A simulation model of the within-host dynamics of Plasmodium vivax infection

Background The benign reputation of Plasmodium vivax is at odds with the burden and severity of the disease. This reputation, combined with restricted in vitro techniques, has slowed efforts to gain an understanding of the parasite biology and interaction with its human host. Methods A simulation model of the within-host dynamics of P. vivax infection is described, incorporating distinctive characteristics of the parasite such as the preferential invasion of reticulocytes and hypnozoite production. The developed model is fitted using digitized time-series’ from historic neurosyphilis studies, and subsequently validated against summary statistics from a larger study of the same population. The Chesson relapse pattern was used to demonstrate the impact of released hypnozoites. Results The typical pattern for dynamics of the parasite population is a rapid exponential increase in the first 10 days, followed by a gradual decline. Gametocyte counts follow a similar trend, but are approximately two orders of magnitude lower. The model predicts that, on average, an infected naïve host in the absence of treatment becomes infectious 7.9 days post patency and is infectious for a mean of 34.4 days. In the absence of treatment, the effect of hypnozoite release was not apparent as newly released parasites were obscured by the existing infection. Conclusions The results from the model provides useful insights into the dynamics of P. vivax infection in human hosts, in particular the timing of host infectiousness and the role of the hypnozoite in perpetuating infection.

Model refinement through high-performance computing: an agent-based HIV example

Background Recent advances in Immunology highlighted the importance of local properties on the overall progression of HIV infection. In particular, the gastrointestinal tract is seen as a key area during early infection, and the massive cell depletion associated with it may influence subsequent disease progression. This motivated the development of a large-scale agent-based model. Results Lymph nodes are explicitly implemented, and considerations on parallel computing permit large simulations and the inclusion of local features. The results obtained show that GI tract inclusion in the model leads to an accelerated disease progression, during both the early stages and the long-term evolution, compared to a theoretical, uniform model. Conclusions These results confirm the potential of treatment policies currently under investigation, which focus on this region. They also highlight the potential of this modelling framework, incorporating both agent-based and network-based components, in the context of complex systems where scaling-up alone does not result in models providing additional insights.

Testing times for the implementation of curriculum change: Analysis and extension of a curriculum change model

School curriculum change processes have traditionally been managed internally. However, in Queensland, Australia, as a response to the current high-stakes accountability regime, more and more principals are outsourcing this work to external change agents (ECAs). In 2009, one of the authors (a university lecturer and ECA) developed a curriculum change model (the Controlled Rapid Approach to Curriculum Change (CRACC)), specifically outlining the involvement of an ECA in the initiation phase of a school’s curriculum change process. The purpose of this paper is to extend the CRACC model by unpacking the implementation phase, drawing on data from a pilot study of a single school. Interview responses revealed that during the implementation phase, teachers wanted to be kept informed of the wider educational context; use data to constantly track students; relate pedagogical practices to testing practices; share information between departments and professional levels; and, own whole school performance. It is suggested that the findings would be transferable to other school settings and internal leadership of curriculum change. The paper also strikes a chord of concern – Do the responses from teachers operating in such an accountability regime live their professional lives within this corporate and globalised ideology whether they want to or not?

Learning to lead: The development and testing of a model of leadership learning

Drawing upon an action learning perspective, we hypothesized that a leader’s learning of project leadership skills would be related to facilitative leadership, team reflexivity, and team performance. Secondly, we proposed that new and experienced leaders would differ in the amount they learn from their current and recent experience as project managers, and in the strength of the relationship between their self-reported learning, facilitative leadership, and team reflexivity. We conducted a 1-year longitudinal study of 50 R&D teams, led by 25 new and 25 experienced leaders, with 313 team members and 22 project customers, collecting both quantitative and qualitative data. We found evidence of a significant impact of the leader’s learning on subsequent facilitative leadership and team performance 8 and 12 months later, suggesting a lag between learning leadership skills and translating these skills into leadership behavior. The findings contribute to an understanding of how leaders consolidate their learned experience into facilitative leadership behavior.

