concurrent choice task. These effects were observed in both WT and Ido1 -/- mice. Finally, SNI mice developed a conditioned place preference based on relief from pain in an IDO1-independent manner. These findings demonstrate that the motivational effects of inflammation do not require IDO1. Further, they indicate that the motivational component of inflammation-induced depression is mechanistically distinct from that measured by behavioral tests of antidepressant activity.

77 FR 17334 - Approval and Promulgation of Air Quality Implementation Plans; State of Nevada; Regional Haze...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-26

... Progress Goal B. Long-Term Strategy C. BART for SO 2 and PM 10 at Reid Gardner D. Corrections to EPA's... a long- term strategy with enforceable measures to ensure reasonable progress toward achieving the... corresponding emission limits and schedules of compliance for NO X at RGGS in the SIP's long-term strategy...

25 CFR 900.132 - Once a contract and/or grant is awarded, how will the Indian tribe or tribal organization receive...

Code of Federal Regulations, 2010 CFR

2010-04-01

... schedule for advance payments shall be developed based on progress, need, and other considerations in... project based on progress and need. (b) Payments shall be made to the Indian tribe or tribal organization... amounts measured by time or measured by phase of the project (e.g., planning, design, construction). (d...

Civics Framework for the 2006 National Assessment of Educational Progress. NAEP Civics Project

ERIC Educational Resources Information Center

National Assessment Governing Board, 2007

2007-01-01

To gauge the civic knowledge and skills of the nation's 4th-, 8th-, and 12th-grade students, an assessment has been scheduled for 2006 by the National Assessment of Educational Progress (NAEP). This assessment will enable NAEP to report on trends in civics achievement from 1998 to 2006. The National Assessment Governing Board (NAGB), NAEP's…

The Effects of Baseline Estimation on the Reliability, Validity, and Precision of CBM-R Growth Estimates

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Christ, Theodore J.; Zopluoglu, Cengiz

2013-01-01

This study examined the effect of baseline estimation on the quality of trend estimates derived from Curriculum Based Measurement of Oral Reading (CBM-R) progress monitoring data. The authors used a linear mixed effects regression (LMER) model to simulate progress monitoring data for schedules ranging from 6-20 weeks for datasets with high and low…

Evolution of resistance to anti-cancer therapy during general dosing schedules

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

Anti-cancer drugs targeted to specific oncogenic pathways have shown promising therapeutic results in the past few years; however, drug resistance remains an important obstacle for these therapies. Resistance to these drugs can emerge due to a variety of reasons including genetic or epigenetic changes which alter the binding site of the drug target, cellular metabolism or export mechanisms. Obtaining a better understanding of the evolution of resistant populations during therapy may enable the design of more effective therapeutic regimens which prevent or delay progression of disease due to resistance. In this paper, we use stochastic mathematical models to study the evolutionary dynamics of resistance under time-varying dosing schedules and pharmacokinetic effects. The populations of sensitive and resistant cells are modeled as multi-type non-homogeneous birth-death processes in which the drug concentration affects the birth and death rates of both the sensitive and resistant cell populations in continuous time. This flexible model allows us to consider the effects of generalized treatment strategies as well as detailed pharmacokinetic phenomena such as drug elimination and accumulation over multiple doses. We develop estimates for the probability of developing resistance and moments of the size of the resistant cell population. With these estimates, we optimize treatment schedules over a subspace of tolerated schedules to minimize the risk of disease progression due to resistance as well as locate ideal schedules for controlling the population size of resistant clones in situations where resistance is inevitable. Our methodology can be used to describe dynamics of resistance arising due to a single (epi)genetic alteration in any tumor type. PMID:20004211

User interface issues in supporting human-computer integrated scheduling

NASA Technical Reports Server (NTRS)

Cooper, Lynne P.; Biefeld, Eric W.

1991-01-01

Explored here is the user interface problems encountered with the Operations Missions Planner (OMP) project at the Jet Propulsion Laboratory (JPL). OMP uses a unique iterative approach to planning that places additional requirements on the user interface, particularly to support system development and maintenance. These requirements are necessary to support the concepts of heuristically controlled search, in-progress assessment, and iterative refinement of the schedule. The techniques used to address the OMP interface needs are given.

Improved Scheduling Mechanisms for Synchronous Information and Energy Transmission.

PubMed

Qin, Danyang; Yang, Songxiang; Zhang, Yan; Ma, Jingya; Ding, Qun

2017-06-09

Wireless energy collecting technology can effectively reduce the network time overhead and prolong the wireless sensor network (WSN) lifetime. However, the traditional energy collecting technology cannot achieve the balance between ergodic channel capacity and average collected energy. In order to solve the problem of the network transmission efficiency and the limited energy of wireless devices, three improved scheduling mechanisms are proposed: improved signal noise ratio (SNR) scheduling mechanism (IS2M), improved N-SNR scheduling mechanism (INS2M) and an improved Equal Throughput scheduling mechanism (IETSM) for different channel conditions to improve the whole network performance. Meanwhile, the average collected energy of single users and the ergodic channel capacity of three scheduling mechanisms can be obtained through the order statistical theory in Rayleig, Ricean, Nakagami- m and Weibull fading channels. It is concluded that the proposed scheduling mechanisms can achieve better balance between energy collection and data transmission, so as to provide a new solution to realize synchronous information and energy transmission for WSNs.

Improved Scheduling Mechanisms for Synchronous Information and Energy Transmission

PubMed Central

Qin, Danyang; Yang, Songxiang; Zhang, Yan; Ma, Jingya; Ding, Qun

2017-01-01

Wireless energy collecting technology can effectively reduce the network time overhead and prolong the wireless sensor network (WSN) lifetime. However, the traditional energy collecting technology cannot achieve the balance between ergodic channel capacity and average collected energy. In order to solve the problem of the network transmission efficiency and the limited energy of wireless devices, three improved scheduling mechanisms are proposed: improved signal noise ratio (SNR) scheduling mechanism (IS2M), improved N-SNR scheduling mechanism (INS2M) and an improved Equal Throughput scheduling mechanism (IETSM) for different channel conditions to improve the whole network performance. Meanwhile, the average collected energy of single users and the ergodic channel capacity of three scheduling mechanisms can be obtained through the order statistical theory in Rayleig, Ricean, Nakagami-m and Weibull fading channels. It is concluded that the proposed scheduling mechanisms can achieve better balance between energy collection and data transmission, so as to provide a new solution to realize synchronous information and energy transmission for WSNs. PMID:28598395

Influence of Schizotypy on Responding and Contingency Awareness on Free-Operant Schedules of Reinforcement

ERIC Educational Resources Information Center

Randell, Jordan; Searle, Rob; Reed, Phil

2012-01-01

Schedules of reinforcement typically produce reliable patterns of behaviour, and one factor that can cause deviations from these normally reliable patterns is schizotypy. Low scorers on the unusual experiences subscale of the Oxford-Liverpool Inventory of Feelings and Experiences performed as expected on a yoked random-ratio (RR), random-interval…

Request-Driven Schedule Automation for the Deep Space Network

NASA Technical Reports Server (NTRS)

Johnston, Mark D.; Tran, Daniel; Arroyo, Belinda; Call, Jared; Mercado, Marisol

2010-01-01

The DSN Scheduling Engine (DSE) has been developed to increase the level of automated scheduling support available to users of NASA s Deep Space Network (DSN). We have adopted a request-driven approach to DSN scheduling, in contrast to the activity-oriented approach used up to now. Scheduling requests allow users to declaratively specify patterns and conditions on their DSN service allocations, including timing, resource requirements, gaps, overlaps, time linkages among services, repetition, priorities, and a wide range of additional factors and preferences. The DSE incorporates a model of the key constraints and preferences of the DSN scheduling domain, along with algorithms to expand scheduling requests into valid resource allocations, to resolve schedule conflicts, and to repair unsatisfied requests. We use time-bounded systematic search with constraint relaxation to return nearby solutions if exact ones cannot be found, where the relaxation options and order are under user control. To explore the usability aspects of our approach we have developed a graphical user interface incorporating some crucial features to make it easier to work with complex scheduling requests. Among these are: progressive revelation of relevant detail, immediate propagation and visual feedback from a user s decisions, and a meeting calendar metaphor for repeated patterns of requests. Even as a prototype, the DSE has been deployed and adopted as the initial step in building the operational DSN schedule, thus representing an important initial validation of our overall approach. The DSE is a core element of the DSN Service Scheduling Software (S(sup 3)), a web-based collaborative scheduling system now under development for deployment to all DSN users.

Scheduling Independent Partitions in Integrated Modular Avionics Systems

PubMed Central

Du, Chenglie; Han, Pengcheng

2016-01-01

Recently the integrated modular avionics (IMA) architecture has been widely adopted by the avionics industry due to its strong partition mechanism. Although the IMA architecture can achieve effective cost reduction and reliability enhancement in the development of avionics systems, it results in a complex allocation and scheduling problem. All partitions in an IMA system should be integrated together according to a proper schedule such that their deadlines will be met even under the worst case situations. In order to help provide a proper scheduling table for all partitions in IMA systems, we study the schedulability of independent partitions on a multiprocessor platform in this paper. We firstly present an exact formulation to calculate the maximum scaling factor and determine whether all partitions are schedulable on a limited number of processors. Then with a Game Theory analogy, we design an approximation algorithm to solve the scheduling problem of partitions, by allowing each partition to optimize its own schedule according to the allocations of the others. Finally, simulation experiments are conducted to show the efficiency and reliability of the approach proposed in terms of time consumption and acceptance ratio. PMID:27942013

Regulator of calmodulin signaling (RCS) knockout mice display anxiety-like behavior and motivational deficits

PubMed Central

Davis, Maya M.; Olausson, Peter; Greengard, Paul; Taylor, Jane R.; Nairn, Angus C.

2013-01-01

Regulator of calmodulin (CaM) signaling (RCS), when phosphorylated by protein kinase A (PKA) on Ser55, binds to CaM and inhibits CaM-dependent signaling. RCS expression is high in the dorsal striatum, nucleus accumbens and amygdala, suggesting that the protein is involved in limbic-striatal function. To test this hypothesis, we examined RCS knockout (KO) mice in behavioral models dependent on these brain areas. Mice were tested for food-reinforced instrumental conditioning and responding under a progressive ratio (PR) schedule of reinforcement and in models of anxiety (elevated plus maze and open field). While RCS KO mice showed normal acquisition of a food-motivated instrumental response, they exhibited a lower breakpoint value when tested on responding under a PR schedule of reinforcement. RCS KO mice also displayed decreased exploration in both the open arms of an elevated plus maze and in the center region of an open field, suggesting an enhanced anxiety response. Biochemical studies revealed a reduction in the levels of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the striatum of RCS KO mice. DARPP-32 is important in reward-mediated behavior, suggestive of a possible role for DARPP-32 in mediating some of the effects of RCS. Together these results implicate a novel PKA-regulated phosphoprotein, RCS, in the etiology of motivational deficits and anxiety. PMID:22250817

Observing strategies for future solar facilities: the ATST test case

NASA Astrophysics Data System (ADS)

Uitenbroek, H.; Tritschler, A.

2012-12-01

Traditionally solar observations have been scheduled and performed very differently from night time efforts, in particular because we have been observing the Sun for a long time, requiring new combinations of observables to make progress, and because solar physics observations are often event driven on time scales of hours to days. With the proposal pressure that is expected for new large-aperture facilities, we can no longer afford the time spent on custom setups, and will have to rethink our scheduling and operations. We will discuss our efforts at Sac Peak in preparing for this new era, and outline the planned scheduling and operations planning for the ATST in particular.

Building Construction Progress Monitoring Using Unmanned Aerial System (uas), Low-Cost Photogrammetry, and Geographic Information System (gis)

NASA Astrophysics Data System (ADS)

Bognot, J. R.; Candido, C. G.; Blanco, A. C.; Montelibano, J. R. Y.

2018-05-01

Monitoring the progress of building's construction is critical in construction management. However, measuring the building construction's progress are still manual, time consuming, error prone, and impose tedious process of analysis leading to delays, additional costings and effort. The main goal of this research is to develop a methodology for building construction progress monitoring based on 3D as-built model of the building from unmanned aerial system (UAS) images, 4D as-planned model (with construction schedule integrated) and, GIS analysis. Monitoring was done by capturing videos of the building with a camera-equipped UAS. Still images were extracted, filtered, bundle-adjusted, and 3D as-built model was generated using open source photogrammetric software. The as-planned model was generated from digitized CAD drawings using GIS. The 3D as-built model was aligned with the 4D as-planned model of building formed from extrusion of building elements, and integration of the construction's planned schedule. The construction progress is visualized via color-coding the building elements in the 3D model. The developed methodology was conducted and applied from the data obtained from an actual construction site. Accuracy in detecting `built' or `not built' building elements ranges from 82-84 % and precision of 50-72 %. Quantified progress in terms of the number of building elements are 21.31% (November 2016), 26.84 % (January 2017) and 44.19 % (March 2017). The results can be used as an input for progress monitoring performance of construction projects and improving related decision-making process.

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.

PubMed

Persons, Amanda L; Tedford, Stephanie E; Celeste Napier, T

2017-07-03

Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward. Accordingly, we developed a novel variable-ratio task in rats wherein intracranial self-stimulation was used as the positive reinforcer. Using lever pressing for various levels of brain stimulation, the operant task provided choices between a small brain stimulation current delivered on a fixed-ratio schedule (i.e., a predictable reward) and a large brain stimulation delivered following an unpredictable number of responses (i.e., a variable-ratio schedule). This task allowed for demonstration of individualized preference and detection of shifts in motivational influences during a pharmacological treatment. Once baseline preference was established, we determined that pretreatment with mirtazapine or ketanserin significantly decreased preference for the large reinforcer presented after gambling-like schedules of reinforcement. When the rats were tested the next day without drug, preference for the unpredictable large reinforcer option was restored. These data demonstrate that mirtazapine and ketanserin can reduce preference for larger, costlier reinforcement options, and illustrate the potential for these drugs to alter behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Progress Monitoring in Reading: Comparison of Weekly, Bimonthly, and Monthly Assessments for Students at Risk for Reading Difficulties in Grades 2-4

ERIC Educational Resources Information Center

January, Stacy-Ann A.; Van Norman, Ethan R.; Christ, Theodore J.; Ardoin, Scott P.; Eckert, Tanya L.; White, Mary Jane

2018-01-01

The present study examined the utility of two progress monitoring assessment schedules (bimonthly and monthly) as alternatives to monitoring once weekly with curriculum-based measurement in reading (CBM-R). General education students (N = 93) in Grades 2-4 who were at risk for reading difficulties but not yet receiving special education services…

Programmatic Research to Develop and Disseminate Improved Instructional Technology for Handicapped Children. Project MORE Quarterly Progress Report, September 1 to December 1, 1972.

ERIC Educational Resources Information Center

Schiefelbusch, Richard L.; Lent, James R.

During the past reporting period the curriculum development staff of Project MORE (Mediated Operational Research for Education) has made substantial progress in attaining its program objectives. Design and development phases have proceeded on schedule. Four programs are currently in the field-testing stage, and four others are under development.…

Peer-to-peer Cooperative Scheduling Architecture for National Grid Infrastructure

NASA Astrophysics Data System (ADS)

Matyska, Ludek; Ruda, Miroslav; Toth, Simon

For some ten years, the Czech National Grid Infrastructure MetaCentrum uses a single central PBSPro installation to schedule jobs across the country. This centralized approach keeps a full track about all the clusters, providing support for jobs spanning several sites, implementation for the fair-share policy and better overall control of the grid environment. Despite a steady progress in the increased stability and resilience to intermittent very short network failures, growing number of sites and processors makes this architecture, with a single point of failure and scalability limits, obsolete. As a result, a new scheduling architecture is proposed, which relies on higher autonomy of clusters. It is based on a peer to peer network of semi-independent schedulers for each site or even cluster. Each scheduler accepts jobs for the whole infrastructure, cooperating with other schedulers on implementation of global policies like central job accounting, fair-share, or submission of jobs across several sites. The scheduling system is integrated with the Magrathea system to support scheduling of virtual clusters, including the setup of their internal network, again eventually spanning several sites. On the other hand, each scheduler is local to one of several clusters and is able to directly control and submit jobs to them even if the connection of other scheduling peers is lost. In parallel to the change of the overall architecture, the scheduling system itself is being replaced. Instead of PBSPro, chosen originally for its declared support of large scale distributed environment, the new scheduling architecture is based on the open-source Torque system. The implementation and support for the most desired properties in PBSPro and Torque are discussed and the necessary modifications to Torque to support the MetaCentrum scheduling architecture are presented, too.

Baseline response rates affect resistance to change.

PubMed

Kuroda, Toshikazu; Cook, James E; Lattal, Kennon A

2018-01-01

The effect of response rates on resistance to change, measured as resistance to extinction, was examined in two experiments. In Experiment 1, responding in transition from a variable-ratio schedule and its yoked-interval counterpart to extinction was compared with pigeons. Following training on a multiple variable-ratio yoked-interval schedule of reinforcement, in which response rates were higher in the former component, reinforcement was removed from both components during a single extended extinction session. Resistance to extinction in the yoked-interval component was always either greater or equal to that in the variable-ratio component. In Experiment 2, resistance to extinction was compared for two groups of rats that exhibited either high or low response rates when maintained on identical variable-interval schedules. Resistance to extinction was greater for the lower-response-rate group. These results suggest that baseline response rate can contribute to resistance to change. Such effects, however, can only be revealed when baseline response rate and reinforcement rate are disentangled (Experiments 1 and 2) from the more usual circumstance where the two covary. Furthermore, they are more cleanly revealed when the programmed contingencies controlling high and low response rates are identical, as in Experiment 2. © 2017 Society for the Experimental Analysis of Behavior.

77 FR 57633 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

... liquidity'' ratio.\\11\\ The Exchange believes this amendment to Footnotes 12 and 13 supports the Exchange's... transparency for its Members. \\11\\ The ``add liquidity'' ratio is the ratio of the ``added'' flags/(``added... Exchange's fee schedule for Non-Displayed Orders that add liquidity using the Route Peg Order type.\\4\\ The...

Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH

PubMed Central

Oh, Sukho; Hwang, DongYeop; Kim, Ki-Hyung; Kim, Kangseok

2018-01-01

Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology. PMID:29659508

Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH.

PubMed

Oh, Sukho; Hwang, DongYeop; Kim, Ki-Hyung; Kim, Kangseok

2018-04-16

Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology.

Basic PK/PD principles of drug effects in circular/proliferative systems for disease modelling.

PubMed

Jacqmin, Philippe; McFadyen, Lynn; Wade, Janet R

2010-04-01

Disease progression modelling can provide information about the time course and outcome of pharmacological intervention on the disease. The basic PK/PD principles of proliferative and circular systems within the context of modelling disease progression and the effect of treatment thereupon are illustrated with the goal to better understand/predict eventual clinical outcome. Circular/proliferative systems can be very complex. To facilitate the understanding of how a dosing regimen can be defined in such systems we have shown the derivation of a system parameter named the Reproduction Minimum Inhibitory Concentration (RMIC) which represents the critical concentration at which the system switches from growth to extinction. The RMIC depends on two parameters (RMIC = (R(0) - 1) x IC(50)): the basic reproductive ratio (R(0)) a fundamental parameter of the circular/proliferative system that represents the number of offspring produced by one replicating species during its lifespan, and the IC(50), the potency of the drug to inhibit the proliferation of the system. The RMIC is constant for a given system and a given drug and represents the lowest concentration that needs to be achieved for eradication of the system. When exposure is higher than the RMIC, success can be expected in the long term. Time varying inhibition of replicating species proliferation is a natural consequence of the time varying inhibitor drug concentrations and when combined with the dynamics of the circular/proliferative system makes it difficult to predict the eventual outcome. Time varying inhibition of proliferative/circular systems can be handled by calculating the equivalent effective constant concentration (ECC), the constant plasma concentration that would give rise to the average inhibition at steady state. When ECC is higher than the RMIC, eradication of the system can be expected. In addition, it is shown that scenarios that have the same steady state ECC whatever the dose, dosage schedule or PK parameters have also the same average R (0) in the presence of the inhibitor (i.e. R (0-INH)) and therefore lead to the same outcome. This allows predicting equivalent active doses and dosing schedules in circular and proliferative systems when the IC(50) and pharmacokinetic characteristics of the drugs are known. The results from the simulations performed demonstrate that, for a given system (defined by its RMIC), treatment success depends mainly on the pharmacokinetic characteristics of the drug and the dosing schedule.

