Theoretical Hyperbolic Model of a Partial Agonism: Explicit Formulas for Affinity, Efficacy and Amplification

The quantitative analysis of receptor-mediated effect is based on experimental concentration-response data in which the independent variable, the concentration of a receptor ligand, is linked with a dependent variable, the biological response. The steps between the drug–receptor interaction and the subsequent biological effect are to some extent unknown. The shape of the fitting curve of the experimental data may give some in-sights into the nature of the concentration–receptor–response (C-R-R) mechanism. It can be evaluated by non-linear regression analysis of the experimental data points of the independent and dependent variables, which could be considered as a history of the interaction between the drug and receptors. However, this information is not enough to evaluate such important parameters of the mechanism as the dissociation constant (affinity) and efficacy. There are two ways to provide more detailed information about the C-R-R mechanism: (i) an experimental way for obtaining data with new or

A minimal model of partial synchrony

Acknowledgement We wish to acknowledge A. Pikovsky and M. Zaks for useful discussions. This work has been financially supported by the EU project COSMOS (642563).

A minimal model of partial synchrony

We wish to acknowledge A Pikovsky and M Zaks for useful discussions. This work has been financially supported by the EU project COSMOS (642563).

An R-package for the Estimation and Testing of Multiple Covariates and Biomarker Interactions for Survival Data Based on Local Partial Likelihood

When we study the variables that a ffect survival time, we usually estimate their eff ects by the Cox regression model. In biomedical research, e ffects of the covariates are often modi ed by a biomarker variable. This leads to covariates-biomarker interactions. Here biomarker is an objective measurement of the patient characteristics at baseline. Liu et al. (2015) has built up a local partial likelihood bootstrap model to estimate and test this interaction e ffect of covariates and biomarker, but the R code developed by Liu et al. (2015) can only handle one variable and one interaction term and can not t the model with adjustment to nuisance variables. In this project, we expand the model to allow adjustment to nuisance variables, expand the R code to take any chosen interaction terms, and we set up many parameters for users to customize their research. We also build up an R package called "lplb" to integrate the complex computations into a simple interface. We conduct numerical simulation to show that the new method has excellent fi nite sample properties under both the null and alternative hypothesis. We also applied the method to analyze data from a prostate cancer clinical trial with acid phosphatase (AP) biomarker.

Partial Cooperation in Location Choice: Salop’s Model with Three Firms

We consider how three firms compete in a Salop location model and how cooperation in location choice by two of these firms affects the outcomes. We con- sider the classical case of linear transportation costs as a two-stage game in which the firms select first a location on a unit circle along which consumers are dispersed evenly, followed by the competitive selection of a price. Standard analysis restricts itself to purely competitive selection of location; instead, we focus on the situation in which two firms collectively decide about location, but price their products competitively after the location choice has been effectuated. We show that such partial coordination of location is beneficial to all firms, since it reduces the number of equilibria significantly and, thereby, the resulting coordination problem. Subsequently, we show that the case of quadratic transportation costs changes the main conclusions only marginally.

Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery

A bioactive and bioresorbable scaffold fabricated from medical grade poly (epsilon-caprolactone) and incorporating 20% beta-tricalcium phosphate (mPCL–TCP) was recently developed for bone regeneration at load bearing sites. In the present study, we aimed to evaluate bone ingrowth into mPCL–TCP in a large animal model of lumbar interbody fusion. Six pigs underwent a 2-level (L3/4; L5/6) anterior lumbar interbody fusion (ALIF) implanted with mPCL–TCP þ 0.6 mg rhBMP-2 as treatment group while four other pigs implanted with autogenous bone graft served as control. Computed tomographic scanning and histology revealed complete defect bridging in all (100%) specimen from the treatment group as early as 3 months. Histological evidence of continuing bone remodeling and maturation was observed at 6 months. In the control group, only partial bridging was observed at 3 months and only 50% of segments in this group showed complete defect bridging at 6 months. Furthermore, 25% of segments in the control group showed evidence of graft fracture, resorption and pseudoarthrosis. In contrast, no evidence of graft fractures, pseudoarthrosis or foreign body reaction was observed in the treatment group. These results reveal that mPCL–TCP scaffolds could act as bone graft substitutes by providing a suitable environment for bone regeneration in a dynamic load bearing setting such as in a porcine model of interbody spine fusion.

