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Lever
Terms modified by Lever Selected AbstractsThe CEFR, a Lever for the Improvement of Language Professionals in EuropeMODERN LANGUAGE JOURNAL, Issue 4 2007NEUS FIGUERAS No abstract is available for this article. [source] Design of an MR-compatible piezoelectric actuator for MR elastographyCONCEPTS IN MAGNETIC RESONANCE, Issue 4 2002Kai Uffmann Abstract Magnetic Resonance (MR) elastography is a method for measuring tissue elasticity via phase images acquired with an MR scanner. The propagation of periodic mechanical waves through the tissue can be captured by means of a modified phase contrast sequence. These waves are generated with a mechanical oscillator (actuator) and coupled into the tissue through the skin. The actuator must be capable of generating a sinusoidal excitation with excellent phase and amplitude stability, while not disturbing the MR imaging process. In this work, an actuator based on a piezoelectric principle was developed. Based on the imaging evaluation of several material samples, the housing for the piezoelectric ceramic was constructed of aluminum. Smaller parts of the housing were manufactured from brass and titanium to fulfill the mechanical constraints. A lever was used to transfer the oscillation generated by the piezoelectric ceramic to the point of excitation. The lever amplifies the piezoelectric motion, allowing for a more compact design. Three different lever designs were characterized by an acceleration sensor both outside and inside the magnet. It was shown that the rigidity of the lever, as determined by its material and form, was decisive in determining the resonant frequency of the system and therefore the maximum practical frequency of operation. It was also shown that the motion of the oscillator is unaffected by the electromagnetic fields of the MR imager. The final design can be placed directly in the magnet bore within a few centimeters of the tissue volume to be imaged without generating significant artifacts. An amplitude range of 0,1 mm in the frequency range from 0 to over 300 Hz was achieved, sufficient for performing most MR elastography applications. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 239,254, 2002 [source] Foster mother care but not prenatal morphine exposure enhances cocaine self-administration in young adult male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2007I. Vathy Abstract The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11,18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 463-473, 2007. [source] Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Jeremy J. Day Abstract Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS,, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS, were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed ,phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS, onset, while the inhibitory subpopulation showed no change in firing during the CS, period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans. [source] Stimulation of D1-like or D2 dopamine receptors in the shell, but not the core, of the nucleus accumbens reinstates cocaine-seeking behaviour in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Heath D. Schmidt Abstract Although increases in dopamine transmission in the brain are clearly involved in the reinstatement of cocaine seeking, the role of nucleus accumbens dopamine in cocaine priming-induced reinstatement remains controversial. The goal of these experiments was to evaluate the relative contributions of D1-like and D2-like dopamine receptors in the nucleus accumbens core and shell in the reinstatement of cocaine-seeking behaviour. Initially, rats were trained to press a lever for cocaine (0.25 mg, i.v.) using a fixed-ratio 5 (FR5) schedule of reinforcement. Responding was then extinguished by substituting saline for cocaine. During the reinstatement phase, subtype-specific dopamine receptor agonists were microinjected into the nucleus accumbens core or medial shell in order to assess their ability to induce cocaine seeking. Administration of the D1/D5 dopamine receptor agonist SKF-81297 (1.0 µg) into the nucleus accumbens shell, but not core, reinstated drug-seeking behaviour. Similarly, microinjection of quinpirole (3.0 µg), a D2/D3 dopamine receptor agonist, into the nucleus accumbens shell and not core reinstated drug-seeking behaviour. In contrast, administration of the D3- or D4-preferring dopamine receptor agonists PD 128,907 (1.5 and 3.0 µg) and PD 168,077 (0.3 and 3.0 µg), respectively, did not promote reinstatement when administered into either the core or the shell. Taken together, these results indicate that activation of D1/D5 or D2 dopamine receptors, in the limbic shell subregion of the nucleus accumbens but not the basal ganglia-orientated accumbens core, promotes the reinstatement of cocaine-seeking behaviour. [source] Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2005Helen H. J. Pothuizen Abstract The nucleus accumbens can be subdivided into at least two anatomically distinct subregions: a dorsolateral ,core' and a ventromedial ,shell', and this distinction may extend to a functional dissociation. Here, we contrasted the effects of selective excitotoxic core and medial shell lesions on impulsive-choice behaviour using a delayed reward choice paradigm and