Assessment of function and clinical utility of alcohol and other drug web sites : an observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed.

A new tip area function for instrumented nanoindentation at extremely small contact depths

The accuracy of measurement of mechanical properties of a material using instrumented nanoindentation at extremely small penetration depths heavily relies on the determination of the contact area of the indenter. Our experiments have demonstrated that the conventional area function could lead to a significant error when the contact depth was below 40. nm, due to the singularity in the first derivation of the function in this region and thus, the resultant unreasonable sharp peak on the function curve. In this paper, we proposed a new area function that was used to calculate the contact area for the indentations where the contact depths varied from 10 to 40. nm. The experimental results have shown that the new area function has produced better results than the conventional function. © 2011 Elsevier B.V.

Regulation of proteasome structure and function

Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.

Corneal nerve structure and function as markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterisation and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression and assess new therapies. This thesis evaluates novel corneal methods of assessing diabetic neuropathy. Over the past several years two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy (CCM) allows quantification of corneal nerve parameters and non-contact corneal aesthesiometry (NCCA), the presumed functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and with automatic analysis paradigms developed, are suitable for clinical settings. Each has advantages and disadvantages over established techniques for assessing diabetic neuropathy. New information is presented regarding measurement bias of CCM images, and a unique sampling paradigm and associated accuracy determination method of combinations is described. A novel high-speed corneal nerve mapping procedure has been developed and application of this procedure in individuals with neuropathy has revealed regions of sub-basal nerve plexus that dictate further evaluation, as they appear to show earlier signs of damage than the central region of the cornea that has to date been examined. The discriminative capacity of corneal sensitivity measured by NCCA is revealed to have reasonable potential as a marker of diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Human proximal tubule epithelial cells modulate autologous dendritic cell function

Background We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context. Methods Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability. Results The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses. Conclusions Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.

The relationship between drivers’ perceptions toward police speed enforcement and self-reported speeding behaviour