Effect of inaccuracies in anthropometric data and linked-segment inverse dynamic modeling on kinetics of gait in persons with partial foot amputation

The accuracy of data derived from linked-segment models depends on how well the system has been represented. Previous investigations describing the gait of persons with partial foot amputation did not account for the unique anthropometry of the residuum or the inclusion of a prosthesis and footwear in the model and, as such, are likely to have underestimated the magnitude of the peak joint moments and powers. This investigation determined the effect of inaccuracies in the anthropometric input data on the kinetics of gait. Toward this end, a geometric model was developed and validated to estimate body segment parameters of various intact and partial feet. These data were then incorporated into customized linked-segment models, and the kinetic data were compared with that obtained from conventional models. Results indicate that accurate modeling increased the magnitude of the peak hip and knee joint moments and powers during terminal swing. Conventional inverse dynamic models are sufficiently accurate for research questions relating to stance phase. More accurate models that account for the anthropometry of the residuum, prosthesis, and footwear better reflect the work of the hip extensors and knee flexors to decelerate the limb during terminal swing phase.

The role of self-efficacy in dental patients’ brushing and flossing: Testing an extended Health Belief Model

Objective: In an effort to examine the decreasing oral health trend of Australian dental patients, the Health Belief Model (HBM) was utilised to understand the beliefs underlying brushing and flossing self-care. The HBM states that perception of severity and susceptibility to inaction and an estimate of the barriers and benefits of behavioural performance influences people’s health behaviours. Self-efficacy, confidence in one’s ability to perform oral self-care, was also examined. Methods: In dental waiting rooms, a community sample (N = 92) of dental patients completed a questionnaire assessing HBM variables and self-efficacy, as well as their performance of the oral hygiene behaviours of brushing and flossing. Results: Partial support only was found for the HBM with barriers emerging as the sole HBM factor influencing brushing and flossing behaviours. Self-efficacy significantly predicted both oral hygiene behaviours also. Conclusion: Support was found for the control factors, specifically a consideration of barriers and self-efficacy, in the context of understanding dental patients’ oral hygiene decisions. Practice implications: Dental professionals should encourage patients’ self-confidence to brush and floss at recommended levels and discuss strategies that combat barriers to performance, rather than emphasising the risks of inaction or the benefits of oral self-care.

Enhancing transition : an enhanced model of clinical placement for final year nursing students

Specialised support for student nurses making the transition to graduate nurse can be crucial to successful and smooth adjustment, and can create a path to positive and stable career experiences. This paper describes an enhanced model of final year nursing student placements which was trialled in 2006 at the Queensland University of Technology. The model involved collaboration with two major urban health services and resources were developed to support effective transition experiences. Ninety-two students, including 29 trial participants and 63 non-trial participants were assessed on preparedness for professional practice, before and after the trial semester. Results indicated an increase in preparedness across the entire sample, but students participating in the trial did not differ significantly in overall preparedness change from those who did not participate. Higher baseline preparedness in the trial group highlighted the possibility that proactive students who choose enrichment experiences tend to be likelier to gain benefit from such options than those who do not. Qualitative findings from focus groups conducted with 12 transition group students highlighted that one of the main beneficial aspects of the experience for students was the sense of belonging to a team that understood their learning needs and could work constructively with them.

Local adjustment and global adaptation of control periods for QoC management of control systems

Linking real-time schedulability directly to the Quality of Control (QoC), the ultimate goal of a control system, a hierarchical feedback QoC management framework with the Fixed Priority (FP) and the Earliest-Deadline-First (EDF) policies as plug-ins is proposed in this paper for real-time control systems with multiple control tasks. It uses a task decomposition model for continuous QoC evaluation even in overload conditions, and then employs heuristic rules to adjust the period of each of the control tasks for QoC improvement. If the total requested workload exceeds the desired value, global adaptation of control periods is triggered for workload maintenance. A sufficient stability condition is derived for a class of control systems with delay and period switching of the heuristic rules. Examples are given to demonstrate the proposed approach.

