826 resultados para ligand-based virtual screening


Relevância:

30.00% 30.00%

Publicador:

Resumo:

Articular cartilage is a complex structure with an architecture in which fluid-swollen proteoglycans constrained within a 3D network of collagen fibrils. Because of the complexity of the cartilage structure, the relationship between its mechanical behaviours at the macroscale level and its components at the micro-scale level are not completely understood. The research objective in this thesis is to create a new model of articular cartilage that can be used to simulate and obtain insight into the micro-macro-interaction and mechanisms underlying its mechanical responses during physiological function. The new model of articular cartilage has two characteristics, namely: i) not use fibre-reinforced composite material idealization ii) Provide a framework for that it does probing the micro mechanism of the fluid-solid interaction underlying the deformation of articular cartilage using simple rules of repartition instead of constitutive / physical laws and intuitive curve-fitting. Even though there are various microstructural and mechanical behaviours that can be studied, the scope of this thesis is limited to osmotic pressure formation and distribution and their influence on cartilage fluid diffusion and percolation, which in turn governs the deformation of the compression-loaded tissue. The study can be divided into two stages. In the first stage, the distributions and concentrations of proteoglycans, collagen and water were investigated using histological protocols. Based on this, the structure of cartilage was conceptualised as microscopic osmotic units that consist of these constituents that were distributed according to histological results. These units were repeated three-dimensionally to form the structural model of articular cartilage. In the second stage, cellular automata were incorporated into the resulting matrix (lattice) to simulate the osmotic pressure of the fluid and the movement of water within and out of the matrix; following the osmotic pressure gradient in accordance with the chosen rule of repartition of the pressure. The outcome of this study is the new model of articular cartilage that can be used to simulate and study the micromechanical behaviours of cartilage under different conditions of health and loading. These behaviours are illuminated at the microscale level using the socalled neighbourhood rules developed in the thesis in accordance with the typical requirements of cellular automata modelling. Using these rules and relevant Boundary Conditions to simulate pressure distribution and related fluid motion produced significant results that provided the following insight into the relationships between osmotic pressure gradient and associated fluid micromovement, and the deformation of the matrix. For example, it could be concluded that: 1. It is possible to model articular cartilage with the agent-based model of cellular automata and the Margolus neighbourhood rule. 2. The concept of 3D inter connected osmotic units is a viable structural model for the extracellular matrix of articular cartilage. 3. Different rules of osmotic pressure advection lead to different patterns of deformation in the cartilage matrix, enabling an insight into how this micromechanism influences macromechanical deformation. 4. When features such as transition coefficient were changed, permeability (representing change) is altered due to the change in concentrations of collagen, proteoglycans (i.e. degenerative conditions), the deformation process is impacted. 5. The boundary conditions also influence the relationship between osmotic pressure gradient and fluid movement at the micro-scale level. The outcomes are important to cartilage research since we can use these to study the microscale damage in the cartilage matrix. From this, we are able to monitor related diseases and their progression leading to potential insight into drug-cartilage interaction for treatment. This innovative model is an incremental progress on attempts at creating further computational modelling approaches to cartilage research and other fluid-saturated tissues and material systems.