Solubilisation of drugs within liposomal bilayers:alternatives to cholesterol as a membrane stabilising agent

Objectives The aim of this work was to investigate the effect of cholesterol on the bilayer loading of drugs and their subsequent release and to investigate fatty alcohols as an alternative bilayer stabiliser to cholesterol. Methods The loading and release rates of four low solubility drugs (diazepam, ibuprofen, midazolam and propofol) incorporated within the bilayer of multilamellar liposomes which contained a range of cholesterol (0–33 mol/mol%) or a fatty alcohol (tetradecanol, hexadecanol and octadecanol) were investigated. The molecular packing of these various systems was also investigated in Langmuir monolayer studies. Key findings Loading and release of drugs within the liposome bilayer was shown to be influenced by their cholesterol content: increasing cholesterol content was shown to reduce drug incorporation and inclusion of cholesterol in the bilayer changed the release profile of propofol from zero-order, for phosphatidyl choline only liposomes, to a first-order model when 11 to 33 total molar % of cholesterol was present in the formulation. At higher bilayer concentrations substitution of cholesterol with tetradecanol was shown to have less of a detrimental impact on bilayer drug loading. However, the presence of cholesterol within the liposome bilayer was shown to reduce drug release compared with fatty alcohols. Monolayer studies undertaken showed that effective mean area per molecule for a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) : cholesterol mixture deviated by 9% from the predicted area compared with 5% with a similar DSPC : tetradecanol mixture. This evidence, combined with cholesterol being a much more bulky structure, indicated that the condensing influence of tetradecanol was less compared with cholesterol, thus supporting the reduced impact of tetradecanol on drug loading and drug retention. Conclusions Liposomes can be effectively formulated using fatty alcohols as an alternative bilayer stabiliser to cholesterol. The general similarities in the characteristics of liposomes containing fatty alcohols or cholesterol suggest a common behavioural influence for both compounds within the bilayer.

Journey to work:exploring difficulties, solutions and the impact of aging

A study was conducted in the UK, as part of the New Dynamics of Ageing Working Late project, of the journey to work among 1215 older workers (age groups 45-49, 50-55, 56-60 and 60 + ). The aim was to identify problems or concerns that they might have with their commute, strategies that have been adopted to address them, and the role that employers can play to assist them. Follow-up interviews with 36 employees identified many strategies for assisting with the problems of journeys to work, ranging from car share and using public transport to flexible working and working some days from home. Further interviews with a sample of 12 mainly larger companies showed that employers feel a responsibility for their workers’ commute, with some offering schemes to assist them, such as adjusting work shift timings to facilitate easier parking. The research suggests that the journey to work presents difficulties for a significant minority of those aged over 45, including issues with cost, stress, health, fatigue and journey time. It may be possible to reduce the impact of these difficulties on employee decisions to change jobs or retire by assisting them to adopt mitigating strategies. It does not appear that the likelihood of experiencing a problem with the journey to work increases as the employee approaches retirement; therefore, any mitigating strategy is likely to help employees of all ages. These strategies have been disseminated to a wider audience through an online resource at www.workinglate.org.

The impact of national cultures and interpersonal factors on managerial communication

This study was undertaken for two primary purposes. The first was to discover whether or not two of the four cultural dimensions depicted by Hof-stede (1980), namely Power Distance and Uncertainty Avoidance, could be repeated using samples from seven organizations operating in three distinct cultural settings. The second was to assess the degree to which these dimensions affect superior-subordinate communication across the culturally-different groups. Also, the impact of the three interpersonal factors: Trust in Superior, Upward Influence and Mobility Aspirations was investigated cross-culturally. Participants were 291 managers from seven organizations; four Sudanese, two white British and an organization in Britain run by a group of British citizens of Pakistani extraction. It was hypothesized that the Power Distance and Uncertainty Avoidance of the three groups would replicate Hof-stede's. Specific implications of these dimensions for organizational communication and in particular for superior-subordinate communication were also hypothesized. Multiple regression analyses were performed with items of the two cultural dimensions and the three interpersonal factors (each in turn) forming the independent variables, while the organizational communication aspects formed the dependent variables. T-tests between means were also used to compare and contrast issues such as directionality of information flow across organizations operating in these settings. Work-related values of each of the three cultural groups provided support for Hofstede's model. However, only tentative support was given to the hypothesized relationships between the cultural dimensions and organizational communication. Similarly, weak associations were found between the three interpersonal factors and superior-subordinate communication behaviour. Some practical and theoretical implications are offered. An evaluation of the study and recommendation for further research are also given.