DSN Scheduling Engine

NASA Technical Reports Server (NTRS)

Clement, Bradley; Johnston, Mark; Wax, Allan; Chouinard, Caroline

2008-01-01

The DSN (Deep Space Network) Scheduling Engine targets all space missions that use DSN services. It allows clients to issue scheduling, conflict identification, conflict resolution, and status requests in XML over a Java Message Service interface. The scheduling requests may include new requirements that represent a set of tracks to be scheduled under some constraints. This program uses a heuristic local search to schedule a variety of schedule requirements, and is being infused into the Service Scheduling Assembly, a mixed-initiative scheduling application. The engine resolves conflicting schedules of resource allocation according to a range of existing and possible requirement specifications, including optional antennas; start of track and track duration ranges; periodic tracks; locks on track start, duration, and allocated antenna; MSPA (multiple spacecraft per aperture); arraying/VLBI (very long baseline interferometry)/delta DOR (differential one-way ranging); continuous tracks; segmented tracks; gap-to-track ratio; and override or block-out of requirements. The scheduling models now include conflict identification for SOA(start of activity), BOT (beginning of track), RFI (radio frequency interference), and equipment constraints. This software will search through all possible allocations while providing a best-effort solution at any time. The engine reschedules to accommodate individual emergency tracks in 0.2 second, and emergency antenna downtime in 0.2 second. The software handles doubling of one mission's track requests over one week (to 42 total) in 2.7 seconds. Further tests will be performed in the context of actual schedules.

Orion GN and C Mitigation Efforts for Van Allen Radiation

NASA Technical Reports Server (NTRS)

King, Ellis T.; Jackson, Mark

2013-01-01

The Orion Crew Module (CM) is NASA's next generation manned space vehicle, scheduled to return humans to lunar orbit in the coming decade. The Orion avionics and GN&C architectures have progressed through a number of project phases and are nearing completion of a major milestone. The first unmanned test mission, dubbed "Exploration Flight Test One" (EFT-1) is scheduled to launch from NASA Kennedy Space Center late next year and provides the first integrated test of all the vehicle systems, avionics and software.

Illegal drugs laws: clearing a 50-year-old obstacle to research.

PubMed

Nutt, David

2015-01-01

The United Nations drug control conventions of 1960 and 1971 and later additions have inadvertently resulted in perhaps the greatest restrictions of medical and life sciences research. These conventions now need to be revised to allow neuroscience to progress unimpeded and to assist in the innovation of treatments for brain disorders. In the meantime, local changes, such as the United Kingdom moving cannabis from Schedule 1 to Schedule 2, should be implemented to allow medical research to develop appropriately.

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 the effort-related deficits observed in depressed patients. PMID:24937131

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 the effort-related deficits observed in depressed patients.

Aggression as Positive Reinforcement in Mice under Various Ratio- and Time-Based Reinforcement Schedules

ERIC Educational Resources Information Center

May, Michael E.; Kennedy, Craig H.

2009-01-01

There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression…

Reinforcer magnitude and demand under fixed-ratio schedules with domestic hens.

PubMed

Grant, Amber A; Foster, T Mary; Temple, William; Jackson, Surrey; Kinloch, Jennifer; Poling, Alan

2014-03-01

This study compared three methods of normalizing demand functions to allow comparison of demand for different commodities and examined how varying reinforcer magnitudes affected these analyses. Hens responded under fixed-ratio schedules in 40-min sessions with response requirement doubling each session and with 2-s, 8-s, and 12-s access to wheat. Over the smaller fixed ratios overall response rates generally increased and were higher the shorter the magazine duration. The logarithms of the number of reinforcers obtained (consumption) and the fixed ratio (price) were well fitted by curvilinear demand functions (Hursh et al., 1988. Journal of the Experimental Analysis of Behavior 50, 419-440) that were inelastic (b negative) over small fixed-ratios. The fixed ratio with maximal response rate (Pmax) increased, and the rate of change of elasticity (a) and initial consumption (L) decreased with increased magazine duration. Normalizing consumption using measures of preference for various magazine durations (3-s vs. 3-s, 2-s vs. 8-s, and 2-s vs. 12-s), obtained using concurrent schedules, gave useful results as it removed the differences in L. Normalizing consumption and price (Hursh and Winger, 1995. Journal of the Experimental Analysis of Behavior 64, 373-384) unified the data functions as intended by that analysis. The exponential function (Hursh and Silberberg, 2008. Psychological Review, 115, 186-198) gave an essential value that increased (i.e., α decreased significantly) as magazine duration decreased. This was not as predicted, since α should be constant over variations in magazine duration, but is similar to previous findings using a similar procedure with different food qualities (hens) and food quantities (rats). Copyright © 2014 Elsevier B.V. All rights reserved.

Progress of Crew Autonomous Scheduling Test (CAST) On the ISS

NASA Technical Reports Server (NTRS)

Healy, Matthew; Marquez, Jessica; Hillenius, Steven; Korth, David; Bakalyar, Lauren Rush; Woodbury, Neil; Larsen, Crystal M.; Bates, Shelby; Kockler, Mikayla; Rhodes, Brooke;

ISS Progress 24 Rollout

NASA Image and Video Library

2007-01-16

JSC2007-E-03082 (16 Jan. 2007) --- Roll-out of the Progress 24 vehicle occurred on schedule at 7:00 a.m., Jan. 16, 2007 at the Baikonur Cosmodrome, Kazakhstan. The vehicle was in the vertical and hard-down at the pad by 9:30 a.m. The gantry towers were placed around the vehicle shortly thereafter. Progress is targeted for launch on Jan. 18, 2007 for a two-day trip to the International Space Station carrying 2 1/2 tons of food, fuel and supplies for the Expedition 14 crew. Photo Credit: NASA

Space Shuttle External Tank Project status

NASA Technical Reports Server (NTRS)

Davis, R. M.

1980-01-01

The External Tank Project is reviewed with emphasis on the DDT&E and production phases and the lightweight tank development. It is noted that the DDT&E phase is progressing well with the structural and ground vibration test article programs complete, the propulsion test article program progressing well, and the component qualification and verification testing 92% complete. New tools and facilities are being brought on line to support the increased build rate for the production phase. The lightweight tank, which will provide additional payload in orbit, is progressing to schedule with first delivery in early 1982.

The design of the run Clever randomized trial: running volume, -intensity and running-related injuries.

PubMed

Ramskov, Daniel; Nielsen, Rasmus Oestergaard; Sørensen, Henrik; Parner, Erik; Lind, Martin; Rasmussen, Sten

2016-04-23

Injury incidence and prevalence in running populations have been investigated and documented in several studies. However, knowledge about injury etiology and prevention is needed. Training errors in running are modifiable risk factors and people engaged in recreational running need evidence-based running schedules to minimize the risk of injury. The existing literature on running volume and running intensity and the development of injuries show conflicting results. This may be related to previously applied study designs, methods used to quantify the performed running and the statistical analysis of the collected data. The aim of the Run Clever trial is to investigate if a focus on running intensity compared with a focus on running volume in a running schedule influences the overall injury risk differently. The Run Clever trial is a randomized trial with a 24-week follow-up. Healthy recreational runners between 18 and 65 years and with an average of 1-3 running sessions per week the past 6 months are included. Participants are randomized into two intervention groups: Running schedule-I and Schedule-V. Schedule-I emphasizes a progression in running intensity by increasing the weekly volume of running at a hard pace, while Schedule-V emphasizes a progression in running volume, by increasing the weekly overall volume. Data on the running performed is collected by GPS. Participants who sustain running-related injuries are diagnosed by a diagnostic team of physiotherapists using standardized diagnostic criteria. The members of the diagnostic team are blinded. The study design, procedures and informed consent were approved by the Ethics Committee Northern Denmark Region (N-20140069). The Run Clever trial will provide insight into possible differences in injury risk between running schedules emphasizing either running intensity or running volume. The risk of sustaining volume- and intensity-related injuries will be compared in the two intervention groups using a competing risks approach. The trial will hopefully result in a better understanding of the relationship between the running performed and possible differences in running-related injury risk and the injuries developed. Clinical Trials NCT02349373 - January 23, 2015.

The Effect of Ratio and Interval Training on Pavlovian-Instrumental Transfer in Mice

PubMed Central

Wiltgen, Brian J.; Sinclair, Courtney; Lane, Chadrick; Barrows, Frank; Molina, Martín; Chabanon-Hicks, Chloe

2012-01-01

Conditional stimuli (CS) that are paired with reward can be used to motivate instrumental responses. This process is called Pavlovian-instrumental transfer (PIT). A recent study in rats suggested that habitual responses are particularly sensitive to the motivational effects of reward cues. The current experiments examined this idea using ratio and interval training in mice. Two groups of animals were trained to lever press for food pellets that were delivered on random ratio or random interval schedules. Devaluation tests revealed that interval training led to habitual responding while ratio training produced goal-directed actions. The presentation of CSs paired with reward led to positive transfer in both groups, however, the size of this effect was much larger in mice that were trained on interval schedules. This result suggests that habitual responses are more sensitive to the motivational influence of reward cues than goal-directed actions. The implications for neurobiological models of motivation and drug seeking behaviors are discussed. PMID:23144742

A treatment schedule of conventional physical therapy provided to enhance upper limb sensorimotor recovery after stroke: expert criterion validity and intra-rater reliability.

PubMed

Donaldson, Catherine; Tallis, Raymond C; Pomeroy, Valerie M

2009-06-01

Inadequate description of treatment hampers progress in stroke rehabilitation. To develop a valid, reliable, standardised treatment schedule of conventional physical therapy provided for the paretic upper limb after stroke. Eleven neurophysiotherapists participated in the established methodology: semi-structured interviews, focus groups and piloting a draft treatment schedule in clinical practice. Different physiotherapists (n=13) used the treatment schedule to record treatment given to stroke patients with mild, moderate and severe upper limb paresis. Rating of adequacy of the treatment schedule was made using a visual analogue scale (0 to 100mm). Mean (95% confidence interval) visual analogue scores were calculated (expert criterion validity). For intra-rater reliability, each physiotherapist observed a video tape of their treatment and immediately completed a treatment schedule recording form on two separate occasions, 4 to 6 weeks apart. The Kappa statistic was calculated for intra-rater reliability. The treatment schedule consists of a one-page A4 recording form and a user booklet, detailing 50 treatment activities. Expert criterion validity was 79 (95% confidence interval 74 to 84). Intra-rater Kappa was 0.81 (P<0.001). This treatment schedule can be used to document conventional physical therapy in subsequent clinical trials in the geographical area of its development. Further work is needed to investigate generalisability beyond this geographical area.

Diffuse intrinsic pontine glioma in children and adolescents: a single-center experience.

PubMed

Vallero, Stefano Gabriele; Bertin, Daniele; Basso, Maria Eleonora; Pittana, Laura Stefania; Mussano, Anna; Fagioli, Franca

2014-06-01

Patients with diffuse intrinsic pontine glioma (DIPG) have a very poor prognosis. Only radiotherapy (XRT) has proven to be effective in delaying the disease progression. Several chemotherapy schedules have been applied so far, but none demonstrated significant improvements in progression and survival. We retrospectively analyzed the clinical data of children diagnosed with DIPG at our center (Pediatric Hospital "Regina Margherita," Turin, Italy) between 1999 and 2013. Progression-free survival (PFS) and overall survival (OS) were used to describe the outcomes. Twenty-four children were included in our report. Patients diagnosed before March 2003 (n = 12) were treated with XRT and vincristine (VCR); the remaining 12 patients received XRT and temozolomide (TMZ). Progression-free survival was 18.8 % at 1 year (SE = 7.6 %), while overall survival was 44.1 % at 1 year (SE = 9.9 %). Median PFS was 8.1 months, whereas median OS was 11.2 months. No statistically significant difference in PFS or OS was evidenced between the two treatment groups. Radiotherapy followed by VCR or TMZ allows obtaining results that are in line with previous reports, with no advantages over other similar treatment schedules. DIPGs are challenging tumors with a dismal outcome. Further research and newer therapies are urgently needed in order to achieve improvements in survival.

Constraining response output on conjunctive fixed-ratio 1 fixed-time reinforcement schedules: Effects on the postreinforcement pause.

PubMed

Lopez, F; Pereira, C

1985-03-01

Two experiments used response-restriction procedures in order to test the independence of the factors determining response rate and the factors determining the size of the postreinforcement pause on interval schedules. Responding was restricted by response-produced blackout or by retracting the lever. In Experiment 1 with a Conjunctive FR 1 FT schedule, the blackout procedure reduced the postreinforcement pause more than the lever-retraction procedure did, and both procedures produced shorter pauses than did the schedule without response restriction. In Experiment 2 the interreinforcement interval was also manipulated, and the size of the pause was an increasing function of the interreinforcement interval, but the rate of increase was lower than that produced by fixed interval schedules of comparable interval durations. The assumption of functional independence of the postreinforcement pause and terminal rate in fixed interval schedules is questioned since data suggest that pause reductions resulted from constraining variation in response number compared to equivalent periodic schedules in which response number was allowed to vary. Copyright © 1985. Published by Elsevier B.V.

Exploring a QoS Driven Scheduling Approach for Peer-to-Peer Live Streaming Systems with Network Coding

PubMed Central

Cui, Laizhong; Lu, Nan; Chen, Fu

2014-01-01

Most large-scale peer-to-peer (P2P) live streaming systems use mesh to organize peers and leverage pull scheduling to transmit packets for providing robustness in dynamic environment. The pull scheduling brings large packet delay. Network coding makes the push scheduling feasible in mesh P2P live streaming and improves the efficiency. However, it may also introduce some extra delays and coding computational overhead. To improve the packet delay, streaming quality, and coding overhead, in this paper are as follows. we propose a QoS driven push scheduling approach. The main contributions of this paper are: (i) We introduce a new network coding method to increase the content diversity and reduce the complexity of scheduling; (ii) we formulate the push scheduling as an optimization problem and transform it to a min-cost flow problem for solving it in polynomial time; (iii) we propose a push scheduling algorithm to reduce the coding overhead and do extensive experiments to validate the effectiveness of our approach. Compared with previous approaches, the simulation results demonstrate that packet delay, continuity index, and coding ratio of our system can be significantly improved, especially in dynamic environments. PMID:25114968

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 may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; (d) the GABAB receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol. PMID:22486245

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

PubMed Central

Traina, Tiffany A.; Dugan, Ute; Higgins, Brian; Kolinsky, Kenneth; Theodoulou, Maria; Hudis, Clifford A.; Norton, Larry

2011-01-01

Background To hasten and improve anticancer drug development, we created a novel approach to generating and analyzing preclinical dose-scheduling data so as to optimize benefit-to-toxicity ratios. Methods We applied mathematical methods based upon Norton-Simon growth kinetic modeling to tumor-volume data from breast cancer xenografts treated with capecitabine (Xeloda®, Roche) at the conventional schedule of 14 days of treatment followed by a 7-day rest (14 - 7). Results The model predicted that 7 days of treatment followed by a 7-day rest (7 - 7) would be superior. Subsequent preclinical studies demonstrated that this biweekly capecitabine schedule allowed for safe delivery of higher daily doses, improved tumor response, and prolonged animal survival. Conclusions We demonstrated that the application of Norton-Simon modeling to the design and analysis of preclinical data predicts an improved capecitabine dosing schedule in xenograft models. This method warrants further investigation and application in clinical drug development. PMID:20519801

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus.

PubMed

McCue, D L; Kasper, J M; Hommel, J D

2017-01-01

Motivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be neuromedin U (NMU), a highly-conserved neuropeptide that influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects. The motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive-ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have used a progressive-ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects. We found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU. These results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.

40 CFR 62.14565 - How do I comply with the increment of progress for achieving final compliance?

Code of Federal Regulations, 2011 CFR

2011-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and...

40 CFR 62.14565 - How do I comply with the increment of progress for achieving final compliance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and...

Adaptation of Timing Behavior to a Regular Change in Criterion

PubMed Central

Sanabria, Federico; Oldenburg, Liliana

2013-01-01

This study examined how operant behavior adapted to an abrupt but regular change in the timing of reinforcement. Pigeons were trained on a fixed interval (FI) 15-s schedule of reinforcement during half of each experimental session, and on an FI 45-s (Experiment 1), FI 60-s (Experiment 2), or extinction schedule (Experiment 3) during the other half. FI performance was well characterized by a mixture of two gamma-shaped distributions of responses. When a longer FI schedule was in effect in the first half of the session (Experiment 1), a constant interference by the shorter FI was observed. When a shorter FI schedule was in effect in the first half of the session (Experiments 1, 2, and 3), the transition between schedules involved a decline in responding and a progressive rightward shift in the mode of the response distribution initially centered around the short FI. These findings are discussed in terms of the constraints they impose to quantitative models of timing, and in relation to the implications for information-based models of associative learning. PMID:23962672

Distribution of a Generic Mission Planning and Scheduling Toolkit for Astronomical Spacecraft

NASA Technical Reports Server (NTRS)

Kleiner, Steven C.

1996-01-01

Work is progressing as outlined in the proposal for this contract. A working planning and scheduling system has been documented and packaged and made available to the WIRE Small Explorer group at JPL, the FUSE group at JHU, the NASA/GSFC Laboratory for Astronomy and Solar Physics and the Advanced Planning and Scheduling Branch at STScI. The package is running successfully on the WIRE computer system. It is expected that the WIRE will reuse significant portions of the SWAS code in its system. This scheduling system itself was tested successfully against the spacecraft hardware in December 1995. A fully automatic scheduling module has been developed and is being added to the toolkit. In order to maximize reuse, the code is being reorganized during the current build into object-oriented class libraries. A paper describing the toolkit has been written and is included in the software distribution. We have experienced interference between the export and production versions of the toolkit. We will be requesting permission to reprogram funds in order to purchase a standalone PC onto which to offload the export version.

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.

[Effects of irrigation and planting pattern on winter wheat water consumption characteristics and dry matter production].

PubMed

Dong, Hao; Chen, Yu-Hai; Zhou, Xun-Bo

2013-07-01

Taking high-yield winter wheat cultivar 'Jimai 22' as test material, a field experiment was conducted in 2008-2010 to study the effects of different irrigation and planting modes on the water consumption characteristics and dry matter accumulation and distribution of winter wheat. Three planting patterns (uniform row, wide-narrow row, and furrow) and four irrigation schedules (no irrigation, W0; irrigation at jointing stage, W1; irrigation at jointing and anthesis stages, W2; and irrigation at jointing, anthesis, and milking stages, W3; with 60 mm per irrigation) were installed. With increasing amount of irrigation, the total water consumption and the ratio of irrigation water to total water consumption under different planting patterns all increased, while the soil water consumption and its ratio to total water consumption decreased significantly. As compared with W0, the other three irrigation schedules had a higher dry matter accumulation after anthesis and a higher grain yield, but a lower water use efficiency (WUE). Under the same irrigation schedules, furrow pattern had higher water consumption ratio, grain yield, and WUE. Taking the grain yield and WUE into consideration, furrow pattern combined with irrigation at jointing and anthesis stages would be the optimal water-saving and planting modes for the winter wheat production in North China Plain.

Construction Management Activities of Governmental Agencies in the New England Area During the Construction Phase.

DTIC Science & Technology

1980-02-01

automatic data exchange ... 56 There are currently 12 Data Systems available: I. Integrated Disbursing and Accounting (IDA) 2. Integrated Program Management...construction project progress through the use of a CPM scheduling and progress reporting system . It automatically generates invoices for payment and payment...posted on the project. Water will be drained daily from tanks of vehicle air brake systems . Rtigging, hooks, pendants and slings will be examined

Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis

PubMed Central

Sidana, Surbhi; Narkhede, Mayur; Elson, Paul; Hastings, Debbie; Faiman, Beth; Valent, Jason; Samaras, Christy; Hamilton, Kimberly; Liu, Hien K.; Smith, Mitchell R.; Reu, Frederic J.

2017-01-01

Introduction Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial. Methods Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules. Results Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26–4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58–2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001). Conclusions Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy. PMID:28278302

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.

Statistical and operational summaries

NASA Technical Reports Server (NTRS)

Disalvo, J.

1972-01-01

Statistical progress indicator forms are presented on the financial management of the research allocations. Promotional activities, conference participants, and services are tabulated. The staffing and activity levels are also discussed, as well as the fee schedule revision and the standard interest profile offerings.

Status report on CIP/CUP progress

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

Larkin, W.J.

1975-01-01

Work on the Cascade Improvement Program (CIP) and the Cascade Uprating Program (CUP) continues basically on schedule. When completed the productive capability of the gaseous diffusion facilities at Paducah, Oak Ridge, and Portsmouth will be increased by 60 percent. (JGB)

49 CFR 22.41 - Application procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... local taxes are current; business tax returns; business financial statements; personal income tax returns; personal financial statements; schedule of work in progress; signed and dated copy of... approval memo and analysis and other third-party credit verifications obtained. (c) Application packages...