A novel population balance model for the dilute acid hydrolysis of hemicellulose

Acid hydrolysis is a popular pretreatment for removing hemicellulose from lignocelluloses in order to produce a digestible substrate for enzymatic saccharification. In this work, a novel model for the dilute acid hydrolysis of hemicellulose within sugarcane bagasse is presented and calibrated against experimental oligomer profiles. The efficacy of mathematical models as hydrolysis yield predictors and as vehicles for investigating the mechanisms of acid hydrolysis is also examined. Experimental xylose, oligomer (degree of polymerisation 2 to 6) and furfural yield profiles were obtained for bagasse under dilute acid hydrolysis conditions at temperatures ranging from 110C to 170C. Population balance kinetics, diffusion and porosity evolution were incorporated into a mathematical model of the acid hydrolysis of sugarcane bagasse. This model was able to produce a good fit to experimental xylose yield data with only three unknown kinetic parameters ka, kb and kd. However, fitting this same model to an expanded data set of oligomeric and furfural yield profiles did not successfully reproduce the experimental results. It was found that a ``hard-to-hydrolyse'' parameter, $\alpha$, was required in the model to ensure reproducibility of the experimental oligomer profiles at 110C, 125C and 140C. The parameters obtained through the fitting exercises at lower temperatures were able to be used to predict the oligomer profiles at 155C and 170C with promising results. The interpretation of kinetic parameters obtained by fitting a model to only a single set of data may be ambiguous. Although these parameters may correctly reproduce the data, they may not be indicative of the actual rate parameters, unless some care has been taken to ensure that the model describes the true mechanisms of acid hydrolysis. It is possible to challenge the robustness of the model by expanding the experimental data set and hence limiting the parameter space for the fitting parameters. The novel combination of ``hard-to-hydrolyse'' and population balance dynamics in the model presented here appears to stand up to such rigorous fitting constraints.

Socio-environmental drivers and suicide in Australia: Bayesian spatial analysis

Background The impact of socio-environmental factors on suicide has been examined in many studies. Few of them, however, have explored these associations from a spatial perspective, especially in assessing the association between meteorological factors and suicide. This study examined the association of meteorological and socio-demographic factors with suicide across small areas over different time periods. Methods Suicide, population and socio-demographic data (e.g., population of Aboriginal and Torres Strait Islanders (ATSI), and unemployment rate (UNE) at the Local Government Area (LGA) level were obtained from the Australian Bureau of Statistics for the period of 1986 to 2005. Information on meteorological factors (rainfall, temperature and humidity) was supplied by Australian Bureau of Meteorology. A Bayesian Conditional Autoregressive (CAR) Model was applied to explore the association of socio-demographic and meteorological factors with suicide across LGAs. Results In Model I (socio-demographic factors), proportion of ATSI and UNE were positively associated with suicide from 1996 to 2000 (Relative Risk (RR)ATSI = 1.0107, 95% Credible Interval (CI): 1.0062-1.0151; RRUNE = 1.0187, 95% CI: 1.0060-1.0315), and from 2001 to 2005 (RRATSI = 1.0126, 95% CI: 1.0076-1.0176; RRUNE = 1.0198, 95% CI: 1.0041-1.0354). Socio-Economic Index for Area (SEIFA) and IND, however, had negative associations with suicide between 1986 and 1990 (RRSEIFA = 0.9983, 95% CI: 0.9971-0.9995; RRATSI = 0.9914, 95% CI: 0.9848-0.9980). Model II (meteorological factors): a 1°C higher yearly mean temperature across LGAs increased the suicide rate by an average by 2.27% (95% CI: 0.73%, 3.82%) in 1996–2000, and 3.24% (95% CI: 1.26%, 5.21%) in 2001–2005. The associations between socio-demographic factors and suicide in Model III (socio-demographic and meteorological factors) were similar to those in Model I; but, there is no substantive association between climate and suicide in Model III. Conclusions Proportion of Aboriginal and Torres Strait Islanders, unemployment and temperature appeared to be statistically associated with of suicide incidence across LGAs among all selected variables, especially in recent years. The results indicated that socio-demographic factors played more important roles than meteorological factors in the spatial pattern of suicide incidence.