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Purpose – It is predicted that virtual business and related research possibilities will expand significantly. In this context, the aim of this paper is to use insights from a virtual research project to present a theoretically-informed toolbox of practical suggestions to guide the conduct of virtual world business research. Design/methodology/approach – Archival evidence is presented, and data from a study conducted in Second Lifew in 2007 is interpreted through Llewellyn’s framework (physical, structural, agential, cultural and mental dimensions). Findings – With the burgeoning of virtual business applications, appropriate systems that encompass the dynamics of both the real and the virtual will need to be developed by and for accountants, auditors and business professionals. Researchers of virtual business activities will need to adapt to the physical, structural, agential, cultural and mental dimensions unique to virtual worlds. Research limitations/implications – While based on reflections from a single study in Second Life, this paper identifies possibilities for future virtual research on issues of accountability and accounting relating to virtual worlds. Practical implications – The practical toolbox will assist virtual researchers to deal with the possibilities and practicalities of conducting research in virtual worlds. Originality/value – Despite the proliferation of virtual worlds, predictions of virtual business applications, and consequent accountability and accounting implications, there is a paucity of academic literature on conducting business research in virtual settings. This prescient paper develops a conceptual framework to guide the conduct of research in virtual worlds, and identifies the unique opportunities and challenges they present.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Communication processes are vital in the lifecycle of BPM projects. With this in mind, much research has been performed into facilitating this key component between stakeholders. Amongst the methods used to support this process are personalized process visualisations. In this paper, we review the development of this visualization trend, then, we propose a theoretical analysis framework based upon communication theory. We use this framework to provide theoretical support to the conjecture that 3D virtual worlds are powerful tools for communicating personalised visualisations of processes within a workplace. Meta requirements are then derived and applied, via 3D virtual world functionalities, to generate example visualisations containing personalized aspects, which we believe enhance the process of communcation between analysts and stakeholders in BPM process (re)design activities.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Depression in childhood or adolescence is associated with increased rates of depression in adulthood. Does this justify efforts to detect (and treat) those with symptoms of depression in early childhood or adolescence? The aim of this study was to determine how well symptoms of anxiety/depression (A-D) in early childhood and adolescence predict adult mental health. The study sample is taken from a population-based prospective birth cohort study. Of the 8556 mothers initially approached to participate 8458 agreed, of whom 7223 mothers gave birth to a live singleton baby. Children were screened using modified Child Behaviour Checklist (CBCL) scales for internalizing and total problems (T-P) at age 5 and the CBCL and Youth Self Report (YSR) A-D subscale and T-P scale at age 14. At age 21, a sub-sample of 2563 young adults in this cohort were administered the CIDI-Auto. Results indicated that screening at age 5 would detect few later cases of significant mental ill-health. Using a cut-point of 20% for internalizing at child age 5 years the CBCL had sensitivities of only 25% and 18% for major depression and anxiety disorders at 21 years, respectively. At age 14, the YSR generally performed a little better than the CBCL as a screening instrument, but neither performed at a satisfactory level. Of the children who were categorised as having YSR A-D at 14 years 30% and 37% met DSM-IV criteria for major depression and anxiety disorders, respectively, at age 21. Our findings challenge an existing movement encouraging the detection and treatment of those with symptoms of mental illness in early childhood.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background: Nutrition screening is usually administered by nurses. However, most studies on nutrition screening tools have not used nurses to validate the tools. The 3-Minute Nutrition Screening (3-MinNS) assesses weight loss, dietary intake and muscle wastage, with the composite score of each used to determine risk of malnutrition. The aim of the study was to determine the validity and reliability of 3-MinNS administered by nurses, who are the intended assessors. Methods: In this cross sectional study, three ward-based nurses screened 121 patients aged 21 years and over using 3-MinNS in three wards within 24 hours of admission. A dietitian then assessed the patients’ nutritional status using Subjective Global Assessment within 48 hours of admission, whilst blinded to the results of the screening. To assess the reliability of 3-MinNS, 37 patients screened by the first nurse were re-screened by a second nurse within 24 hours, who was blinded to the results of the first nurse. The sensitivity, specificity and best cutoff score for 3-MinNS were determined using the Receiver Operator Characteristics Curve. Results: The best cutoff score to identify all patients at risk of malnutrition using 3-MinNS was three, with sensitivity of 89% and specificity of 88%. This cutoff point also identified all (100%) severely malnourished patients. There was strong correlation between 3-MinNS and SGA (r=0.78, p<0.001). The agreement between two nurses conducting the 3-MinNS tool was 78.3%. Conclusion: 3-Minute Nutrition Screening is a valid and reliable tool for nurses to identify patients at risk of malnutrition.