851 resultados para Well-established biomarkers


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Motivational interviewing (MI)can be applied as a brief, low intensity (LI) intervention of 1-4 individualised sessions (typically 45-60 minutes in duration), including screening, assessment feedback, and psycho-education. MI is a client-centred, directive therapeutic style that enhances readiness for change by helping clients explore and resolve ambivalence (Miller and Rollnick 2002). A summary of the key components of brief MI interventions is provided in Table 16.1. There is a well-established evidence base for MI in the treatment of substance misuse (particularly alcohol misuse; Moyer et al. 2002), as well as a growing evidence for the use of MI in the treatment of other mental disorders (e.g. depression, PTSD, OCD), as well as suicidality and physical health problems (Hettema et al. 2005). Brief MI intervention can be delivered as a standalone treatment or as a motivational prelude to pharmacological and/or other psychological treatments (Hettema et al. 2005). MI has been used as an accompaniment to cognitive behavioural therapy (CBT) in the treatment of both depression and anxiety for resolving ambivalence about change and developing strategies for responding to resistance (e.g. treatment attendance, homework/medication compliance; Arkowitz et al. 2008a, 2008b). This chapter will describe how to apply brief MI interventions to the treatment of depression and anxiety as applied to the case of Megan (see Box 16.1) along with some of the challenges and potential solutions to applying MI in practice.

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Community engagement with time poor and seemingly apathetic citizens continues to challenge local governments. Capturing the attention of a digitally literate community who are technology and socially savvy adds a new quality to this challenge. Community engagement is resource and time intensive, yet local governments have to manage on continually tightened budgets. The benefits of assisting citizens in taking ownership in making their community and city a better place to live in collaboration with planners and local governments are well established. This study investigates a new collaborative form of civic participation and engagement for urban planning that employs in-place digital augmentation. It enhances people’s experience of physical spaces with digital technologies that are directly accessible within that space, in particular through interaction with mobile phones and public displays. The study developed and deployed a system called Discussions in Space (DIS) in conjunction with a major urban planning project in Brisbane. Planners used the system to ask local residents planning-related questions via a public screen, and passers-by sent responses via SMS or Twitter onto the screen for others to read and reflect, hence encouraging in-situ, real-time, civic discourse. The low barrier of entry proved to be successful in engaging a wide range of residents who are generally not heard due to their lack of time or interest. The system also reflected positively on the local government for reaching out in this way. Challenges and implications of the short-texted and ephemeral nature of this medium were evaluated in two focus groups with urban planners. The paper concludes with an analysis of the planners’ feedback evaluating the merits of the data generated by the system to better engage with Australia’s new digital locals.

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Intelligible and accurate risk-based decision-making requires a complex balance of information from different sources, appropriate statistical analysis of this information and consequent intelligent inference and decisions made on the basis of these analyses. Importantly, this requires an explicit acknowledgement of uncertainty in the inputs and outputs of the statistical model. The aim of this paper is to progress a discussion of these issues in the context of several motivating problems related to the wider scope of agricultural production. These problems include biosecurity surveillance design, pest incursion, environmental monitoring and import risk assessment. The information to be integrated includes observational and experimental data, remotely sensed data and expert information. We describe our efforts in addressing these problems using Bayesian models and Bayesian networks. These approaches provide a coherent and transparent framework for modelling complex systems, combining the different information sources, and allowing for uncertainty in inputs and outputs. While the theory underlying Bayesian modelling has a long and well established history, its application is only now becoming more possible for complex problems, due to increased availability of methodological and computational tools. Of course, there are still hurdles and constraints, which we also address through sharing our endeavours and experiences.

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Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. Analysing the tissue engineering literature it can be concluded that bone regeneration has become a focus area in the field. Hence, a considerable number of research groups and commercial entities work on the development of tissue engineered constructs for bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. In translational orthopaedic research, the utilisation of large preclinical animal models is a conditio sine qua non. Consequently, to allow comparison between different studies and their outcomes, it is essential that animal models, fixation devices, surgical procedures and methods of taking measurements are well standardized to produce reliable data pools as a base for further research directions. The following chapter reviews animal models of the weight-bearing lower extremity utilized in the field which include representations of fracture-healing, segmental bone defects, and fracture non-unions.