Effect of fatigue on consumers' advertising processing

Huge advertising budgets are invested by firms to reach and convince potential consumers to buy their products. To optimize these investments, it is fundamental not only to ensure that appropriate consumers will be reached, but also that they will be in appropriate reception conditions. Marketing research has focused on the way consumers react to advertising, as well as on some individual and contextual factors that could mediate or moderate the ad impact on consumers (e.g. motivation and ability to process information or attitudes toward advertising). Nevertheless, a factor that potentially influences consumers’ advertising reactions has not yet been studied in marketing research: fatigue. Fatigue can yet impact key variables of advertising processing, such as cognitive resources availability (Lieury 2004). Fatigue is felt when the body warns to stop an activity (or inactivity) to have some rest, allowing the individual to compensate for fatigue effects. Dittner et al. (2004) defines it as “the state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.’’ It signals that resources will lack if we continue with the ongoing activity. According to Schmidtke (1969), fatigue leads to troubles in information reception, in perception, in coordination, in attention getting, in concentration and in thinking. In addition, for Markle (1984) fatigue generates a decrease in memory, and in communication ability, whereas it increases time reaction, and number of errors. Thus, fatigue may have large effects on advertising processing. We suggest that fatigue determines the level of available resources. Some research about consumer responses to advertising claim that complexity is a fundamental element to take into consideration. Complexity determines the cognitive efforts the consumer must provide to understand the message (Putrevu et al. 2004). Thus, we suggest that complexity determines the level of required resources. To study this complex question about need and provision of cognitive resources, we draw upon Resource Matching Theory. Anand and Sternthal (1989, 1990) are the first to state the Resource Matching principle, saying that an ad is most persuasive when the resources required to process it match the resources the viewer is willing and able to provide. They show that when the required resources exceed those available, the message is not entirely processed by the consumer. And when there are too many available resources comparing to those required, the viewer elaborates critical or unrelated thoughts. According to the Resource Matching theory, the level of resource demanded by an ad can be high or low, and is mostly determined by the ad’s layout (Peracchio and Myers-Levy, 1997). We manipulate the level of required resources using three levels of ad complexity (low – high – extremely high). On the other side, the resource availability of an ad viewer is determined by lots of contextual and individual variables. We manipulate the level of available resources using two levels of fatigue (low – high). Tired viewers want to limit the processing effort to minimal resource requirements by making heuristics, forming overall impression at first glance. It will be easier for them to decode the message when ads are very simple. On the contrary, the most effective ads for viewers who are not tired are complex enough to draw their attention and fully use their resources. They will use more analytical strategies, looking at the details of the ad. However, if ads are too complex, they will be too difficult to understand. The viewer will be discouraged to process information and will overlook the ad. The objective of our research is to study fatigue as a moderating variable of advertising information processing. We run two experimental studies to assess the effect of fatigue on visual strategies, comprehension, persuasion and memorization. In study 1, thirty-five undergraduate students enrolled in a marketing research course participated in the experiment. The experimental design is 2 (tiredness level: between subjects) x 3 (ad complexity level: within subjects). Participants were randomly assigned a schedule time (morning: 8-10 am or evening: 10-12 pm) to perform the experiment. We chose to test subjects at various moments of the day to obtain maximum variance in their fatigue level. We use Morningness / Eveningness tendency of participants (Horne & Ostberg, 1976) as a control variable. We assess fatigue level using subjective measures - questionnaire with fatigue scales - and objective measures - reaction time and number of errors. Regarding complexity levels, we have designed our own ads in order to keep aspects other than complexity equal. We ran a pretest using the Resource Demands scale (Keller and Bloch 1997) and by rating them on complexity like Morrison and Dainoff (1972) to check for our complexity manipulation. We found three significantly different levels. After having completed the fatigue scales, participants are asked to view the ads on a screen, while their eye movements are recorded by the eye-tracker. Eye-tracking allows us to find out patterns of visual attention (Pieters and Warlop 1999). We are then able to infer specific respondents’ visual strategies according to their level of fatigue. Comprehension is assessed with a comprehension test. We collect measures of attitude change for persuasion and measures of recall and recognition at various points of time for memorization. Once the effect of fatigue will be determined across the student population, it is interesting to account for individual differences in fatigue severity and perception. Therefore, we run study 2, which is similar to the previous one except for the design: time of day is now within-subjects and complexity becomes between-subjects