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Passenger flow studies in airport terminals have shown consistent statistical relationships between airport spatial layout and pedestrian movement, facilitating prediction of movement from terminal designs. However, these studies are done at an aggregate level and do not incorporate how individual passengers make decisions at a microscopic level. Therefore, they do not explain the formation of complex movement flows. In addition, existing models mostly focus on standard airport processing procedures such as immigration and security, but seldom consider discretionary activities of passengers, and thus are not able to truly describe the full range of passenger flows within airport terminals. As the route-choice decision-making of passengers involves many uncertain factors within the airport terminals, the mechanisms to fulfill the capacity of managing the route-choice have proven difficult to acquire and quantify. Could the study of cognitive factors of passengers (i.e. human mental preferences of deciding which on-airport facility to use) be useful to tackle these issues? Assuming the movement in virtual simulated environments can be analogous to movement in real environments, passenger behaviour dynamics can be similar to those generated in virtual experiments. Three levels of dynamics have been devised for motion control: the localised field, tactical level, and strategic level. A localised field refers to basic motion capabilities, such as walking speed, direction and avoidance of obstacles. The other two fields represent cognitive route-choice decision-making. This research views passenger flow problems via a "bottom-up approach", regarding individual passengers as independent intelligent agents who can behave autonomously and are able to interact with others and the ambient environment. In this regard, passenger flow formation becomes an emergent phenomenon of large numbers of passengers interacting with others. In the thesis, first, the passenger flow in airport terminals was investigated. Discretionary activities of passengers were integrated with standard processing procedures in the research. The localised field for passenger motion dynamics was constructed by a devised force-based model. Next, advanced traits of passengers (such as their desire to shop, their comfort with technology and their willingness to ask for assistance) were formulated to facilitate tactical route-choice decision-making. The traits consist of quantified measures of mental preferences of passengers when they travel through airport terminals. Each category of the traits indicates a decision which passengers may take. They were inferred through a Bayesian network model by analysing the probabilities based on currently available data. Route-choice decision-making was finalised by calculating corresponding utility results based on those probabilities observed. Three sorts of simulation outcomes were generated: namely, queuing length before checkpoints, average dwell time of passengers at service facilities, and instantaneous space utilisation. Queuing length reflects the number of passengers who are in a queue. Long queues no doubt cause significant delay in processing procedures. The dwell time of each passenger agent at the service facilities were recorded. The overall dwell time of passenger agents at typical facility areas were analysed so as to demonstrate portions of utilisation in the temporal aspect. For the spatial aspect, the number of passenger agents who were dwelling within specific terminal areas can be used to estimate service rates. All outcomes demonstrated specific results by typical simulated passenger flows. They directly reflect terminal capacity. The simulation results strongly suggest that integrating discretionary activities of passengers makes the passenger flows more intuitive, observing probabilities of mental preferences by inferring advanced traits make up an approach capable of carrying out tactical route-choice decision-making. On the whole, the research studied passenger flows in airport terminals by an agent-based model, which investigated individual characteristics of passengers and their impact on psychological route-choice decisions of passengers. Finally, intuitive passenger flows in airport terminals were able to be realised in simulation.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

