Sex, drugs, and deterrence : applying Stafford and Warr’s reconceptualization of deterrence theory to drug driving across the genders

A consistent finding in the literature is that males report greater usage of drugs and subsequently greater amounts of drug driving. Research also suggests that vicarious influences may be more pertinent to males than to females. Utilising Stafford and Warr’s (1993) reconceptualization of deterrence theory, this study sought to determine if the relative deterrent impact of zero-tolerance drug driving laws is disparate between genders. A sample of motorists’ (N = 899) completed a self-report questionnaire assessing participants frequency of drug driving and personal and vicarious experiences with punishment and punishment avoidance. Results show that males were significantly more likely to report future intentions of drug driving. Additionally, vicarious experiences of punishment avoidance was a more influential predictor of future drug driving instances for males with personal experiences of punishment avoidance a more influential predictor for females. These findings can inform gender sensitive media campaigns and interventions for convicted drug drivers.

Contribution of transmembrane domain V amino acids to β1l-adrenoceptor activity and affinity

There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation (reviewed Kaumann and Molenaar, 2008). Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site (Baker et al 2002) and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Our aim was to investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 or (-)-isoprenaline in the absence or presence of (-)-bupranolol. _______________________________________________________________________ (-)-CGP 12177 (-)-Bupranolol affinity (pKB) pEC50 vs (-)-CGP 12177 vs (-)-isoprenaline _______________________________________________________________________ β1AR 8.00 ± 0.11 (11) 7.23 ± 0.23 (5) 9.52 ± 0.28 (5) β2AR (high density) 9.24 ± 0.14 (5) 9.82 ± 0.52 (8) xPaulxxxxxxx β2AR (low density) no effect β1(β2TMV)AR 8.86 ± 0.10 (15) 8.06 ± 0.17 (8) 9.08 ± 0.22 (6) β1(V230I)AR 9.07 ± 0.07 (10) 7.64 ± 0.12 (8) 9.36 ± 0.28 (9) β1(R222Q)AR 8.09 ± 0.29 (6) 7.33 ± 0.23 (5) 9.36 ± 0.08 (6) β1(V230A)AR 7.59 ± 0.09 (6) 7.32 ± 0.24 (4) 8.62 ± 0.18 (5) _______________________________________________________________________ The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR) but not β2AR. The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol at β1AR and mutants was higher when determined with (-)-isoprenaline than with (-)-CGP 12177. The affinity of (-)-bupranolol determined against (-)-CGP 12177 was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion V230 of the β1AR contributes in part to the low affinity binding site of β1AR. Baker JG, Hall IP, Hill SJ (2002). Pharmacological characterization of CGP12177 at the human β2-adrenoceptor. Br J Pharmacol 137, 400−408 Kaumann AJ, Molenaar P (2008) The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology. Pharmacol Ther 118, 303-336

Empirical basis for adopting a theory-driven approach to preventing alcohol and other drug impairment (AOD) in the workplace

Background: A State-based industry in Australia is in the process of developing a programme to prevent AOD impairment in the workplace. The objective of this study was to determine whether the Theory of Planned Behaviour can help explain the mechanisms by which behaviour change occurs with regard to AOD impairment in the workplace. ---------- Method: A survey of 1165 employees of a State-based industry in Australia was conducted, and a response rate of 98% was achieved. The survey included questions relevant to the Theory of Planned Behaviour: behaviour; behavioural intentions; attitude; perceptions of social pressure; and perceived behavioural control with regard to workplace AOD impairment. ---------- Findings: Less than 3% of participants reported coming to work impaired by AODs. Fewer than 2% of participants reported that they intended to come to work impaired by AODs. The majority of participants (over 80%) reported unfavourable attitudes toward AOD impairment at work. Logistic regression analyses suggest that, consistent with the theory of planned behaviour: attitudes, perceptions of social pressure, and perceived behavioural control with regard to workplace AOD impairment, all predict behavioural intentions (P < .001); and behavioural intentions predict (self-reported) behaviour regarding workplace AOD impairment (P < .001). ---------- Conclusions: The Theory of Planned Behaviour appears to assist with understanding the mechanisms by which behaviour change occurs with regard to AOD impairment in the workplace. An occupational AOD programme which targets those mechanisms for change may improve its impact in preventing workplace AOD impairment.