A mathematical model of chlamydial infection incorporating movement of chlamydial particles

We present a spatiotemporal mathematical model of chlamydial infection, host immune response and spatial movement of infectious particles. The re- sulting partial differential equations model both the dynamics of the infection and changes in infection profile observed spatially along the length of the host genital tract. This model advances previous chlamydia modelling by incorporating spatial change, which we also demonstrate to be essential when the timescale for movement of infectious particles is equal to, or shorter than, the developmental cycle timescale. Numerical solutions and model analysis are carried out, and we present a hypothesis regarding the potential for treatment and prevention of infection by increasing chlamydial particle motility.

Prediction model of the buildup of volatile organic compounds on urban roads

A model to predict the buildup of mainly traffic-generated volatile organic compounds or VOCs (toluene, ethylbenzene, ortho-xylene, meta-xylene, and para-xylene) on urban road surfaces is presented. The model required three traffic parameters, namely average daily traffic (ADT), volume to capacity ratio (V/C), and surface texture depth (STD), and two chemical parameters, namely total suspended solid (TSS) and total organic carbon (TOC), as predictor variables. Principal component analysis and two phase factor analysis were performed to characterize the model calibration parameters. Traffic congestion was found to be the underlying cause of traffic-related VOC buildup on urban roads. The model calibration was optimized using orthogonal experimental design. Partial least squares regression was used for model prediction. It was found that a better optimized orthogonal design could be achieved by including the latent factors of the data matrix into the design. The model performed fairly accurately for three different land uses as well as five different particle size fractions. The relative prediction errors were 10–40% for the different size fractions and 28–40% for the different land uses while the coefficients of variation of the predicted intersite VOC concentrations were in the range of 25–45% for the different size fractions. Considering the sizes of the data matrices, these coefficients of variation were within the acceptable interlaboratory range for analytes at ppb concentration levels.

A continuous time model for election timing

We consider a continuous time model for election timing in a Majoritarian Parliamentary System where the government maintains a constitutional right to call an early election. Our model is based on the two-party-preferred data that measure the popularity of the government and the opposition over time. We describe the poll process by a Stochastic Differential Equation (SDE) and use a martingale approach to derive a Partial Differential Equation (PDE) for the government’s expected remaining life in office. A comparison is made between a three-year and a four-year maximum term and we also provide the exercise boundary for calling an election. Impacts on changes in parameters in the SDE, the probability of winning the election and maximum terms on the call exercise boundaries are discussed and analysed. An application of our model to the Australian Federal Election for House of Representatives is also given.

