Silicon Superconducting Quantum Interference Device

We have studied a Superconducting Quantum Interference SQUID device made from a single layer thin film of superconducting silicon. The superconducting layer is obtained by heavily doping a silicon wafer with boron atoms using the Gas Immersion Laser Doping (GILD) technique. The SQUID device is composed of two nano-bridges (Dayem bridges) in a loop and shows magnetic flux modulation at low temperature and low magnetic field. The overall behavior shows very good agreement with numerical simulations based on the Ginzburg-Landau equations.Comment: Published in Applied Physics Letters (August 2015

Sex-specific ultrasonic vocalization patterns and alcohol consumption in high alcohol-drinking (HAD-1) rats

Ultrasonic vocalizations (USVs) have been established as an animal model of emotional status and are often utilized in drug abuse studies as motivational and emotional indices. Further USV functionality has been demonstrated in our recent work showing accurate identification of selectively-bred high versus low alcohol-consuming male rats ascertained exclusively from 22 to 28 kHz and 50–55 kHz FM USV acoustic parameters. With the hypothesis that alcohol-sensitive sex differences could be revealed through USV acoustic parameters, the present study examined USVs and alcohol consumption in male and female selectively bred high-alcohol drinking (HAD-1) rats. For the current study, we examined USV data collected during a 12-week experiment in male and female HAD-1 rats. Experimental phases included Baseline (2 weeks), 4-h EtOH Access (4 weeks), 24-h EtOH Access (4 weeks) and Abstinence (2 weeks). Findings showed that both male and female HAD-1 rats spontaneously emitted a large number of 22–28 kHz and 50–55 kHz FM USVs and that females drank significantly more alcohol compared to males over the entire course of the experiment. Analyses of USV acoustic characteristics (i.e. mean frequency, duration, bandwidth and power) revealed distinct sex-specific phenotypes in both 50–55 kHz FM and 22–28 kHz USV transmission that were modulated by ethanol exposure. Moreover, by using a linear combination of these acoustic characteristics, we were able to develop binomial logistic regression models able to discriminate between male and female HAD-1 rats with high accuracy. Together these results highlight unique emotional phenotypes in male and female HAD-1 rats that are differentially modulated by alcohol experience

Negative Affect-Associated USV Acoustic Characteristics Predict Future Excessive Alcohol Drinking and Alcohol Avoidance in Male P and NP Rats

BACKGROUND: Negative emotional status and adverse emotional events increase vulnerability to alcohol abuse. Ultrasonic vocalizations (USVs) emitted by rats are a well-established model of emotional status that can reflect positive or negative affective responses in real time. Most USV studies assess counts, yet each USV is a multidimensional data point characterized by several acoustic characteristics that may provide insight into the neurocircuitry underlying emotional response. METHODS: USVs emitted from selectively bred alcohol-naïve and alcohol-experienced alcohol-preferring and nonpreferring rats (P and NP rats) were recorded during 4-hour sessions on alternating days over 4 weeks. Linear mixed modeling (LMM) and linear discriminant analysis (LDA) were applied to USV acoustic characteristics (e.g., frequency, duration, power, and bandwidth) of negative affect (22 to 28 kilohertz [kHz])- and positive (50 to 55 kHz) affect-related USVs. RESULTS: Hundred percent separation between alcohol-naïve P and NP rats was achieved through a linear combination (produced by LDA) of USV acoustic characteristics of 22- to 28-kHz USVs, whereas poor separation (36.5%) was observed for 50- to 55-kHz USVs. 22- to 28-kHz LDA separation was high (87%) between alcohol-experienced P and NP rats, but was poor for 50- to 55-kHz USVs (57.3%). USV mean frequency and duration were the highest weighted characteristics in both the naïve and experienced 22- to 28-kHz LDA representations suggesting that alcohol experience does not alter the representations. LMM analyses of 22- to 28-kHz USV acoustic characteristics matched the LDA results. Poor LDA separation was observed between alcohol-naïve and alcohol-experienced P rats for both 22- to 28-kHz and 50- to 55-kHz USVs. CONCLUSIONS: Advanced statistical analysis of negative affect-associated USV data predicts future behaviors of excessive alcohol drinking and alcohol avoidance in selectively bred rats. USV characteristics across rat lines reveal affect-related motivation to consume alcohol and may predict neural pathways mediating emotional response. Further characterization of these differences could delineate particular neurocircuitry and methods to ameliorate dysregulated emotional states often observed in human alcohol abusers

Sex differences in cognitive performance and alcohol consumption in High Alcohol-Drinking (HAD-1) rats

Excessive alcohol (ethanol) consumption negatively impacts social, emotional, as well as cognitive function and well-being. Thus, identifying behavioral and/or biological predictors of excessive ethanol consumption is important for developing prevention and treatment strategies against alcohol use disorders (AUDs). Sex differences in alcohol consumption patterns are observed in humans, primates, and rodents. Selectively bred high alcohol-drinking rat lines, such as the “HAD-1” lines are recognized animal models of alcoholism. The present work examined sex differences in alcohol consumption, object recognition, and exploratory behavior in male and female HAD-1 rats. Naïve male and female HAD-1 rats were tested in an object recognition test (ORT) prior to a chronic 24 h intermittent ethanol access procedure for five weeks. Object recognition parameters measured included exploratory behavior, object investigation, and time spent near objects. During the initial training trial, rearing, active object investigation and amount of time spent in the object-containing section was significantly greater in female HAD-1 rats compared to their male counterparts. During the subsequent testing trial, time spent in the object-containing section was greater in female, compared to male, rats; but active object investigation and rearing did not statistically differ between females and males. In addition, female HAD-1 rats consumed significantly more ethanol than their male counterparts, replicating previous findings. Moreover, across all animals there was a significant positive correlation between exploratory behavior in ORT and ethanol consumption level. These results indicate there are significant sex differences in cognitive performance and alcohol consumption in HAD-1 rats, which suggests neurobiological differences as well

Effects of perceived cocaine availability on subjective and objective responses to the drug

<p>Abstract</p> <p>Rationale</p> <p>Several lines of evidence suggest that cocaine expectancy and craving are two related phenomena. The present study assessed this potential link by contrasting reactions to varying degrees of the drug's perceived availability.</p> <p>Method</p> <p>Non-treatment seeking individuals with cocaine dependence were administered an intravenous bolus of cocaine (0.2 mg/kg) under 100% ('unblinded'; N = 33) and 33% ('blinded'; N = 12) probability conditions for the delivery of drug. Subjective ratings of craving, high, rush and low along with heart rate and blood pressure measurements were collected at baseline and every minute for 20 minutes following the infusions.</p> <p>Results</p> <p>Compared to the 'blinded' subjects, their 'unblinded' counterparts had similar craving scores on a multidimensional assessment several hours before the infusion, but reported higher craving levels on a more proximal evaluation, immediately prior to the receipt of cocaine. Furthermore, the 'unblinded' subjects displayed a more rapid onset of high and rush cocaine responses along with significantly higher cocaine-induced heart rate elevations.</p> <p>Conclusion</p> <p>These results support the hypothesis that cocaine expectancy modulates subjective and objective responses to the drug. Provided the important public health policy implications of heavy cocaine use, health policy makers and clinicians alike may favor cocaine craving assessments performed in the settings with access to the drug rather than in more neutral environments as a more meaningful marker of disease staging and assignment to the proper level of care.</p

Pharmacokinetics of pitolisant in children and adolescents with narcolepsy

Objective: To evaluate the pharmacokinetic profile and tolerability of pitolisant, a selective histamine 3 (H3) 12receptor antagonist/inverse agonist, in children and adolescents with narcolepsy. Methods: This multicenter, open-label, single-dose study of pitolisant 17.8 mg enrolled patients aged 6 through 17 years with a diagnosis of narcolepsy. Blood samples were collected at prespecified time points for analysis of pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the serum concentration\u2013time curve from time 0\u201310 h (AUC0\u201310h). Pharmacokinetic parameters were compared across three prespecified age groups: younger pediatric patients (aged 6 to &lt;12 years), older pediatric patients (aged 12 to &lt;18 years), and a historical comparison group of young adults (aged 18 to &lt;45 years). Results: Of the 25 enrolled patients, 24 were included in the pharmacokinetic analysis. Pitolisant Cmax and AUC0\u201310h were greater (by 52% and 73%, respectively) in the younger (n = 12) versus older (n = 12) pediatric subgroup. These parameters were lower in the young adult group (n = 13) by 51% and 48%, respectively, compared with the older pediatric patients, and by 68% and 70%, respectively, compared with the younger pediatric patients. There were six treatment-emergent adverse events: headache (three), dizziness (one), diarrhea (one), and vomiting (one). Conclusions: After single-dose administration, the exposure parameters of pitolisant were significantly greater in the younger compared with older pediatric patients with narcolepsy. Pitolisant doses up to 17.8 mg/d (in children with body weight &lt;40 kg) or 35.6 mg/d are appropriate for further evaluation in pediatric patients. Trial registration: EudraCT Number: 2013-001505-93