a differential reward for low rates of responding (DRL) test, against a form of salience learning known as latent inhibition (LI). Core lesions led to enhanced impulsive choices as evidenced by a more pronounced shift from choosing a continuously reinforced lever to a partially reinforced lever, when a delay between lever press and reward delivery was imposed selectively on the former. The core lesions also impaired performance on a DRL task that required withholding the response for a fixed period of time in order to earn a reward. Medial shell lesions had no effect on these two tasks, but abolished the LI effect, as revealed by the failure of stimulus pre-exposure to retard subsequent conditioning to that stimulus in an active avoidance procedure in the lesioned animals. As expected, selective core lesions spared LI. The double dissociations demonstrated here support a functional segregation between nucleus accumbens core and shell, and add weight to the hypothesis that the core, but not the shell, subregion of the nucleus accumbens is preferentially involved in the control of choice behaviour under delayed reinforcement conditions and in the inhibitory control of goal-directed behaviour. [source] Blockade of NMDA receptors in the dorsomedial striatum prevents action,outcome learning in instrumental conditioningEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Henry H. Yin Abstract Although there is consensus that instrumental conditioning depends on the encoding of action,outcome associations, it is not known where this learning process is localized in the brain. Recent research suggests that the posterior dorsomedial striatum (pDMS) may be the critical locus of these associations. We tested this hypothesis by examining the contribution of N -methyl- d -aspartate receptors (NMDARs) in the pDMS to action,outcome learning. Rats with bilateral cannulae in the pDMS were first trained to perform two actions (left and right lever presses), for sucrose solution. After the pre-training phase, they were given an infusion of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (APV, 1 mg/mL) or artificial cerebral spinal fluid (ACSF) before a 30-min session in which pressing one lever delivered food pellets and pressing the other delivered fruit punch. Learning during this session was tested the next day by sating the animals on either the pellets or fruit punch before assessing their performance on the two levers in extinction. The ACSF group selectively reduced responding on the lever that, in training, had earned the now devalued outcome, whereas the APV group did not. Experiment 2 replicated the effect of APV during the critical training session but found no effect of APV given after acquisition and before test. Furthermore, Experiment 3 showed that the effect of APV on instrumental learning was restricted to the pDMS; infusion into the dorsolateral striatum did not prevent learning. These experiments provide the first direct evidence that, in instrumental conditioning, NMDARs in the dorsomedial striatum are involved in encoding action,outcome associations. [source] Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcoholEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001D. N. Stephens Abstract Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS,). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS, presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity. [source] A Comparison of Syndicated Loan Pricing at Investment and Commercial BanksFINANCIAL MANAGEMENT, Issue 4 2006Maretno Harjoto We reject the hypothesis that investment and commercial banks have identical loan-pricing policies. We find that compared to commercial banks, investment banks lend to less profitable, more lever aged firms, price riskier classes of term loans more generously, and offer relatively longer-term credits, usually with term, not commitment contracts. Investment banks typically establish higher credit spreads, although the premium declines when a commercial bank joins as syndicate co-arranger. Investment banks also price riskier classes of term loans more generously to borrowers than do commercial banks. Commercial-bank funding advantages do not appear to be a source of the pricing differences. [source] The Financialization of Urban RedevelopmentGEOGRAPHY COMPASS (ELECTRONIC), Issue 8 2010Ted Rutland Spurred by the conviction that not only financial capital but also changes in finance and changes in its relations with non-financial activities have immense and complicated consequences for ongoing processes of urban redevelopment, this article puts the presently separate financialization and urban redevelopment literatures in conversation. The article begins with a review of the financialization literature, outlining and evaluating four different approaches to the topic and seeking to consider what, if anything, they might have to offer to an area of inquiry that has long considered finance to be a central concern. The second section examines how financial capital has been analyzed in the urban redevelopment literature since the pioneering work of David Harvey in the 1970s. The final section examines how financialization has played out in the medium-sized port city of Halifax, Nova Scotia. Drawing on interviews with financiers and property developments, as well as secondary research materials, the