Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking

Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long-Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self-administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol- and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucrose-seeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanol-seeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future.

Thermodynamic modeling of ethanol fumigation in a diesel engine

Due to rapidly diminishing international supplies of fossil fuels, such as petroleum and diesel, the cost of fuel is constantly increasing, leading to higher costs of living, as a result of the significant reliance of many industries on motor vehicles. Many technologies have been developed to replace part or all of a fossil fuel with bio-fuels. One of the dual fuel technologies is fumigation of ethanol in diesel engines, which injects ethanol into the intake air stream of the engine. The advantage of this is that it avoids any costly modification of the engine high pressure diesel injection system, while reducing the volume of diesel required and potentially increasing the power output and efficiency. This paper investigates the performance of a diesel engine, converted to implement ethanol fumigation. The project will use both existing experimental data, along with generating computer modeled results using the program AVL Boost. The data from both experiments and the numerical simulation indicate desirable results for the peak pressure and the indicated mean effective pressure (IMEP). Increase in ethanol substitution resulted in elevated combustion pressure and an increase in the IMEP, while the variation of ethanol injection location resulted in negligible change. These increases in cylinder pressure led to a higher work output and total efficiency in the engine as the ethanol substitution was increased. In comparing the numerical and experimental results, the simulation showed a slight elevation, due to the inaccuracies in the heat release models. Future work is required to improve the combustion model and investigate the effect of the variation of the location of ethanol injection.

Nb2O5 Schottky based ethanol vapour sensors : effect of metallic catalysts

The aim of this paper is to compare the performances of the highly porous Nb2O5 Schottky based sensors formed using different catalytic metals for ethanol vapour sensing. The fabricated sensors consist of a fairly ordered nano-vein like porous Nb2O5 prepared via an elevated temperature anodization method. Subsequently, Pt, Pd and Au were sputtered as both Schottky contacts and catalysts for the comparative studies. These metals are chosen as they have large work functions in comparison to the electron affinity of the anodized Nb2O5. It is demonstrated that the device based on Pd/Nb2O5 Schottky contact has the highest sensitivity amongst the developed sensors. The sensing behaviors were studied in terms of the Schottky barrier height variations and properties of the metal catalysts.

Assessment of angiogenic potential--the use of AIDS-KS cell supernatants as an in vitro model

Metastasis, the passage of primary tumour cells throughout the body via the vascular system and their subsequent proliferation into secondary lesions in distant organs, represents a poor prognosis and therefore an understandably feared event for cancer patients. Despite considerable advances in cancer diagnosis and treatment, most deaths are the result of metastases resistant to conventional treatment [1]. Rather than being a random process, metastasis involves a series of organised steps leading to the growth of a secondary tumour. Malignant tumours stimulate the production of new vessels by the host, and this process is a prerequisite for the increase in size of a new tumour [2]. Angiogenesis, not only permits tumour expansion but also allows the entry of tumour cells into the circulation and is probably the most vital event for the metastatic process [3]. Metastasis and angiogenesis [4] have received much attention in recent years. A biological understanding of both phenomena seems to be an urgent priority towards the search for an effective prevention and treatment of tumour progression. Studies in vitro and in vivo have shown that one of the most important barriers to the passage of malignant cells is the basement membrane. The crossing of such barriers is a vital step in the formation of a metastasis [5].

A comparative investigation of C6-C15 hydrocarbons emitted from a passenger car powered by unleaded petrol and 10% ethanol fuel

Twenty-three non-methane hydrocarbons were captured from the exhaust of a car operating on unleaded petrol (ULP) and 10% ethanol fuels at steady speed on a chassis dynamometer. The compounds were identified and quantified by GC/MS/FID and their emission concentrations at 60 km/h, 80km/h and idle speed were evaluated. The most abundant compounds in the exhaust included n-hexane, n-heptane, benzene, toluene, ethyl benzene, m- and p-xylenes, and methylcyclopentane. Because of the large number of compounds involved, no attempt was made to compare the emission concentrations of the compounds. Rather the sum of the emission concentrations for the suite of compounds identified was compared when the car was powered by ULP and 10% ethanol fuel. It was evident from the results that the emission concentrations and factors were generally higher with ULP than with 10% ethanol fuel. The total emission concentrations with the ULP fuel were 2.8, 4.2 and 2.6 times the corresponding values for the 10% ethanol fuel at 60km/h, 80km/h and idle speed, respectively. The implications of the results on the environment are discussed in the paper.