Exceeding the speed limit and driving too fast for the conditions are regularly cited as significant contributing factors in traffic crashes, particularly fatal and serious injury crashes. Despite an extensive body of research highlighting the relationship between increased vehicle speeds and crash risk and severity, speeding remains a pervasive behaviour on Australian roads. The development of effective countermeasures designed to reduce the prevalence of speeding behaviour requires that this behaviour is well understood. The primary aim of this program of research was to develop a better understanding of the influence of drivers’ perceptions and attitudes toward police speed enforcement on speeding behaviour. Study 1 employed focus group discussions with 39 licensed drivers to explore the influence of perceptions relating to specific characteristics of speed enforcement policies and practices on drivers’ attitudes towards speed enforcement. Three primary factors were identified as being most influential: site selection; visibility; and automaticity (i.e., whether the enforcement approach is automated/camera-based or manually operated). Perceptions regarding these enforcement characteristics were found to influence attitudes regarding the perceived legitimacy and transparency of speed enforcement. Moreover, misperceptions regarding speed enforcement policies and practices appeared to also have a substantial impact on attitudes toward speed enforcement, typically in a negative direction. These findings have important implications for road safety given that prior research has suggested that the effectiveness of speed enforcement approaches may be reduced if efforts are perceived by drivers as being illegitimate, such that they do little to encourage voluntary compliance. Study 1 also examined the impact of speed enforcement approaches varying in the degree of visibility and automaticity on self-reported willingness to comply with speed limits. These discussions suggested that all of the examined speed enforcement approaches (see Section 1.5 for more details) generally showed potential to reduce vehicle speeds and encourage compliance with posted speed limits. Nonetheless, participant responses suggested a greater willingness to comply with approaches operated in a highly visible manner, irrespective of the corresponding level of automaticity of the approach. While less visible approaches were typically associated with poorer rates of driver acceptance (e.g., perceived as “sneaky” and “unfair”), participants reported that such approaches would likely encourage long-term and network-wide impacts on their own speeding behaviour, as a function of the increased unpredictability of operations and increased direct (specific deterrence) and vicarious (general deterrence) experiences with punishment. Participants in Study 1 suggested that automated approaches, particularly when operated in a highly visible manner, do little to encourage compliance with speed limits except in the immediate vicinity of the enforcement location. While speed cameras have been criticised on such grounds in the past, such approaches can still have substantial road safety benefits if implemented in high-risk settings. Moreover, site-learning effects associated with automated approaches can also be argued to be a beneficial by-product of enforcement, such that behavioural modifications are achieved even in the absence of actual enforcement. Conversely, manually operated approaches were reported to be associated with more network-wide impacts on behaviour. In addition, the reported acceptance of such methods was high, due to the increased swiftness of punishment, ability for additional illegal driving behaviours to be policed and the salutary influence associated with increased face-to-face contact with authority. Study 2 involved a quantitative survey conducted with 718 licensed Queensland drivers from metropolitan and regional areas. The survey sought to further examine the influence of the visibility and automaticity of operations on self-reported likelihood and duration of compliance. Overall, the results from Study 2 corroborated those of Study 1. All examined approaches were again found to encourage compliance with speed limits, such that all approaches could be considered to be “effective”. Nonetheless, significantly greater self-reported likelihood and duration of compliance was associated with visibly operated approaches, irrespective of the corresponding automaticity of the approach. In addition, the impact of automaticity was influenced by visibility; such that significantly greater self-reported likelihood of compliance was associated with manually operated approaches, but only when they are operated in a less visible fashion. Conversely, manually operated approaches were associated with significantly greater durations of self-reported compliance, but only when they are operated in a highly visible manner. Taken together, the findings from Studies 1 and 2 suggest that enforcement efforts, irrespective of their visibility or automaticity, generally encourage compliance with speed limits. However, the duration of these effects on behaviour upon removal of the enforcement efforts remains questionable and represents an area where current speed enforcement practices could possibly be improved. Overall, it appears that identifying the optimal mix of enforcement operations, implementing them at a sufficient intensity and increasing the unpredictability of enforcement efforts (e.g., greater use of less visible approaches, random scheduling) are critical elements of success. Hierarchical multiple regression analyses were also performed in Study 2 to investigate the punishment-related and attitudinal constructs that influence self-reported frequency of speeding behaviour. The research was based on the theoretical framework of expanded deterrence theory, augmented with three particular attitudinal constructs. Specifically, previous research examining the influence of attitudes on speeding behaviour has typically focussed on attitudes toward speeding behaviour in general only. This research sought to more comprehensively explore the influence of attitudes by also individually measuring and analysing attitudes toward speed enforcement and attitudes toward the appropriateness of speed limits on speeding behaviour. Consistent with previous research, a number of classical and expanded deterrence theory variables were found to significantly predict self-reported frequency of speeding behaviour. Significantly greater speeding behaviour was typically reported by those participants who perceived punishment associated with speeding to be less certain, who reported more frequent use of punishment avoidance strategies and who reported greater direct experiences with punishment. A number of interesting differences in the significant predictors among males and females, as well as younger and older drivers, were reported. Specifically, classical deterrence theory variables appeared most influential on the speeding behaviour of males and younger drivers, while expanded deterrence theory constructs appeared more influential for females. These findings have important implications for the development and implementation of speeding countermeasures. Of the attitudinal factors, significantly greater self-reported frequency of speeding behaviour was reported among participants who held more favourable attitudes toward speeding and who perceived speed limits to be set inappropriately low. Disappointingly, attitudes toward speed enforcement were found to have little influence on reported speeding behaviour, over and above the other deterrence theory and attitudinal constructs. Indeed, the relationship between attitudes toward speed enforcement and self-reported speeding behaviour was completely accounted for by attitudes toward speeding. Nonetheless, the complexity of attitudes toward speed enforcement are not yet fully understood and future research should more comprehensively explore the measurement of this construct. Finally, given the wealth of evidence (both in general and emerging from this program of research) highlighting the association between punishment avoidance and speeding behaviour, Study 2 also sought to investigate the factors that influence the self-reported propensity to use punishment avoidance strategies. A standard multiple regression analysis was conducted for exploratory purposes only. The results revealed that punishment-related and attitudinal factors significantly predicted approximately one fifth of the variance in the dependent variable. The perceived ability to avoid punishment, vicarious punishment experience, vicarious punishment avoidance and attitudes toward speeding were all significant predictors. Future research should examine these relationships more thoroughly and identify additional influential factors. In summary, the current program of research has a number of implications for road safety and speed enforcement policy and practice decision-making. The research highlights a number of potential avenues for the improvement of public education regarding enforcement efforts and provides a number of insights into punishment avoidance behaviours. In addition, the research adds strength to the argument that enforcement approaches should not only demonstrate effectiveness in achieving key road safety objectives, such as reduced vehicle speeds and associated crashes, but also strive to be transparent and legitimate, such that voluntary compliance is encouraged. A number of potential strategies are discussed (e.g., point-to-point speed cameras, intelligent speed adaptation. The correct mix and intensity of enforcement approaches appears critical for achieving optimum effectiveness from enforcement efforts, as well as enhancements in the unpredictability of operations and swiftness of punishment. Achievement of these goals should increase both the general and specific deterrent effects associated with enforcement through an increased perceived risk of detection and a more balanced exposure to punishment and punishment avoidance experiences.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Tax evasion, inequality, and progressive taxes : a political economy perspective