study describes how a recent urban design process in Halifax enlisted urban images and ideas to rewrite development regulations, eliminate popular political involvement in the development approvals process, and lever open the downtown landscape to the whims of worldwide financial markets. The essay concludes that studies of urban redevelopment would indeed gain something by engaging with the financialization literature, so long as the former continue to attend not just to financial capital but also to the material and ideological mechanisms through which property is continually reproduced as a financial asset. [source] Microsoft implements readiness as a strategic forceGLOBAL BUSINESS AND ORGANIZATIONAL EXCELLENCE, Issue 5 2008Dustin Grosse The success of Microsoft's global product launches and solutions for a huge, diverse customer base hinges upon readiness in the field. To make workforce readiness a strategic lever, field training is aligned with business objectives, the role, and the task, and delivered to highly mobile communities at the right time, in the right place, and on the right device. The Sales, Marketing, and Services Group Readiness group builds its training offerings on three pillars of content development: an operating model that aligns priorities across businesses, regions, and customer segments; strong partnerships with business groups and subject matter experts; and metrics for assessing results. © 2008 Wiley Periodicals, Inc. [source] Joaquin Maria Albarran Y Dominguez: Microbiologist, histologist, and urologist,a lifetime from orphan in Cuba to Nobel nomineeINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2006ROWAN G CASEY Abstract, Joaquin Albarran was an extraordinary late 19th century urologist. His early career was in the field of microbiology and histopathology in Paris at a time of great medical developments and innovations. His later contributions to urology included the Albarran lever, Albarrans sign, Albarran,Ormond syndrome and seminal works on testicular and renal tumors. He also wrote treatizes on the pathophysiology of acute urinary retention, nephritis and calculus ureteric obstruction. He died at the young age of 52 from the effects of tuberculosis and in this same year was nominated for the Nobel prize in medicine. [source] Implementing Quality Improvement Strategies in Brazilian Hospitals: A Model for Guidance of the Initial Stage of ImplementationINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 1 2002T. Diana. Since the early 1990s, Brazilian hospitals have increasingly adopted quality improvement strategies with a view to attending more demanding customers and to the higher performance standards required by the Ministry of Health. However, most efforts have not been successful, partly because hospitals lack adequate methodologies, namely implementation models. This paper presents a two-stage model to help Brazilian hospitals deploy such strategies more effectively. It focusses on the development and pilot-test of the model for the buy-in stage. Distinctive features of the model were found to be critical for results at this stage: 1) An ad hoc structure to manage the changes involved; 2) A performance measurement system to lever and monitor its implementation, while aligning the actions taken with strategy objectives. Other aspects found to be crucial for success were creative application of model elements to the culture of the hospital and to Brazilian contingencies. [source] Ethanol Is Self-Administered Into the Nucleus Accumbens Shell, But Not the Core: Evidence of Genetic SensitivityALCOHOLISM, Issue 12 2009Eric A. Engleman Background:, A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the posterior ventral tegmental area at lower concentrations than Wistar rats. The present study was undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH reinforcement, and a relationship between genetic selection for high alcohol preference and sensitivity of the Acb to the reinforcing effects of EtOH. Methods:, Adult P and Wistar rats were assigned to groups that self-infused 0 to 300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into 2-lever (active and inactive) operant chambers and given EtOH for the first 4 sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate. Results:, Alcohol-preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for EtOH, and reinstated responding in session 7 when EtOH was restored. EtOH was not self-infused into the AcbC by P or Wistar rats. Conclusions:, The present results indicate that the AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh of P rats is more sensitive to the reinforcing effects of EtOH. [source] Reduction of Alcohol's Reinforcing and Motivational Properties by the Positive Allosteric Modulator of the GABAB Receptor, BHF177, in Alcohol-Preferring RatsALCOHOLISM, Issue 10 2009Paola Maccioni Background:, The positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, have been found to reduce alcohol self-administration in alcohol-preferring rats. The present study was designed to assess the effect of the newly synthesized positive allosteric modulator of the GABAB receptor, BHF177, on alcohol's reinforcing and motivational properties in selectively bred Sardinian alcohol-preferring (sP) rats. Methods:, sP rats were initially trained to respond on a lever [on a fixed ratio 