Levo-Tetrahydropalmatine Attenuates Cocaine Self-Administration under a Progressive-Ratio Schedule and Cocaine Discrimination in Rats

Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese herbal preparations and has a unique pharmacological profile that includes dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced reinstatement in rats at doses that do not alter food-reinforced responding. This study examined the effects of l-THP on cocaine and food SA under progressive-ratio (PR) schedules of reinforcement and the discriminative stimulus effects of cocaine. In adult male Sprague–Dawley rats self-administering cocaine (0.5 or 1.0 mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5 mg/kg doses. l-THP also reduced the breaking point and response rate for PR SA of sucrose-sweetened food pellets, although the decrease was significant only at the 7.5 mg/kg l-THP dose. In rats trained to discriminate cocaine (10 mg/kg, ip) from saline, l-THP (1.875, 3.75 and 7.5 mg/kg) produced a rightward shift in the dose–response curve for cocaine generalization. During generalization testing, l-THP reduced response rate, but only at the 7.5 mg/kg dose. l-THP also prevented substitution of the dopamine D2/D3 receptor agonist, (±) 7-OH-DPAT, for cocaine suggesting a potential role for antagonism of D2 and/or D3 receptors in the effects of l-THP. These data further demonstrate that l-THP attenuates the reinforcing and subjective effects of cocaine at doses that do not produce marked motor effects and provide additional evidence that l-THP may have utility for the management of cocaine addiction

Complexity of childhood sexual abuse: predictors of current post-traumatic stress disorder, mood disorders, substance use, and sexual risk behavior among adult men who have sex with men

Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46 %. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections, and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR 2.64: CI 1.24–5.63), two times higher odds of substance use disorder (OR 2.1: CI 1.02–2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04–7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56–6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16–6.36), and a greater number of casual sexual partners (p = 0.02). Both CSA with Physical Injury (OR 4.05: CI 1.9–8.7) and CSA with Intense Fear (OR 5.16: CI 2.5–10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including post-traumatic stress disorder, substance use, and sexual risk taking, and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities.This study was supported by a Grant from the NIMH (R01 MH095624) PI: O'Cleirigh; Author time (Safren) was supported, in part, by Grant 5K24MH094214. (R01 MH095624 - NIMH; 5K24MH094214)Accepted manuscrip

Evaluation and application of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry for complex sample analysis.

An evaluation of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS) has been undertaken to assess its applicability for the determination of 32 volatile compounds (VCs). The key experimental variables of sample incubation time and temperature have been evaluated alongside the MCC-GC variables of column polarity, syringe temperature, injection temperature, injection volume, column temperature and carrier gas flow rate coupled with the IMS variables of temperature and drift gas flow rate. This evaluation resulted in six sets of experimental variables being required to separate the 32 VCs. The optimum experimental variables for SHS-MCC-GC-IMS, the retention time and drift time operating parameters were determined; to normalise the operating parameters, the relative drift time and normalised reduced ion mobility for each VC were determined. In addition, a full theoretical explanation is provided on the formation of the monomer, dimer and trimer of a VC. The optimum operating condition for each VC calibration data was obtained alongside limit of detection (LOD) and limit of quantitation (LOQ) values. Typical detection limits ranged from 0.1ng bis(methylthio)methane, ethylbutanoate and (E)-2-nonenal to 472ng isovaleric acid with correlation coefficient (R(2)) data ranging from 0.9793 (for the dimer of octanal) through to 0.9990 (for isobutyric acid). Finally, the developed protocols were applied to the analysis of malodour in sock samples. Initial work involved spiking an inert matrix and sock samples with appropriate concentrations of eight VCs. The average recovery from the inert matrix was 101±18% (n=8), while recoveries from the sock samples were lower, that is, 54±30% (n=8) for sock type 1 and 78±24% (n=6) for sock type 2. Finally, SHS-MCC-GC-IMS was applied to sock malodour in a field trial based on 11 volunteers (mixed gender) over a 3-week period. By applying the SHS-MCC-GC-IMS database, four VCs were identified and quantified: ammonia, dimethyl disulphide, dimethyl trisulphide and butyric acid. A link was identified between the presence of high ammonia and dimethyl disulphide concentrations and a high malodour odour grading, that is, ≥ 6. Statistical analysis did not find any correlation between the occurrence of dimethyl disulphide and participant gender

Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>

Molecular and morphometric variation within and between population samples of the articulate brachiopod &lt;i&gt;Terebratulina&lt;/i&gt; spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