This study aimed to identify new peptide antigens from Chlamydia (C.) trachomatis in a proof of concept approach which could be used to develop an epitope-based serological diagnostic for C. trachomatis related infertility in women. A bioinformatics analysis was conducted examining several immunodominant proteins from C. trachomatis to identify predicted immunoglobulin epitopes unique to C. trachomatis. A peptide array of these epitopes was screened against participant sera. The participants (all female) were categorized into the following cohorts based on their infection and gynecological history; acute (single treated infection with C. trachomatis), multiple (more than one C. trachomatis infection, all treated), sequelae (PID or tubal infertility with a history of C. trachomatis infection), and infertile (no history of C. trachomatis infection and no detected tubal damage). The bioinformatics strategy identified several promising epitopes. Participants who reacted positively in the peptide 11 ELISA were found to have an increased likelihood of being in the sequelae cohort compared to the infertile cohort with an odds ratio of 16.3 (95% c.i. 1.65 – 160), with 95% specificity and 46% sensitivity (0.19-0.74). The peptide 11 ELISA has the potential to be further developed as a screening tool for use during the early IVF work up and provides proof of concept that there may be further peptide antigens which could be identified using bioinformatics and screening approaches.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

3D virtual reality, including the current generation of multi-user virtual worlds, has had a long history of use in education and training, and it experienced a surge of renewed interest with the advent of Second Life in 2003. What followed shortly after were several years marked by considerable hype around the use of virtual worlds for teaching, learning and research in higher education. For the moment, uptake of the technology seems to have plateaued, with academics either maintaining the status quo and continuing to use virtual worlds as they have previously done or choosing to opt out altogether. This paper presents a brief review of the use of virtual worlds in the Australian and New Zealand higher education sector in the past and reports on its use in the sector at the present time, based on input from members of the Australian and New Zealand Virtual Worlds Working Group. It then adopts a forward-looking perspective amid the current climate of uncertainty, musing on future directions and offering suggestions for potential new applications in light of recent technological developments and innovations in the area.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background Nutrition screening is usually administered by nurses. However, most studies on nutrition screening tools have not used nurses to validate the tools. The 3-Minute Nutrition Screening (3-MinNS) assesses weight loss, dietary intake and muscle wastage, with the composite score of each used to determine risk of malnutrition. The aim of the study was to determine the validity and reliability of 3-MinNS administered by nurses, who are the intended assessors. Methods In this cross sectional study, three ward-based nurses screened 121 patients aged 21 years and over using 3-MinNS in three wards within 24 hours of admission. A dietitian then assessed the patients’ nutritional status using Subjective Global Assessment within 48 hours of admission, whilst blinded to the results of the screening. To assess the reliability of 3-MinNS, 37 patients screened by the first nurse were re-screened by a second nurse within 24 hours, who was blinded to the results of the first nurse. The sensitivity, specificity and best cutoff score for 3-MinNS were determined using the Receiver Operator Characteristics Curve. Results The best cutoff score to identify all patients at risk of malnutrition using 3-MinNS was three, with sensitivity of 89% and specificity of 88%. This cutoff point also identified all (100%) severely malnourished patients. There was strong correlation between 3-MinNS and SGA (r=0.78, p<0.001). The agreement between two nurses conducting the 3-MinNS tool was 78.3%. Conclusion 3-Minute Nutrition Screening is a valid and reliable tool for nurses to identify patients at risk of malnutrition.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Articular cartilage is the load-bearing tissue that consists of proteoglycan macromolecules entrapped between collagen fibrils in a three-dimensional architecture. To date, the drudgery of searching for mathematical models to represent the biomechanics of such a system continues without providing a fitting description of its functional response to load at micro-scale level. We believe that the major complication arose when cartilage was first envisaged as a multiphasic model with distinguishable components and that quantifying those and searching for the laws that govern their interaction is inadequate. To the thesis of this paper, cartilage as a bulk is as much continuum as is the response of its components to the external stimuli. For this reason, we framed the fundamental question as to what would be the mechano-structural functionality of such a system in the total absence of one of its key constituents-proteoglycans. To answer this, hydrated normal and proteoglycan depleted samples were tested under confined compression while finite element models were reproduced, for the first time, based on the structural microarchitecture of the cross-sectional profile of the matrices. These micro-porous in silico models served as virtual transducers to produce an internal noninvasive probing mechanism beyond experimental capabilities to render the matrices micromechanics and several others properties like permeability, orientation etc. The results demonstrated that load transfer was closely related to the microarchitecture of the hyperelastic models that represent solid skeleton stress and fluid response based on the state of the collagen network with and without the swollen proteoglycans. In other words, the stress gradient during deformation was a function of the structural pattern of the network and acted in concert with the position-dependent compositional state of the matrix. This reveals that the interaction between indistinguishable components in real cartilage is superimposed by its microarchitectural state which directly influences macromechanical behavior.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Purpose: This is one of the first studies to report that the Achenbach internalising scales were much more effective at identifying those with current comorbid depression and anxiety, rather than individual mood disorder. Introduction: The Achenbach behaviour checklists (YSR,YASR) are widely used, low cost screening tools used to assess problem behaviour. Several studies report good association between the checklists and psychiatric diagnoses; although with varying degrees of agreement. Most are cross-sectional studies involving adolescents referred to mental health services; few are in large community-based studies. This study examined the usefulness of the Achenbach internalising scales in the primary screening (both predictive and concurrent)for depression and anxiety. Methods: The sample was 2400 young adults from an Australian population-based prospective birth cohort study. The association between the empirical anxiety and depression scales were individually assessed against DSM-IV depression and anxiety diagnoses. Odds ratios and diagnostic efficiency tests report the findings. Results: Adolescents with internalising symptoms were twice (OR 2.3, 95%CI 1.7 to 3.1) as likely to be diagnosed with later DSM-IV depression. YASR internalising scale predicted DSM-IV mood disorders (depression OR = 6.9, 95% CI 5.0–9.5; anxiety OR = 5.1, 95% CI 3.8–6.7) in the previous 12 months. The internalising scales were much more effective at identifying those with comorbid depression and anxiety. Conclusions: Adolescence and early adulthood are key risk periods for the onset of anxiety and depression. This study found that young people with internalising behaviour problems were more likely to have comorbid depression and anxiety DSM-IV disorder.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