4 (FR4) schedule of reinforcement] to orally self-administer alcohol (15%, v/v) or sucrose (1 to 3%, w/v) in daily 30-minute sessions. Once responding reached stable levels, rats were allocated to 2 different experiments: in the first experiment, rats were exposed to sessions with the FR4 schedule of reinforcement; in the second experiment, rats were exposed to sessions with a conventional progressive ratio (PR) schedule of reinforcement. In both experiments, the effect of BHF177 (0, 12.5, 25, and 50 mg/kg; i.g.) on responding for alcohol and sucrose (FR experiment: 1%, w/v; PR experiment: 3%, w/v) was determined. Results:, In the FR experiment, pretreatment with 25 and 50 mg/kg BHF177 produced a 30 and 45% reduction, respectively, in responding for alcohol. In the PR experiment, pretreatment with 50 mg/kg BHF177 resulted in a 35% reduction in breakpoint for alcohol (defined as the lowest response requirement not achieved by each rat and used as index of the motivational strength of alcohol). In both experiments, the effect of BHF177 on alcohol self-administration was specific, since responding for sucrose was unaltered by BHF177 pretreatment. Conclusions:, The present results extend to BHF177 the capacity of the 2 previously tested positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, to specifically suppress alcohol's reinforcing and motivational properties in alcohol-preferring rats. [source] The Alcohol Deprivation Effect in C57BL/6J Mice is Observed Using Operant Self-Administration Procedures and is Modulated by CRF-1 Receptor SignalingALCOHOLISM, Issue 1 2009Dennis R. Sparta Background:, The alcohol deprivation effect (ADE) is characterized by transient excessive alcohol consumption upon reinstatement of ethanol following a period of ethanol deprivation. While this phenomenon has been observed in rats using both bottle drinking (consummatory behavior) and operant self-administration (consummatory and appetitive "ethanol-seeking" behavior) procedures, ADE studies in mice have primarily relied on bottle drinking measures. Furthermore, the neurochemical pathways that modulate the ADE are not well understood. Therefore, we determined whether the ADE can be observed in C57BL/6J mice using operant self-administration procedures and if expression of the ADE is modulated by the corticotropin releasing factor-1 (CRF-1) receptor. Methods:, C57BL/6J mice were trained in a 2-hour operant self-administration paradigm to lever press for 10% ethanol or water on separate response keys. Between operant sessions, mice had access to ethanol in their homecage. Once stable responding occurred, mice were deprived of ethanol for 4 days and were then retested with ethanol in the operant paradigm for 3 consecutive days. Next, to assess the role of the CRF-1 receptor, mice were given intraperitoneal (i.p.) injection (0, 10, or 20 mg/kg) of the CRF-1 receptor antagonist CP-154,526 30 minutes before ADE testing. Additional experiments assessed (i) ADE responding in which the alternate response lever was inactive, (ii) the effects of CP-154,526 on self-administration of a 1% sucrose solution following 4 days of deprivation, and (iii) ADE responding in which mice did not received i.p. injections throughout the experiment. Results:, Mice exhibited a significant increase in postdeprivation lever responding for ethanol with either a water reinforced or inactive alternate lever. Interestingly, i.p. injection of a 10 mg/kg dose of CP-154,526 protected against the ADE while not affecting lever responding for a sucrose solution. Finally, baseline and deprivation-induced increases of ethanol reinforced lever responding were greater in mice not given i.p. injections. Conclusions:, The ADE in C57BL/6J mice can be modeled using the operant self-administration paradigm and increased ethanol self-administration associated with the ADE is modulated by CRF-1 receptor signaling. [source] Zolpidem Generalization and Antagonism in Male and Female Cynomolgus Monkeys Trained to Discriminate 1.0 or 2.0 g,/,kg EthanolALCOHOLISM, Issue 7 2008Christa M. Helms Background:, The subtypes of , -aminobutyric acid (GABA)A receptors mediating the discriminative stimulus effects of ethanol in nonhuman primates are not completely identified. The GABAA receptor positive modulator zolpidem has high, intermediate, and low activity at receptors containing ,1, ,2/3, and ,5 subunits, respectively, and partially generalizes from ethanol in several species. The partial inverse agonist Ro15-4513 has the greatest affinity for ,4/6 -containing receptors, higher affinity for ,5 - and lower, but equal, affinity for ,1 - and ,2/3 -, containing GABAA receptors, and antagonizes the discriminative stimulus effects of ethanol. Methods:, This study assessed Ro15-4513 antagonism of the generalization of zolpidem from ethanol in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 g/kg (n = 10) or 2.0 g/kg (n = 7) ethanol (i.g.) from water with a 30-minute pretreatment interval. Results:, Zolpidem (0.017 to 5.6 mg/kg, i.m.) completely generalized from ethanol (,80% of total session responses on the ethanol-appropriate lever) for 6/7 monkeys trained to discriminate 2.0 g/kg and 4/10 monkeys trained to discriminate 1.0 g/kg ethanol. Zolpidem partially generalized from 1.0 or 2.0 g/kg ethanol in 6/7 remaining monkeys. Ro15-4513 (0.003 to 0.30 mg/kg, i.m., 