Prototype solar heating and hot water systems

NASA Technical Reports Server (NTRS)

1978-01-01

Progress made in the development of a solar hot water and space heating system is described in four quarterly reports. The program schedules, technical status and other program activities from 6 October 1976 through 30 September 1977 are provided.

Public Expenditure and Scheduled Community Enrolment in Higher Education: A Comparison across Indian States

ERIC Educational Resources Information Center

Sumithra, S.; Vardhan, R. Vishnu; Aruna, C.

2014-01-01

In India, the gross enrolment ratio has increased from 13.1 per cent in 2007-2008 to 15 per cent in 2011-2012 which moves the country from elite to a mass higher education system. This article seeks to examine the enrolment of scheduled caste (SC) students across various states in the country and the expenditure by each state and its effect on SC…

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.

N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats.

PubMed

Zhu, Huaqiang; Lai, Miaojun; Chen, Weisheng; Mei, Disen; Zhang, Fuqiang; Liu, Huifeng; Zhou, Wenhua

2017-08-01

Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i.p.), an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin self-administration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroin priming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG, via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.

Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.

PubMed

Zhou, Luyi; Sun, Wei-Lun; Young, Amy B; Lee, Kunhee; McGinty, Jacqueline F; See, Ronald E

2014-10-31

Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: a randomized study of a single dose vs. two different two-dose schedules.

PubMed

Vesikari, Timo; Hardt, Roland; Rümke, Hans C; Icardi, Giancarlo; Montero, Jordi; Thomas, Stéphane; Sadorge, Christine; Fiquet, Anne

2013-04-01

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax(®), would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02-1.22 and 0.78, 95% CI 0.73-0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96-1.17 and 1.08, 95% CI 0.98-1.19, respectively). Similar immune responses were observed in participants aged 70-79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

Kotov practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006656 (22 Nov. 2013) --- Russian cosmonaut Oleg Kotov, Expedition 38 commander, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Kotov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070857 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

Tyurin practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006663 (22 Nov. 2013) --- Russian cosmonaut Mikhail Tyurin, Expedition 38 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Tyurin, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070859 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

No Exacerbation of Knee Joint Pain and Effusion Following Preoperative Progressive Resistance Training in Patients Scheduled for Total Knee Arthroplasty: Secondary Analyses From a Randomized Controlled Trial.

PubMed

Skoffer, Birgit; Dalgas, Ulrik; Maribo, Thomas; Søballe, Kjeld; Mechlenburg, Inger

2017-11-09

Preoperative progressive resistance training (PRT) is controversial in patients scheduled for total knee arthroplasty (TKA), because of the concern that it may exacerbate knee joint pain and effusion. To examine whether preoperative PRT initiated 5 weeks prior to TKA would exacerbate pain and knee effusion, and would allow a progressively increased training load throughout the training period that would subsequently increase muscle strength. Secondary analyses from a randomized controlled trial. University Hospital and a Regional Hospital. A total of 30 patients who were scheduled for TKA due to osteoarthritis and assigned as the intervention group. Patients underwent unilateral PRT (3 sessions per week). Exercise loading was 12 repetitions maximum (RM) with progression toward 8 RM. The training program consisted of 6 exercises performed unilaterally. Before and after each training session, knee joint pain was rated on an 11-point scale, effusion was assessed by measuring the knee joint circumference, and training load was recorded. The first and last training sessions were initiated by 1 RM testing of unilateral leg press, unilateral knee extension, and unilateral knee flexion. The median pain change score from before to after each training session was 0 at all training sessions. The average increase in knee joint effusion across the 12 training sessions was a mean 0.16 cm ± 0.23 cm. No consistent increase in knee joint effusion after training sessions during the training period was found (P = .21). Training load generally increased, and maximal muscle strength improved as follows: unilateral leg press: 18% ± 30% (P = .03); unilateral knee extension: 81% ± 156% (P < .001); and unilateral knee flexion: 53% ± 57% (P < .001). PRT of the affected leg initiated shortly before TKA does not exacerbate knee joint pain and effusion, despite a substantial progression in loading and increased muscle strength. Concerns for side effects such as pain and effusion after PRT seem unfounded. To be determined. Copyright © 2017. Published by Elsevier Inc.

Airplane takeoff and landing performance monitoring system

NASA Technical Reports Server (NTRS)

Middleton, David B. (Inventor); Srivatsan, Raghavachari (Inventor); Person, Lee H. (Inventor)

1989-01-01

The invention is a real-time takeoff and landing performance monitoring system which provides the pilot with graphic and metric information to assist in decisions related to achieving rotation speed (V sub R) within the safe zone of the runway or stopping the aircraft on the runway after landing or take off abort. The system processes information in two segments: a pretakeoff segment and a real-time segment. One-time inputs of ambient conditions and airplane configuration information are used in the pretakeoff segment to generate scheduled performance data. The real-time segment uses the scheduled performance data, runway length data and transducer measured parameters to monitor the performance of the airplane throughout the takeoff roll. An important feature of this segment is that it updates the estimated runway rolling friction coefficient. Airplane performance predictions also reflect changes in headwind occurring as the takeoff roll progresses. The system displays the position of the airplane on the runway, indicating runway used and runway available, summarizes the critical information into a situation advisory flag, flags engine failures and off-nominal acceleration performance, and indicates where on the runway particular events such as decision speed (V sub 1), rotation speed (V sub R) and expected stop points will occur based on actual or predicted performance. The display also indicates airspeed, wind vector, engine pressure ratios, second segment climb speed, and balanced field length (BFL). The system detects performance deficiencies by comparing the airplane's present performance with a predicted nominal performance based upon the given conditions.

Selective reward deficit in mice lacking beta-endorphin and enkephalin.

PubMed

Hayward, Michael D; Pintar, John E; Low, Malcolm J

2002-09-15

It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of beta-endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in beta-endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both beta-endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.

Influence of intravenous self-administered psychomotor stimulants on performance of rhesus monkeys in a multiple schedule paradigm.

PubMed

Hoffmeister, F

1980-01-01

Rhesus monkeys were trained to complete three multiple schedules. The schedules consisted of three components: a fixed interval (component 1), a variable interval (component 2), and a fixed ratio (component 3). During components 1 and 2, pressing lever 1 was always reinforced by food delivery. During component 3, pressing lever 2 resulted in either food delivery or intravenous infusions of saline solution, solutions of cocaine, of d-amphetamine, of phenmetrazine, or fenetylline. In schedule I, animals were presented with all three components independent of key-pressing behavior during components 1 and 2. In schedule II the availability of component 2 was dependent on completion of component 1. Component 3 was made available only on completion of component 2. Noncompletion of components 1 or 2 resulted in time-out of 15 and 10 min, respectively. Schedule III was identical with schedule II, except that in schedule III the completion of components was indicated only by a change in the lever lights. The influence of self-administered drugs on behavior in all three components was evaluated. Self-administration of psychomotor stimulants impaired the performance of animals and delayed completion of components 1 and 2 of schedules I, II, and III. The effects on behavior were similar with low drug intake in schedule III, moderate intake in schedule II, and high drug intake in schedule I. These effects were strong with self-administration of phenmetrazine, moderate with self-administration of cocaine and d-amphetamine, and weak with self-administration of fenetylline.

Measuring Chemotherapy Appointment Duration and Variation Using Real-Time Location Systems.

PubMed

Barysauskas, Constance M; Hudgins, Gina; Gill, Katie Kupferberg; Camuso, Kristen M; Bagley, Janet; Rozanski, Sheila; Kadish, Sarah

Clinical schedules drive resource utilization, cost, and patient wait time. Accurate appointment duration allocation ensures appropriate staffing ratios to daily caseloads and maximizes scarce resources. Dana-Farber Cancer Institute (DFCI) infusion appointment duration is adjusted by regimen using a consensus method of experts including pharmacists, nurses, and administrators. Using real-time location system (RTLS), we examined the accuracy of observed appointment duration compared with the scheduled duration. Appointment duration was calculated using RTLS at DFCI between August 1, 2013, and September 30, 2013. Duration was defined as the total time a patient occupied an infusion chair. The top 10 administered infusion regimens were investigated (n = 805). Median observed appointment durations were statistically different than the scheduled durations. Appointment durations were shorter than scheduled 98% (C), 95% (I), and 75% (F) of the time and longer than scheduled 77% (A) and 76% (G) of the time. Fifty-six percent of the longer than scheduled (A) appointments were at least 30 minute longer. RTLS provides reliable and unbiased data to improve schedule accuracy. Replacing consensus with system-based data may improve clinic flow, relieve staff stress, and increase patient satisfaction. Further investigation is warranted to elucidate factors that impact variation in appointment duration.

Nevada's Class-Size Reduction Program. Nevada Revised Statutes 388.700-388.730: "Program To Reduce the Pupil-Teacher Ratio." Background Paper 97-7.

ERIC Educational Resources Information Center

Sturm, H. Pepper

In 1989, the Nevada Legislature enacted the Class-Size Reduction (CSR) Act. The measure was designed to reduce the pupil-teacher ratio in the public schools, particularly in the earliest grades. The program was scheduled to proceed in several phases. The first step reduced the student-teacher ratio in selected kindergartens and first grade classes…

Performance and control study of a low-pressure-ratio turbojet engine for a drone aircraft

NASA Technical Reports Server (NTRS)

Seldner, K.; Geyser, L. C.; Gold, H.; Walker, D.; Burgner, G.

1972-01-01

The results of analog and digital computer studies of a low-pressure-ratio turbojet engine system for use in a drone vehicle are presented. The turbojet engine consists of a four-stage axial compressor, single-stage turbine, and a fixed area exhaust nozzle. Three simplified fuel schedules and a generalized parameter fuel control for the engine system are presented and evaluated. The evaluation is based on the performance of each schedule or control during engine acceleration from a windmill start at Mach 0.8 and 6100 meters to 100 percent corrected speed. It was found that, because of the higher acceleration margin permitted by the control, the generalized parameter control exhibited the best dynamic performance.

48 CFR 307.7106 - Acquisition milestones.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Acquisition milestones. 307.7106 Section 307.7106 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES COMPETITION... to track progress of the acquisition. The milestone schedule signatories (see the Requirements and...

48 CFR 307.7106 - Acquisition milestones.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Acquisition milestones. 307.7106 Section 307.7106 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES COMPETITION... to track progress of the acquisition. The milestone schedule signatories (see the Requirements and...

40 CFR Table 4 to Subpart Ggg of... - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... Part 62-Site-Specific Compliance Schedules and Increments of Progress Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills...

40 CFR Table 4 to Subpart Ggg of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... Part 62-Site-Specific Compliance Schedules and Increments of Progress Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills...

76 FR 71079 - Records Schedules; Availability and Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... Rico, Canada, Japan, Turkey, and the nations of Western Europe. 11. Department of Defense, Defense... or initiation letters, cost reports, financial statements, correspondence, progress reports, and..., certifications, notices, reports, and facility assessments. 17. Department of Homeland Security, Transportation...

Combatting Terrorism: A Guide for U. S. Naval Forces Afloat

DTIC Science & Technology

1985-12-01

weaponry at an alarming rate . Because of this progress "large numbers of these new weapons will quickly become obsolete and disposed of through arms... rate qualification processes. Consequently, it is many times given to an -: inexperienced, new individual while "more important" posi- 0A * tions are...so as not to unduly tax the regular training schedule. While the training of the crew in anti-terrorist and counterterrorist techniques is in progress

Visual Schedule System in Dental Care for Patients with Autism: A Pilot Study.

PubMed

Mah, Janet Wt; Tsang, Phoebe

A pilot study to test whether a visual schedule system using picture communication symbols can help children with autism have successful routine dental cleaning visits. 14 boys with autism between three- to eight-years-old presented to the dental clinic for four weekly consecutive dental appointments. Patients were randomly assigned to either the control group who received the tell-show-do method (i.e., standard of care), or the test group who received the tell-show-do method plus the visual schedule system. Patients in the test group completed an average of 1.38 more steps, at 35.52 seconds per step faster, and with 18.7% lower levels of behavioral distress than those in the control group. The use of a visual schedule system, along with repeated weekly visits, showed some promise in helping children with autism successfully complete more steps, progress at a quicker rate, and exhibit lower levels of behavioral distress within a dental appointment, compared to a traditional tell-show-do approach.

Temporal Context in Concurrent Chains: I. Terminal-Link Duration

ERIC Educational Resources Information Center

Grace, Randolph C.

2004-01-01

Two experiments are reported in which the ratio of the average times spent in the terminal and initial links ("Tt/Ti") in concurrent chains was varied. In Experiment 1, pigeons responded in a three-component procedure in which terminal-link variable-interval schedules were in constant ratio, but their average duration increased across components…

"Pack[superscript2]": VM Resource Scheduling for Fine-Grained Application SLAs in Highly Consolidated Environment

ERIC Educational Resources Information Center

Sukwong, Orathai

2013-01-01

Virtualization enables the ability to consolidate multiple servers on a single physical machine, increasing the infrastructure utilization. Maximizing the ratio of server virtual machines (VMs) to physical machines, namely the consolidation ratio, becomes an important goal toward infrastructure cost saving in a cloud. However, the consolidation…

Intermittent Punishment of Self-stimulation: Effectiveness During Application and Extinction

ERIC Educational Resources Information Center

Romanczyk, Raymond G.

1977-01-01

Two studies were performed comparing the effectiveness of fixed-ratio (FR) and variable-ratio (VR) schedules of punishment during application and extinction. Subjects were two young children. Both studies found significant positive "side effects" of punishment in terms of increased play and social behavior as well as increased performance of…

Performance and policy dimensions in internet routing

NASA Technical Reports Server (NTRS)

Mills, David L.; Boncelet, Charles G.; Elias, John G.; Schragger, Paul A.; Jackson, Alden W.; Thyagarajan, Ajit

1995-01-01

The Internet Routing Project, referred to in this report as the 'Highball Project', has been investigating architectures suitable for networks spanning large geographic areas and capable of very high data rates. The Highball network architecture is based on a high speed crossbar switch and an adaptive, distributed, TDMA scheduling algorithm. The scheduling algorithm controls the instantaneous configuration and swell time of the switch, one of which is attached to each node. In order to send a single burst or a multi-burst packet, a reservation request is sent to all nodes. The scheduling algorithm then configures the switches immediately prior to the arrival of each burst, so it can be relayed immediately without requiring local storage. Reservations and housekeeping information are sent using a special broadcast-spanning-tree schedule. Progress to date in the Highball Project includes the design and testing of a suite of scheduling algorithms, construction of software reservation/scheduling simulators, and construction of a strawman hardware and software implementation. A prototype switch controller and timestamp generator have been completed and are in test. Detailed documentation on the algorithms, protocols and experiments conducted are given in various reports and papers published. Abstracts of this literature are included in the bibliography at the end of this report, which serves as an extended executive summary.

The application of artificial intelligence to astronomical scheduling problems

NASA Technical Reports Server (NTRS)

Johnston, Mark D.

1992-01-01

Efficient utilization of expensive space- and ground-based observatories is an important goal for the astronomical community; the cost of modern observing facilities is enormous, and the available observing time is much less than the demand from astronomers around the world. The complexity and variety of scheduling constraints and goals has led several groups to investigate how artificial intelligence (AI) techniques might help solve these kinds of problems. The earliest and most successful of these projects was started at Space Telescope Science Institute in 1987 and has led to the development of the Spike scheduling system to support the scheduling of Hubble Space Telescope (HST). The aim of Spike at STScI is to allocate observations to timescales of days to a week observing all scheduling constraints and maximizing preferences that help ensure that observations are made at optimal times. Spike has been in use operationally for HST since shortly after the observatory was launched in Apr. 1990. Although developed specifically for HST scheduling, Spike was carefully designed to provide a general framework for similar (activity-based) scheduling problems. In particular, the tasks to be scheduled are defined in the system in general terms, and no assumptions about the scheduling timescale are built in. The mechanisms for describing, combining, and propagating temporal and other constraints and preferences are quite general. The success of this approach has been demonstrated by the application of Spike to the scheduling of other satellite observatories: changes to the system are required only in the specific constraints that apply, and not in the framework itself. In particular, the Spike framework is sufficiently flexible to handle both long-term and short-term scheduling, on timescales of years down to minutes or less. This talk will discuss recent progress made in scheduling search techniques, the lessons learned from early HST operations, the application of Spike to other problem domains, and plans for the future evolution of the system.

Big Creek Flood Control Project, Cleveland, Ohio. Phase II. General Design Memorandum.

DTIC Science & Technology

1979-08-01

enviromental measure to -minii polluted leachate, if say, from flowing down the embashment. 1. Comnt 12(a). The freboard on the chute will be revised...cost ratio); (3) operational dependability; and (4) socio -environmental effects, including external damage effects. Each of these alternative plans is...schedule for the utility relocations will not be in conflict with the construction schedule for the major components of the project outlined above. 112

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

PubMed

Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

2016-11-03

The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5 . The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

PubMed

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. Janssen Research & Development, LLC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer

PubMed Central

Vergote, Ignace B.; Garcia, Agustin; Micha, John; Pippitt, Charles; Bendell, Johanna; Spitz, Daniel; Reed, Nicholas; Dark, Graham; Fracasso, Paula M.; Ibrahim, Emad N.; Armenio, Vincent A.; Duska, Linda; Poole, Chris; Gennigens, Christine; Dirix, Luc Y.; Leung, Abraham C.F.; Zhao, Carol; Soufi-Mahjoubi, Raoudha; Rustin, Gordon

2013-01-01

Purpose Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. Patients and Methods A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m2 every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS). Results The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days. Conclusion Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m2 once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant ovarian cancer. PMID:24081946

Intercell scheduling: A negotiation approach using multi-agent coalitions

NASA Astrophysics Data System (ADS)

Tian, Yunna; Li, Dongni; Zheng, Dan; Jia, Yunde

2016-10-01

Intercell scheduling problems arise as a result of intercell transfers in cellular manufacturing systems. Flexible intercell routes are considered in this article, and a coalition-based scheduling (CBS) approach using distributed multi-agent negotiation is developed. Taking advantage of the extended vision of the coalition agents, the global optimization is improved and the communication cost is reduced. The objective of the addressed problem is to minimize mean tardiness. Computational results show that, compared with the widely used combinatorial rules, CBS provides better performance not only in minimizing the objective, i.e. mean tardiness, but also in minimizing auxiliary measures such as maximum completion time, mean flow time and the ratio of tardy parts. Moreover, CBS is better than the existing intercell scheduling approach for the same problem with respect to the solution quality and computational costs.

Comparison of menstrual disorders in hospital nursing staff according to shift work pattern.

PubMed

Albert-Sabater, Josep Amílcar; Martínez, José Miguel; Baste, Valborg; Moen, Bente E; Ronda-Perez, Elena

2016-11-01

To assess the association between work in a rotating shift schedule and menstruation characteristics among nurse staff in a prospective study. Rotating shifts have been linked to alterations in the reproductive cycle. In the case of menstrual alterations, the conclusions are not clear. Prospective epidemiological study with follow-up over four months. All the female nurse staff (<40 years) in a hospital were interviewed, collecting sociodemographic and employment information. They were given a menstrual diary to keep a record of their shifts and characteristics of their menstruation (duration, amount of blood, dysmenorrhoea). They had two types of shifts: (1) Rotating shift schedule (two mornings, two afternoons, one night and two days off) including morning shifts (8:00-15:00), afternoon/evening shifts (15:00-22:00) and night shifts (22:00-8:00), and (2) Day shift schedule including morning shifts (8:00-15:00) and/or afternoon/evening shifts (15:00-22:00). The crude and adjusted odds ratios with 95% confidence interval were calculated using logistic generalised estimating equations (GEE) taking into account the correlations of multiple cycles per worker. One hundred and thirteen workers on the rotating shift and 75 on the day shift participated, and information from 730 menstrual cycles were obtained. There were no differences in prolonged duration, dysmenorrhoea, prolonged duration dysmenorrhoea and excessive bleeding among nurses on rotating shift compared to those on the day shift. For prolonged duration of menstruation, workers with more than five years on the rotating shift showed a slightly lower (nonsignificant) risk compared with those with <5 years. Nurse staff on the rotating shift did not show increased risk of having menstrual disorders comparing with day staff. Shifts with short rotation cycles and a progressive sequence do not appear to cause menstrual disorders in nurse staff who work rotating shifts. © 2016 John Wiley & Sons Ltd.

T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.