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The ability to differentiate from competitors through the selection of unique offerings is an important cornerstone of competitive performance. Developing unique products and services to offer in the marketplace is not only important for established firms, but also an important strategic choice for young firms (Baum and Haveman, 1997). Unlike large and established firms, young firms tend to have less access to adequate resources, well-developed sources of information, contact networks, and considerable experience and management know-how. That is, these firms differ significantly in their attributes and performance from larger and well-established firms (c.f. Miller and Chen, 1994). Although young firms are disadvantaged by the paucity of resources in putting together its unique product offering(s), they develop different pathways in advancing their assortment of capabilities that enables them to stay ahead of competitors.

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Background: People with cardiac disease and type 2 diabetes have higher hospital readmission rates (22%)compared to those without diabetes (6%). Self-management is an effective approach to achieve better health outcomes; however there is a lack of specifically designed programs for patients with these dual conditions. This project aims to extend the development and pilot test of a Cardiac-Diabetes Self-Management Program incorporating user-friendly technologies and the preparation of lay personnel to provide follow-up support. Methods/Design: A randomised controlled trial will be used to explore the feasibility and acceptability of the Cardiac-Diabetes Self-Management Program incorporating DVD case studies and trained peers to provide follow-up support by telephone and text-messaging. A total of 30 cardiac patients with type 2 diabetes will be randomised, either to the usual care group, or to the intervention group. Participants in the intervention group will received the Cardiac-Diabetes Self-Management Program in addition to their usual care. The intervention consists of three faceto- face sessions as well as telephone and text-messaging follow up. The face-to-face sessions will be provided by a trained Research Nurse, commencing in the Coronary Care Unit, and continuing after discharge by trained peers. Peers will follow up patients for up to one month after discharge using text messages and telephone support. Data collection will be conducted at baseline (Time 1) and at one month (Time 2). The primary outcomes include self-efficacy, self-care behaviour and knowledge, measured by well established reliable tools. Discussion: This paper presents the study protocol of a randomised controlled trial to pilot evaluates a Cardiac- Diabetes Self-Management program, and the feasibility of incorporating peers in the follow-ups. Results of this study will provide directions for using such mode in delivering a self-management program for patients with both cardiac condition and diabetes. Furthermore, it will provide valuable information of refinement of the intervention program.

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In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

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Differential axial deformation between column elements and shear wall elements of cores increase with building height and geometric complexity. Adverse effects due to the differential axial deformation reduce building performance and life time serviceability. Quantifying axial deformations using ambient measurements from vibrating wire, external mechanical and electronic strain gauges in order to acquire adequate provisions to mitigate the adverse effects is well established method. However, these gauges require installing in or on elements to acquire continuous measurements and hence use of these gauges is uneconomical and inconvenient. This motivates to develop a method to quantify the axial deformations. This paper proposes an innovative method based on modal parameters to quantify axial deformations of shear wall elements in cores of buildings. Capabilities of the method are presented though an illustrative example.

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The use of stable isotope ratios δ18O and δ2H are well established in assessment of groundwater systems and their hydrology. The conventional approach is based on x/y plots and relation to various MWL’s, and plots of either ratio against parameters such as Clor EC. An extension of interpretation is the use of 2D maps and contour plots, and 2D hydrogeological vertical sections. An enhancement of presentation and interpretation is the production of “isoscapes”, usually as 2.5D surface projections. We have applied groundwater isotopic data to a 3D visualisation, using the alluvial aquifer system of the Lockyer Valley. The 3D framework is produced in GVS (Groundwater Visualisation System). This format enables enhanced presentation by displaying the spatial relationships and allowing interpolation between “data points” i.e. borehole screened zones where groundwater enters. The relative variations in the δ18O and δ2H values are similar in these ambient temperature systems. However, δ2H better reflects hydrological processes, whereas δ18O also reflects aquifer/groundwater exchange reactions. The 3D model has the advantage that it displays borehole relations to spatial features, enabling isotopic ratios and their values to be associated with, for example, bedrock groundwater mixing, interaction between aquifers, relation to stream recharge, and to near-surface and return irrigation water evaporation. Some specific features are also shown, such as zones of leakage of deeper groundwater (in this case with a GAB signature). Variations in source of recharging water at a catchment scale can be displayed. Interpolation between bores is not always possible depending on numbers and spacing, and by elongate configuration of the alluvium. In these cases, the visualisation uses discs around the screens that can be manually expanded to test extent or intersections. Separate displays are used for each of δ18O and δ2H and colour coding for isotope values.