5-minute pretreatment) shifted the zolpidem dose,response curve to the right in all monkeys showing generalization. Analysis of apparent pKB from antagonism tests suggested that the discriminative stimulus effects of ethanol common with zolpidem are mediated by low-affinity Ro15-4513 binding sites. Main effects of sex and training dose indicated greater potency of Ro15-4513 in males and in monkeys trained to discriminate 1.0 g/kg ethanol. Conclusions:, Ethanol and zolpidem share similar discriminative stimulus effects most likely through GABAA receptors that contain ,1 subunits, however, antagonism by Ro15-4513 of zolpidem generalization from the lower training dose of ethanol (1.0 g/kg) may involve additional zolpidem-sensitive GABAA receptor subtypes (e.g., ,2/3 and ,5). [source] Reinstatement of Ethanol-Seeking Behavior Following Intravenous Self-Administration in Wistar RatsALCOHOLISM, Issue 9 2007Justin T. Gass Background: In animal models of alcoholism, subjects are traditionally trained to self-administer ethanol via the oral route. However, ethanol is also self-administered intravenously (IV), a paradigm which offers several advantages over oral self-administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration. Methods: Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self-administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever-pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light-tone complex stimulus. After stabilization of response patterns, IV self-administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol-seeking behavior: presentation of ethanol-associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle. Results: During the maintenance phase of self-administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol-seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever. Conclusions: Ethanol serves as a reinforcer when self-administered IV, and following extinction, ethanol-seeking behavior can be reinstated by ethanol-associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration may be a novel animal model of relapse. [source] Increased Consumption but Not Operant Self-administration of Ethanol in Mice Lacking the RII, Subunit of Protein Kinase AALCOHOLISM, Issue 5 2006Frank M. Ferraro III Background: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RII, subunit of PKA (RII,,/,) voluntarily consume more ethanol than wild-type controls (RII,+/+) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RII,,/, mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. Methods: RII,,/, (n=8) and RII,+/+ (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RII,+/+ and RII,,/, mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RII,+/+ and RII,,/, mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. Results: The RII,,/, mice displayed lower operant responding for ethanol and food reinforcement compared with RII,+/+ controls. However, this effect was driven by a significant increase in lever responses made by female RII,+/+ mice. When the excessive lever responses of the female RII,+/+ mice are accounted for, the RII,,/, mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RII,,/, mice of both sexes consumed more ethanol solution compared with RII,+/+ mice during 2-bottle testing. Conclusions: Increased ingestion of ethanol by RII,,/, mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RII, subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RII,,/, mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior. [source] Operant Self-Administration of Ethanol in Sardinian Alcohol-Preferring RatsALCOHOLISM, Issue 11 2002Giovanni Vacca Background "Work" for ethanol, that is, the ability of a laboratory animal to press a lever to gain access to ethanol, has been proposed as (a) a requirement for definition of an animal model of alcoholism and (b) a measure of ethanol-reinforcing properties. The present study evaluated oral self-administration of ethanol under an operant (lever pressing) procedure in selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. Methods Rats from both lines were initiated to self-administer 10% ethanol, on a fixed ratio 1 schedule and in daily 30 min sessions, by using the Samson sucrose fading procedure. Subsequently, rats were exposed to increasing concentrations of ethanol up to 30% on a fixed ratio 4 schedule. Finally, the extinction responding for ethanol, defined as the maximal number of lever responses reached by each rat in the absence of ethanol reinforcement, was determined. Results The results indicated that sP rats acquired and maintained lever pressing for ethanol, self-administering mean amounts of ethanol in the range of 0.6 to 1.1 g/kg/session, which gave rise to mean blood ethanol levels in the 30 to 45 mg% range. Extinction responding for ethanol in sP rats averaged 73. In contrast, once sucrose was faded out, sNP rats displayed minimal levels of responding for ethanol, and extinction responding averaged 6. Conclusions The results of the present study extend to the sP/sNP rat lines the finding that ethanol can be established as a reinforcer in selectively bred alcohol-preferring rats, whereas it has modest, if any, reinforcing properties in alcohol-nonpreferring rats. [source] Long-Lasting Resistance to Extinction of Response Reinstatement Induced by Ethanol-Related Stimuli: Role of Genetic