PubMed

Uslaner, Jason M; Vardigan, Joshua D; Drott, Jason M; Uebele, Victor N; Renger, John J; Lee, Ariel; Li, Zhaoxia; Lê, A D; Hutson, Pete H

2010-10-15

Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Design and implementation of priority and time-window based traffic scheduling and routing-spectrum allocation mechanism in elastic optical networks

NASA Astrophysics Data System (ADS)

Wang, Honghuan; Xing, Fangyuan; Yin, Hongxi; Zhao, Nan; Lian, Bizhan

2016-02-01

With the explosive growth of network services, the reasonable traffic scheduling and efficient configuration of network resources have an important significance to increase the efficiency of the network. In this paper, an adaptive traffic scheduling policy based on the priority and time window is proposed and the performance of this algorithm is evaluated in terms of scheduling ratio. The routing and spectrum allocation are achieved by using the Floyd shortest path algorithm and establishing a node spectrum resource allocation model based on greedy algorithm, which is proposed by us. The fairness index is introduced to improve the capability of spectrum configuration. The results show that the designed traffic scheduling strategy can be applied to networks with multicast and broadcast functionalities, and makes them get real-time and efficient response. The scheme of node spectrum configuration improves the frequency resource utilization and gives play to the efficiency of the network.

Report: EPA Plans for Managing Counter Terrorism/ Emergency Response Equipment and Protecting Critical Assets Not Fully Implemented

EPA Pesticide Factsheets

Report #09-P-0087, January 27, 2009. EPA has progressed in implementing the counter terrorism/emergency response (CT/ER) initiatives, but is behind schedule in implementing the Radiation Ambient Monitoring (RadNet) System.

75 FR 26218 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... Mississippi, Inc submits executed Rate Schedule providing for cost-based power sales for partial requirements...: Florida Power Corporation. Description: Progress Energy Florida, Inc submits its annual cost factor... Friday, May 21, 2010. Docket Numbers: ER10-720-001. Applicants: Northeastern Power Company. Description...

Rapid COJEC versus standard induction therapies for high-risk neuroblastoma.

PubMed

Peinemann, Frank; Tushabe, Doreen A; van Dalen, Elvira C; Berthold, Frank

2015-05-19

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome. In the rapid COJEC induction schedule, higher single doses of selected drugs than standard induction schedules are administered over a substantially shorter treatment period, with shorter intervals between cycles. Shorter intervals and higher doses increase the dose intensity of chemotherapy and might improve survival. The aim of this study was to evaluate the efficacy and adverse events of the rapid COJEC induction schedule as compared to standard induction schedules in patients with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). Outcomes of interest were complete response, early toxicity and treatment-related mortality as primary endpoints and overall survival, progression- and event-free survival, late non-hematological toxicity, and health-related quality of life as secondary endpoints. We searched the electronic databases CENTRAL (2014, Issue 11), MEDLINE (PubMed), and EMBASE (Ovid) for articles from inception to 11 November 2014. Further searches included trial registries, conference proceedings, and reference lists of recent reviews and relevant articles. We did not apply limits on publication year or languages. Randomized controlled trials evaluating the rapid COJEC induction schedule for high-risk neuroblastoma patients compared to standard induction schedules. Two review authors performed study selection, abstracted data on study and patient characteristics, and assessed risk of bias independently. We resolved differences by discussion or by appeal to a third review author. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We used the five GRADE considerations, study limitations, consistency of effect, imprecision, indirectness, and publication bias, to judge the quality of the evidence. We downgraded for risk of bias and imprecision We identified one randomized controlled trial (CCLG-ENSG-5) that included 262 patients with high-risk neuroblastoma who were randomized to receive either rapid COJEC (N = 130) or standard OPEC/COJEC (N = 132) induction chemotherapy. We graded the evidence as low quality; we downgraded for risk of bias and imprecision.There was no clear evidence of a difference between the treatment groups in complete response (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.71 to 1.38), treatment-related mortality (RR 1.21, 95% CI 0.33 to 4.39), overall survival (hazard ratio (HR) 0.83, 95% CI 0.63 to 1.10), and event-free survival (HR 0.86, 95% CI 0.65 to 1.13). We calculated the HRs using the complete follow-up period of the trial.Febrile neutropenia (two or more episodes), proven fungal infections, septicemia (one or more episodes), gastrointestinal toxicity (grade 3 or 4), renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73 m(2)), neurological toxicity (grade 3 or 4), and ototoxicity (Brock grade 2 to 4) were addressed as early toxicities (during pre-operative chemotherapy). For febrile neutropenia, septicemia, and renal toxicity, a statistically significant difference in favor of the standard treatment arm was identified; for all other early toxicities no clear evidence of a difference between treatment groups was identified. With regard to late non-hematological toxicities (median follow-up 12.7 years; range 6.9 to 16.5 years), the study provided data on any complication, renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73m(2)), ototoxicity (Brock grade 1 to 4), endocrine complications, neurocognitive complications (i.e. behavioral, speech, or learning difficulties), and second malignancies. For endocrine complications and neurocognitive complications, a statistically significant difference in favor of the rapid COJEC arm was found; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified.Data on progression-free survival and health-related quality of life were not reported. We identified one randomized controlled trial that evaluated rapid COJEC versus standard induction therapy in patients with high-risk neuroblastoma. No clear evidence of a difference in complete response, treatment-related mortality, overall survival, and event-free survival between the treatment alternatives was found. This could be the result of low power or too short a follow-up period. Results of both early and late toxicities were ambiguous. Information on progression-free survival and health-related quality of life were not available. This trial was performed in the 1990s. Since then, many changes in, for example, treatment and risk classification have occurred. Therefore, based on the currently available evidence, we are uncertain about the effects of rapid COJEC and standard induction therapy in patients with high-risk neuroblastoma. More research is needed for a definitive conclusion.

On the distinction between open and closed economies.

PubMed Central

Timberlake, W; Peden, B F

1987-01-01

Open and closed economies have been assumed to produce opposite relations between responding and the programmed density of reward (the amount of reward divided by its cost). Experimental procedures that are treated as open economies typically dissociate responding and total reward by providing supplemental income outside the experimental session; procedures construed as closed economies do not. In an open economy responding is assumed to be directly related to reward density, whereas in a closed economy responding is assumed to be inversely related to reward density. In contrast to this predicted correlation between response-reward relations and type of economy, behavior regulation theory predicts both direct and inverse relations in both open and closed economies. Specifically, responding should be a bitonic function of reward density regardless of the type of economy and is dependent only on the ratio of the schedule terms rather than on their absolute size. These predictions were tested by four experiments in which pigeons' key pecking produced food on fixed-ratio and variable-interval schedules over a range of reward magnitudes and under several open- and closed-economy procedures. The results better supported the behavior regulation view by showing a general bitonic function between key pecking and food density in all conditions. In most cases, the absolute size of the schedule requirement and the magnitude of reward had no effect; equal ratios of these terms produced approximately equal responding. PMID:3625103

Its Cerenkov Radiation

DTIC Science & Technology

1989-12-01

Report 2b Declassification Downgrading Schedule Approved for public release; distribution is unlimited. 4 Performing Organization Report Number(s) 5...Monitoring Organization Report Number(s) 6a Name of Performing Organization 6b Office Symbol 7a Name of Monitoring Organization Naval Postraduate School (if... Prodcution Ratio. DS vs. MIT........................ 29 Figure 15. Cerenkov Weights at Detector ........... I.................... 30 Figure 16. Ratio at

Computational Analysis of the Combustion Processes in an Axisymmetric, RBCC Flowpath

NASA Technical Reports Server (NTRS)

Steffen, Christopher J., Jr.; Yungster, Shaye

2001-01-01

Computational fluid dynamic simulations have been used to study the combustion processes within an axisymmetric, RBCC flowpath. Two distinct operating modes have been analyzed to date, including the independent ramjet stream (IRS) cycle and the supersonic combustion ramjet (scramJet) cycle. The IRS cycle investigation examined the influence of fuel-air ratio, fuel distribution, and rocket chamber pressure upon the combustion physics and thermal choke characteristics. Results indicate that adjustment of the amount and radial distribution of fuel can control the thermal choke point. The secondary massflow rate was very sensitive to the fuel-air ratio and the rocket chamber pressure. The scramjet investigation examined the influence of fuel-air ratio and fuel injection schedule upon combustion performance estimates. An analysis of the mesh-dependence of these calculations was presented. Jet penetration data was extracted from the three-dimensional simulations and compared favorably with experimental correlations of similar flows. Results indicate that combustion efficiency was very sensitive to the fuel schedule.

1 Tbit/inch2 Recording in Angular-Multiplexing Holographic Memory with Constant Signal-to-Scatter Ratio Schedule

NASA Astrophysics Data System (ADS)

Hosaka, Makoto; Ishii, Toshiki; Tanaka, Asato; Koga, Shogo; Hoshizawa, Taku

2013-09-01

We developed an iterative method for optimizing the exposure schedule to obtain a constant signal-to-scatter ratio (SSR) to accommodate various recording conditions and achieve high-density recording. 192 binary images were recorded in the same location of a medium in approximately 300×300 µm2 using an experimental system embedded with a blue laser diode with a 405 nm wavelength and an objective lens with a 0.85 numerical aperture. The recording density of this multiplexing corresponds to 1 Tbit/in.2. The recording exposure time was optimized through the iteration of a three-step sequence consisting of total reproduced intensity measurement, target signal calculation, and recording energy density calculation. The SSR of pages recorded with this method was almost constant throughout the entire range of the reference beam angle. The signal-to-noise ratio of the sampled pages was over 2.9 dB, which is higher than the reproducible limit of 1.5 dB in our experimental system.

Physical and Organizational Job Stressors in Pregnancy and Associations With Primary Cesarean Deliveries.

PubMed

Guendelman, Sylvia; Gemmill, Alison; Hosang, Nap; MacDonald, Leslie A

2017-06-01

The aim of this study was to assess the relationship between exposure to physical and organizational job stressors during pregnancy and cesarean delivery. We sampled 580 employed women in California who participated in a nested population-based case-control study of birth outcomes. Adjusted multivariate regression analyses estimated associations between heavy lifting, frequent bending, high noise, extreme temperature, prolonged standing and organizational stressors (shift work, inflexible schedules, effort-reward ratio), and primary cesarean (vs vaginal) delivery, controlling for covariates. Women occupationally exposed had higher odds of cesarean. Those exposed to daily manual lifting more than 15 pounds [adjusted odds ratio = 2.54; 95% confidence interval (95% CI) 1.21 to 5.32] and at least four physical job stressors (adjusted odds ratio = 3.49; 95% CI 1.21 to 10.09) had significantly elevated odds of cesarean delivery. Exposed morbid women experienced greater risk; risk was lower among those with schedule flexibility. Associations were found between modifiable exposure to physical job stressors during pregnancy and cesarean delivery.

Workflow as a Service in the Cloud: Architecture and Scheduling Algorithms.

PubMed

Wang, Jianwu; Korambath, Prakashan; Altintas, Ilkay; Davis, Jim; Crawl, Daniel

2014-01-01

With more and more workflow systems adopting cloud as their execution environment, it becomes increasingly challenging on how to efficiently manage various workflows, virtual machines (VMs) and workflow execution on VM instances. To make the system scalable and easy-to-extend, we design a Workflow as a Service (WFaaS) architecture with independent services. A core part of the architecture is how to efficiently respond continuous workflow requests from users and schedule their executions in the cloud. Based on different targets, we propose four heuristic workflow scheduling algorithms for the WFaaS architecture, and analyze the differences and best usages of the algorithms in terms of performance, cost and the price/performance ratio via experimental studies.

Thermal energy storage subsystems. A collection of quarterly reports

NASA Technical Reports Server (NTRS)

1978-01-01

The design, development, and progress toward the delivery of three subsystems is discussed. The subsystem used a salt hydrate mixture for thermal energy storage. The program schedules, technical data, and other program activities from October 1, 1976, through December 31, 1977 are presented.

40 CFR 52.134 - Compliance schedules.

Code of Federal Regulations, 2013 CFR

2013-07-01

... beyond July 31, 1975, shall apply any reasonable interim measures of control designed to reduce the... progress shall include, but not be limited to: Submittal of the final control plan to the Administrator... of component parts to accomplish emission control equipment or process modification; completion of...

40 CFR 52.134 - Compliance schedules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... beyond July 31, 1975, shall apply any reasonable interim measures of control designed to reduce the... progress shall include, but not be limited to: Submittal of the final control plan to the Administrator... of component parts to accomplish emission control equipment or process modification; completion of...

40 CFR 52.134 - Compliance schedules.

Code of Federal Regulations, 2012 CFR

2012-07-01

... beyond July 31, 1975, shall apply any reasonable interim measures of control designed to reduce the... progress shall include, but not be limited to: Submittal of the final control plan to the Administrator... of component parts to accomplish emission control equipment or process modification; completion of...

40 CFR 52.134 - Compliance schedules.

Code of Federal Regulations, 2014 CFR

2014-07-01

... beyond July 31, 1975, shall apply any reasonable interim measures of control designed to reduce the... progress shall include, but not be limited to: Submittal of the final control plan to the Administrator... of component parts to accomplish emission control equipment or process modification; completion of...

40 CFR 52.134 - Compliance schedules.

Code of Federal Regulations, 2011 CFR

2011-07-01

... beyond July 31, 1975, shall apply any reasonable interim measures of control designed to reduce the... progress shall include, but not be limited to: Submittal of the final control plan to the Administrator... of component parts to accomplish emission control equipment or process modification; completion of...

The Middle Income Squeeze

ERIC Educational Resources Information Center

Glover, Steve

1978-01-01

Complaints about a middle income family's hardships in sending their children to private colleges and universities are examined. The difficulty may be attributable to a progressive College Scholarship Service (CSS) taxation rate schedule that causes larger proportionate reductions in the standard of living for some families than others.…

Historical overfishing and the recent collapse of coastal ecosystems

USGS Publications Warehouse

Jackson, J.B.C.; Kirby, M.X.; Berger, W.H.; Bjorndal, K.A.; Botsford, L.W.; Bourque, B.J.; Bradbury, R.; Cooke, R.; Erlandson, J.; Estes, J.A.; Hughes, T.P.; Kidwell, S.; Lange, C.B.; Lenihan, H.S.; Pandolfi, J.M.; Peterson, C.H.; Steneck, R.S.; Tegner, M.J.; Warner, R.

2001-01-01

A method for calculating parameters necessary to maintain stable populations is described and the management implications of the method are discussed. This method depends upon knowledge of the population mortality rate schedule, the age at which the species reaches maturity, and recruitment rates or age ratios in the population. Four approaches are presented which yield information about the status of the population: (1) necessary production for a stable population, (2) allowable mortality for a stable population, (3) annual rate of change in population size, and (4) age ratios in the population which yield a stable condition. General formulas for these relationships, and formulas for several special cases, are presented. Tables are also presented showing production required to maintain a stable population with the simpler (more common) mortality and fecundity schedules.

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PubMed

Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

2017-12-01

The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Modelling of project cash flow on construction projects in Malang city

NASA Astrophysics Data System (ADS)

Djatmiko, Bambang

2017-09-01

Contractors usually prepare a project cash flow (PCF) on construction projects. The flow of cash in and cash out within a construction project may vary depending on the owner, contract documents, and construction service providers who have their own authority. Other factors affecting the PCF are down payment, termyn, progress schedule, material schedule, equipment schedule, manpower schedules, and wages of workers and subcontractors. This study aims to describe the cash inflow and cash outflow based on the empirical data obtained from contractors, develop a PCF model based on Halpen & Woodhead's PCF model, and investigate whether or not there is a significant difference between the Halpen & Woodhead's PCF model and the empirical PCF model. Based on the researcher's observation, the PCF management has never been implemented by the contractors in Malang in serving their clients (owners). The research setting is in Malang City because physical development in all field and there are many new construction service providers. The findings in this current study are summarised as follows: 1) Cash in included current assets (20%), owner's down payment (20%), termyin I (5%-25%), termyin II (20%), termyin III (25%), termyin IV (25%) and retention (5%). Cash out included direct cost (65%), indirect cost (20%), and profit + informal cost(15%), 2)the construction work involving the empirical PCF model in this study was started with the funds obtained from DP or current assets and 3) The two models bear several similarities in the upward trends of direct cost, indirect cost, Pro Ic, progress billing, and S-curve. The difference between the two models is the occurrence of overdraft in the Halpen and Woodhead's PCF model only.

Permutation flow-shop scheduling problem to optimize a quadratic objective function

NASA Astrophysics Data System (ADS)

Ren, Tao; Zhao, Peng; Zhang, Da; Liu, Bingqian; Yuan, Huawei; Bai, Danyu

2017-09-01

A flow-shop scheduling model enables appropriate sequencing for each job and for processing on a set of machines in compliance with identical processing orders. The objective is to achieve a feasible schedule for optimizing a given criterion. Permutation is a special setting of the model in which the processing order of the jobs on the machines is identical for each subsequent step of processing. This article addresses the permutation flow-shop scheduling problem to minimize the criterion of total weighted quadratic completion time. With a probability hypothesis, the asymptotic optimality of the weighted shortest processing time schedule under a consistency condition (WSPT-CC) is proven for sufficiently large-scale problems. However, the worst case performance ratio of the WSPT-CC schedule is the square of the number of machines in certain situations. A discrete differential evolution algorithm, where a new crossover method with multiple-point insertion is used to improve the final outcome, is presented to obtain high-quality solutions for moderate-scale problems. A sequence-independent lower bound is designed for pruning in a branch-and-bound algorithm for small-scale problems. A set of random experiments demonstrates the performance of the lower bound and the effectiveness of the proposed algorithms.

Two-Level Scheduling for Video Transmission over Downlink OFDMA Networks

PubMed Central

Tham, Mau-Luen

2016-01-01

This paper presents a two-level scheduling scheme for video transmission over downlink orthogonal frequency-division multiple access (OFDMA) networks. It aims to maximize the aggregate quality of the video users subject to the playback delay and resource constraints, by exploiting the multiuser diversity and the video characteristics. The upper level schedules the transmission of video packets among multiple users based on an overall target bit-error-rate (BER), the importance level of packet and resource consumption efficiency factor. Instead, the lower level renders unequal error protection (UEP) in terms of target BER among the scheduled packets by solving a weighted sum distortion minimization problem, where each user weight reflects the total importance level of the packets that has been scheduled for that user. Frequency-selective power is then water-filled over all the assigned subcarriers in order to leverage the potential channel coding gain. Realistic simulation results demonstrate that the proposed scheme significantly outperforms the state-of-the-art scheduling scheme by up to 6.8 dB in terms of peak-signal-to-noise-ratio (PSNR). Further test evaluates the suitability of equal power allocation which is the common assumption in the literature. PMID:26906398

Environmental factors impact Passalora sequoiae conidia counts from Leyland Cypress

USDA-ARS?s Scientific Manuscript database

Needle blight disease, caused by Passalora sequoiae, results in a progressive lost of leaf tissue on Leyland cypress (×Cupressocyparis leylandii) within container and field tree nurseries, in the landscape, and on Christmas tree farms. Fungicide schedules were developed in response to seasonal sympt...

18 CFR 5.15 - Conduct of studies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Conduct of studies. 5... Conduct of studies. (a) Implementation. The potential applicant must gather information and conduct studies as provided for in the approved study plan and schedule. (b) Progress reports. The potential...

18 CFR 5.15 - Conduct of studies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Conduct of studies. 5... Conduct of studies. (a) Implementation. The potential applicant must gather information and conduct studies as provided for in the approved study plan and schedule. (b) Progress reports. The potential...

40 CFR Table 1 to Subpart Bbbb of... - Model Rule-Compliance Schedules and Increments of Progress

Code of Federal Regulations, 2010 CFR

2010-07-01

... modification after June 26, 1987, comply with the dioxins/furans and mercury limits by the later of two dates... the dioxins/furans limits must be achieved no later than December 6, 2005, even if the date one year...

PDP-11 Meeting School District Administrative Data Processing Challenges.

ERIC Educational Resources Information Center

Technological Horizons in Education, 1983

1983-01-01

Elmhurst Community Unit School District 205 (Illinois) is currently using a Digital PDP-11/70 computer system and administrative software to handle administrative functions with ease and efficiency. These functions include production of reports and payroll, student scheduling, reporting grades and student progress, and maintaining student…

46 CFR 380.24 - Schedule of retention periods and description of records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... bonds, salvage data, and claim files; (4) Contracts, agreements, franchises, licenses, etc., such as subsidy, charter, ship construction, and pooling agreements; (5) Vessel operating records such as log... Administration: (1) Ship construction or reconversion records such as bids, plans, progress payments, and...