During the evolution of the music industry, developments in the media environment have required music firms to adapt in order to survive. Changes in broadcast radio programming during the 1950s; the Compact Cassette during the 1970s; and the deregulation of media ownership during the 1990s are all examples of changes which have heavily affected the music industry. This study explores similar contemporary dynamics, examines how decision makers in the music industry perceive and make sense of the developments, and reveals how they revise their business strategies, based on their mental models of the media environment. A qualitative system dynamics model is developed in order to support the reasoning brought forward by the study. The model is empirically grounded, but is also based on previous music industry research and a theoretical platform constituted by concepts from evolutionary economics and sociology of culture. The empirical data primarily consist of 36 personal interviews with decision makers in the American, British and Swedish music industrial ecosystems. The study argues that the model which is proposed, more effectively explains contemporary music industry dynamics than music industry models presented by previous research initiatives. Supported by the model, the study is able to show how “new” media outlets make old music business models obsolete and challenge the industry’s traditional power structures. It is no longer possible to expose music at one outlet (usually broadcast radio) in the hope that it will lead to sales of the same music at another (e.g. a compact disc). The study shows that many music industry decision makers still have not embraced the new logic, and have not yet challenged their traditional mental models of the media environment. Rather, they remain focused on preserving the pivotal role held by the CD and other physical distribution technologies. Further, the study shows that while many music firms remain attached to the old models, other firms, primarily music publishers, have accepted the transformation, and have reluctantly recognised the realities of a virtualised environment.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

This paper describes the development of a novel vision-based autonomous surface vehicle with the purpose of performing coordinated docking manoeuvres with a target, such as an autonomous underwater vehicle, at the water's surface. The system architecture integrates two small processor units; the first performs vehicle control and implements a virtual force based docking strategy, with the second performing vision-based target segmentation and tracking. Furthermore, the architecture utilises wireless sensor network technology allowing the vehicle to be observed by, and even integrated within an ad-hoc sensor network. Simulated and experimental results are presented demonstrating the autonomous vision- based docking strategy on a proof-of-concept vehicle.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Introduction Delirium research in palliative care, particularly in the dying phase, is possible but is frequently met with ethical and methodological challenges. This paper describes the challenges faced in a previous delirium screening study. Methods Within 72 hours of admission to an acute inpatient specialist palliative care unit one hundred consecutive patients over 18 years of age with advanced cancer were invited to be screened for delirium using validated screening tools. Results Of the 100 consecutive admissions 49 patients were unable to participate including seven who did not meet the inclusion criteria and nine (six families and three patients) who withheld consent. The remaining 33 patients were more unwell and closer to death than those who were recruited. Reasons for non- participation included being too unwell (ten), unresponsive (nine), died (two) or discharged (three) before recruitment and exceeding the 72hour time limit (nine). Conclusion Gate keeping and physical condition of patients were the main obstacles to recruitment and is consistent with barriers faced in previous studies involving palliative care and dying patients. While it is possible and necessary to conduct studies in palliative care, including the terminal phase, as reflective practitioners we must maintain the balance between the demands for evidence-based practice and our compassion and respect for our most vulnerable of patients.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Mothers represent a large segment of marketing dollars and traditionally, word of mouth was spread from mother to mother in a face-to-face environment, such as the school car park or mother’s groups. As families have evolved, so too has the traditional mother’s group. Limited academic studies have explored online mothers’ groups and how they impact on consumption. In order to explore the nature of this online influence and how mothers are influenced by other mothers online, a study was conducted through the use of observation and qualitative questioning. The data suggests that trust between mothers is generally high and mothers tend to trust the opinions of other mothers when they recommend a product. This is similar in other reference group contexts, however, mothers are communicating about brands frequently and influencing behaviour. This leads to a number of managerial and theoretical implications discussed in the paper.