Ethanol PreferenceALCOHOLISM, Issue 10 2001Roberto Ciccocioppo Background: The conditioning of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with alcoholism. To study the significance of such learning factors in the addictive potential of ethanol, this experiment was designed (1) to characterize the effects of stimuli associated with alcohol availability on the reinstatement of responding at a previously ethanol-paired lever in rats with genetically determined ethanol preference versus nonpreference and (2) to examine the persistence of the motivating effects of these stimuli over time. Methods: Male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were trained to operantly self-administer ethanol (10% w/v) or water on a fixed-ratio 1 schedule in a 30-min daily session. Ethanol and water sessions were scheduled in random sequence across training days. Ethanol availability was signaled by an olfactory discriminative stimulus (banana extract, S+), and each lever press was paired with brief presentation of the conditioning chamber's house light (CS+). The discriminative stimulus signaling water availability (i.e., nonreward) consisted of anise odor (S,), and lever-responses during water sessions were paired with a brief white noise generation (CS,). The rats then were placed on extinction conditions during which ethanol and water, as well as the corresponding stimuli, were withheld. The effects of noncontingent exposure to the S+ versus S, paired with response-contingent presentation of the CS+ versus CS, on responding at the previously active lever were then determined in 30-min reinstatement sessions. To study the resistance to extinction of the effects of the ethanol-associated stimuli, additional tests were conducted at 3-day intervals for a total of 50 days. Results: The number of ethanol-reinforced responses during self-administration training was significantly greater in P than in NP rats (p < 0.01). After extinction, a significant recovery of responding was observed in both groups of rats under the stimulus conditions associated with ethanol (S+/CS+) but not those associated with water (S,/CS,). However, the response reinstatement was significantly greater in P than NP rats (p < 0.01). In addition, the results revealed a considerable resistance to extinction to the effects of the ethanol-associated stimuli. Throughout the 50-day test period, responding remained significantly above extinction levels in both P and NP rats (p < 0.01), but with an overall greater number of responses in P than NP rats (p < 0.05). Conclusions: The results support the hypothesis that conditioning factors contribute importantly to compulsive ethanol seeking and long-lasting vulnerability to relapse. In addition, the results suggest that genetic predisposition toward heightened ethanol intake extends to greater susceptibility to the motivating effects of ethanol-related environmental stimuli. [source] Educational developers: The multiple structures and influences that support our workNEW DIRECTIONS FOR TEACHING & LEARNING, Issue 122 2010Mary Deane Sorcinelli Recognizing that educational development is an important strategic lever for ensuring institutional quality, this chapter examines aspects of the careers of educational developers, including the kinds of positions they hold, the influences on their educational practice, and the factors that affect their programmatic priorities. [source] The (Fo,Fc) Fourier synthesis: a probabilistic studyACTA CRYSTALLOGRAPHICA SECTION A, Issue 5 2008Rocco Caliandro (Fo,Fc) and (2Fo,Fc) Fourier syntheses are considered the most powerful tools for recovering the remainder of a structure and for correcting crystal structure models. A probabilistic approach has been applied to derive the formula for the variance for the expected value of the coefficient (Fo,Fc). This has allowed a better understanding of the features of the difference Fourier synthesis; in particular, a subset of well phased reflections has been separated from the subset of reflections best phased by the standard Fo Fourier synthesis. An iterative procedure, based on the electron-density modification of the difference Fourier map, has been devised which aims to improve phase and modulus estimates of the reflections with higher variance value, by using as lever arm the set of reflections with lower variance value. The new procedure (DEDM) has been implemented and verified on a wide set of test structures, the partial models of which were obtained by molecular replacement or by automatic model-building routines applied to experimental electron-density maps. Phase and modulus estimates of the difference Fourier syntheses improve in all the test cases; as a consequence, the quality of the difference Fourier maps also improves in the region where the target structure deviates from the partial model. A new procedure is suggested, combining DEDM with standard electron-density modification techniques, which leads to significant reduction of the phase errors. The procedure may be considered a starting point for further developments. [source] Experimenting with organisational development in Bhutan: A tool for reform and the achievement of multi-level goals?PUBLIC ADMINISTRATION & DEVELOPMENT, Issue 2 2009Janine O'Flynn Abstract In this article we present a unique study of how a nation, Bhutan, is using a