46 CFR 380.24 - Schedule of retention periods and description of records.

Code of Federal Regulations, 2014 CFR

2014-10-01

... bonds, salvage data, and claim files; (4) Contracts, agreements, franchises, licenses, etc., such as subsidy, charter, ship construction, and pooling agreements; (5) Vessel operating records such as log... Administration: (1) Ship construction or reconversion records such as bids, plans, progress payments, and...

46 CFR 380.24 - Schedule of retention periods and description of records.

Code of Federal Regulations, 2012 CFR

2012-10-01

... bonds, salvage data, and claim files; (4) Contracts, agreements, franchises, licenses, etc., such as subsidy, charter, ship construction, and pooling agreements; (5) Vessel operating records such as log... Administration: (1) Ship construction or reconversion records such as bids, plans, progress payments, and...

46 CFR 380.24 - Schedule of retention periods and description of records.

Code of Federal Regulations, 2011 CFR

2011-10-01

... bonds, salvage data, and claim files; (4) Contracts, agreements, franchises, licenses, etc., such as subsidy, charter, ship construction, and pooling agreements; (5) Vessel operating records such as log... Administration: (1) Ship construction or reconversion records such as bids, plans, progress payments, and...

46 CFR 380.24 - Schedule of retention periods and description of records.

Code of Federal Regulations, 2013 CFR

2013-10-01

... bonds, salvage data, and claim files; (4) Contracts, agreements, franchises, licenses, etc., such as subsidy, charter, ship construction, and pooling agreements; (5) Vessel operating records such as log... Administration: (1) Ship construction or reconversion records such as bids, plans, progress payments, and...

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

48 CFR 1852.234-1 - Notice of Earned Value Management System.

Code of Federal Regulations, 2014 CFR

2014-10-01

... according to paragraph (a); (vi) Provide documentation describing the process and results, including..., provide a schedule of events leading up to formal validation and Government acceptance of the Contractor's...) outlines the requirements for conducting a progress assistance visit and validation compliance review. (2...

48 CFR 1852.234-1 - Notice of Earned Value Management System.

Code of Federal Regulations, 2013 CFR

2013-10-01

... according to paragraph (a); (vi) Provide documentation describing the process and results, including..., provide a schedule of events leading up to formal validation and Government acceptance of the Contractor's...) outlines the requirements for conducting a progress assistance visit and validation compliance review. (2...

48 CFR 1852.234-1 - Notice of Earned Value Management System.

Code of Federal Regulations, 2012 CFR

2012-10-01

... according to paragraph (a); (vi) Provide documentation describing the process and results, including..., provide a schedule of events leading up to formal validation and Government acceptance of the Contractor's...) outlines the requirements for conducting a progress assistance visit and validation compliance review. (2...

48 CFR 1852.234-1 - Notice of Earned Value Management System.

Code of Federal Regulations, 2011 CFR

2011-10-01

... according to paragraph (a); (vi) Provide documentation describing the process and results, including..., provide a schedule of events leading up to formal validation and Government acceptance of the Contractor's...) outlines the requirements for conducting a progress assistance visit and validation compliance review. (2...

Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.

PubMed

Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

2013-08-01

The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4). Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison. During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

PubMed

Mena, Guillermo; García-Basteiro, Alberto L; Llupià, Anna; Díez, Consolación; Costa, Josep; Gatell, Josep-María; García, Felipe; Bayas, José-María

2013-08-12

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of proton beam radiotherapy and hyper-fractionated accelerated chemoradiotherapy for locally advanced pancreatic cancer.

PubMed

Maemura, Kosei; Mataki, Yuko; Kurahara, Hiroshi; Kawasaki, Yota; Iino, Satoshi; Sakoda, Masahiko; Ueno, Shinichi; Arimura, Takeshi; Higashi, Ryutaro; Yoshiura, Takashi; Shinchi, Hiroyuki; Natsugoe, Shoji

We compared the clinical outcomes of proton beam radiotherapy (PBRT) and those of conventional chemoradiotherapy via hyper-fractionated acceleration radiotherapy (HART) after induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC). Twenty-five consecutive patients with LAPC received induction chemotherapy comprising gemcitabine and S-1 before radiotherapy. Of these, 15 and 10 were enrolled in the HART and PBRT groups, respectively. Moderate hematological toxicities were observed only in the HART group, whereas two patients in the PBRT group developed duodenal ulcers. All patients underwent scheduled radiotherapy, with overall disease control rates of 93% and 80% in the HART and PBRT groups, respectively. Local progression was observed in 60% and 40% of patients in the HART and PBRT groups, respectively. However, there was no statistical significance between the two groups regarding the median time to progression (15.4 months in both) and the median overall survival (23.4 v.s. 22.3 months). PBRT was feasible and tolerable, and scheduled protocols could be completed with careful attention to gastrointestinal ulcers. Despite the lower incidence of local recurrence, PBRT did not yield obvious progression control and survival benefits relative to conventional chemoradiotherapy. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

A randomised controlled trial comparing two schedules of antenatal visits: the antenatal care project.

PubMed Central

Sikorski, J.; Wilson, J.; Clement, S.; Das, S.; Smeeton, N.

1996-01-01

OBJECTIVE--To compare the clinical and psychological effectiveness of the traditional British antenatal visit schedule (traditional care) with a reduced schedule of visits (new style care) for low risk women, together with maternal and professional satisfaction with care. DESIGN--Randomised controlled trial. SETTING--Places in south east London providing antenatal care for women receiving shared care and planning to deliver in one of three hospitals or at home. SUBJECT--2794 women at low risk fulfilling the trial's inclusion criteria between June 1993 and July 1994. MAIN OUTCOME MEASURES--Measures of fetal and maternal morbidity, health service use, psychosocial outcomes, and maternal and professional satisfaction. RESULTS--Pregnant women allocated to new style care had fewer day admissions (0.8 v 1.0; P=0.002) and ultrasound scans (1.6 v 1.7; P=0.003) and were less often suspected of carrying fetuses that were small for gestational age (odds ratio 0.73; 95% confidence interval 0.54 to 0.99). They also had some poorer psychosocial outcomes; for example, they were more worried about fetal wellbeing antenatally and coping with the baby postnatally, and they had more negative attitudes to their babies, both in pregnancy and postnatally. These women were also more dissatisfied with the number of visits they received (odds ratio 2.50; 2.00 to 3.11). CONCLUSIONS--Patterns of antenatal care involving fewer routine visits for women at low risk may lead to reduced psychosocial effectiveness and dissatisfaction with frequency of visits. The number of antenatal day admissions and ultrasound scans performed may also be reduced. For the variables reported, the visit schedules studied are similar in their clinical effectiveness. Uncertainty remains as to the clinical effectiveness of reduced visit schedules for rare pregnancy problems. PMID:8595286

Effects of Pre-Trial Response Requirements on Self-Control Choices by Rats and Pigeons

ERIC Educational Resources Information Center

Mazur, James E.

2012-01-01

Parallel experiments with rats and pigeons examined whether the size of a pre-trial ratio requirement would affect choices in a self-control situation. In different conditions, either 1 response or 40 responses were required before each trial. In the first half of each experiment, an adjusting-ratio schedule was used, in which subjects could…

A cost-benefit analysis of demand for food.

PubMed Central

Hursh, S R; Raslear, T G; Shurtleff, D; Bauman, R; Simmons, L

1988-01-01

Laboratory studies of consumer demand theory require assumptions regarding the definition of price in the absence of a medium of exchange (money). In this study we test the proposition that the fundamental dimension of price is a cost-benefit ratio expressed as the effort expended per unit of food value consumed. Using rats as subjects, we tested the generality of this "unit price" concept by varying four dimensions of price: fixed-ratio schedule, number of food pellets per fixed-ratio completion, probability of reinforcement, and response lever weight or effort. Two levels of the last three factors were combined in a 2 x 2 x 2 design giving eight groups. Each group was studied under a series of six FR schedules. Using the nominal values of all factors to determine unit price, we found that grams of food consumed plotted as a function of unit price followed a single demand curve. Similarly, total work output (responses x effort) conformed to a single function when plotted in terms of unit price. These observations provided a template for interpreting the effects of biological factors, such as brain lesions or drugs, that might alter the cost-benefit ratio. PMID:3209958

Progressively safer, cheaper demolition of Fernald

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

Robert Nichols; Norman Pennington

2000-09-29

Fluor Fernald, Inc. has been progressively improving Decontamination and Dismantlement (D&D) at the Department of Energy's Fernald Environmental Management Project by applying new technologies and better methodologies to the work. Demolition issues existed in the past that necessitated new or improved solutions to maintain worker safety, protect the environment and accomplish the work in a cost effective manner. Lessons learned from D&D of 80 structures has led to a systematic approach, which can be implemented in various D&D arenas. When facility production was halted, hold-up material and process residues remained in the process piping and components. Over 500,000 pounds ofmore » material was removed by workers who completed the tasks two years ahead of schedule, $7 million under budget and with an excellent safety record. This success was the result of detailed planning and irdision of lessons learned as work progressed from facility to facility. Work sequences were developed that reduced airborne contamination. Demolition of structures has been performed at Fernald by carefully selected and qualified subcontractors. Asbestos and lead abatement, equipment, piping and conduit removal, and structural demolition have been completed to progressively higher performance specifications developed by Fluor Fernald based on lessons learned during execution. Safety continues to be the primary consideration in performing potentially hazardous work. Technologies such as hydraulic shears have been developed and used to keep workers away from danger. A new technology, ''Cool Suits,'' has been demonstrated to help prevent heat stress when anti-contamination clothing is required in elevated temperature working conditions. For tall structures, implosion technologies have been employed with progressively improved results, Several other new technologies have been evaluated by Fluor Fernald and applied by subcontractors. The improved technologies included the oxy-gas torch, which uses gasoline instead of acetylene gas, and a vacuum system for asbestos removal of wall insulation. These new methods proved effective and beneficial. Fluor Fernald has integrated demolition activities with waste disposal requirements to enhance overall efficiency. The relatively straight steel configurations required for recycling, and waste acceptance criteria that dictate waste sizes are typically included in the subcontract specifications The progressive improvements by Fluor Fernald have led to cost savings and schedule acceleration without increased risk to workers or the environment. When Fluor Fernald came to the site in 1992, the remediation baseline reflected a completion schedule of 2020 and a cost of $7.2 billion. The current projection is 2008 and $4.2 billion.« less

HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

PubMed

Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

2018-05-18

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

Solenoid-free plasma start-up in spherical tokamaks

NASA Astrophysics Data System (ADS)

Raman, R.; Shevchenko, V. F.

2014-10-01

The central solenoid is an intrinsic part of all present-day tokamaks and most spherical tokamaks. The spherical torus (ST) confinement concept is projected to operate at high toroidal beta and at a high fraction of the non-inductive bootstrap current as required for an efficient reactor system. The use of a conventional solenoid in a ST-based fusion nuclear facility is generally believed to not be a possibility. Solenoid-free plasma start-up is therefore an area of extensive worldwide research activity. Solenoid-free plasma start-up is also relevant to steady-state tokamak operation, as the central transformer coil of a conventional aspect ratio tokamak reactor would be located in a high radiation environment but would be needed only during the initial discharge initiation and current ramp-up phases. Solenoid-free operation also provides greater flexibility in the selection of the aspect ratio and simplifies the reactor design. Plasma start-up methods based on induction from external poloidal field coils, helicity injection and radio frequency current drive have all made substantial progress towards meeting this important need for the ST. Some of these systems will now undergo the final stages of test in a new generation of large STs, which are scheduled to begin operations during the next two years. This paper reviews research to date on methods for inducing the initial start-up current in STs without reliance on the conventional central solenoid.

Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

PubMed Central

de Jong, Johannes W; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E; Luijendijk, Mieneke C M; van der Eerden, Harrie A M; Garner, Keith M; Vanderschuren, Louk J M J; Adan, Roger A H

2015-01-01

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior. PMID:25735756

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.

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

PubMed

Goetz, Matthew P; Toi, Masakazu; Campone, Mario; Sohn, Joohyuk; Paluch-Shimon, Shani; Huober, Jens; Park, In Hae; Trédan, Olivier; Chen, Shin-Cheh; Manso, Luis; Freedman, Orit C; Garnica Jaliffe, Georgina; Forrester, Tammy; Frenzel, Martin; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Di Leo, Angelo

2017-11-10

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder.

PubMed

Kaasinen, Eero; Wijkström, Hans; Rintala, Erkki; Mestad, Oddvar; Jahnson, Staffan; Malmström, Per-Uno

2016-10-01

The aim of this study was to compare the long-term efficacy of BCG monotherapy to alternating therapy of mitomycin C (MMC) and BCG in patients with carcinoma in situ (CIS). Between 1992 and 1997, 321 patients with CIS were randomized from Finland, Norway and Sweden in a prospective multicenter trial into two treatment groups. The alternating therapy comprised six weekly instillations of MMC 40 mg followed by 10 instillations of BCG (Connaught 120 mg) or MMC alternating monthly for 1 year. BCG monotherapy followed the same 6 + 10 schedule. Stratification was done by nationality and CIS category. Primary endpoints were time to first recurrence and time to progression. Secondary endpoints were disease-specific mortality and overall survival. The main statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model with the cumulative incidence and Kaplan-Meier analyses. The median follow-up time was 9.9 years (maximum 19.9 years) in the BCG group and 8.9 years (maximum 20.3 years) in the alternating group. The risk of recurrence was significantly lower in the BCG group than in the alternating group (49 vs 59% at 15 years, respectively; hazard ratio 0.74, 95% confidence interval 0.54-1.00, p = 0.048). There were no significant differences in the other endpoints. Patients who progressed after 2 years were particularly prone to dying from bladder carcinoma. Younger patients performed worse than older ones. BCG monotherapy including monthly maintenance was effective and better than the alternating therapy. The risk of dying from bladder carcinoma after progression was high.

Social context has differential effects on acquisition of nicotine self-administration in male and female rats.

PubMed

Peartree, Natalie A; Hatch, Kayla N; Goenaga, Julianna G; Dado, Nora R; Molla, Hanna; Dufwenberg, Martin A; Campagna, Allegra; Mendoza, Rachel; Cheung, Timothy H C; Talboom, Joshua S; Neisewander, Janet L

2017-06-01

Smoking typically begins during adolescence or early adulthood in a social context, yet the role of social context in animal models is poorly understood. The present study examined the effect of social context on acquisition of nicotine self-administration. Sixty-day-old male and female Sprague-Dawley rats were trained to press a lever for nicotine (0.015 mg/kg, IV) or saline infusions (males only) on a fixed ratio (FR1) schedule of reinforcement across nine sessions in duplex chambers that were conjoined with either a solid wall or a wall containing wire mesh creating a social context between rat dyads (social visual, auditory, and olfactory cues). In a subsequent experiment, sex differences and dose-dependent effects of nicotine [0 (saline), 0.015 or 0.03 mg/kg, IV] were directly compared in rats trained in the isolated or social context on a schedule progressing from FR1 to FR3. These rats were given 20 sessions followed by 3 extinction sessions. We consistently found transient social facilitation of low-dose nicotine self-administration in males during the first session. However, across training overall, we found social suppression of nicotine intake that was most prominent in females during later sessions. Collectively, these findings suggest that at the age of transition from adolescence to adulthood, a social context enhances the initial reinforcing effects of nicotine in males, but protects against nicotine intake during later sessions especially in females. These findings highlight the importance of sex and social context in studying neural mechanisms involved in initiation of nicotine use.

Nicotine enhancement and reinforcer devaluation: Interaction with opioid receptors.

PubMed

Kirshenbaum, Ari P; Suhaka, Jesse A; Phillips, Jessie L; Voltolini de Souza Pinto, Maiary

In rats, nicotine enhances responding maintained by non-pharmacological reinforcers, and discontinuation of nicotine devalues those same reinforcers. The goal of this study was to assess the interaction of nicotine and opioid receptors and to evaluate the degree to which nicotine enhancement and nicotine-induced devaluation are related to opioid activation. Nicotine (0.4mg/kg), or nicotine plus naloxone (0.3 or 3.0mg/kg), was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. PR-schedule responding was assessed during ten daily sessions of drug delivery, and for three post-dosing days/sessions. Control groups for this investigation included a saline-only condition, and naloxone-only (0.3 or 3.0mg/kg) conditions. When administered in conjunction with nicotine, both naloxone doses attenuated nicotine enhancement of the sucrose reinforcer, and the combination of the larger dose of naloxone (3.0mg/kg) with nicotine produced significant impairments in sucrose reinforced responding. When administered alone, neither dose of naloxone (0.3 & 3.0mg/kg) significantly altered responding in comparison to saline. Furthermore, when dosing was discontinued after ten once-daily doses, all nicotine groups (nicotine-only and nicotine+naloxone combination) demonstrated significant decreases in sucrose reinforcement compared to the saline group. Although opioid antagonism attenuated reinforcement enhancement by nicotine, it did not prevent reinforcer devaluation upon discontinuation of nicotine dosing, and the higher dose of naloxone (3.0mg/kg) produced decrements upon discontinuation on its own in the absence of nicotine. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys.

PubMed

Weed, M R; Paul, I A; Dwoskin, L P; Moore, S E; Woolverton, W L

1997-10-01

The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission and stimulation of central nervous system (CNS) dopamine (DA) receptors. Consistent with this notion, some drugs that directly stimulate DA receptors have been found to function as positive reinforcers. The present experiments were designed to examine why some, but not all, D1 receptor agonists can function as reinforcers in rhesus monkeys by comparing behavioral and CNS in vitro measures of potency and efficacy. Seven rhesus monkeys were allowed to self-administer cocaine under a progressive-ratio (PR) schedule until stable responding was established. Various doses of D1 agonists, previously reported to function as positive reinforcers, were then made available for self-administration. Stimulation of cAMP production in rhesus and rat striatal tissue was studied for these compounds and for D1 agonists previously reported not to function as positive reinforcers in monkeys (SKF 38393, SKF 77434 and S(-)-6-BrAPB). Blockade of DA uptake in rat striata was also examined for all compounds. SKF 81297, SKF 82958 and R(+)-6-BrAPB maintained responding under the PR schedule and did not differ significantly in efficacy as positive reinforcers; SKF 81297 was less potent than the other two agonists. SKF 81297, SKF 82958 and R(+)-6-BrAPB stimulated higher levels of cAMP production in rhesus striata than did SKF 38393, SKF 77434 and S(-)-6-BrAPB. In contrast, all compounds blocked DA uptake. Thus, reinforcing efficacy among D1 agonists increases with efficacy in stimulating D1 receptors.

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.

Lecture: fotemustine in brain tumors.

PubMed

Silvani, A; Gaviani, P; Lamperti, E; Botturi, A; Ferrari, D; Simonetti, G; Salmaggi, A

2011-11-01

Fotemustine (FTMS) is a third-generation nitrosourea, in preclinical studies, FTMS compared favorably with carmustine (BCNU) and lomustine (CCNU) against several human tumor cell lines. In conventional schedule, FTMS is administered at a dose of 100 mg/sqm/week for three consecutive weeks as induction (I) treatment, followed by 100 mg/sqm every three weeks, after a 5-week rest, as maintenance (M). Several Italian groups reported the results using FTMS in malignant glioma patients recurring after temozolomide standard treatment. In these papers, the 6-progression free survival are ranging from 20 to 52%. With the schedule (I + M) myelosuppression is observed in more than 30% of patients, and thrombocytopenia and leukopenia are more frequent and significant in Temozolomide pretreated patients. On the bases of the hematological toxicities several authors experimented new schedules of FTMS administrated at low doses. Recently, some authors reported the interesting results of a multicenter study on recurrent glioblastoma multiforme patients combining FTMS with new antiangiogentic agent bevacizumab.

Integrating LMINET with TAAM and SIMMOD: A Feasibility Study

NASA Technical Reports Server (NTRS)

Long, Dou; Stouffer-Coston, Virginia; Kostiuk, Peter; Kula, Richard; Yackovetsky, Robert (Technical Monitor)

2001-01-01

LMINET is a queuing network air traffic simulation model implemented at 64 large airports and the entire National Airspace System in the United States. TAAM and SIMMOD are two widely used air traffic event-driven simulation models mostly for airports. Based on our proposed Progressive Augmented window approach, TAAM and SIMMOD are integrated with LMINET though flight schedules. In the integration, the flight schedules are modified through the flight delays reported by the other models. The benefit to the local simulation study is to let TAAM or SIMMOD take the modified schedule from LMINET, which takes into account of the air traffic congestion and flight delays at the national network level. We demonstrate the value of the integrated models by the case studies at Chicago O'Hare International Airport and Washington Dulles International Airport. Details of the integration are reported and future work for a full-blown integration is identified.