Interactive content analysis : evaluating interactive variants of non-negative Matrix Factorisation and Latent Dirichlet Allocation as qualitative content analysis aids

This thesis addressed issues that have prevented qualitative researchers from using thematic discovery algorithms. The central hypothesis evaluated whether allowing qualitative researchers to interact with thematic discovery algorithms and incorporate domain knowledge improved their ability to address research questions and trust the derived themes. Non-negative Matrix Factorisation and Latent Dirichlet Allocation find latent themes within document collections but these algorithms are rarely used, because qualitative researchers do not trust and cannot interact with the themes that are automatically generated. The research determined the types of interactivity that qualitative researchers require and then evaluated interactive algorithms that matched these requirements. Theoretical contributions included the articulation of design guidelines for interactive thematic discovery algorithms, the development of an Evaluation Model and a Conceptual Framework for Interactive Content Analysis.

Fischer rats consume 20% ethanol in a long-term intermittent-access two-bottle-choice paradigm

The 20% ethanol intermittent-access (IAE) two-bottle-choice drinking procedure has been shown to produce high voluntary ethanol consumption in a number of rat strains. For this study, we applied this procedure to male Fischer (F344) rats, a strain previously reported to exhibit low levels of ethanol consumption. We also subjected these animals to a two-week ethanoldeprivation- period to see if they would exhibit an alcohol deprivation effect (ADE) signified by a transient increase in alcohol consumption following deprivation. Our data show a separation between high and low consuming animals within this strain, with high-consumers exhibiting an escalation in consumption. In contrast, Fischer rats did not show a significant separation between high and low consumers or any significant escalation in consumption, using the 20% ethanol continuous-access two-bottle-choice drinking protocol. Following the two-week deprivation period, animals in the high (but not the low) IAE group exhibited the transient increase in ethanol consumption and preference typically associated with an ADE. Together, the data suggest that the intermittent access protocol is a useful protocol for increasing ethanol consumption.

Re-evaluation of the effect of smoking on the methylation of N-terminal valine in haemoglobin

In view of the established extrapulmonary cancer sites targeted by smoking a multiplicity of compounds, and mechanisms might be involved. It has been debated that smoking caused increased incidence of N-methylvaline at the N-terminus of haemoglobin. Because this could indicate a relevance of methylating nitrosamines in tobacco smoke, data are presented from an industrial cohort of 35 smokers and 21 non-smokers repeatedly monitored between 1994 and 1999. In general, N-methylvaline adduct levels in haemoglobin of smokers were approximately 50% higher than those of non-smokers. The smoking-induced methylation of haemoglobin is likely to be caused by dimethylnitrosamine (N-nitroso-dimethylamine), a major nitrosamine in side-stream tobacco smoke. The biomonitoring data emphasise the potential value of N-methylvaline as a smoking-related biomarker and call for intensified research on tobacco smoke compounds that lead to macromolecular methylation process.

Rapid and highly efficient growth of graphene on copper by chemical vapor deposition of ethanol

The growth of graphene by chemical vapor deposition on metal foils is a promising technique to deliver large-area films with high electron mobility. Nowadays, the chemical vapor deposition of hydrocarbons on copper is the most investigated synthesis method, although many other carbon precursors and metal substrates are used too. Among these, ethanol is a safe and inexpensive precursor that seems to offer favorable synthesis kinetics. We explored the growth of graphene on copper from ethanol, focusing on processes of short duration (up to one min). We investigated the produced films by electron microscopy, Raman and X-ray photoemission spectroscopy. A graphene film with high crystalline quality was found to cover the entire copper catalyst substrate in just 20 s, making ethanol appear as a more efficient carbon feedstock than methane and other commonly used precursors.