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That the cultural industries are highly networked and operate in clusters is now well established. The notion of cluster is linked to the idea of place-based advantage with cultural industries gaining competitive advantage from mobilising the resources of places to compete in global markets. ‘Place’ in the cultural industries is frequently taken to be the city where city is seen as the key resource for cultural industry clusters and a primary point of intervention for cultural industry policy in creative city policy making. In this article I want to look at some of the implications of these moves for both academic research and policy discussion. The reasons for this emphasis on policy relates to some large questions of urban governance and cultural politics surrounding the proactive government of clusters which are raised by recent work on the cultural industries, notably by Alan Scott.

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Understanding the relationship between diet, physical activity and health in humans requires accurate measurement of body composition and daily energy expenditure. Stable isotopes provide a means of measuring total body water and daily energy expenditure under free-living conditions. While the use of isotope ratio mass spectrometry (IRMS) for the analysis of 2H (Deuterium) and 18O (Oxygen-18) is well established in the field of human energy metabolism research, numerous questions remain regarding the factors which influence analytical and measurement error using this methodology. This thesis was comprised of four studies with the following emphases. The aim of Study 1 was to determine the analytical and measurement error of the IRMS with regard to sample handling under certain conditions. Study 2 involved the comparison of TEE (Total daily energy expenditure) using two commonly employed equations. Further, saliva and urine samples, collected at different times, were used to determine if clinically significant differences would occur. Study 3 was undertaken to determine the appropriate collection times for TBW estimates and derived body composition values. Finally, Study 4, a single case study to investigate if TEE measures are affected when the human condition changes due to altered exercise and water intake. The aim of Study 1 was to validate laboratory approaches to measure isotopic enrichment to ensure accurate (to international standards), precise (reproducibility of three replicate samples) and linear (isotope ratio was constant over the expected concentration range) results. This established the machine variability for the IRMS equipment in use at Queensland University for both TBW and TEE. Using either 0.4mL or 0.5mL sample volumes for both oxygen-18 and deuterium were statistically acceptable (p>0.05) and showed a within analytical variance of 5.8 Delta VSOW units for deuterium, 0.41 Delta VSOW units for oxygen-18. This variance was used as “within analytical noise” to determine sample deviations. It was also found that there was no influence of equilibration time on oxygen-18 or deuterium values when comparing the minimum (oxygen-18: 24hr; deuterium: 3 days) and maximum (oxygen-18: and deuterium: 14 days) equilibration times. With regard to preparation using the vacuum line, any order of preparation is suitable as the TEE values fall within 8% of each other regardless of preparation order. An 8% variation is acceptable for the TEE values due to biological and technical errors (Schoeller, 1988). However, for the automated line, deuterium must be assessed first followed by oxygen-18 as the automated machine line does not evacuate tubes but merely refills them with an injection of gas for a predetermined time. Any fractionation (which may occur for both isotopes), would cause a slight elevation in the values and hence a lower TEE. The purpose of the second and third study was to investigate the use of IRMS to measure the TEE and TBW of and to validate the current IRMS practices in use with regard to sample collection times of urine and saliva, the use of two TEE equations from different research centers and the body composition values derived from these TEE and TBW values. Following the collection of a fasting baseline urine and saliva sample, 10 people (8 women, 2 men) were dosed with a doubly labeled water does comprised of 1.25g 10% oxygen-18 and 0.1 g 100% deuterium/kg body weight. The samples were collected hourly for 12 hrs on the first day and then morning, midday, and evening samples were collected for the next 14 days. The samples were analyzed using an isotope ratio mass spectrometer. For the TBW, time to equilibration was determined using three commonly employed data analysis approaches. Isotopic equilibration was reached in 90% of the sample by hour 6, and in 100% of the sample by hour 7. With regard to the TBW estimations, the optimal time for urine collection was found to be between hours 4 and 10 as to where there was no significant difference between values. In contrast, statistically significant differences in TBW estimations were found between hours 1-3 and from 11-12 when compared with hours 4-10. Most of the individuals in this study were in equilibrium after 7 hours. The TEE equations of Prof Dale Scholler (Chicago, USA, IAEA) and Prof K.Westerterp were compared with that of Prof. Andrew Coward (Dunn Nutrition Centre). When comparing values derived from samples collected in the morning and evening there was no effect of time or equation on resulting TEE values. The fourth study was a pilot study (n=1) to test the variability in TEE as a result of manipulations in fluid consumption and level of physical activity; the magnitude of change which may be expected in a sedentary adult. Physical activity levels were manipulated by increasing the number of steps per day to mimic the increases that may result when a sedentary individual commences an activity program. The study was comprised of three sub-studies completed on the same individual over a period of 8 months. There were no significant changes in TBW across all studies, even though the elimination rates changed with the supplemented water intake and additional physical activity. The extra activity may not have sufficiently strenuous enough and the water intake high enough to cause a significant change in the TBW and hence the CO2 production and TEE values. The TEE values measured show good agreement based on the estimated values calculated on an RMR of 1455 kcal/day, a DIT of 10% of TEE and activity based on measured steps. The covariance values tracked when plotting the residuals were found to be representative of “well-behaved” data and are indicative of the analytical accuracy. The ratio and product plots were found to reflect the water turnover and CO2 production and thus could, with further investigation, be employed to identify the changes in physical activity.