Obstetrician call schedule and obstetric outcomes among women eligible for a trial of labor after cesarean.

PubMed

Yee, Lynn M; Liu, Lilly Y; Grobman, William A

2017-01-01

Reducing cesarean deliveries is a major public health goal. The low rate of vaginal birth after cesarean has been attributed largely to a decrease in the likelihood of choosing a trial of labor after cesarean, despite evidence suggesting a majority of women with 1 prior low transverse cesarean are trial of labor after cesarean candidates. Although a number of reasons for this decrease have been explored, it remains unclear how systems issues such as physician call schedules influence delivery approach and mode in this context. The objective of the study was to investigate the relationship between obstetricians' call schedule and obstetric outcomes among women eligible for a trial of labor after cesarean. This is a retrospective cohort study of the likelihood of attempting a trial of labor after cesarean and achieving vaginal birth after cesarean among women with 1 prior low transverse cesarean delivery and a term, cephalic singleton gestation based on the delivering provider's call schedule. Attending obstetrician call schedules were classified as traditional or night float call. Night float call was defined as a schedule in which the provider had clinical responsibilities only for a day or night shift, without other clinical responsibilities before or after the period of responsibility for laboring patients. Call schedules are determined by individual provider groups. Bivariable analyses and random-effects logistic regression were used to examine the relationship between obstetricians' call schedule and the frequency of trial of labor after cesarean. Secondary outcomes including frequency of vaginal birth after cesarean and maternal and neonatal outcomes also were assessed. Of 1502 eligible patients, 556 (37%) were delivered by physicians in a night float call system. A total of 22.6% underwent a trial of labor after cesarean and 12.8% achieved vaginal birth after cesarean; the vaginal birth after cesarean rate for women attempting a trial of labor after cesarean was 56.5%. Women were more likely to undergo a trial of labor after cesarean (33.1% vs 16.5%, P < .001) and achieve vaginal birth after cesarean (18.7% vs 9.3%, P < .001) when cared for by physicians with a night float call schedule. Regression analyses demonstrated physicians with a night float call schedule remained significantly more likely to have patients undergo trial of labor after cesarean (adjusted odds ratio, 2.64, 95% confidence interval, 1.65-4.25) and experience vaginal birth after cesarean (adjusted odds ratio, 2.17, 95% confidence interval, 1.36-3.45) after adjusting for potential confounders. However, the likelihood of achieving vaginal birth after cesarean if a trial of labor after cesarean was attempted was not different based on provider call type (adjusted odds ratio, 0.96, 95% confidence interval, 0.57-1.62). Although women delivered by providers with a night float schedule were more likely to experience uterine rupture (1.8% vs 0.6%, P = .03), chorioamnionitis (4.3% vs 1.7%, P = .002), postpartum hemorrhage (7.6% vs 4.8%, P = .03), and neonates admitted to the neonatal intensive care unit (6.8% vs 3.9%, P = .01), these associations did not persist when the population was limited to women attempting trial of labor after cesarean. Although physicians working on a night float call system were significantly more likely to have patients with a prior cesarean undergo trial of labor after cesarean and achieve vaginal birth after cesarean, their patients also were more likely to experience maternal and neonatal morbidity. However, these differences did not persist when limiting analyses to women attempting a trial of labor after cesarean. Using a night float call schedule may be an effective measure to promote a trial of labor after cesarean and vaginal birth after cesarean. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 12755 - Federal Acquisition Regulation; Submission for OMB Review; Schedules for Construction Contracts

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... Paperwork Reduction Act, the Regulatory Secretariat will be submitting to the Office of Management and... contract when other management approaches for ensuring adequate progress are not used. If the Contractor... extension of the information collection would violate the fundamental purpose of the Paperwork Reduction Act...

24 CFR 1000.530 - What corrective and remedial actions will HUD request or recommend to address performance...

Code of Federal Regulations, 2013 CFR

2013-04-01

... URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability... is repeated; (2) Request the recipient to submit progress schedules for completing activities or... incur costs for the affected activity; (4) Recommend that the recipient redirect funds from affected...

24 CFR 1000.530 - What corrective and remedial actions will HUD request or recommend to address performance...

Code of Federal Regulations, 2014 CFR

2014-04-01

... URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability... is repeated; (2) Request the recipient to submit progress schedules for completing activities or... incur costs for the affected activity; (4) Recommend that the recipient redirect funds from affected...

77 FR 16235 - Agency Information Collection Activities: Proposed Collection; Comment Request; Guidance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... is entered into the appropriate tracking databases. Use of the information in the Agency's tracking databases enables the Agency to monitor progress on the activities attendant to scheduling and holding a... collection of information on respondents, including through the use of automated collection techniques, when...

AJ26 engine test

NASA Image and Video Library

2011-09-28

NASA conducted a Sept. 28 test of an Aerojet AJ26 flight engine that will power the first stage of Orbital Sciences Corporation's Taurus II space launch vehicle, continuing progress in a key commercial space transport partnership. Orbital is scheduled to begin commercial cargo flights to the International Space Station in 2012.

Space fabrication demonstration system

NASA Technical Reports Server (NTRS)

1978-01-01

The lower right aluminum beam cap roll forming mill was delivered and installed in the beam builder. The beam was brought to full operational status and beams of one to six bay lengths were produced to demonstrate full system capability. Although the cap flange waviness problem persists, work is progressing within cost and schedule.

Embedding Support for Students Transitioning into Higher Education: Evaluation of a New Model

ERIC Educational Resources Information Center

Hebdon, Sharon

2015-01-01

The Learning Academic Skills Support program was designed to improve progression and retention rates for students articulating from vocational education into the Bachelor of Hospitality Management at Holmesglen Institute. The program is scheduled around the student experience during their first semester in higher education and incorporates…

Secondary School Transition: Planning for Success.

ERIC Educational Resources Information Center

Hemphill, Rae

Parents of adolescents with attention deficit disorders are offered suggestions for easing the transition of their teen from elementary to secondary school. Careful scheduling of classes with the guidance counselor to "fit" the individual teen's needs is urged. The importance of ongoing communication with the school concerning class progress,…

May Babies and Posttenure Babies: Maternal Decisions of Women Professors

ERIC Educational Resources Information Center

Armenti, Carmen

2004-01-01

This research explores the maternal and career progression decisions of different generations of women professors in Canada. Nineteen women, interviewed in-depth, reveal how they carefully plan childbearing and childrearing experiences around their demanding work schedules, by having May babies or posttenure babies. Results demonstrate the need…

The Morning After.

ERIC Educational Resources Information Center

Taylor, John H.

1996-01-01

After a college or university has received the large gift it has solicited, there are still a variety of follow-through tasks to attend to, including considering an appropriate sign of appreciation, notifying campus officials and encouraging them to send thank-you notes, creating a payment schedule, keeping the donor apprised of progress toward…

Manual for physical fitness

NASA Technical Reports Server (NTRS)

Coleman, A. E.

1981-01-01

Training manual used for preflight conditioning of NASA astronauts is written for audience with diverse backgrounds and interests. It suggests programs for various levels of fitness, including sample starter programs, safe progression schedules, and stretching exercises. Related information on equipment needs, environmental coonsiderations, and precautions can help readers design safe and effective running programs.

NOVA, A BRIEF .....

ERIC Educational Resources Information Center

WHITING, RICHARD; AND OTHERS

NOVA IS AN EXPERIMENTAL, 6-YEAR JUNIOR-SENIOR HIGH SCHOOL. ASPECTS OF THE PROGRAM INCLUDE THE TRIMESTER SYSTEM, THE CONTINUOUS PROGRESS CURRICULUM, TEAM TEACHING, A CLASS SCHEDULE OF FOUR 70-MINUTE PERIODS PER WEEK, THE USE OF DATA-PROCESSING EQUIPMENT, AND MODERN INSTRUCTIONAL AIDS. NOVA IS ORGANIZED CAMPUS-STYLE WITH INDIVIDUAL BUILDINGS DEVOTED…

RTI Scheduling Processes for Middle Schools. Information Brief

ERIC Educational Resources Information Center

Prewett, Sara; Mellard, Daryl; Lieske-Lupo, Jessica

2011-01-01

Response to intervention integrates assessment and intervention within a multi-level prevention system to maximize student achievement and to reduce behavior problems. With RTI, schools identify students at risk for poor learning outcomes, monitor student progress, provide evidence-based interventions and adjust the intensity and nature of those…

Fluent Reading in Special Primary Education

ERIC Educational Resources Information Center

Houtveen, Anthonia A. M.; van de Grift, Wim J. C. M.; Brokamp, Saskia K.

2014-01-01

The learning gains in reading of students in 57 classrooms in special primary education doubled as a result of implementing the Reading Impulse in Special Education (RISE) programme. Raising the scheduled reading time with 1.5 hr in all classrooms and implementing standards-based teaching characterised by "monitoring of pupil progress",…

12 CFR 213.4 - Content of disclosures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mathematical progression of how the scheduled periodic payment is derived, in a format substantially similar to... the end of the lease term; and the amount or a description of the method for determining the amount of... specify the amount or method for determining any charge for excess mileage. (i) Purchase option. A...

40 CFR 82.16 - Phaseout schedule of class II controlled substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... uses or defense applications. (8) A formulator for, or an agency, department, or instrumentality of the... exemption allowances. (1) Effective January 21, 2003, a formulator of HCFC-141b, an agency, department, or... continuing investigations into and progress on possible alternatives and substitutes; (xii) A list of...

40 CFR 82.16 - Phaseout schedule of class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... uses or defense applications. (8) A formulator for, or an agency, department, or instrumentality of the... exemption allowances. (1) Effective January 21, 2003, a formulator of HCFC-141b, an agency, department, or... continuing investigations into and progress on possible alternatives and substitutes; (xii) A list of...

Infant Sign Training and Functional Analysis

ERIC Educational Resources Information Center

Normand, Matthew P.; Machado, Mychal A.; Hustyi, Kristin M.; Morley, Allison J.

2011-01-01

We taught manual signs to typically developing infants using a reversal design and caregiver-nominated stimuli. We delivered the stimuli on a time-based schedule during baseline. During the intervention, we used progressive prompting and reinforcement, described by Thompson et al. (2004, 2007), to establish mands. Following sign training, we…

Strategic Plan for Standards-Based Reform. Report of Progress.

ERIC Educational Resources Information Center

Hawaii State Dept. of Education, Honolulu. Office of the Superintendent.

This report summarizes the expectations, mission, guiding principles, standards, assessments, and time line for standards implementation for the state of Hawai'i. Implementation was scheduled for completion by August 2000. A technical reference matrix tracks the development of the assessment and accountability system. The completion of specific…

Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma

PubMed Central

Motzer, Robert J.; Hutson, Thomas E.; Tomczak, Piotr; Michaelson, M. Dror; Bukowski, Ronald M.; Oudard, Stéphane; Negrier, Sylvie; Szczylik, Cezary; Pili, Roberto; Bjarnason, Georg A.; Garcia-del-Muro, Xavier; Sosman, Jeffrey A.; Solska, Ewa; Wilding, George; Thompson, John A.; Kim, Sindy T.; Chen, Isan; Huang, Xin; Figlin, Robert A.

2009-01-01

Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-α group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor–signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-α (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-α (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion Sunitinib demonstrates longer overall survival compared with IFN-α plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. PMID:19487381

Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

PubMed Central

Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

2015-01-01

Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.

PubMed

Raghu, Ganesh; Behr, Juergen; Brown, Kevin K; Egan, Jim J; Kawut, Steven M; Flaherty, Kevin R; Martinez, Fernando J; Nathan, Steven D; Wells, Athol U; Collard, Harold R; Costabel, Ulrich; Richeldi, Luca; de Andrade, Joao; Khalil, Nasreen; Morrison, Lake D; Lederer, David J; Shao, Lixin; Li, Xiaoming; Pedersen, Patty S; Montgomery, A Bruce; Chien, Jason W; O'Riordan, Thomas G

2013-05-07

Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). Academic and private hospitals. Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. Ambrisentan, 10 mg/d, or placebo. Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. The study was terminated early. Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. Gilead Sciences.

Response allocation to concurrent fixed-ratio reinforcement schedules with work requirements by adults with mental retardation and typical preschool children.

PubMed Central

Cuvo, A J; Lerch, L J; Leurquin, D A; Gaffaney, T J; Poppen, R L

1998-01-01

The present experiments examined the effect of work requirements in combination with reinforcement schedule on the choice behavior of adults with mental retardation and preschool children. The work requirements of age-appropriate tasks (i.e., sorting silverware, jumping hurdles, tossing beanbags) were manipulated. Participants were presented with their choice of two response options for each trial that varied simultaneously on both work requirement and reinforcement schedule. Results showed that when responding to both choices occurred on the same reinforcement schedule, participants allocated most of their responses to the option with the easier work requirement. When the response option requiring less work was on a leaner reinforcement schedule, most participants shifted their choice to exert more work. There were individual differences across participants regarding their pattern of responding and when they switched from the lesser to the greater work requirement. Data showed that participants' responding was largely controlled by the reinforcement received for responding to each level of work. Various conceptualizations regarding the effects of work requirements on choice behavior are discussed. PMID:9532750

Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A "Game Changer" for Prostate Treatment?

PubMed

Pathmanathan, Angela U; van As, Nicholas J; Kerkmeijer, Linda G W; Christodouleas, John; Lawton, Colleen A F; Vesprini, Danny; van der Heide, Uulke A; Frank, Steven J; Nill, Simeon; Oelfke, Uwe; van Herk, Marcel; Li, X Allen; Mittauer, Kathryn; Ritter, Mark; Choudhury, Ananya; Tree, Alison C

2018-02-01

Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Workflow as a Service in the Cloud: Architecture and Scheduling Algorithms

PubMed Central

Wang, Jianwu; Korambath, Prakashan; Altintas, Ilkay; Davis, Jim; Crawl, Daniel

2017-01-01

With more and more workflow systems adopting cloud as their execution environment, it becomes increasingly challenging on how to efficiently manage various workflows, virtual machines (VMs) and workflow execution on VM instances. To make the system scalable and easy-to-extend, we design a Workflow as a Service (WFaaS) architecture with independent services. A core part of the architecture is how to efficiently respond continuous workflow requests from users and schedule their executions in the cloud. Based on different targets, we propose four heuristic workflow scheduling algorithms for the WFaaS architecture, and analyze the differences and best usages of the algorithms in terms of performance, cost and the price/performance ratio via experimental studies. PMID:29399237

Research in Distributed Real-Time Systems

NASA Technical Reports Server (NTRS)

Mukkamala, R.

1997-01-01

This document summarizes the progress we have made on our study of issues concerning the schedulability of real-time systems. Our study has produced several results in the scalability issues of distributed real-time systems. In particular, we have used our techniques to resolve schedulability issues in distributed systems with end-to-end requirements. During the next year (1997-98), we propose to extend the current work to address the modeling and workload characterization issues in distributed real-time systems. In particular, we propose to investigate the effect of different workload models and component models on the design and the subsequent performance of distributed real-time systems.

X-ray satellite

NASA Technical Reports Server (NTRS)

1985-01-01

The 3rd Quarter Status Report on DFVLR's ROSAT project confirms that with regard to technical performance and costs the project is on schedule. The valid schedule for engineering model and flight model completion on May 7, 1985 leads to a launch date on October 30, 1987. Progress in each department is compared to and explained with regard to the milestone plan. Continued problems with the gold damping of the FM-mirror system and contamination of the sterile rooms where the mirrors are stored have led to postponement of milestone 7. It is not yet completely clear to what extent all successive milestones will be affected by this factor.

The influence of "preparedness" on autoshaping, schedule performance, and choice.

PubMed

Burns, J D; Malone, J C

1992-11-01

Two groups of experimentally naive pigeons were exposed to an autoshaping procedure in which the response key was mounted on the wall (the conventional location) or on the floor of the chamber. In two experiments, subjects readily responded to the wall key, but floor-key subjects required shaping. A subsequent experiment compared performance of wall- and floor-key groups on an ascending series of fixed-ratio schedule values, resistance to extinction, differential reinforcement of other behavior, and reversal of key assignment. Each experiment was followed by several sessions of fixed-ratio training; the performance of the wall- and floor-key groups was almost identical throughout. In the final experiment, a fixed-ratio requirement could be completed on either or both keys. Birds initially chose the key on which they had responded during the preceding (reversal of key assignment) experiment. However, within a few sessions both groups showed almost exclusive preference for the floor key. Preference for a key located on the floor may follow from the fact that pigeons are ground feeders and may thus be more "prepared" to peck the floor than to peck a wall. However, autoshaping, under the conditions prevailing here, occurred much more readily to the wall key, suggesting that pecking a vertical surface is more highly prepared. Difficulties in determining relative preparedness seem moot, however, given the lack of between-group differences in the intervening experiments. It is thus unlikely that schedule performances critically depend upon the specific operant response involved.

Effects of response-independent stimuli on fixed-interval and fixed-ratio performance of rats: a model for stressful disruption of cyclical eating patterns.

PubMed

Reed, Phil

2011-03-01

Binge eating is often associated with stress-induced disruption of typical eating patterns. Three experiments were performed with the aim of developing a potential model for this effect by investigating the effect of presenting response-independent stimuli on rats' lever-pressing for food reinforcement during both fixed-interval (FI) and fixed-ratio (FR) schedules of reinforcement. In Experiment 1, a response-independent brief tone (500-ms, 105-dB, broadband, noisy signal, ranging up to 16 kHz, with spectral peaks at 3 and 500 Hz) disrupted the performance on an FI 60-s schedule. Responding with the response-independent tone was more vigorous than in the absence of the tone. This effect was replicated in Experiment 2 using a within-subject design, but no such effect was noted when a light was employed as a disrupter. In Experiment 3, a 500-ms tone, but not a light, had a similar effect on rats' performance on FR schedules. This tone-induced effect may represent a release from response-inhibition produced by an aversive event. The implications of these results for modeling binge eating are discussed.

Link Scheduling Algorithm with Interference Prediction for Multiple Mobile WBANs

PubMed Central

Le, Thien T. T.

2017-01-01

As wireless body area networks (WBANs) become a key element in electronic healthcare (e-healthcare) systems, the coexistence of multiple mobile WBANs is becoming an issue. The network performance is negatively affected by the unpredictable movement of the human body. In such an environment, inter-WBAN interference can be caused by the overlapping transmission range of nearby WBANs. We propose a link scheduling algorithm with interference prediction (LSIP) for multiple mobile WBANs, which allows multiple mobile WBANs to transmit at the same time without causing inter-WBAN interference. In the LSIP, a superframe includes the contention access phase using carrier sense multiple access with collision avoidance (CSMA/CA) and the scheduled phase using time division multiple access (TDMA) for non-interfering nodes and interfering nodes, respectively. For interference prediction, we define a parameter called interference duration as the duration during which disparate WBANs interfere with each other. The Bayesian model is used to estimate and classify the interference using a signal to interference plus noise ratio (SINR) and the number of neighboring WBANs. The simulation results show that the proposed LSIP algorithm improves the packet delivery ratio and throughput significantly with acceptable delay. PMID:28956827

Kurs antenna on the Progress

NASA Image and Video Library

2007-02-22

ISS014-E-14451 (22 Feb. 2007) --- A close-up view of the Kurs antenna on the Progress vehicle docked to the International Space Station's Zvezda Service Module was photographed during a session of extravehicular activity (EVA) on Feb. 22, 2007. During the 6-hour, 18-minute spacewalk, astronaut Michael E. Lopez-Alegria (out of frame), Expedition 14 commander and NASA space station science officer; and cosmonaut Mikhail Tyurin (out of frame), flight engineer representing Russia's Federal Space Agency, were able to retract the stuck antenna which did not properly retract when the Progress docked to the station on Oct. 26, 2006. Moving the antenna was necessary to ensure it would not interfere with the undocking scheduled in April.

Parental work schedules and child overweight and obesity.