specific change management approach,organisational development,as the lever for system-level change in pursuit of a complex, multi-level suite of goals to, ultimately, enhance Gross National Happiness (GNH). We argue that this represents one of the first attempts at using OD for wide-scale change, something hinted at decades ago, and flagged by recent work coming out of the United Nations Development Program and civil society organisations (CSOs). Conceptually, we point to a high level of fit between the Bhutanese development philosophy and OD, and argue there is great potential for using OD in the context. However, we raise a series of issues around the practical feasibility of this approach highlighting important points of tension which pose major challenges for the Bhutanese experiment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Functional anatomy of the olecranon process in hominoids and plio-pleistocene homininsAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2004Michelle S.M. Drapeau Abstract This study examines the functional morphology of the olecranon process in hominoids and fossil hominins. The length of the bony lever of the triceps brachii muscle (TBM) is measured as the distance between the trochlear articular center and the most distant insertion site of the TBM, and olecranon orientation is measured as the angle that this bony lever makes with the long axis of the ulna. Results show that Homo, Pan, Gorilla, most monkeys, and the Australopithecus fossils studied have similar relative olecranon lengths. Suspensory hominoids and Ateles have shorter olecranons, suggesting, in some instances, selection for greater speed in extension. The orientation that the lever arm of the TBM makes with the long axis of the ulna varies with preferred locomotor mode. Terrestrial primates have olecranons that are more posteriorly oriented as body size increases, fitting general models of terrestrial mammalian posture. Arboreal quadrupeds have more proximally oriented lever arms than any terrestrial quadrupeds, which suggests use of the TBM with the elbow in a more flexed position. Olecranon orientation is not consistent in suspensory hominoids, although they are all characterized by orientations that are either similar or more posterior than those observed in quadrupeds. Homo and the fossils have olecranons that are clearly more proximally oriented than expected for a quadruped of their size. This suggests that Homo and Australopithecus used their TBM in a flexed position, a position most consistent with manipulatory activities. Am J Phys Anthropol, 2003. © 2003 Wiley-Liss, Inc. [source] Jaw Mechanics in Basal Ceratopsia (Ornithischia, Dinosauria)THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 9 2009Kyo Tanoue Abstract Ceratopsian dinosaurs were a dominant group of herbivores in Cretaceous terrestrial ecosystems. We hypothesize that an understanding of the feeding system will provide important insight into the evolutionary success of these animals. The mandibular mechanics of eight genera of basal ceratopsians was examined to understand the variability in shape of the jaws and the early evolution of the masticatory system in Ceratopsia. Data were collected on lever arms, cranial angles and tooth row lengths. The results indicate that psittacosaurids had higher leverage at the beak and in the rostral part of the tooth row than basal neoceratopsians, but lower leverage in the caudal part of the tooth row. Although the vertebrate mandible is generally considered as a third-class lever, that of basal neoceratopsians acted as a second-class lever at the caudal part of the tooth row, as is also true in ceratopsids. When total input force from the mandibular adductor muscles on both sides of the skull is considered, the largest bite force in basal ceratopsian tooth rows was exerted in the caudal part of the tooth row at the caudal extremity of the zone with near-maximum input force. Medially positioned teeth generate higher leverage than laterally positioned teeth. The largest bite force in all basal ceratopsians is smaller than the maximum input force, a limit imposed by the morphology of the basal ceratopsian masticatory system. In ceratopsids, caudal extension of the tooth row resulted in a much larger bite force, even exceeding the maximum input force. Anat Rec, 292:1352,1369, 2009. © 2009 Wiley-Liss, Inc. [source] The Influence of Testosterone Combined with a PDE5-inhibitor on Cognitive, Affective, and Physiological Sexual Functioning in Women Suffering from Sexual DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2009Flip Van Der Made MD ABSTRACT Introduction., Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function. Aim., To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods., In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital,physiological and subjective reactions. Main Outcome Measures., A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used. Results., In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning. Conclusion., In women suffering from low sexual desire,associated with low attention for sexual cues,the combination of testosterone and vardenafil may be a promising new treatment. van der Made F, Bloemers J, Yassem WE, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, and Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009;6:777,790. [source] Upstream