Validating the is-impact model in the Malaysian public sector

This research is one of several ongoing studies conducted within the IT Professional Services (ITPS) research programme at Queensland University of Technology (QUT). In 2003, ITPS introduced the IS-Impact model, a measurement model for measuring information systems success from the viewpoint of multiple stakeholders. The model, along with its instrument, is robust, simple, yet generalisable, and yields results that are comparable across time, stakeholders, different systems and system contexts. The IS-Impact model is defined as “a measure at a point in time, of the stream of net benefits from the Information System (IS), to date and anticipated, as perceived by all key-user-groups”. The model represents four dimensions, which are ‘Individual Impact’, ‘Organizational Impact’, ‘Information Quality’ and ‘System Quality’. The two Impact dimensions measure the up-to-date impact of the evaluated system, while the remaining two Quality dimensions act as proxies for probable future impacts (Gable, Sedera & Chan, 2008). To fulfil the goal of ITPS, “to develop the most widely employed model” this research re-validates and extends the IS-Impact model in a new context. This method/context-extension research aims to test the generalisability of the model by addressing known limitations of the model. One of the limitations of the model relates to the extent of external validity of the model. In order to gain wide acceptance, a model should be consistent and work well in different contexts. The IS-Impact model, however, was only validated in the Australian context, and packaged software was chosen as the IS understudy. Thus, this study is concerned with whether the model can be applied in another different context. Aiming for a robust and standardised measurement model that can be used across different contexts, this research re-validates and extends the IS-Impact model and its instrument to public sector organisations in Malaysia. The overarching research question (managerial question) of this research is “How can public sector organisations in Malaysia measure the impact of information systems systematically and effectively?” With two main objectives, the managerial question is broken down into two specific research questions. The first research question addresses the applicability (relevance) of the dimensions and measures of the IS-Impact model in the Malaysian context. Moreover, this research question addresses the completeness of the model in the new context. Initially, this research assumes that the dimensions and measures of the IS-Impact model are sufficient for the new context. However, some IS researchers suggest that the selection of measures needs to be done purposely for different contextual settings (DeLone & McLean, 1992, Rai, Lang & Welker, 2002). Thus, the first research question is as follows, “Is the IS-Impact model complete for measuring the impact of IS in Malaysian public sector organisations?” [RQ1]. The IS-Impact model is a multidimensional model that consists of four dimensions or constructs. Each dimension is represented by formative measures or indicators. Formative measures are known as composite variables because these measures make up or form the construct, or, in this case, the dimension in the IS-Impact model. These formative measures define different aspects of the dimension, thus, a measurement model of this kind needs to be tested not just on the structural relationship between the constructs but also the validity of each measure. In a previous study, the IS-Impact model was validated using formative validation techniques, as proposed in the literature (i.e., Diamantopoulos and Winklhofer, 2001, Diamantopoulos and Siguaw, 2006, Petter, Straub and Rai, 2007). However, there is potential for improving the validation testing of the model by adding more criterion or dependent variables. This includes identifying a consequence of the IS-Impact construct for the purpose of validation. Moreover, a different approach is employed in this research, whereby the validity of the model is tested using the Partial Least Squares (PLS) method, a component-based structural equation modelling (SEM) technique. Thus, the second research question addresses the construct validation of the IS-Impact model; “Is the IS-Impact model valid as a multidimensional formative construct?” [RQ2]. This study employs two rounds of surveys, each having a different and specific aim. The first is qualitative and exploratory, aiming to investigate the applicability and sufficiency of the IS-Impact dimensions and measures in the new context. This survey was conducted in a state government in Malaysia. A total of 77 valid responses were received, yielding 278 impact statements. The results from the qualitative analysis demonstrate the applicability of most of the IS-Impact measures. The analysis also shows a significant new measure having emerged from the context. This new measure was added as one of the System Quality measures. The second survey is a quantitative survey that aims to operationalise the measures identified from the qualitative analysis and rigorously validate the model. This survey was conducted in four state governments (including the state government that was involved in the first survey). A total of 254 valid responses were used in the data analysis. Data was analysed using structural equation modelling techniques, following the guidelines for formative construct validation, to test the validity and reliability of the constructs in the model. This study is the first research that extends the complete IS-Impact model in a new context that is different in terms of nationality, language and the type of information system (IS). The main contribution of this research is to present a comprehensive, up-to-date IS-Impact model, which has been validated in the new context. The study has accomplished its purpose of testing the generalisability of the IS-Impact model and continuing the IS evaluation research by extending it in the Malaysian context. A further contribution is a validated Malaysian language IS-Impact measurement instrument. It is hoped that the validated Malaysian IS-Impact instrument will encourage related IS research in Malaysia, and that the demonstrated model validity and generalisability will encourage a cumulative tradition of research previously not possible. The study entailed several methodological improvements on prior work, including: (1) new criterion measures for the overall IS-Impact construct employed in ‘identification through measurement relations’; (2) a stronger, multi-item ‘Satisfaction’ construct, employed in ‘identification through structural relations’; (3) an alternative version of the main survey instrument in which items are randomized (rather than blocked) for comparison with the main survey data, in attention to possible common method variance (no significant differences between these two survey instruments were observed); (4) demonstrates a validation process of formative indexes of a multidimensional, second-order construct (existing examples mostly involved unidimensional constructs); (5) testing the presence of suppressor effects that influence the significance of some measures and dimensions in the model; and (6) demonstrates the effect of an imbalanced number of measures within a construct to the contribution power of each dimension in a multidimensional model.