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The use of metal stripes for the guiding of plasmons is a well established technique for the infrared regime and has resulted in the development of a myriad of passive optical components and sensing devices. However, the plasmons suffer from large losses around sharp bends, making the compact design of nanoscale sensors and circuits problematic. A compact alternative would be to use evanescent coupling between two sufficiently close stripes, and thus we propose a compact interferometer design using evanescent coupling. The sensitivity of the design is compared with that achieved using a hand-held sensor based on the Kretschmann style surface plasmon resonance technique. Modeling of the new interferometric sensor is performed for various structural parameters using finite-difference time-domain and COMSOL Multiphysics. The physical mechanisms behind the coupling and propagation of plasmons in this structure are explained in terms of the allowed modes in each section of the device.

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The measurement error model is a well established statistical method for regression problems in medical sciences, although rarely used in ecological studies. While the situations in which it is appropriate may be less common in ecology, there are instances in which there may be benefits in its use for prediction and estimation of parameters of interest. We have chosen to explore this topic using a conditional independence model in a Bayesian framework using a Gibbs sampler, as this gives a great deal of flexibility, allowing us to analyse a number of different models without losing generality. Using simulations and two examples, we show how the conditional independence model can be used in ecology, and when it is appropriate.

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p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the 'high-p53'Mdm4+/- mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/- background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/- mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

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Community engagement with time poor and seemingly apathetic citizens continues to challenge local governments. Capturing the attention of a digitally literate community who are technology and socially savvy adds a new quality to this challenge. Community engagement is resource and time intensive, yet local governments have to manage on continually tightened budgets. The benefits of assisting citizens in taking ownership in making their community and city a better place to live in collaboration with planners and local governments are well established. This study investigates a new collaborative form of civic participation and engagement for urban planning that employs in-place digital augmentation. It enhances people’s experience of physical spaces with digital technologies that are directly accessible within that space, in particular through interaction with mobile phones and public displays. The study developed and deployed a system called Discussions in Space (DIS) in conjunction with a major urban planning project in Brisbane. Planners used the system to ask local residents planning-related questions via a public screen, and passers-by sent responses via SMS or Twitter onto the screen for others to read and reflect, hence encouraging in-situ, real-time, civic discourse. The low barrier of entry proved to be successful in engaging a wide range of residents who are generally not heard due to their lack of time or interest. The system also reflected positively on the local government for reaching out in this way. Challenges and implications of the short-texted and ephemeral nature of this medium were evaluated in two focus groups with urban planners. The paper concludes with an analysis of the planners’ feedback evaluating the merits of the data generated by the system to better engage with Australia’s new digital locals.