The standard approach to tax compliance applies the economics-of-crime methodology pioneered by Becker (1968): in its first application, due to Allingham and Sandmo (1972) it models the behaviour of agents as a decision involving a choice of the extent of their income to report to tax authorities, given a certain institutional environment, represented by parameters such as the probability of detection and penalties in the event the agent is caught. While this basic framework yields important insights on tax compliance behavior, it has some critical limitations. Specifically, it indicates a level of compliance that is significantly below what is observed in the data. This thesis revisits the original framework with a view towards addressing this issue, and examining the political economy implications of tax evasion for progressivity in the tax structure. The approach followed involves building a macroeconomic, dynamic equilibrium model for the purpose of examining these issues, by using a step-wise model building procedure starting with some very simple variations of the basic Allingham and Sandmo construct, which are eventually integrated to a dynamic general equilibrium overlapping generations framework with heterogeneous agents. One of the variations involves incorporating the Allingham and Sandmo construct into a two-period model of a small open economy of the type originally attributed to Fisher (1930). A further variation of this simple construct involves allowing agents to initially decide whether to evade taxes or not. In the event they decide to evade, the agents then have to decide the extent of income or wealth they wish to under-report. We find that the ‘evade or not’ assumption has strikingly different and more realistic implications for the extent of evasion, and demonstrate that it is a more appropriate modeling strategy in the context of macroeconomic models, which are essentially dynamic in nature, and involve consumption smoothing across time and across various states of nature. Specifically, since deciding to undertake tax evasion impacts on the consumption smoothing ability of the agent by creating two states of nature in which the agent is ‘caught’ or ‘not caught’, there is a possibility that their utility under certainty, when they choose not to evade, is higher than the expected utility obtained when they choose to evade. Furthermore, the simple two-period model incorporating an ‘evade or not’ choice can be used to demonstrate some strikingly different political economy implications relative to its Allingham and Sandmo counterpart. In variations of the two models that allow for voting on the tax parameter, we find that agents typically choose to vote for a high degree of progressivity by choosing the highest available tax rate from the menu of choices available to them. There is, however, a small range of inequality levels for which agents in the ‘evade or not’ model vote for a relatively low value of the tax rate. The final steps in the model building procedure involve grafting the two-period models with a political economy choice into a dynamic overlapping generations setting with more general, non-linear tax schedules and a ‘cost-of evasion’ function that is increasing in the extent of evasion. Results based on numerical simulations of these models show further improvement in the model’s ability to match empirically plausible levels of tax evasion. In addition, the differences between the political economy implications of the ‘evade or not’ version of the model and its Allingham and Sandmo counterpart are now very striking; there is now a large range of values of the inequality parameter for which agents in the ‘evade or not’ model vote for a low degree of progressivity. This is because, in the ‘evade or not’ version of the model, low values of the tax rate encourages a large number of agents to choose the ‘not-evade’ option, so that the redistributive mechanism is more ‘efficient’ relative to the situations in which tax rates are high. Some further implications of the models of this thesis relate to whether variations in the level of inequality, and parameters such as the probability of detection and penalties for tax evasion matter for the political economy results. We find that (i) the political economy outcomes for the tax rate are quite insensitive to changes in inequality, and (ii) the voting outcomes change in non-monotonic ways in response to changes in the probability of detection and penalty rates. Specifically, the model suggests that changes in inequality should not matter, although the political outcome for the tax rate for a given level of inequality is conditional on whether there is a large or small or large extent of evasion in the economy. We conclude that further theoretical research into macroeconomic models of tax evasion is required to identify the structural relationships underpinning the link between inequality and redistribution in the presence of tax evasion. The models of this thesis provide a necessary first step in that direction.