Solutions: Does the Supplemental Security Income Program Reduce Disability in the Elderly?THE MILBANK QUARTERLY, Issue 1 2008PAMELA HERD Context: The robust relationship between socioeconomic factors and health suggests that social and economic policies might substantially affect health, while other evidence suggests that medical care, the main focus of current health policy, may not be the primary determinant of population health. Income support policies are one promising avenue to improve population health. This study examines whether the federal cash transfer program to poor elderly, the Supplemental Security Income (SSI) program, affects old-age disability. Methods: This study uses the 1990 and 2000 censuses, employing state and year fixed-effect models, to test whether within-state changes in maximum SSI benefits over time lead to changes in disability among people aged sixty-five and older. Findings: Higher benefits are linked to lower disability rates. Among all single elderly individuals, 30 percent have mobility limitations, and an increase of $100 per month in the maximum SSI benefit caused the rate of mobility limitations to fall by 0.46 percentage points. The findings were robust to sensitivity analyses. First, analyses limited to those most likely to receive SSI produced larger effects, but analyses limited to those least likely to receive SSI produced no measurable effect. Second, varying the disability measure did not meaningfully alter the findings. Third, excluding the institutionalized, immigrants, individuals living in states with exceptionally large benefit changes, and individuals living in states with no SSI supplements did not change the substantive conclusions. Fourth, Medicaid did not confound the effects. Finally, these results were robust for married individuals. Conclusions: Income support policy may be a significant new lever for improving population health, especially that of lower-income persons. Even though the findings are robust, further analyses are needed to confirm their reliability. Future research should examine a variety of different income support policies, as well as whether a broader range of social and economic policies affect health. [source] Comparison of FlexibladeÔ and Macintosh laryngoscopes: cervical extension angles during orotracheal intubationANAESTHESIA, Issue 7 2010S. Uzun Summary The FlexibladeTM is a new laryngoscope with a flexible blade, a handle and a lever, allowing gradual flexion over the distal half of the blade. In this study, we aimed to compare cervical vertebral movements during tracheal intubation with the Flexiblade and Macintosh laryngoscope in 32 patients undergoing elective surgery requiring general anaesthesia (n = 16 per group). Fluoroscopic images of cervical movement were captured before, during and after intubation and evaluated by a radiologist. C1,C2 cervical vertebral movement was significantly reduced during the intubation in the Flexiblade group (p < 0.0001). C2,C3 cervical movement was similar in both groups (p = 0.81). No significant differences were noted in success rates for intubation, oxygen saturation levels, haemodynamic variables or intubation-related injury. The decreased extension angle between C1,C2 during Flexiblade laryngoscopy compared with Macintosh laryngoscopy may be an advantage where neurological damage with cervical movement is a concern. [source] Genetic and morphological variation in a Mediterranean glacial refugium: evidence from Italian pygmy shrews, Sorex minutus (Mammalia: Soricomorpha)BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 4 2010RODRIGO VEGA At the Last Glacial Maximum (LGM), the southern European peninsulas were important refugia for temperate species. Current genetic subdivision of species within these peninsulas may reflect past population subdivision at the LGM, as in ,refugia within refugia', and/or at other time periods. In the present study, we assess whether pygmy shrew populations from different regions within Italy are genetically and morphologically distinct. One maternally and two paternally inherited molecular markers (cytochrome b and Y-chromosome introns, respectively) were analysed using several phylogenetic methods. A geometric morphometric analysis was performed on mandibles to evaluate size and shape variability between populations. Mandible shape was also explored with a functional approach that considered the mandible as a first-order lever affecting bite force. We found genetically and morphologically distinct European, Italian, and southern Italian groups. Mandible size increased with decreasing latitude and southern Italian pygmy shrews exhibited mandibles with the strongest bite force. It is not clear whether or not the southern Italian and Italian groups of pygmy shrews occupied different refugia within the Italian peninsula at the LGM. It is likely, however, that geographic isolation earlier than the LGM on islands at the site of present-day Calabria was important in generating the distinctive southern Italian group of pygmy shrews, and also the genetic groups in other small vertebrates that we review here. Calabria is an important hotspot for genetic diversity, and is worthy of conservation attention. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100, 774,787. [source] | ||||||||||||||||||||||||||||