PubMed

Champion, S L; Rumbold, A R; Steele, E J; Giles, L C; Davies, M J; Moore, V M

2012-04-01

Studies in school-age children have consistently shown a positive association between maternal paid work hours and child obesity. However, there is conflicting evidence about the impact of maternal work hours scheduled at nonstandard times (for example, evenings, nights or weekends), and no previous examination of paternal work schedules and child weight. We examined the associations between maternal, paternal and combined parental paid work schedules and overweight/obesity in children at age 9 years. Data were analysed from the most recent follow-up of 9-year-old children (n=434) in an Australian birth cohort study. Children were measured and classified as overweight/obese using the International Obesity Taskforce body mass index cutoff points. Current working conditions of parents were obtained from a structured interview with the primary caregiver. Logistic regression analyses were used to investigate the effect of parental work schedules on child overweight/obesity with adjustment for a range of sociodemographic and household factors associated with parental employment and child weight. At 9 years of age, 99 children (22.8%) were overweight or obese. When parental work schedules were examined separately, child overweight/obesity was significantly associated with paternal nonstandard work schedules (adjusted odds ratio (OR) 1.97, 95% confidence interval (CI) 1.08-3.61). There was no association with any type of maternal work schedule. We also found an association between child overweight/obesity and circumstances in which both parents worked nonstandard schedules; however, this was of borderline statistical significance in the adjusted models (adjusted OR 2.26, 95% CI 0.99-5.16). Work hours scheduled at nonstandard times, when worked by the father or both parents, were associated with child overweight and obesity. These findings indicate the potential importance of fathers' paid work arrangements for child overweight/obesity, which until recently has largely been ignored.

Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

PubMed

Saarela, Ville; Falck, Aura; Airaksinen, P Juhani; Tuulonen, Anja

2012-03-01

To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT. © 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.

Integrating Behavioral Health in Primary Care Using Lean Workflow Analysis: A Case Study.

PubMed

van Eeghen, Constance; Littenberg, Benjamin; Holman, Melissa D; Kessler, Rodger

2016-01-01

Primary care offices are integrating behavioral health (BH) clinicians into their practices. Implementing such a change is complex, difficult, and time consuming. Lean workflow analysis may be an efficient, effective, and acceptable method for use during integration. The objectives of this study were to observe BH integration into primary care and to measure its impact. This was a prospective, mixed-methods case study in a primary care practice that served 8,426 patients over a 17-month period, with 652 patients referred to BH services. Secondary measures included primary care visits resulting in BH referrals, referrals resulting in scheduled appointments, time from referral to the scheduled appointment, and time from the referral to the first visit. Providers and staff were surveyed on the Lean method. Referrals increased from 23 to 37 per 1000 visits (P < .001). Referrals resulted in more scheduled (60% to 74%; P < .001) and arrived visits (44% to 53%; P = .025). Time from referral to the first scheduled visit decreased (hazard ratio, 1.60; 95% confidence interval, 1.37-1.88) as did time to first arrived visit (hazard ratio, 1.36; 95% confidence interval, 1.14-1.62). Survey responses and comments were positive. This pilot integration of BH showed significant improvements in treatment initiation and other measures. Strengths of Lean analysis included workflow improvement, system perspective, and project success. Further evaluation is indicated. © Copyright 2016 by the American Board of Family Medicine.

Modeling Tumor Clonal Evolution for Drug Combinations Design.

PubMed

Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

2016-03-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs.

Primary malignant tumours of the bony pelvis: US-guided high intensity focused ultrasound ablation.

PubMed

Wang, Yang; Wang, Wei; Tang, Jie

2013-11-01

The aim of this review is to evaluate the value of ultrasound (US)-guided high intensity focused ultrasound (HIFU) ablation in the treatment of primary malignant tumours of the bony pelvis. Eleven patients with primary malignant tumours of the bony pelvis received US-guided HIFU ablation. The maximum tumour size ranged from 5.6 to 25.0 cm (median 10.5 cm). Treatment was curative in four patients and palliative in seven patients. During follow-up, the effectiveness of HIFU ablation was assessed by contrast-enhanced magnetic resonance (MR). Significant coagulative necrosis was obtained in all patients after scheduled HIFU ablations; the volume ablation ratio was 86.7% ± 12.5% (range 65-100%). Complete tumour necrosis was achieved in all patients receiving curative HIFU ablation. No major complications were encountered. No patients died of local tumour progression during follow-up. US-guided HIFU ablation may be a safe and effective minimally invasive technique for the local treatment of primary malignant tumours of the bony pelvis.

Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration.

PubMed

Bauer, David J; Kerr, Abigail L; Swain, Rodney A

2011-02-01

Recently identified pathways from the dentate nuclei of the cerebellum to the rostral cerebral cortex via the thalamus suggest a cerebellar role in frontal and prefrontal non-motor functioning. Disturbance of cerebellar morphology and connectivity, particularly involving these cerebellothalamocortical (CTC) projections, has been implicated in motivational and cognitive deficits. The current study explored the effects of CTC disruption on motivation in male Long Evans rats. The results of two experiments demonstrate that electrolytic lesions of the cerebellar dentate nuclei lower breaking points on an operant conditioning progressive ratio schedule and decrease open field exploration compared to sham controls. Changes occurred in the absence of motor impairment, assessed via lever pressing frequency and rotarod performance. Similar elevated plus maze performances between lesioned and sham animals indicated that anxiety did not influence task performance. Our results demonstrate hedonic and purposive motivational reduction and suggest a CTC role in global motivational processes. These implications are discussed in terms of psychiatric disorders such as schizophrenia and autism, in which cerebellar damage and motivational deficits often present concomitantly. Copyright © 2010 Elsevier Inc. All rights reserved.

Alcohol preference influences the subthalamic nucleus control on motivation for alcohol in rats.

PubMed

Lardeux, Sylvie; Baunez, Christelle

2008-02-01

In addition to its role in motor and attentional processes, the subthalamic nucleus (STN) has also been recently demonstrated to be involved in motivational function. Indeed, bilateral STN lesions modulate differentially the motivation for natural rewards and drugs of abuse, increasing motivation for food and decreasing motivation for cocaine in rats. Here, we show that in outbred rats, the STN can modulate the motivation for alcohol according to alcohol preference, without affecting alcohol intake. When performed on 'High-Drinker' rats, STN lesions enhanced the breaking point (BP) under a progressive ratio schedule of reinforcement and increased the time spent in the environment previously paired with alcohol access in the place preference paradigm. In contrast, when performed on 'Low-Drinker' rats, STN lesions decreased the BP and increased the time spent in the environment paired with water. These results show that STN lesions enhance the motivation for alcohol in rats showing a high alcohol preference, whereas they decrease it in rats showing a low preference for alcohol. These results suggest that the STN plays a complex role in the reward circuit, that is not limited to a

The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

PubMed

Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

2016-02-01

Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ultrasonographic wall thickness measurement of the upper and lower uterine segments in the prediction of the progress of preterm labour.

PubMed

Sayed Ahmed, W A; Madny, E H; Habash, Y H; Ibrahim, Z M; Morsy, A G K; Said, M E

2015-01-01

To assess the role of ultrasonographic measurement of the upper and lower uterine segments wall thickness in predicting the progress of preterm labour in patients presenting with preterm labour pains. Fifty pregnant women presenting at Obstetrics Department - Suez Canal University, Egypt with regular lower abdominal pains and diagnosed as having preterm labour were enrolled in the study. Measurements of the upper and lower uterine segments wall thickness by transabdominal ultrasonography in-between contractions and with full bladder were taken. The upper/lower uterine wall thickness ratio was calculated and correlated to the progress of the preterm labour and to the response to tocolytics. The ultrasonographic upper/lower uterine wall thickness ratio was directly related to the progress of preterm delivery (PTD). The change in this ratio is correlated inversely with the response to tocolysis. Using the ROC curve, when the upper/lower uterine wall thickness ratio was ≤ 1.26 the sensitivity was 94.74 and the specificity was 100.00, and when the ratio was ≤ 1.52 the sensitivity was 100.00 and the specificity was 83.33. These data may serve as a baseline ultrasonographic reference values for further studies in prediction the progress of preterm labour in patients presenting with preterm labour pains.

Orbital Observatory for Planetary Science on Low Cost Autonomous Platform

NASA Astrophysics Data System (ADS)

Tavrov, Alexander; Bisikalo, Dmitry; Vedenkin, Nikolay; Korablev, Oleg; Markov, Alexander; Kiselev, Alexander; Kokorich, Mikhail

The Space Research Institute of Russian Academy of Science (IKI RAS) and Dauria Aerospace are currently developing the middle class space telescope project aiming to observe Solar system planets by a long term spectroscopy and polarimetry monitoring, as well aiming to extra solar planets (exoplanets) engineering and scientific goals. The spacecraft is scheduled to be launched in 2017. It is planned first to be delivered on board of the ISS by the Progress spacecraft, then it will be released to the desired orbit approx. 550 km by the Progress in the way to its final destination. The “Planetary monitoring” telescope has a 0.6 meter primary mirror diameter Telescope currently includes 5 science instruments: NIR: 1000..4000 nm high-resolution spectrometer with the spectral resolution of R>10000; Visible Field camera with filters wheel; UV-VIS field resolved Fourier spectrometer; UV-VIS spectropolarimeter; Stellar coronagraph linked with a low-resolution spectrometer. The scientific goals of the “Planetary monitoring” telescope are devoted to explore not yet well studied questions on Mars (methane, ozone, dust and clouds, isotope ratio of HDO/H2O), on Venus (UV absorber, night glow, atmosphere dynamics), icy and gaseous Solar system planets, Jovian moons, Lunar exosphere, comets, meteorites. This telescope aims also for engineering development of exoplanet study by stellar coronagraphy linked with a low-resolution spectrometry. This Orbital Observatory mission uses the first low cost small satellite platform developed by the Dauria Aerospace® - Russian private company and reuses the Progress to elevate the observatory orbit. The Progress launches four times per year to provide supplies and scientific instruments to the ISS. The Progress is capable of raising the height of the orbit for the piggyback scientific missions; therefore, the implementation of the Orbital Observatory mission is considered not just as a development of a successful science mission so it is most importantly developing an affordable and frequent flight opportunities for space sciences research in Russia and worldwide. The paper describes the scientific objectives and corresponding instruments, and introduces the low cost satellite platform and launch opportunities.

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

Social reinforcement as alternative to sucrose reinforcement is increased by nicotine and methylphenidate in male Fischer-344 rats.

PubMed

Martin, Connor D; Bool, Heather M; George, Anthony M; Carr, Katelyn A; Epstein, Leonard H; Hawk, Larry W; Richards, Jerry B

2018-04-24

Stimulant drugs such as nicotine (NIC) and methylphenidate (MPH) are hypothesized to increase the reinforcing value of sensory stimuli, thus increasing the effectiveness of such reinforcers as alternatives to sucrose reinforcers. Inbred Fischer-344 rats (n = 30) were assigned to three groups: saline (SAL; n = 10), nicotine (NIC; n = 10), or methylphenidate (MPH; n = 10). Testing was done in three phases: sucrose only, (SUC), sucrose and drug (SUC/DRUG), and sucrose, drug, and social reinforcement (SUC/DRUG/SOC). During the SUC phase, rats were trained on a progressive ratio 5 (PR5) reinforcement schedule for sucrose (20% solution). In the SUC/DRUG phase, animals were treated with SAL, NIC (0.4 mg/kg, n = 10 SC), or MPH (2.0 mg/kg, n = 10 IP) 30 min prior to testing. In the SUC/DRUG/SOC phase, animals continued receiving drug treatment, and social reinforcement was introduced concurrently with the sucrose reinforcer. The progressive ratio for each reinforcer ran independently of the others. Reinforcing value was measured as break point (BP), the highest number of responses resulting in a reinforcer. SAL-treated animals showed no significant change in sucrose BP. MPH-treated animals showed decreased sucrose BP in the SUC/DRUG phase, with a further reduction in the SUC/DRUG/SOC phase. NIC-treated animals decreased sucrose BP only when a social alternative was offered. Both NIC and MPH reduce the sucrose BP in the presence of a social alternative. The decrease in sucrose responding, coupled with increased social responding, suggests that the social alternative acted as an effective alternative reinforcer to sucrose. From a translational perspective, these results suggest that stimulant drugs such as NIC and MPH may increase the effectiveness of treatments that use alternative social reinforcers to decrease eating.

ISS Progress 24 Rollout

NASA Image and Video Library

2007-01-16

JSC2007-E-03079 (16 Jan. 2007) --- Roll-out of the Progress 24 vehicle occurred on schedule at 7:00 a.m., Jan. 16, 2007 (local time) at the Baikonur Cosmodrome, Kazakhstan. Progress 24 bears on the side of the Soyuz launch vehicle the name of Sergei Korolev, the "Great Designer" of Soviet spacecraft, whose 100th birthday was celebrated on Jan. 12. A portrait of him is painted on the external payload fairing. Korolev, named in his memory, is now the suburb of Moscow where the Russian Mission Control Center resides. After it reaches orbit, a series of pre-programmed engine firings will lead to the automated docking of Progress 24 to the now-vacant Pirs Docking Compartment at 9:00 p.m. CST on Jan. 19. (6:00 a.m. on Jan. 20, Moscow time). Photo Credit: NASA

Prototype solar heating and combined heating and cooling systems

NASA Technical Reports Server (NTRS)

1977-01-01

Schedules and technical progress in the development of eight prototype solar heating and combined solar heating and cooling systems are reported. Particular emphasis is given to the analysis and preliminary design for the cooling subsystem, and the setup and testing of a horizontal thermal energy storage tank configuration and collector shroud evaluation.

Role of Diet Modulation and AMPK in Ovarian Cancer Progression and Outcome

DTIC Science & Technology

2013-10-01

For this purpose, we had proposed to use two compounds: metformin and 9 berberine . Unfortunately, while berebine showed good initial results, the...mice begin to have the complication of acute constipation at the dose and schedule we were following. Hence, we had to discontinue the use of berberine

Solar heating and cooling systems design and development. [prototype development

NASA Technical Reports Server (NTRS)

1977-01-01

The development of twelve prototype solar heating/cooling systems, six heating and six heating and cooling systems, two each for single family, multi-family, and commercial applications, is reported. Schedules and technical discussions, along with illustrations on the progress made from April 1, 1977 through June 30, 1977 are detailed.

40 CFR 82.16 - Phaseout schedule of class II controlled substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

40 CFR 82.16 - Phaseout schedule of class II controlled substances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

40 CFR 82.16 - Phaseout schedule of class II controlled substances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

40 CFR 62.14565 - How do I comply with the increment of progress for achieving final compliance?

Code of Federal Regulations, 2013 CFR

2013-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and... complete retrofit construction of control devices, as specified in the final control plan, so that, when...

Chronic Ethanol During Adolescence Impacts Corticolimbic Dendritic Spines and Behavior.

PubMed

Jury, Nicholas J; Pollack, Gabrielle A; Ward, Meredith J; Bezek, Jessica L; Ng, Alexandra J; Pinard, Courtney R; Bergstrom, Hadley C; Holmes, Andrew

2017-07-01

Risk for alcohol use disorders (AUDs) in adulthood is linked to alcohol drinking during adolescence, but understanding of the neural and behavioral consequences of alcohol exposure during adolescence remains incomplete. Here, we examined the neurobehavioral impact of adolescent chronic intermittent EtOH (CIE) vapor exposure in mice. C57BL/6J-background Thy1-EGFP mice were CIE-exposed during adolescence or adulthood and examined, as adults, for alterations in the density and morphology of dendritic spines in infralimbic (IL) cortex, prelimbic (PL) cortex, and basolateral amygdala (BLA). In parallel, adolescent- and adult-exposed C57BL/6J mice were tested as adults for 2-bottle EtOH drinking, sensitivity to EtOH intoxication (loss of righting reflex [LORR]), blood EtOH clearance, and measures of operant responding for food reward. CIE during adolescence decreased IL neuronal spine density and increased the head width of relatively wide-head IL and BLA spines, whereas CIE decreased head width of relatively narrow-head BLA spines. Adolescents had higher EtOH consumption prior to CIE than adults, while CIE during adulthood, but not adolescence, increased EtOH consumption relative to pre-CIE baseline. CIE produced a tolerance-like decrease in LORR sensitivity to EtOH challenge, irrespective of the age at which mice received CIE exposure. Mice exposed to CIE during adolescence, but not adulthood, required more sessions than AIR controls to reliably respond for food reward on a fixed-ratio (FR) 1, but not subsequent FR3, reinforcement schedule. On a progressive ratio reinforcement schedule, break point responding was higher in the adolescent- than the adult-exposed mice, regardless of CIE. Finally, footshock punishment markedly suppressed responding for reward in all groups. Exposure to CIE during adolescence altered dendritic spine density and morphology in IL and BLA neurons, in parallel with a limited set of behavioral alterations. Together, these data add to growing evidence that key corticolimbic circuits are vulnerable to the effects of alcohol during adolescence, with lasting, potentially detrimental, consequences for behavior. Copyright © 2017 by the Research Society on Alcoholism.

Chronic ethanol during adolescence impacts corticolimbic dendritic spines and behavior

PubMed Central

Jury, Nicholas J.; Pollack, Gabrielle A.; Ward, Meredith J.; Bezek, Jessica L.; Ng, Alexandra J.; Pinard, Courtney R.; Bergstrom, Hadley C.; Holmes, Andrew

2017-01-01

Background Risk for alcohol use disorders (AUDs) is linked to alcohol drinking during adolescence, but understanding of the neural and behavioral consequences of alcohol exposure during adolescence remains incomplete. Here, we examined the neurobehavioral impact of adolescent chronic intermittent EtOH (CIE) vapor exposure in mice. Methods C57BL/6J-background Thy1-EGFP mice were CIE-exposed during adolescence or adulthood and examined, as adults, for alterations in the density and morphology of dendritic spines in infralimbic cortex (IL), prelimbic cortex (PL) and basolateral amygdala (BLA). In parallel, adolescent- and adult-exposed C57BL/6J mice were tested as adults for two-bottle EtOH drinking, sensitivity to EtOH intoxication (loss of righting reflex, LORR), blood EtOH clearance, and measures of operant responding for food reward. Results CIE during adolescence decreased IL neuronal spine density and increased the head-width of relatively wide-head IL and BLA spines, whereas CIE decreased head-width of relatively narrow-head BLA spines. Adolescents had higher EtOH consumption prior to CIE than adults, while CIE during adulthood, but not adolescence, increased EtOH consumption relative to pre-CIE baseline. CIE produced a tolerance-like decrease in LORR sensitivity to EtOH challenge, irrespective of the age at which mice received CIE exposure. Mice exposed to CIE during adolescence, but not adulthood, required more sessions than AIR controls to reliably respond for food reward on a fixed-ratio (FR1), but not subsequent FR3, reinforcement schedule. On a progressive ratio reinforcement schedule, breakpoint responding was higher in the adolescent- than the adult-exposed mice, regardless of CIE. Finally, footshock-punishment markedly suppressed responding for reward in all groups. Conclusions Exposure to CIE during adolescence altered dendritic spine density and morphology in IL and BLA neurons, in parallel with a limited set of behavioral alterations. Together, these data add to growing evidence that key corticolimbic circuits are vulnerable to the effects of alcohol during adolescence, with lasting, potentially detrimental, consequences for behavior. PMID:28614590

Sex differences in methamphetamine seeking in rats: Impact of oxytocin

PubMed Central

Cox, Brittney M.; Young, Amy B.; See, Ronald E.; Reichel, Carmela M.

2013-01-01

Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1 mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1 mg/kg, IP) 30 min before a meth priming injection (1 mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The results suggest that oxytocin may have efficacy as a treatment of meth addiction in both sexes; however, females may show greater response to oxytocin treatment for the prevention of relapse. PMID:23764194

Scheduling reinforcement about once a day.

PubMed

Eckerman, D A

1999-04-01

A pigeon earned its daily food by pecking a key according to reinforcement schedules that produced food about once per day. Fixed-interval (FI), Fixed-time (FT), and various complex schedules were arranged to demonstrate the degree to which a scalloped pattern of responding remained. Pausing continued until about an hour before the reinforcer could be earned for FIs of 12, 24, and 48 h. Pausing was not as long for FIs of 18, 19, and 23 h. Pausing of about 24 h was seen for FI 36 h. FT 24 h produced continued responding but at a diminished frequency. The pattern of responding was strongly controlled by the schedule of reinforcement and seemed relatively independent of the cycle of human activity in the surrounding laboratory. Effects of added ratio contingencies and of signaling the availability of reinforcement in FT were also examined. Signaled FTs of 5 min-3 h produced more responding during the signal (autoshaping) than did FTs of 19 or 24 h.

FI schedules and persistence at gambling in the U.K. betting office.

PubMed Central

Dickerson, M G

1979-01-01

This study reports on the direct observations of customers in two U.K. betting offices gambling on horse and dog races. These observations revealed that bets were more frequently placed in the last minutes just prior to the start (the OFF), and that this was caused by high-frequency gamblers (customers who had eight or more bets in a session) consistently placing their bets in the last two minutes prior to the OFF. Low-frequency gamblers (three or fewer bets/session) avoided this time period placing their bets earlier, or after the OFF, i.e., on a later race. It was argued that the betting behavior of the "gamblers" could not be explained either in terms of "skillful betting" or solely in terms of variable ratio schedules but was more adequately accounted for in terms of an interval schedule. It was further suggested that time-based schedules might be of heuristic value in generally understanding persistence at gambling while losing. PMID:511799

A Pilot Study of Reasons and Risk Factors for "No-Shows" in a Pediatric Neurology Clinic.