Peculiar Velocity Reconstruction with Fast Action Method: Tests on Mock Redshift Surveys

We present extensive tests of the Fast Action Method (FAM) for recovering the past orbits of mass tracers in an expanding universe from their redshift-space coordinates at the present epoch. The tests focus on the reconstruction of present-day peculiar velocities using mock catalogs extracted from high resolution $N$-body simulations. The method allows for a self-consistent treatment of redshift-space distortions by direct minimization of a modified action for a cosmological gravitating system. When applied to ideal, volume limited catalogs, FAM recovers unbiased peculiar velocities with a 1-D, 1\sigma error of ~220 km/s, if velocities are smoothed on a scale of 5 Mpc/h. Alternatively, when no smoothing is applied, FAM predicts nearly unbiased velocities for objects residing outside the highest density regions. In this second case the 1\sigma$error decreases to a level of ~150 km/s. The correlation properties of the peculiar velocity fields are also correctly recovered on scales larger than 5 Mpc/h. Similar results are obtained when FAM is applied to flux limited catalogs mimicking the IRAS PSCz survey. In this case FAM reconstructs peculiar velocities with similar intrinsic random errors, while velocity-velocity correlation properties are well reproduced beyond scales of ~8 Mpc/h. We also show that FAM provides better velocity predictions than other, competing methods based on linear theory or Zel'dovich approximation. These results indicate that FAM can be successfully applied to presently available galaxy redshift surveys such as IRAS PSCz.Comment: 26 pages, 16 figures. Figures 1,2,3,4,5,7,11,12 and 16 are also included as separate gif files. Added 2 new sections(5.3 and 6.3) and figures (11 and 16). More discussion added to section 7 (Summary and Conclusions). MNRAS accepte

Necessary but not sufficient? Engaging young people in the development of an avatar-based online intervention designed to provide psychosocial support to young people affected by their own or a family member's cancer diagnosis

Objective: This paper discusses the challenges and successes of engaging young people in a project aimed at developing an online counselling intervention for young people affected by cancer. Context: For younger people with a diagnosis of cancer or who are caring for someone with cancer the psychosocial consequences can create significant challenges for their social and educational development. Whilst young people have been shown to be reluctant to make use of traditional face-to-face counselling, research is beginning to suggest that effective therapeutic relationships can be formed with young people online. Design: The first phase of the study involved working with a “Young Persons Panel” of healthy school pupils and university students to develop and pilot an online counselling intervention and study materials in preparation for a pilot evaluation of the intervention. Intervention: An avatar-based virtual reality counselling world was created where young people can create their own avatar and receive counselling over the internet from a qualified counsellor via an avatar in a virtual reality world. Findings: The process of engaging young people in the C:EVOLVE project enabled a unique intervention to be developed and demonstrated positive developmental opportunities. However, despite the rigorous approach to the development of the intervention, initial attempts within the pilot evaluation phase of the study showed difficulties recruiting to the study and this phase of the study has currently ceased whilst further exploratory work takes place Conclusion: This study has demonstrated the complexities of intervention development and evaluation research targeted at young people and the challenges created when attempting to bring clinical practice and research evaluation together. Keywords: online counselling, cancer, young people, intervention development, avatar counselling

Novel hydrocarbon monooxygenase genes in the metatranscriptome of a natural deep‐sea hydrocarbon plume

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102241/1/emi12182.pd

Gendered work culture in free/libre open source software development

This article adopts a feminist perspective to examine masculine work culture in the development of free/libre open source software. The authors draw on a case study of ‘the Heidi Bug’ discovered during the development of the Mozilla Firefox web browser to examine how 'gendered talk' was (en)-acted to facilitate 'bricolage' in an online work environment. Such gendered talks contain cultural references familiar to male developers. Though seemingly innocuous, such acts could be seen as a performance of gender that simply reflects the hegemonic heterosexual masculine culture manifested in online virtual work space. The virtual work space therefore can be exclusive to those who shared the cultural references. Although it may not necessarily be ignorance or insensitivity of male developers, a more gender-balanced, women-friendly and inclusive work place certainly would benefit from a more diverse environment. This paper highlights the gendered aspect of software development through examining the language use and mainstream 'bricolage' practice, and establishes a compelling ground for enlarging the talent pool to include more women and integrating gender ethics (e.g., raising awareness of sensitive languages and design approaches) into computer ethics education