Fatigue crack growth behaviour in molten-metal processed SiC particle-reinforced aluminium alloys

Fatigue crack initiation and subsequent short crack growth behaviour of 2014-5wt%SiC aluminium alloy composites has been examined in 4-point bend loading using smooth bar specimens. The growth rates of long fatigue cracks have also been measured at different stress ratios using pre-cracked specimens. The distributions of SiC particles and of coarse constituent particles in the matrix (which arise as a result of the molten-metal processing and relatively slow cooling rate) have been investigated. Preferential crack initiation sites were found to be SiC-matrix interfaces, SiC particles associated with constituent particles and the coarse constituent particles themselves. For microstructurally short cracks the dispersed SiC particles also act as temporary crack arresters. In the long crack growth tests, higher fatigue crack growth rates were obtained than for monolithic alloys. This effect is attributed to the contribution of void formation, due to the decohesion of SiC particles, to the fatigue crack growth process in the composite. Above crack depths of about 200 μm 'short' crack growth rates were in good agreement with the long crack data, showing a Pris exponent, m = 4 in both cases. For the long crack and short crack growth tests little effect of specimen orientation and grain size was observed on fatigue crack growth rates, but, specimen orientation affected the toughness. No effect of stress ratio in the range R = 0.2-0.5 was seen for long crack data in the Paris region.

Fracture and viscoelastic properties of asphalt binders during fatigue and rest periods

Viscoelastic asphalt binder plays an important role in bonding individual aggregate particles and contributes to the durability and stability of asphalt pavement. When asphalt binder is subjected to cyclic loading, deformation and fracture may develop simultaneously within it, leading to the deterioration of material properties and eventually fatigue failure. Research has found that some degree of recovery may develop if rest periods are applied after fatigue deterioration. However, it is not clear whether such recovery is caused by fracture healing, viscoelastic recovery, or both. This paper presents an analysis to differentiate the contributions of fracture healing and viscoelastic recovery to the asphalt binder during rest periods. It also evaluates the damage caused by deformation and fracture during a fatigue process. It is found that viscoelastic recovery plays an important role in the instant increase in the dynamic shear modulus at the beginning of the rest period. The effect of fracture healing on dynamic shear modulus recovery is more dominant in the long term. A healing index is developed based only on the fracture healing of asphalt binder, excluding the effect of viscoelastic recovery. It can be used to evaluate the true healing properties of different asphalt binders. Copyright © 2014 by ASTM International.

On the impact of Cu dispersion on CO2 photoreduction over Cu/TiO2

A family of Cu/TiO2 catalysts was prepared using a refined sol–gel method, and tested in the photocatalytic reduction of CO2 by H2O to CH4 using a stirred batch, annular reactor. The resulting photoactivity was benchmarked against pure TiO2 nanoparticles (synthesised by an identical sol–gel route). CO2 photoreduction exhibited a strong volcano dependence on Cu loading, reflecting the transition from 2-dimensional CuOx nanostructures to 3-dimensional crystallites, with optimum CH4 production observed for 0.03 wt.% Cu/TiO2.

Effects of truck traffic on top-down fatigue cracking performance of flexible pavements using a new mechanics-based analysis framework

The mechanics-based analysis framework predicts top-down fatigue cracking initiation time in asphalt concrete pavements by utilising fracture mechanics and mixture morphology-based property. To reduce the level of complexity involved, traffic data were characterised and incorporated into the framework using the equivalent single axle load (ESAL) approach. There is a concern that this kind of simplistic traffic characterisation might result in erroneous performance predictions and pavement structural designs. This paper integrates axle load spectra and other traffic characterisation parameters into the mechanics-based analysis framework and studies the impact these traffic characterisation parameters have on predicted fatigue cracking performance. The traffic characterisation inputs studied are traffic growth rate, axle load spectra, lateral wheel wander and volume adjustment factors. For this purpose, a traffic integration approach which incorporates Monte Carlo simulation and representative traffic characterisation inputs was developed. The significance of these traffic characterisation parameters was established by evaluating a number of field pavement sections. It is evident from the results that all the traffic characterisation parameters except truck wheel wander have been observed to have significant influence on predicted top-down fatigue cracking performance.