PubMed

Guzek, Lindsay M; Fadel, William F; Golomb, Meredith R

2015-09-01

Missed clinic appointments lead to decreased patient access, worse patient outcomes, and increased healthcare costs. The goal of this pilot study was to identify reasons for and risk factors associated with missed pediatric neurology outpatient appointments ("no-shows"). This was a prospective cohort study of patients scheduled for 1 week of clinic. Data on patient clinical and demographic information were collected by record review; data on reasons for missed appointments were collected by phone interviews. Univariate and multivariate analyses were conducted using chi-square tests and multiple logistic regression to assess risk factors for missed appointments. Fifty-nine (25%) of 236 scheduled patients were no-shows. Scheduling conflicts (25.9%) and forgetting (20.4%) were the most common reasons for missed appointments. When controlling for confounding factors in the logistic regression, Medicaid (odds ratio 2.36), distance from clinic, and time since appointment was scheduled were associated with missed appointments. Further work in this area is needed. © The Author(s) 2014.

Comparison of job stress and obesity in nurses with favorable and unfavorable work schedules.

PubMed

Han, Kihye; Trinkoff, Alison M; Storr, Carla L; Geiger-Brown, Jeanne; Johnson, Karen L; Park, Sungae

2012-08-01

To compare obesity-related factors between female nurses with favorable work schedules (WSs) and unfavorable WSs. In a cross-sectional study, 1724 female nurses were stratified by WS (favorable vs unfavorable). For each schedule type, the odds of obesity were related to health behaviors, home demands, and job stress using logistic regression models. Among nurses with unfavorable WSs, healthy behaviors (exercise, sleep) were inversely associated with obesity, whereas for those with favorable WSs, obese nurses reported significantly more unhealthy behaviors (smoking, alcohol use; odds ratio [OR], 1.19; 95% confidence interval [CI], 1.02-1.38), more physical lifting of children/dependents (OR, 1.43; 95% CI, 1.06-1.93), having more nurse input into their jobs (OR, 1.21; 95% CI, 1.02-1.44), yet less boss support at work (OR, 0.83; 95% CI, 0.68-0.99). Considering impacts of WSs on obesity and potential obesity-related health outcomes, healthful scheduling should be provided to nurses.

Medicare Program; Revisions to Payment Policies Under the Physician Fee Schedule and Other Revisions to Part B for CY 2017; Medicare Advantage Bid Pricing Data Release; Medicare Advantage and Part D Medical Loss Ratio Data Release; Medicare Advantage Provider Network Requirements; Expansion of Medicare Diabetes Prevention Program Model; Medicare Shared Savings Program Requirements. Final rule.

PubMed

2016-11-15

This major final rule addresses changes to the physician fee schedule and other Medicare Part B payment policies, such as changes to the Value Modifier, to ensure that our payment systems are updated to reflect changes in medical practice and the relative value of services, as well as changes in the statute. This final rule also includes changes related to the Medicare Shared Savings Program, requirements for Medicare Advantage Provider Networks, and provides for the release of certain pricing data from Medicare Advantage bids and of data from medical loss ratio reports submitted by Medicare health and drug plans. In addition, this final rule expands the Medicare Diabetes Prevention Program model.

Hybrid powertrain controller

DOEpatents

Jankovic, Miroslava; Powell, Barry Kay

2000-12-26

A hybrid powertrain for a vehicle comprising a diesel engine and an electric motor in a parallel arrangement with a multiple ratio transmission located on the torque output side of the diesel engine, final drive gearing connecting drivably the output shaft of transmission to traction wheels of the vehicle, and an electric motor drivably coupled to the final drive gearing. A powertrain controller schedules fuel delivered to the diesel engine and effects a split of the total power available, a portion of the power being delivered by the diesel and the balance of the power being delivered by the motor. A shifting schedule for the multiple ratio transmission makes it possible for establishing a proportional relationship between accelerator pedal movement and torque desired at the wheels. The control strategy for the powertrain maintains drivability of the vehicle that resembles drivability of a conventional spark ignition vehicle engine powertrain while achieving improved fuel efficiency and low exhaust gas emissions.

Small dense low density lipoprotein-cholesterol and cholesterol ratios to predict arterial stiffness progression in normotensive subjects over a 5-year period.

PubMed

Li, Gang; Wu, Hui-Kun; Wu, Xiao-Wei; Cao, Zhe; Tu, Yuan-Chao; Ma, Yi; Wang, Wei-Qing; Cheng, Jian; Zhou, Zi-Hua

2018-02-12

Small dense low density lipoprotein-cholesterol (sdLDL-C), cholesterol ratios and carotid-femoral pulse wave velocity (cf-PWV) impart risk for all-cause morbidity and mortality independently of conventional cardiovascular disease (CVD) risk factors. This study was designed to identify feasible indicators for predicting arterial stiffness progression. We followed up 816 normotensive participants without diabetes or CVD for nearly 5.0 years. Cholesterol parameters, ratios and other clinical and laboratory data were collected at baseline. cf-PWV were measured at baseline and the end of follow-up. PWV progression subjects had higher levels of PWV parameters, sdLDL-C and TG/HDL-C ratio. sdLDL-C and TG/HDL-C were significantly correlated with all PWV parameters. Multiple regression models showed that sdLDL-C was closely associated with follow-up PWV (β = 0.222, p < 0.001) and △PWV (β = 0.275, p < 0.001). TG/HDL-C was only one cholesterol ratios that associated with all PWV parameters. sdLDL-C (OR = 2.070, 95%CI: 1.162 to 3.688, p = 0.014) and TG/HDL-C (OR = 1.355, 95%CI: 1.136 to 1.617, p = 0.001) could significantly determine the progression of PWV after correction for covariates. High sd-LDL-C quantiles subjects were more likely to develop arterial stiffness progression than low quantiles (Tertiles 3 vs Tertiles1, RR = 2.867, 95%CI: 1.106 to 7.434, p = 0.03). We founded that sdLDL-C and TG/HDL-C ratio can independently predict arterial stiffness progression in normotensive subjects, and high level sdLDL-C and TG/HDL-C ratio were associated with a higher risk of arterial stiffness.

Fluvoxamine effects on concurrent ethanol- and food-maintained behaviors

PubMed Central

Ginsburg, Brett C.; Lamb, R.J.

2011-01-01

In previous studies, the selective serotonin reuptake inhibitor fluvoxamine preferentially reduced responding for ethanol compared with responding for food under conditions in which each was available alone in separate groups or in the same subjects under a multiple schedule in which baseline response rates were matched. The impact of providing concurrent access to food on pharmacological effects on ethanol self-administration remains largely unexplored. In this study, acute doses of fluvoxamine (3.0-17.8 mg/kg) were administered 30-min before the experimental session to Lewis rats responding under a concurrent fixed-ratio, fixed-ratio schedule of ethanol and food presentation. Ratios for food were adjusted for each subject to provide matched rates of food and ethanol reinforcement across the 30-min session. Although the number of ethanol and food deliveries did not significantly differ under baseline conditions, response rates did differ. Following fluvoxamine administration, responding for food was decreased more than responding for ethanol. This differential effect did not appear to be related to response rate or fixed-ratio size. Thus, the selectivity of fluvoxamine on ethanol- versus food-maintained responding depends upon the context in which the behavior occurs. Such results may help explain inconsistencies between preclinical results and those in humans, and could provide insight into the behavioral determinants of pharmacological effects on ethanol self-administration. PMID:17115876

Advanced construction management for lunar base construction - Surface operations planner

NASA Technical Reports Server (NTRS)

Kehoe, Robert P.

1992-01-01

The study proposes a conceptual solution and lays the framework for developing a new, sophisticated and intelligent tool for a lunar base construction crew to use. This concept integrates expert systems for critical decision making, virtual reality for training, logistics and laydown optimization, automated productivity measurements, and an advanced scheduling tool to form a unique new planning tool. The concept features extensive use of computers and expert systems software to support the actual work, while allowing the crew to control the project from the lunar surface. Consideration is given to a logistics data base, laydown area management, flexible critical progress scheduler, video simulation of assembly tasks, and assembly information and tracking documentation.

Report of the Cost Assessment and Validation Task Force on the International Space Station

NASA Technical Reports Server (NTRS)

1998-01-01

The Cost Assessment and Validation (CAV) Task Force was established for independent review and assessment of cost, schedule and partnership performance on the International Space Station (ISS) Program. The CAV Task Force has made the following key findings: The International Space Station Program has made notable and reasonable progress over the past four years in defining and executing a very challenging and technically complex effort. The Program size, complexity, and ambitious schedule goals were beyond that which could be reasonably achieved within the $2.1 billion annual cap or $17.4 billion total cap. A number of critical risk elements are likely to have an adverse impact on the International Space Station cost and schedule. The schedule uncertainty associated with Russian implementation of joint Partnership agreements is the major threat to the ISS Program. The Fiscal Year (FY) 1999 budget submission to Congress is not adequate to execute the baseline ISS Program, cover normal program growth, and address the known critical risks. Additional annual funding of between $130 million and $250 million will be required. Completion of ISS assembly is likely to be delayed from one to three years beyond December 2003.

Cost Assessment and Validation Task Force on the International Space Station

NASA Technical Reports Server (NTRS)

1998-01-01

The Cost Assessment and Validation (CAV) Task Force was established for independent review and assessment of cost, schedule and partnership performance on the International Space Station (ISS) Program. The CAV Task Force has made the following key findings: The International Space Station Program has made notable and reasonable progress over the past four years in defining and executing a very challenging and technically complex effort; The Program, size, complexity, and ambitious schedule goals were beyond that which could be reasonably achieved within the $2.1 billion annual cap or $17.4 billion total cap; A number of critical risk elements are likely to have an adverse impact on the International Space Station cost and schedule; The schedule uncertainty associated with Russian implementation of joint Partnership agreements is the major threat to the ISS Program; The Fiscal Year (FY) 1999 budget submission to Congress is not adequate to execute the baseline ISS Program, cover normal program, growth, and address the known critical risks. Additional annual funding of between $130 million and $250 million will be required; and Completion of ISS assembly is likely to be delayed from, one to three years beyond December 2003.

Quantifying Social Motivation in Mice Using Operant Conditioning.

PubMed

Martin, Loren; Iceberg, Erica

2015-08-08

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.

Addiction-like Synaptic Impairments in Diet-Induced Obesity.

PubMed

Brown, Robyn Mary; Kupchik, Yonatan Michael; Spencer, Sade; Garcia-Keller, Constanza; Spanswick, David C; Lawrence, Andrew John; Simonds, Stephanie Elise; Schwartz, Danielle Joy; Jordan, Kelsey Ann; Jhou, Thomas Clayton; Kalivas, Peter William

2017-05-01

There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction. Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate currents and the ability to exhibit long-term depression. We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable. Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

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.

Modeling Tumor Clonal Evolution for Drug Combinations Design

PubMed Central

Zhao, Boyang; Hemann, Michael T.; Lauffenburger, Douglas A.

2016-01-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs. PMID:28435907

Defense Contracting: Key Data Not Routinely Used in Progress Payment Reviews

DTIC Science & Technology

1992-01-14

the amount of pay- By .ments based on the fair value of undelivered work. Contractors may Distibtion ] submit requests for progress payments monthly and...exceed the Federal Acquisition Regulation limitations. These checks are based on contractor data and include the fair value and the loss ratio tests. The... fair value test is intended to ensure that progress payments for work in process do not exceed the value of that work. The loss ratio test is intended

The Role of Personal Best (PB) Goals in the Achievement and Behavioral Engagement of Students with ADHD and Students without ADHD

ERIC Educational Resources Information Center

Martin, Andrew J.

2012-01-01

In the context of competitive classroom settings and relativistic assessment schedules, some groups of students may particularly benefit from an emphasis on personal progress and personal growth approaches to their academic development. Building on recent promising results from general samples of high school students (undifferentiated by…

Adapting Institutions to the Adult Learner: Experiments in Progress. Current Issues in Higher Education, 1978 National Conference Series.

ERIC Educational Resources Information Center

Loring, Rosalind K.; And Others

The four conference papers presented here examine specific strategies and programs by which colleges and universities can design and adapt programs for adult students. In "Strategies of Adaptation" Rosalind K. Loring notes six major types of adaptation to which traditional, four-year schools have resorted (flexible schedules, simulated…

Graduate Program Scheduling Gains Flexibility through Container Courses: A Case Study

ERIC Educational Resources Information Center

Rose, Richard

2011-01-01

Online course delivery makes possible one innovation which can provide each student with greater program flexibility as well as some personal ownership of the direction and pace of his degree progress. This concept can be called the "container course." A container course is the offering of more than one course simultaneously under a single course…

40 CFR 62.14560 - How do I comply with the increment of progress for submittal of a control plan?

Code of Federal Regulations, 2010 CFR

2010-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and... requirements of this subpart. (2) The type(s) of waste to be burned. (3) The maximum design waste burning...

40 CFR 62.14560 - How do I comply with the increment of progress for submittal of a control plan?

Code of Federal Regulations, 2011 CFR

2011-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and... requirements of this subpart. (2) The type(s) of waste to be burned. (3) The maximum design waste burning...

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

Kartsaklis, Christos; Civario, G

This paper discusses an ongoing progress regarding the development of a Java-based library for rapid kernel prototyping in NVIDIA PTX and PTX instruction scheduling. It is aimed at developers seeking total control of emitted PTX, highly parametric emission of, and tunable instruction reordering. It is primarily used for code development at ICHEC but is also hoped that NVIDIA GPU community will also find it beneficial.

40 CFR Table 3 to Subpart Ggg of... - Generic Compliance Schedule and Increments of Progress a

Code of Federal Regulations, 2013 CFR

2013-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to May 30, 1991 and Have Not Been Modified or Reconstructed Since May 30, 1991... rate report showing NMOC emissions ≥ 50 Mg/yr.b Increment 3—Begin on-site construction 24 months after...

40 CFR Table 3 to Subpart Ggg of... - Generic Compliance Schedule and Increments of Progress a

Code of Federal Regulations, 2011 CFR

2011-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to May 30, 1991 and Have Not Been Modified or Reconstructed Since May 30, 1991... rate report showing NMOC emissions ≥ 50 Mg/yr.b Increment 3—Begin on-site construction 24 months after...

40 CFR 62.14560 - How do I comply with the increment of progress for submittal of a control plan?

Code of Federal Regulations, 2013 CFR

2013-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and... requirements of this subpart. (2) The type(s) of waste to be burned. (3) The maximum design waste burning...

40 CFR 62.14570 - What must I do if I plan to permanently close my CISWI unit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and Increments of Progress § 62... evaluation of the option to transport your waste offsite to a commercial or municipal waste treatment and/or...

Control of Indian Education in BIA Schools. A Progress Report, September 1974. Research and Evaluation Report Series No. 29.02.

ERIC Educational Resources Information Center

Bureau of Indian Affairs (Dept. of Interior), Albuquerque, NM.

Presenting a brief narrative relative to Bureau of Indian Affairs Area Offices and implementation of the Presidential/Secretarial Objective, this September 1974 monthly summary identifies Area Office problems and accomplishments. Specifically, this report presents: area operating plans; schedules of implementation; definition of the term,…

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

The consummatory and motivational behaviors for natural rewards following long-term withdrawal from morphine: no anhedonia but persistent maladaptive behaviors for high-value rewards.

PubMed

Li, Yingying; Zheng, Xigeng; Xu, Na; Zhang, Yue; Liu, Zhengkui; Bai, Yunjing

2017-04-01

The negative affective state, e.g., anhedonia, emerges after abstinence from abused drugs may be linked to the motivational processes of drug craving and relapse. Although anhedonia diminishes over time with drug abstinence, it is not yet rather explicit whether anhedonia exists or not following protracted withdrawal. The behavioral responses to natural rewards were examined after 2 to 3 weeks withdrawal from morphine. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. The consummatory and motivational behaviors for three natural rewards (sucrose solutions 4, 15, and 60%, social stimulus: male rat, and sexual stimulus: estrous female rat) were examined under varied testing conditions. The morphine-withdrawn rats significantly increased their intake of 15% sucrose solution during the 1-h consumption test and their operant responding for 15% sucrose solution under a progressive ratio (PR) schedule of reinforcement. When obtaining a reinforcer was associated with a 0.5 mA foot shock under a PR-punishment schedule, the morphine-withdrawn rats showed a higher performance for 60% sucrose solution. Meanwhile, the morphine-withdrawn rats displayed a higher motivation to sexual stimulus during the free-approach test and more approaching behaviors towards sexual stimulus in a conflict-based approach test (concurrent presence of reward and aversive stimulus). No anhedonia-like behavior but sensitized behaviors for natural rewards were found after long-term morphine withdrawal. Notably, the morphine-withdrawn rats displayed persistent motivated behaviors for high-value rewards (60% sucrose and sexual stimulus) in the conflict tests suggesting impairments in inhibitory control in morphine-treated rats.

Bupropion and naltrexone combination alters high fructose corn syrup self-administration and gene expression in rats.

PubMed

Levy, AnneMarie; Daniels, Stephen; Hudson, Roger; Horman, Thomas; Flynn, Amanda; Zhou, Yan; Leri, Francesco

2018-06-01

Contrave ® is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX). To further explore the psychopharmacology of this drug combination, male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing: 40 mg/kg/day BUP, 4 mg/kg/day NTX, or 40 + 4 mg/kg/day BUP and NTX (BN). During 12 days of exposure, the animals were tested on operant intraoral self-administration (IOSA) of high fructose corn syrup (HFCS) on continuous (FR1) and progressive ratio (PR) schedules, on home cage drinking of HFCS, and on HFCS taste reactivity. Locomotion activity was also assessed. At the conclusion of the study, mRNA expression of genes involved in reward processing, appetite and mood were quantified. It was found that BN produced effects that could largely be ascribed to either BUP or NTX independently. More specifically, BN-induced reductions of HFCS IOSA on a FR1 schedule and home cage drinking, as well as alterations of MOR and POMC mRNA in the nucleus accumbens core and hypothalamus respectively, were attributable to NTX; while alterations of hippocampal BDNF mRNA was attributable to BUP. But, there was also some evidence of drug synergy: only BN caused persistent reductions of HFCS IOSA and drinking; BN produced the least gain of body weight; and only BN-treated rats displayed altered D2R mRNA in the caudate-putamen. Taken together, these observations support the use of BUP + NTX as a mean to alter consumption of sugars and reducing their impact on brain systems involved in reward, appetite and mood. Copyright © 2018 Elsevier Ltd. All rights reserved.

Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats.

PubMed

Mark, Gregory P; Kinney, Anthony E; Grubb, Michele C; Zhu, Xiaoman; Finn, Deborah A; Mader, Sarah L; Berger, S Paul; Bechtholt, Anita J

2006-12-06

Mesencephalic dopamine neurons form synapses with acetylcholine (ACh)-containing interneurons in the nucleus accumbens (NAcc). Although their involvement in drug reward has not been systematically investigated, these large aspiny interneurons may serve an important integrative function. We previously found that repeated activation of nicotinic cholinergic receptors enhanced cocaine intake in rats but the role of muscarinic receptors in drug reward is less clear. Here we examined the impact of local changes in muscarinic receptor activation within the NAcc on cocaine and food self-administration in rats trained on a progressive ratio (PR) schedule of reinforcement. Animals were given a minimum of 9 continuous days of drug access before testing in order to establish a stable breaking point (BP) for intravenous cocaine infusions (0.75 mg/kg/infusion). Rats in the food group acquired stable responding on the PR schedule within 7 days. On the test day, rats were bilaterally infused in the NAcc with the muscarinic receptor agonist oxotremorine methiodide (OXO: 0.1, 0.3 or 1 nmol/side), OXO plus the M(1) selective antagonist pirenzepine (PIRENZ; 0.3 nmol/side) or aCSF 15 min before cocaine or food access. OXO dose dependently reduced BP values for cocaine reinforcement (-17%, -44% [p<0.05] and -91% [p<0.0001] for 0.1, 0.3 and 1.0 nmol, respectively) and these reductions dissipated by the following session. Pretreatment with PIRENZ blocked the BP-reducing effect of 0.3 nmol OXO. Notably, OXO (0.1, 0.3 and 1.0 nmol/side) injection in the NAcc did not affect BP for food reward. The results suggest that muscarinic ACh receptors in the caudomedial NAcc may play a role in mediating the behavior reinforcing effects of cocaine.