Mortality attributable to smoking in Vietnamese men in 2008

Objective Smoking prevalence among Vietnamese men is among the highest in the world. Our aim was to provide estimates of tobacco attributable mortality to support tobacco control policies. Method We used the Peto–Lopez method using lung cancer mortality to derive a Smoking Impact Ratio (SIR) as a marker of cumulative exposure to smoking. SIRs were applied to relative risks from the Cancer Prevention Study, Phase II. Prevalence-based and hybrid methods, using the SIR for cancers and chronic obstructive pulmonary disease and smoking prevalence for all other outcomes, were used in sensitivity analyses. Results When lung cancer was used to measure cumulative smoking exposure, 28% (95% uncertainty interval 24–31%) of all adult male deaths (> 35 years) in Vietnam in 2008 were attributable to smoking. Lower estimates resulted from prevalence-based methods [24% (95% uncertainty interval 21–26%)] with the hybrid method yielding intermediate estimates [26% (95% uncertainty interval 23–28%)]. Conclusion Despite uncertainty in these estimates of attributable mortality, tobacco smoking is already a major risk factor for death in Vietnamese men. Given the high current prevalence of smoking, this has important implications not only for preventing the uptake of tobacco but also for immediate action to adopt and enforce stronger tobacco control measures.

Creating new folk opera forms of applied theatre for HIV and AIDS education in Papua New Guinea

This research investigated the potential of folk opera as a tool for HIV and AIDS education in Papua New Guinea. It began with an investigation on the indigenous performativities and theatricalities of Papua New Guineans, conducting an audit of eight selected performance traditions in Papua New Guinea. These traditions were analysed, and five cultural forms and twenty performance elements were drawn out for further exploration. These elements were fused and combined with theatre techniques from western theatre traditions, through a script development process involving Australians, Papua New Guineans and international collaborators. The resulting folk opera, entitled Kumul, demonstrates what Murphy (2010) has termed story force, picture force, and feeling force, in the service of a story designed to educate Papua New Guinean audiences about HIV and the need to adopt safer sexual practices. Kumul is the story of a young man faced with decisions on whether or not to engage in risky sexual behaviours. Kumul's narrative is carefully framed within selected Papua New Guinean beliefs drawn from the audit to deliver HIV and AIDS messages using symbolic and metaphoric communication techniques without offending people. The folk opera Kumul was trialled in two communities in Papua New Guinea: a village community and an urban settlement area. Kumul is recognisable to Papua New Guinean audiences because it reflects their lifestyle and a worldview, which connects them to their beliefs and spirituality, and the larger cosmological order. Feedback from audience members indicated that the performance facilitated HIV and AIDS communication, increased people's awareness of HIV and AIDS, and encouraged behaviour change. Tellingly, in one performance venue, forty people queued for Voluntary Testing and Counseling immediately after the performance. Twenty of these people were tested on that night and the other twenty were tested the following day. Many of the volunteers were young men – a demographic historically difficult to engage in HIV testing. This encouraging result indicates that the Kumul folk opera form of applied theatre could be useful for facilitating communication and education regarding sexual health and safer sexual behaviours in Papua New Guinea. Feedback from participants, audience members and other research stakeholders suggests that the form might also be adapted to address other social and development issues, particularly in the areas of health and social justice.

Inter-cycle variability of ignition delay in an ethanol fumigated common rail diesel engine

An experimental study has been performed to investigate the ignition delay of a modern heavy-duty common-rail diesel engine run with fumigated ethanol substitutions up to 40% on an energy basis. The ignition delay was determined through the use of statistical modelling in a Bayesian framework this framework allows for the accurate determination of the start of combustion from single consecutive cycles and does not require any differentiation of the in-cylinder pressure signal. At full load the ignition delay has been shown to decrease with increasing ethanol substitutions and evidence of combustion with high ethanol substitutions prior to diesel injection have also been shown experimentally and by modelling. Whereas, at half load increasing ethanol substitutions have increased the ignition delay. A threshold absolute air to fuel ratio (mole basis) of above ~110 for consistent operation has been determined from the inter-cycle variability of the ignition delay, a result that agrees well with previous research of other in-cylinder parameters and further highlights the correlation between the air to fuel ratio and inter-cycle variability. Numerical modelling to investigate the sensitivity of ethanol combustion has also been performed. It has been shown that ethanol combustion is sensitive to the initial air temperature around the feasible operating conditions of the engine. Moreover, a negative temperature coefficient region of approximately 900{1050 K (the approximate temperature at fuel injection) has been shown with for n-heptane and n-heptane/ethanol blends in the numerical modelling. A consequence of this is that the dominate effect influencing the ignition delay under increasing ethanol substitutions may rather be from an increase in chemical reactions and not from in-cylinder temperature. Further investigation revealed that the chemical reactions at low ethanol substitutions are different compared to the high (> 20%) ethanol substitutions.