Deterring drug drivers : a study into the initial impact of oral random roadside drug testing in Queensland

Objective: The global implementation of oral random roadside drug testing is relatively limited, and correspondingly, the literature that focuses on the effectiveness of this intervention is scant. This study aims to provide a preliminary indication of the impact of roadside drug testing in Queensland. Methods: A sample of Queensland motorists’ (N= 922) completed a self-report questionnaire to investigate their drug driving behaviour, as well as examine the perceived affect of legal sanctions (certainty, severity and swiftness) and knowledge of the countermeasure on their subsequent offending behaviour. Results: Analysis of the collected data revealed that approximately 20% of participants reported drug driving at least once in the last six months. Overall, there was considerable variability in respondent’s perceptions regarding the certainty, severity and swiftness of legal sanctions associated with the testing regime and a considerable proportion remained unaware of testing practices. In regards to predicting those who intended to drug driving again in the future, perceptions of apprehension certainty, more specifically low certainty of apprehension, were significantly associated with self-reported intentions to offend. Additionally, self-reported recent drug driving activity and frequent drug consumption were also identified as significant predictors, which indicates that in the current context, past behaviour is a prominent predictor of future behaviour. To a lesser extent, awareness of testing practices was a significant predictor of intending not to drug drive in the future. Conclusion: The results indicate that drug driving is relatively prevalent on Queensland roads, and a number of factors may influence such behaviour. Additionally, while the roadside testing initiative is beginning to have a deterrent impact, its success will likely be linked with targeted intelligence-led implementation in order to increase apprehension levels as well as the general deterrent effect.

Content and functionality of alcohol and other drug websites : results of an online survey

Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

Indoor and outdoor nitrogen dioxide concentration in residential houses in Australia

As part of a larger indoor environmental study, residential indoor and outdoor levels of nitrogen dioxide (NO2) were measured for 14 houses in a suburb of Brisbane, Queensland, Australia. Passive samplers were used for 48-h sampling periods during the winter of 1999. The average indoor and outdoor NO2 levels were 13.8 ± 6.3 and 16.7 ± 4.2 ppb, respectively. The indoor/outdoor NO2 concentration ratio ranged from 0.4 to 2.3, with a median value of 0.82. The results of statistic analyses indicated that there was no significant correlation between indoor and outdoor NO2 concentrations, or between indoor and fixed site NO2 monitoring station concentrations. However, there was a significant correlation between outdoor and fixed site NO2 monitoring station concentrations. There was also a significant correlation between indoor NO2 concentration and indoor submicrometre (0.007–0.808 μm) aerosol particle number concentrations. The results in this study indicated indoor NO2 levels are significantly affected by indoor NO2 sources, such as a gas stove and cigarette smoking. It implies that the outdoor or fixed site monitoring concentration alone is a poor predictor of indoor NO2 concentration.

Effects of magnesium stearate on the efficient dispersion of salbutamol sulphate from carrier-based dry powder inhaler formulations

Dry powder inhaler (DPI) formulations is one of the most useful aerosol preparations in which drugs may be formulated as carrier-based interactive mixtures with micronised drug particles (<5 μm) adhered onto the surface of large inert carriers (lactose powders). The addition of magnesium stearate (MgSt) (1-3), was found to increase dispersion of various drugs from DPI formulations. Recently, some active compounds coated with 5% (wt/wt) MgSt using the mechanofusion method showed significant improvements in aerosolization behavior due to the reduction in intrinsic cohesion force (4). Application of MgSt in powder formulations is not new; however, no studies demonstrated the minimum threshold level for this excipient in efficient aerosolization of drug powders from the interactive mixtures. Therefore, this study investigated the role of MgSt concentration on the efficient dispersion of salbutamol sulphate (SS) from DPI formulations.

Electrospraying a reproducible method for production of polymeric microspheres for biomedical applications

The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 um. Particles were shown to be spherical with a homogenous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components.

The effects of bioactive akermanite on physiochemical, drug-delivery and biological properties of poly (lactide-co-glycolide) beads

Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug/protein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Experimental study of the concentration field of discharge from a boat propeller

Two-stroke outboard boat engines using total loss lubrication deposit a significant proportion of their lubricant and fuel directly into the water. The purpose of this work is to document the velocity and concentration field characteristics of a submerged swirling water jet emanating from a propeller in order to provide information on its fundamental characteristics. The properties of the jet were examined far enough downstream to be relevant to the eventual modelling of the mixing problem. Measurements of the velocity and concentration field were performed in a turbulent jet generated by a model boat propeller (0.02 m diameter) operating at 1500 rpm and 3000 rpm in a weak co-flow of 0.04 m/s. The measurements were carried out in the Zone of Established Flow up to 50 propeller diameters downstream of the propeller, which was placed in a glass-walled flume 0.4 m wide with a free surface depth of 0.15 m. The jet and scalar plume development were compared to that of a classical free round jet. Further, results pertaining to radial distribution, self similarity, standard deviation growth, maximum value decay and integral fluxes of velocity and concentration were presented and fitted with empirical correlations. Furthermore, propeller induced mixing and pollutant source concentration from a two-stroke engine were estimated.

Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.