Novel approaches for the treatment of psychostimulant and opioid abuse-focus on opioid receptor-based therapies

INTRODUCTION: Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making ‘anti-relapse’ therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. Firstly, there are 3 key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all 3 stimuli. Secondly, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would therefore be effective against all classes of drugs of abuse. AREAS COVERED: In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into 2 categories: ‘memory-based’ and ‘receptor-based’ and the authors discuss the key targets here within. EXPERT OPINION: Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel ‘anti-relapse’ medications targets - research suggests that a ‘non-selective’ approach to targeting opioid receptors will be the most effective

Parametrical modeling and design optimization of blood plasma separation device with microchannel mechanism

This paper presents an analysis of biofluid behavior in a T-shaped microchannel device and a design optimization for improved biofluid performance in terms of particle liquid separation. The biofluid is modeled with single phase shear rate non-Newtonian flow with blood property. The separation of red blood cell from plasma is evident based on biofluid distribution in the microchannels against various relevant effects and findings, including Zweifach-Fung bifurcation law, Fahraeus effect, Fahraeus-Lindqvist effect and cell free phenomenon. The modeling with the initial device shows that this T-microchannel device can separate red blood cell from plasma but the separation efficiency among different bifurcations varies largely. In accordance with the imbalanced performance, a design optimization is conducted. This includes implementing a series of simulations to investigate the effect of the lengths of the main and branch channels to biofluid behavior and searching an improved design with optimal separation performance. It is found that changing relative lengths of branch channels is effective to both uniformity of flow rate ratio among bifurcations and reduction of difference of the flow velocities between the branch channels, whereas extending the length of the main channel from bifurcation region is only effective for uniformity of flow rate ratio

Farmers’ attitudes to disease risk management in England: a comparative analysis of sheep and pig farmers

The UK Department for Environment, Food and Rural Affairs (Defra) identified practices to reduce the risk of animal disease outbreaks. We report on the response of sheep and pig farmers in England to promotion of these practices. A conceptual framework was established from research on factors influencing adoption of animal health practices, linking knowledge, attitudes, social influences and perceived constraints to the implementation of specific practices. Qualitative data were collected from nine sheep and six pig enterprises in 2011. Thematic analysis explored attitudes and responses to the proposed practices, and factors influencing the likelihood of implementation. Most feel they are doing all they can reasonably do to minimise disease risk and that practices not being implemented are either not relevant or ineffective. There is little awareness and concern about risk from unseen threats. Pig farmers place more emphasis than sheep farmers on controlling wildlife, staff and visitor management and staff training. The main factors that influence livestock farmers’ decision on whether or not to implement a specific disease risk measure are: attitudes to, and perceptions of, disease risk; attitudes towards the specific measure and its efficacy; characteristics of the enterprise which they perceive as making a measure impractical; previous experience of a disease or of the measure; and the credibility of information and advice. Great importance is placed on access to authoritative information with most seeing vets as the prime source to interpret generic advice from national bodies in the local context. Uptake of disease risk measures could be increased by: improved risk communication through the farming press and vets to encourage farmers to recognise hidden threats; dissemination of credible early warning information to sharpen farmers’ assessment of risk; and targeted information through training events, farming press, vets and other advisers, and farmer groups, tailored to the different categories of livestock farmer

Composition profiles of InAs–GaAs quantum dots determined by medium-energy ion scattering

The composition profile along the [001] growth direction of low-growth-rate InAs–GaAs quantum dots (QDs) has been determined using medium-energy ion scattering (MEIS). A linear profile of In concentration from 100% In at the top of the QDs to 20% at their base provides the best fit to MEIS energy spectra

Target Selection for the LBTI Exozodi Key Science Program

The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ~300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.Comment: accepted to ApJ

Developmental trajectories of behaviour problems and prosocial behaviours of children with intellectual disabilities in a population-based cohort

BACKGROUND: The study examined developmental trajectories of prosocial behaviours, internalising and externalising behaviour problems in children with intellectual disabilities (ID) between pre-school and middle childhood. METHOD: Growth models examined the best-fitting trajectories for internalising and externalising behaviour problems, as well as prosocial behaviours, in 555 children with ID between the ages of three and 11 years from the UK Millennium Cohort Study. Models were also fitted to examine the association of child outcomes with time-varying maternal psychological distress and life satisfaction. Finally, models were extended to compare trajectories with typically developing children. RESULTS: Externalising behaviour problems and prosocial behaviours generally improved, whereas internalising problems did not change systematically over time. A cubic trend indicated a slowing down of improvement between ages 5 and 7 for prosocial behaviours and externalising problems. Maternal psychological distress positively co-varied with internalising and externalising behaviour problems over time. Life satisfaction was not related to changes in child behaviours over time. Compared to behavioural trajectories in typical development, intercepts were worse and trajectories also differed in the ID group. CONCLUSIONS: Over an 8-year period, externalising behaviour problems and prosocial behaviours of children with ID tended to improve. These behavioural improvements slowed between five and seven years, possibly coinciding with school-related environmental changes. Children with ID significantly differ from children with typical development in both the initial level of difficulties (exhibiting higher externalising and internalising behaviours, and lower prosocial behaviours) and subsequent development as they age, showing comparatively lower decreases in both externalising and internalising behaviours, and lower increases in prosocial behaviours. Findings also highlight the significant role of maternal mental health problems in the trajectory of child behaviour problems

High Thermoelectric Performance in Supersaturated Solid Solutions and Nanostructured nâ Type PbTeâ GeTe

Sbâ doped and GeTeâ alloyed nâ type thermoelectric materials that show an excellent figure of merit ZT in the intermediate temperature range (400â 800 K) are reported. The synergistic effect of favorable changes to the band structure resulting in high Seebeck coefficient and enhanced phonon scattering by point defects and nanoscale precipitates resulting in reduction of thermal conductivity are demonstrated. The samples can be tuned as singleâ phase solid solution (SS) or twoâ phase system with nanoscale precipitates (Nano) based on the annealing processes. The GeTe alloying results in band structure modification by widening the bandgap and increasing the densityâ ofâ states effective mass of PbTe, resulting in significantly enhanced Seebeck coefficients. The nanoscale precipitates can improve the power factor in the low temperature range and further reduce the lattice thermal conductivity (κlat). Specifically, the Seebeck coefficient of Pb0.988Sb0.012Teâ 13%GeTeâ Nano approaches â 280 µV Kâ 1 at 673 K with a low κlat of 0.56 W mâ 1 Kâ 1 at 573 K. Consequently, a peak ZT value of 1.38 is achieved at 623 K. Moreover, a high average ZTavg value of â 1.04 is obtained in the temperature range from 300 to 773 K for nâ type Pb0.988Sb0.012Teâ 13%GeTeâ Nano.Both supersaturated solid solutions and nanostructured nâ type Pb1â xGexTe systems with excellent thermoelectric performance can be prepared via a nonequilibrium process. The nanostructured sample enhances the figure of merit ZT via reducing the lattice thermal conductivity. A ZTavg of â 1.04 is obtained, which is among the highest ZTavg values for nâ type PbTe materials reported so far.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145314/1/adfm201801617-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145314/2/adfm201801617.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145314/3/adfm201801617_am.pd