Family-based programmes for preventing smoking by children and adolescents (Review)

Background There is evidence that family and friends influence children's decisions to smoke. Objectives To assess the effectiveness of interventions to help families stop children starting smoking. Search methods We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO, CINAHL unpublished material, and key articles' reference lists. We performed free-text internet searches and targeted searches of appropriate websites, and hand-searched key journals not available electronically. We consulted authors and experts in the field. The most recent search was 3 April 2014. There were no date or language limitations. Selection criteria Randomised controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and families to deter tobacco use. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. Data collection and analysis We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data for each RCT and assessed them for risk of bias. We pooled risk ratios using a Mantel-Haenszel fixed effect model. Main results Twenty-seven RCTs were included. The interventions were very heterogeneous in the components of the family intervention, the other risk behaviours targeted alongside tobacco, the age of children at baseline and the length of follow-up. Two interventions were tested by two RCTs, one was tested by three RCTs and the remaining 20 distinct interventions were tested only by one RCT. Twenty-three interventions were tested in the USA, two in Europe, one in Australia and one in India. The control conditions fell into two main groups: no intervention or usual care; or school-based interventions provided to all participants. These two groups of studies were considered separately. Most studies had a judgement of 'unclear' for at least one risk of bias criteria, so the quality of evidence was downgraded to moderate. Although there was heterogeneity between studies there was little evidence of statistical heterogeneity in the results. We were unable to extract data from all studies in a format that allowed inclusion in a meta-analysis. There was moderate quality evidence family-based interventions had a positive impact on preventing smoking when compared to a no intervention control. Nine studies (4810 participants) reporting smoking uptake amongst baseline non-smokers could be pooled, but eight studies with about 5000 participants could not be pooled because of insufficient data. The pooled estimate detected a significant reduction in smoking behaviour in the intervention arms (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.68 to 0.84). Most of these studies used intensive interventions. Estimates for the medium and low intensity subgroups were similar but confidence intervals were wide. Two studies in which some of the 4487 participants already had smoking experience at baseline did not detect evidence of effect (RR 1.04, 95% CI 0.93 to 1.17). Eight RCTs compared a combined family plus school intervention to a school intervention only. Of the three studies with data, two RCTS with outcomes for 2301 baseline never smokers detected evidence of an effect (RR 0.85, 95% CI 0.75 to 0.96) and one study with data for 1096 participants not restricted to never users at baseline also detected a benefit (RR 0.60, 95% CI 0.38 to 0.94). The other five studies with about 18,500 participants did not report data in a format allowing meta-analysis. One RCT also compared a family intervention to a school 'good behaviour' intervention and did not detect a difference between the two types of programme (RR 1.05, 95% CI 0.80 to 1.38, n = 388). No studies identified any adverse effects of intervention. Authors' conclusions There is moderate quality evidence to suggest that family-based interventions can have a positive effect on preventing children and adolescents from starting to smoke. There were more studies of high intensity programmes compared to a control group receiving no intervention, than there were for other compairsons. The evidence is therefore strongest for high intensity programmes used independently of school interventions. Programmes typically addressed family functioning, and were introduced when children were between 11 and 14 years old. Based on this moderate quality evidence a family intervention might reduce uptake or experimentation with smoking by between 16 and 32%. However, these findings should be interpreted cautiously because effect estimates could not include data from all studies. Our interpretation is that the common feature of the effective high intensity interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting.