Continuous Nicotine Exposure Does Not Affect Resurgence of Alcohol Seeking in Rats

Alcohol is the most commonly used drug in the United States and alcohol abuse can lead to alcohol use disorder. Alcohol use disorder is a persistent condition and relapse rates following successful remission are high. Many factors have been associated with relapse for alcohol use disorder, but identification of these factors has not been well translated into preventative utility. One potentially important factor, concurrent nicotine use, has not been well investigated as a causal factor in relapse for alcohol use disorder. Nicotine increases the value of other stimuli in the environment and may increase the value of alcohol. If nicotine increases the value of alcohol, then nicotine use during and after treatment may make relapse more probable. In the current study, we investigated the effect of continuous nicotine exposure (using osmotic minipumps to deliver nicotine or saline, depending on group, at a constant rate for 28 days) on resurgence of alcohol seeking in rats. Resurgence is a type of relapse preparation that consists of three phases: Baseline, Alternative Reinforcement, and Resurgence Testing. During Baseline, target responses produced a dipper of alcohol. During Alternative Reinforcement, target responses were extinguished and responses on a chain produced a chocolate pellet. During Resurgence Testing, responses on the chain were also extinguished and a return to responding on the target lever was indicative of resurgence. Multilevel modeling was used to analyze the effect of nicotine on resurgence. Both the nicotine and saline group showed resurgence of alcohol seeking, but there was no difference in the degree of resurgence across groups. Future directions could involve testing alternative drug delivery techniques

The effect of cue type on directive-following in children with moderate to severe autism spectrum disorder

For this study, 11 children with moderate to severe autism spectrum disorder (ASD) were given directives containing prepositions in three cue conditions: (a) spoken alone, (b) a short video clip along with spoken cues, and (c) a sequence of three graphic symbols accompanied by spoken cues. Participants followed directives significantly more accurately with the video clip than with spoken cues only, and significantly more accurately with spoken cues only relative to the sequence of graphic symbols. Results suggest that the short video clip along with spoken cues may be an optimal mode for enhancing learners’ ability to follow directives containing prepositions. In addition, results reveal three statistically significant correlations between participants’ preexisting skills and directive-following accuracy: a positive correlation between spoken preposition preassessment total score and accuracy in the spoken-alone condition; a positive correlation between spoken noun preassessment total score and accuracy in the video-clip condition; and a positive correlation between ASD severity and the need for repetition in the video-clip condition. Results also suggested that, for children with more severe ASD symptoms, the video clips require repetitions so that the relationships illustrated within it can gain more semantic salience. Implications for clinical practice and future research are discussed.http://www.tandfonline.com/loi/iaac20hj2022Centre for Augmentative and Alternative Communication (CAAC

Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature

BACKGROUND: Keeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners. METHODS: Nurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS. RESULTS: Twenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources. CONCLUSION: The use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes

Persistence and Relapse of Reinforced Behavioral Variability

The present study examined persistence and relapse of reinforced behavioral variability in pigeons. Pigeons emitted four‐response sequences across two keys. Sequences produced food according to a lag schedule, in which a response sequence was followed by food if it differed from a certain number of previous sequences. In Experiment 1, food was delivered for sequences that satisfied a lag schedule in both components of a multiple schedule. When reinforcement was removed for one component (i.e., extinction), levels of behavioral variability decreased for only that component. In Experiment 2, food was delivered for sequences satisfying a lag schedule in one component of a multiple schedule. In the other component, food was delivered at the same rate, but without the lag variability requirement (i.e., yoked). Following extinction, levels of behavioral variability returned to baseline for both components after response‐independent food delivery (i.e., reinstatement). In Experiment 3, one group of pigeons responded on a lag variability schedule, and the other group responded on a lag repetition schedule. For both groups, levels of behavioral variability increased when alternative reinforcement was suspended (i.e., resurgence). In each experiment, we observed some evidence for extinction‐induced response variability and for variability as an operant dimension of behavior

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk

ABSTRACT Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding. IMPORTANCE Efforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT

Fermi detection of delayed GeV emission from the short GRB 081024B

We report on the detailed analysis of the high-energy extended emission from the short Gamma-Ray Burst (GRB) 081024B, detected by the Fermi Gamma-ray Space Telescope. Historically, this represents the first clear detection of temporal extended emission from a short GRB. The light curve observed by the Fermi Gamma-ray Burst Monitor lasts approximately 0.8 seconds whereas the emission in the Fermi Large Area Telescope lasts for about 3 seconds. Evidence of longer lasting high-energy emission associated with long bursts has been already reported by previous experiments. Our observations, together with the earlier reported study of the bright short GRB 090510, indicate similarities in the high-energy emission of short and long GRBs and open the path to new interpretations.Comment: 19 pages, 4 figures, 2 tables. Accepted for publication in Ap

Detection of the Small Magellanic Cloud in gamma-rays with Fermi/LAT

The flux of gamma rays with energies >100MeV is dominated by diffuse emission from CRs illuminating the ISM of our Galaxy through the processes of Bremsstrahlung, pion production and decay, and inverse-Compton scattering. The study of this diffuse emission provides insight into the origin and transport of CRs. We searched for gamma-ray emission from the SMC in order to derive constraints on the CR population and transport in an external system with properties different from the Milky Way. We analysed the first 17 months of continuous all-sky observations by the Large Area Telescope of the Fermi mission to determine the spatial distribution, flux and spectrum of the gamma-ray emission from the SMC. We also used past radio synchrotron observations of the SMC to study the population of CR electrons specifically. We obtained the first detection of the SMC in high-energy gamma rays, with an integrated >100MeV flux of (3.7 +/-0.7) x10e-8 ph/cm2/s, with additional systematic uncertainty of <16%. The emission is steady and from an extended source ~3{\deg} in size. It is not clearly correlated with the distribution of massive stars or neutral gas, nor with known pulsars or SNRs, but a certain correlation with supergiant shells is observed. The observed flux implies an upper limit on the average CR nuclei density in the SMC of ~15% of the value measured locally in the Milky Way. The population of high-energy pulsars of the SMC may account for a substantial fraction of the gamma-ray flux, which would make the inferred CR nuclei density even lower. The average density of CR electrons derived from radio synchrotron observations is consistent with the same reduction factor but the uncertainties are large. From our current knowledge of the SMC, such a low CR density does not seem to be due to a lower rate of CR injection and rather indicates a smaller CR confinement volume characteristic size.Comment: 14 pages, 6 figures, accepted for publication in A&

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil