The use of economic evaluation in CAM : an introductory framework

Background For CAM to feature prominently in health care decision-making there is a need to expand the evidence-base and to further incorporate economic evaluation into research priorities. In a world of scarce health care resources and an emphasis on efficiency and clinical efficacy, CAM, as indeed do all other treatments, requires rigorous evaluation to be considered in budget decision-making. Methods Economic evaluation provides the tools to measure the costs and health consequences of CAM interventions and thereby inform decision making. This article offers CAM researchers an introductory framework for understanding, undertaking and disseminating economic evaluation. The types of economic evaluation available for the study of CAM are discussed, and decision modelling is introduced as a method for economic evaluation with much potential for use in CAM. Two types of decision models are introduced, decision trees and Markov models, along with a worked example of how each method is used to examine costs and health consequences. This is followed by a discussion of how this information is used by decision makers. Conclusions Undoubtedly, economic evaluation methods form an important part of health care decision making. Without formal training it can seem a daunting task to consider economic evaluation, however, multidisciplinary teams provide an opportunity for health economists, CAM practitioners and other interested researchers, to work together to further develop the economic evaluation of CAM.

Developing a sustainability assessment model : the sustainable infrastructure, land-use, environment and transport model

Measuring the comparative sustainability levels of cities, regions, institutions and projects is an essential procedure in creating sustainable urban futures. This paper introduces a new urban sustainability assessment model: “The Sustainable Infrastructure, Land-use, Environment and Transport Model (SILENT)”. The SILENT Model is an advanced geographic information system and indicator-based comparative urban sustainability indexing model. The model aims to assist planners and policy makers in their daily tasks in sustainable urban planning and development by providing an integrated sustainability assessment framework. The paper gives an overview of the conceptual framework and components of the model and discusses the theoretical constructs, methodological procedures, and future development of this promising urban sustainability assessment model.

Patterns, heuristics for architectural design support: making use of evolutionary modelling in design

Software used by architectural and industrial designers – has moved from becoming a tool for drafting, towards use in verification, simulation, project management and project sharing remotely. In more advanced models, parameters for the designed object can be adjusted so a family of variations can be produced rapidly. With advances in computer aided design technology, numerous design options can now be generated and analyzed in real time. However the use of digital tools to support design as an activity is still at an early stage and has largely been limited in functionality with regard to the design process. To date, major CAD vendors have not developed an integrated tool that is able to both leverage specialized design knowledge from various discipline domains (known as expert knowledge systems) and support the creation of design alternatives that satisfy different forms of constraints. We propose that evolutionary computing and machine learning be linked with parametric design techniques to record and respond to a designer’s own way of working and design history. It is expected that this will lead to results that impact on future work on design support systems-(ergonomics and interface) as well as implicit constraint and problem definition for problems that are difficult to quantify.

Informed learning: a pedagogical construct attending simultaneously to information use and learning.

The idea of informed learning, applicable in academic, workplace and community settings, has been derived largely from a program of phenomenographic research in the field of information literacy, which has illuminated the experience of using information to learn. Informed learning is about simultaneous attention to information use and learning, where both information and learning are considered to be relational; and is built upon a series of key concepts such as second–order perspective, simultaneity, awareness, and relationality. Informed learning also relies heavily on reflection as a strategy for bringing about learning. As a pedagogical construct, informed learning supports inclusive curriculum design and implementation. This paper reports aspects of the informed learning research agenda which are currently being pursued at the Queensland University of Technology (QUT). The first part elaborates the idea of informed learning, examines the key concepts underpinning this pedagogical construct, and explains its emergence from the research base of the QUT Information Studies research team. The second presents a case, which demonstrates the ongoing development of informed learning theory and practice, through the development of inclusive informed learning for a culturally diverse higher education context.

Health risk from the use of roof-harvested rainwater in Southeast Queensland, Australia, as potable or nonpotable water, determined using quantitative microbial risk assessment

A total of 214 rainwater samples from 82 tanks were collected in urban Southeast Queensland (SEQ) in Australia and analysed for the zoonotic bacterial and protozoan pathogen using real-time binary PCR and quantitative PCR (qPCR). Quantitative Microbial Risk Assessment (QMRA) analysis was used to quantify the risk of infection associated with the exposure to potential pathogens from potable and non-potable uses of roof-harvested rainwater. Of the 214 samples tested, 10.7%, 9.8%, and 5.6%, and 0.4% samples were positive for Salmonella invA, Giardia lamblia β-giardin , Legionella pneumophila mip, and Campylobacter jejuni mapA genes. Cryptosporidium parvum could not be detected. The estimated numbers of viable Salmonella spp., G. lamblia β-giradin, and L. pneumophila genes ranged from 1.6 × 101 to 9.5 × 101 cells, 1.4 × 10-1 to 9.0 × 10-1 cysts, and 1.5 × 101 to 4.3 × 101 per 1000 ml of water, respectively. Six risk scenarios were considered from exposure to Salmonella spp., G. lamblia and L. pneumophila. For Salmonella spp., and G. lamblia, these scenarios were: (1) liquid ingestion due to drinking of rainwater on a daily basis (2) accidental liquid ingestion due to garden hosing twice a week (3) aerosol ingestion due to showering on a daily basis, and (4) aerosol ingestion due to hosing twice a week. For L. pneumophila, these scenarios were: (5) aerosol inhalation due to showering on a daily basis, and (6) aerosol inhalation due to hosing twice a week. The risk of infection from Salmonella spp., G. lamblia, and L. pneumophila associated with the use of rainwater for showering and garden hosing was calculated to be well below the threshold value of one extra infection per 10,000 persons per year in urban SEQ. However, the risk of infection from ingesting Salmonella spp. and G. lamblia via drinking exceeds this threshold value, and indicates that if undisinfected rainwater were ingested by drinking, then the gastrointestinal diseases of Salmonellosis and Giardiasis is expected to range from 5.0 × 100 to 2.8 × 101 (Salmonellosis) and 1.0 × 101 to 6.4 × 101 (Giardiasis) cases per 10,000 persons per year, respectively. Since this health risk seems higher than that expected from the reported incidences of gastroenteritis, the assumptions used to estimate these infection risks are critically examined. Nonetheless, it would seem prudent to disinfect rainwater for potable use.

Optimism about safety and group-serving interpretations of safety among pedestrians and cyclists in relation to road use in general and under low light conditions

Drivers are known to be optimistic about their risk of crash involvement, believing that they are less likely to be involved in a crash than other drivers. However, little comparative research has been conducted among other road users. In addition, optimism about crash risk is conceptualised as applying only to an individual’s assessment of his or her personal risk of crash involvement. The possibility that the self-serving nature of optimism about safety might be generalised to the group-level as a cyclist or a pedestrian, i.e., becoming group-serving rather than self-serving, has been overlooked in relation to road safety. This study analysed a subset of data collected as part of a larger research project on the visibility of pedestrians, cyclists and road workers, focusing on a set of questionnaire items administered to 406 pedestrians, 838 cyclists and 622 drivers. The items related to safety in various scenarios involving drivers, pedestrians and cyclists, allowing predictions to be derived about group differences in agreement with items based on the assumption that the results would exhibit group-serving bias. Analysis of the responses indicated that specific hypotheses about group-serving interpretations of safety and responsibility were supported in 22 of the 26 comparisons. When the nine comparisons relevant to low lighting conditions were considered separately, seven were found to be supported. The findings of the research have implications for public education and for the likely acceptance of messages which are inconsistent with current assumptions and expectations of pedestrians and cyclists. They also suggest that research into group-serving interpretations of safety, even for temporary roles rather than enduring groups, could be fruitful. Further, there is an implication that gains in safety can be made by better educating road users about the limitations of their visibility and the ramifications of this for their own road safety, particularly in low light.

Use of lifts and refuge floors for fire evacuation in high rise apartment buildings

If current population and accommodation trends continue, Australian cities will, in the future, have noticeable numbers of apartment buildings over 60 storeys high. With an aging population it follows that a significant proportion of those occupying these buildings will be senior citizens, many of whom will have some form of disability. For these occupants a fire emergency in a high rise building presents a serious problem. Currently lifts cannot be used for evacuation and going down 60 storeys in a fire isolated staircase would be physically impossible for many. Therefore, for many, the temptation to remain in one’s unit will be very strong. With an awareness of this behaviour trend in older residents, many researchers have, in recent years, explored the possible wider use of lifts in a fire emergency. So far the use of lifts for evacuation has been approved for a small number of buildings but wide acceptance of this solution is still to be achieved. This paper concludes that even in high-rise apartment buildings where lifts are approved for evacuation, architects should design the building with alternative evacuation routes and provide suitable safe refuge areas for those who cannot use the stairs when the lifts are unavailable.

Vectors and alternative hosts of tobacco yellow dwarf virus in southeastern Australia

Factors that determine the epidemiology of Tobacco yellow dwarf virus (TbYDV), including alternative host plants and insect vector(s), were assessed over three consecutive growing seasons at four field sites in Northeastern Victoria in commercial tobacco growing properties. In addition, these factors were assessed for one growing season at three bean growing properties. Overall, 23 leafhopper species were identified at the 7 sites, with Orosius orientalis as the predominant leafhopper. Of the leafhoppers collected, only O. orientalis and Anzygina zealandica tested positive for TbYDV by polymerase chain reaction (PCR). The population dynamics of O. orientalis was assessed using sweep net sampling over three growing seasons and a trimodal distribution was observed. Despite large numbers of O. orientalis occurring early in the growing season (September–October), TbYDV was only detected in these leafhoppers between late November and end of January. The peaks in the detection of TbYDV in O. orientalis correlated with the observation of disease symptoms in tobacco and bean and were associated with warmer temperatures and lower rainfall. Spatial and temporal distribution of vegetation at selected sites was determined using quadrat sampling. Of the 40 plant species identified, TbYDV was detected only in four dicotyledonous species, Amaranthus retroflexus, Phaseolus vulgaris, Nicotiana tabacum and Raphanus raphanistrum. The proportion of host and non-host availability for leafhoppers was associated with climatic conditions.

The use of ZIP and CART to model cryptosporidiosis in relation to climatic variables

This research assesses the potential impact of weekly weather variability on the incidence of cryptosporidiosis disease using time series zero-inflated Poisson (ZIP) and classification and regression tree (CART) models. Data on weather variables, notified cryptosporidiosis cases and population size in Brisbane were supplied by the Australian Bureau of Meteorology, Queensland Department of Health, and Australian Bureau of Statistics, respectively. Both time series ZIP and CART models show a clear association between weather variables (maximum temperature, relative humidity, rainfall and wind speed) and cryptosporidiosis disease. The time series CART models indicated that, when weekly maximum temperature exceeded 31°C and relative humidity was less than 63%, the relative risk of cryptosporidiosis rose by 13.64 (expected morbidity: 39.4; 95% confidence interval: 30.9–47.9). These findings may have applications as a decision support tool in planning disease control and risk management programs for cryptosporidiosis disease.

The impact of managers' characteristics on the use of public relations strategy : an exploratory study in Queensland schools

While previous positive and normative studies have focused on the role public relations should play in organisations and the need for management in all organisations to attend to public relations (Cutlip et al., 2006), there has been little discussion in the public relations literature on why or how managers choose to enact public relations strategies for their organisations. If the discipline of public relations is to cement itself as a management function, then researchers must gain a better understanding of managers themselves given that they are the ones who decide if and how public relations strategies should be employed in the organisation. This study has sought to explore evidence of a relationship between management characteristics and their impact on decisions managers make when choosing which public relations strategies to adopt in response to changes in the organisation’s operating environment. This exploratory research study has been conducted within a specific context of schools in Queensland, Australia. Queensland schools have been facing a number of changes within their operating environment due to changes in Federal funding models in Australia’s education system. This study used an exploratory, qualitative approach to understand the management characteristics demonstrated by managers in schools and how these have impacted on the selection of public relations strategies for responding to their changing and increasingly competitive environment. The unit of analysis for this research study was principals in State (government) schools and in non-government schools. Ten principals were interviewed from four different types of schools in Queensland – the more traditional, elite, private schools (GPS Schools); other Independent Schools; Catholic Schools; and State (or public) schools. These interviews were analysed for quantitative comparisons of the managers’ characteristics across the different schools (in terms of the number of principals in each age bracket, those holding postgraduate qualifications, years of experience etc.); and for qualitative data to provide a greater sense of their understanding of public relations. The 10 schools were selected within a geographic area from Brisbane’s inner city to its outer western suburbs to include an element of competition amongst those managers being interviewed. A detailed review of government, school and other public documents was also conducted to gain an insight into the environment in which principals made decisions about public relations strategy to respond to increasing competition. This study found support for the literature on the relationship between management characteristics and strategy. However, there was also variation in findings warranting further investigation of the literature on the relationship between management characteristics and strategy in a school setting. Key relationships found in this study were between: management characteristics themselves; age and the use of public relations strategies; and gender and the use of public relations strategies. There was also evidence of support for the literature linking the impact that the combination of managers’ age, education and experience had on the use of public relations strategies. While this study was exploratory in nature, it did reveal a number of areas that require further investigation to gain a deeper understanding of how and why managers choose public relations strategies as a response to changes in their operating environment. It also provided a different framework to gain a better understanding of managers’ understanding and support of public relations in schools, which, in conjunction with an analysis of their management characteristics, will hopefully allow public relations scholars and practitioners alike gain an understanding of how and why managers use public relations strategies.

The effects of cognitive ageing on the use of complex interfaces

This paper discusses an experiment investigating the effects of cognitive ageing and prior-experience with technology on using complex interfaces intuitively. Overall 37 participants, between the ages of 18 to 83, participated in this study. All participants were assessed for their cognitive abilities and prior-experience with technology. It was anticipated that the Central Executive function (a component of Working Memory) would emerge as one of the important cognitive functions in using complex interfaces. This was found to be the case with the strongest negative correlation occurring between sustained attention (one of the functions of the Central Executive), the time to complete the task and number of errors made by the participants.

Use of ITS to improve level crossings safety : open issues

Level crossing crashes have been shown to result in enormous human and financial cost to society. According to the Australian Transport Safety Bureau (ATSB) [5] a total of 632 Railway Level crossing (RLX) collisions, between trains and road vehicles, occurred in Australia between 2001 and June 2009. The cost of RLX collisions runs into the tens of millions of dollars each year in Australia [6]. In addition, loss of life and injury are commonplace in instances where collisions occur. Based on estimates that 40% of rail related fatalities occur at level crossings [12], it is estimated that 142 deaths between 2001 and June 2009 occurred at RLX. The aim of this paper is to (i) summarise crash patterns in Australia, (ii) review existing international ITS interventions to improve level crossing and (iii) highlights open human factors research related issues. Human factors (e.g., driver error, lapses or violations) have been evidenced as a significant contributing factor in RLX collisions, with drivers of road vehicles particularly responsible for many collisions. Unintentional errors have been found to contribute to 46% of RLX collisions [6] and appear to be far more commonplace than deliberate violations. Humans have been found to be inherently inadequate at using the sensory information available to them to facilitate safe decision-making at RLX and tend to underestimate the speed of approaching large objects due to the non-linear increases in perceived size [6]. Collisions resulting from misjudgements of train approach speed and distance are common [20]. Thus, a fundamental goal for improved RLX safety is the provision of sufficient contextual information to road vehicle drivers to facilitate safe decision-making regarding crossing behaviours.

Influence of historic land use change on the biosphere-atmosphere-exchange of C and N trace gases in the humid, subtropical region of Queensland

Increases in atmospheric concentrations of the greenhouse gases (GHGs) carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) due to human activities have been linked to climate change. GHG emissions from land use change and agriculture have been identified as significant contributors to both Australia’s and the global GHG budget. This is expected to increase over the coming decades as rates of agriculture intensification and land use change accelerate to support population growth and food production. Limited data exists on CO2, CH4 and N2O trace gas fluxes from subtropical or tropical soils and land uses. To develop effective mitigation strategies a full global warming potential (GWP) accounting methodology is required that includes emissions of the three primary greenhouse gases. Mitigation strategies that focus on one gas only can inadvertently increase emissions of another. For this reason, detailed inventories of GHGs from soils and vegetation under individual land uses are urgently required for subtropical Australia. This study aimed to quantify GHG emissions over two consecutive years from three major land uses; a well-established, unfertilized subtropical grass-legume pasture, a 30 year (lychee) orchard and a remnant subtropical Gallery rainforest, all located near Mooloolah, Queensland. GHG fluxes were measured using a combination of high resolution automated sampling, coarser spatial manual sampling and laboratory incubations. Comparison between the land uses revealed that land use change can have a substantial impact on the GWP on a landscape long after the deforestation event. The conversion of rainforest to agricultural land resulted in as much as a 17 fold increase in GWP, from 251 kg CO2 eq. ha-1 yr-1 in the rainforest to 889 kg CO2 eq. ha-1 yr-1 in the pasture to 2538 kg CO2 eq. ha-1 yr-1 in the lychee plantation. This increase resulted from altered N cycling and a reduction in the aerobic capacity of the soil in the pasture and lychee systems, enhancing denitrification and nitrification events, and reducing atmospheric CH4 uptake in the soil. High infiltration, drainage and subsequent soil aeration under the rainforest limited N2O loss, as well as promoting CH4 uptake of 11.2 g CH4-C ha-1 day-1. This was among the highest reported for rainforest systems, indicating that aerated subtropical rainforests can act as substantial sink of CH4. Interannual climatic variation resulted in significantly higher N2O emission from the pasture during 2008 (5.7 g N2O-N ha day) compared to 2007 (3.9 g N2O-N ha day), despite receiving nearly 500 mm less rainfall. Nitrous oxide emissions from the pasture were highest during the summer months and were highly episodic, related more to the magnitude and distribution of rain events rather than soil moisture alone. Mean N2O emissions from the lychee plantation increased from an average of 4.0 g N2O-N ha-1 day-1, to 19.8 g N2O-N ha-1 day-1 following a split application of N fertilizer (560 kg N ha-1, equivalent to 1 kg N tree-1). The timing of the split application was found to be critical to N2O emissions, with over twice as much lost following an application in spring (emission factor (EF): 1.79%) compared to autumn (EF: 0.91%). This was attributed to the hot and moist climatic conditions and a reduction in plant N uptake during the spring creating conditions conducive to N2O loss. These findings demonstrate that land use change in subtropical Australia can be a significant source of GHGs. Moreover, the study shows that modifying the timing of fertilizer application can be an efficient way of reducing GHG emissions from subtropical horticulture.

Characterisation of the tritrophic interactions between tobacco yellow dwarf virus, its vector and host-plants

Tobacco yellow dwarf virus (TbYDV, family Geminiviridae, genus Mastrevirus) is an economically important pathogen causing summer death and yellow dwarf disease in bean (Phaseolus vulgaris L.) and tobacco (Nicotiana tabacum L.), respectively. Prior to the commencement of this project, little was known about the epidemiology of TbYDV, its vector and host-plant range. As a result, disease control strategies have been restricted to regular poorly timed insecticide applications which are largely ineffective, environmentally hazardous and expensive. In an effort to address this problem, this PhD project was carried out in order to better understand the epidemiology of TbYDV, to identify its host-plant and vectors as well as to characterise the population dynamics and feeding physiology of the main insect vector and other possible vectors. The host-plants and possible leafhopper vectors of TbYDV were assessed over three consecutive growing seasons at seven field sites in the Ovens Valley, Northeastern Victoria, in commercial tobacco and bean growing properties. Leafhoppers and plants were collected and tested for the presence of TbYDV by PCR. Using sweep nets, twenty-three leafhopper species were identified at the seven sites with Orosius orientalis the predominant leafhopper. Of the 23 leafhopper species screened for TbYDV, only Orosius orientalis and Anzygina zealandica tested positive. Forty-two different plant species were also identified at the seven sites and tested. Of these, TbYDV was only detected in four dicotyledonous species, Amaranthus retroflexus, Phaseolus vulgaris, Nicotiana tabacum and Raphanus raphanistrum. Using a quadrat survey, the temporal distribution and diversity of vegetation at four of the field sites was monitored in order to assess the presence of, and changes in, potential host-plants for the leafhopper vector(s) and the virus. These surveys showed that plant composition and the climatic conditions at each site were the major influences on vector numbers, virus presence and the subsequent occurrence of tobacco yellow dwarf and bean summer death diseases. Forty-two plant species were identified from all sites and it was found that sites with the lowest incidence of disease had the highest proportion of monocotyledonous plants that are non hosts for both vector and the virus. In contrast, the sites with the highest disease incidence had more host-plant species for both vector and virus, and experienced higher temperatures and less rainfall. It is likely that these climatic conditions forced the leafhopper to move into the irrigated commercial tobacco and bean crop resulting in disease. In an attempt to understand leafhopper species diversity and abundance, in and around the field borders of commercially grown tobacco crops, leafhoppers were collected from four field sites using three different sampling techniques, namely pan trap, sticky trap and sweep net. Over 51000 leafhopper samples were collected, which comprised 57 species from 11 subfamilies and 19 tribes. Twentythree leafhopper species were recorded for the first time in Victoria in addition to several economically important pest species of crops other than tobacco and bean. The highest number and greatest diversity of leafhoppers were collected in yellow pan traps follow by sticky trap and sweep nets. Orosius orientalis was found to be the most abundant leafhopper collected from all sites with greatest numbers of this leafhopper also caught using the yellow pan trap. Using the three sampling methods mentioned above, the seasonal distribution and population dynamics of O. orientalis was studied at four field sites over three successive growing seasons. The population dynamics of the leafhopper was characterised by trimodal peaks of activity, occurring in the spring and summer months. Although O. orientalis was present in large numbers early in the growing season (September-October), TbYDV was only detected in these leafhoppers between late November and the end of January. The peak in the detection of TbYDV in O. orientalis correlated with the observation of disease symptoms in tobacco and bean and was also associated with warmer temperatures and lower rainfall. To understand the feeding requirements of Orosius orientalis and to enable screening of potential control agents, a chemically-defined artificial diet (designated PT-07) and feeding system was developed. This novel diet formulation allowed survival for O. orientalis for up to 46 days including complete development from first instar through to adulthood. The effect of three selected plant derived proteins, cowpea trypsin inhibitor (CpTi), Galanthus nivalis agglutinin (GNA) and wheat germ agglutinin (WGA), on leafhopper survival and development was assessed. Both GNA and WGA were shown to reduce leafhopper survival and development significantly when incorporated at a 0.1% (w/v) concentration. In contrast, CpTi at the same concentration did not exhibit significant antimetabolic properties. Based on these results, GNA and WGA are potentially useful antimetabolic agents for expression in genetically modified crops to improve the management of O. orientalis, TbYDV and the other pathogens it vectors. Finally, an electrical penetration graph (EPG) was used to study the feeding behaviour of O. orientalis to provide insights into TbYDV acquisition and transmission. Waveforms representing different feeding activity were acquired by EPG from adult O. orientalis feeding on two plant species, Phaseolus vulgaris and Nicotiana tabacum and a simple sucrose-based artificial diet. Five waveforms (designated O1-O5) were observed when O. orientalis fed on P. vulgaris, while only four (O1-O4) and three (O1-O3) waveforms were observed during feeding on N. tabacum and the artificial diet, respectively. The mean duration of each waveform and the waveform type differed markedly depending on the food source. This is the first detailed study on the tritrophic interactions between TbYDV, its leafhopper vector, O. orientalis, and host-plants. The results of this research have provided important fundamental information which can be used to develop more effective control strategies not only for O. orientalis, but also for TbYDV and other pathogens vectored by the leafhopper.

Cognitive behaviour therapy (CBT) for the treatment of co-occurring depression and substance use : current evidence and directions for future research

Issues and Approach: The high rates of co-occurring depression and substance use, and the negative impact of this on illness course and outcomes have been well established. Despite this, few clinical trials have examined the efficacy of cognitive behaviour therapy (CBT). This paper systematically reviews these clinical trials, with an aim of providing recommendations for how future research can develop a more robust evidence base for the treatment of these common comorbidities. Leading electronic databases, including PubMed (ISI) and PsychINFO (CSA), were searched for peer-reviewed journal articles using CBT for the treatment of co-occurring depression and substance use. Of the 55 articles identified, 12 met inclusion criteria and were included in the review. ---------- Key Findings: There is only a limited evidence for the effectiveness of CBT either alone or in combination with antidepressant medication for the treatment of co-occurring depression and substance use. While there is support for the efficacy of CBT over no treatment control conditions, there is little evidence that CBT is more efficacious than other psychotherapies. There is, however, consistent evidence of improvements in both depression and substance use outcomes, regardless of the type of treatment provided and there is growing evidence that that the effects of CBT are durable and increase over time during follow up. ---------- Conclusions. Rather than declaring the ‘dodo bird verdict’ that CBT and all other psychotherapies are equally efficacious, it would be more beneficial to develop more potent forms of CBT by identifying variables that mediate treatment outcomes.