Alive SMC^2: Bayesian model selection for low-count time series models with intractable likelihoods

In this paper we present a new method for performing Bayesian parameter inference and model choice for low count time series models with intractable likelihoods. The method involves incorporating an alive particle filter within a sequential Monte Carlo (SMC) algorithm to create a novel pseudo-marginal algorithm, which we refer to as alive SMC^2. The advantages of this approach over competing approaches is that it is naturally adaptive, it does not involve between-model proposals required in reversible jump Markov chain Monte Carlo and does not rely on potentially rough approximations. The algorithm is demonstrated on Markov process and integer autoregressive moving average models applied to real biological datasets of hospital-acquired pathogen incidence, animal health time series and the cumulative number of poison disease cases in mule deer.

A hierarchical model of social marketing

Purpose This paper aims to set out a new hierarchical and differentiated model of social marketing principles, concepts and techniques that builds on, but supersedes, the existing lists of non-equivalent and undifferentiated benchmark criteria. Design/methodology/approach This is a conceptual paper that proposes a hierarchical model of social marketing principles, concepts and techniques. Findings This new delineation of the social marketing principle, its four core concepts and five techniques, represents a new way to conceptualize and recognize the different elements that constitute social marketing. This new model will help add to and further the development of the theoretical basis of social marketing, building on the definitional work led by the International Social Marketing Association (iSMA), Australian Association of Social Marketing (AASM) and European Social Marketing Association (ESMA). Research limitations/implications This proposed model offers a foundation for future research to expand upon. Further research is recommended to empirically test the proposed model. Originality/value This paper seeks to advance the theoretical base of social marketing by making a reasoned case for the need to differentiate between principles, concepts and techniques when seeking to describe social marketing.

Collaborative learning model of infrastructure construction: A capability perspective

Purpose Performance heterogeneity between collaborative infrastructure projects is typically examined by considering procurement systems and their governance mechanisms at static points in time. The literature neglects to consider the impact of dynamic learning capability, which is thought to reconfigure governance mechanisms over time in response to evolving market conditions. This conceptual paper proposes a new model to show how continuous joint learning of participant organisations improves project performance. Design/methodology/approach There are two stages of conceptual development. In the first stage, the management literature is analysed to explain the Standard Model of dynamic learning capability that emphasises three learning phases for organisations. This Standard Model is extended to derive a novel Circular Model of dynamic learning capability that shows a new feedback loop between performance and learning. In the second stage, the construction management literature is consulted, adding project lifecycle, stakeholder diversity and three organisational levels to the analysis, to arrive at the Collaborative Model of dynamic learning capability. Findings The Collaborative Model should enable construction organisations to successfully adapt and perform under changing market conditions. The complexity of learning cycles results in capabilities that are imperfectly imitable between organisations, explaining performance heterogeneity on projects. Originality/value The Collaborative Model provides a theoretically substantiated description of project performance, driven by the evolution of procurement systems and governance mechanisms. The Model’s empirical value will be tested in future research.

The subcortical confinement hypothesis: A neurological model for schizotypal hallucinations

Introduction Different types of hallucinations are symptomatic of different conditions. Schizotypal hallucinations are unique in that they follow existing delusional narrative patterns: they are often bizarre, they are generally multimodal, and they are particularly vivid (the experience of a newsreader abusing you personally over the TV is both visual and aural. Patients who feel and hear silicone chips under their skin suffer from haptic hallucinations as well as aural ones, etc.) Although there are a number of hypotheses for hallucinations, few cogently grapple the sheer bizarreness of the ones experienced in schizotypal psychosis. Methods A review-based hypothesis, traversing theory from the molecular level to phenomenological expression as a distinct and recognizable symptomatology. Conclusion Hallucinations appear to be caused by a two-fold dysfunction in the mesofrontal dopamine pathway, which is considered here to mediate attention of different types: in the anterior medial frontal lobe, the receptors (largely D1 type) mediate declarative awareness, whereas the receptors in the striatum (largely D2 type) mediate latent awareness of known schemata. In healthy perception, most of the perceptual load is performed by the latter: by the top-down predictive and mimetic engine, with the bottom-up mechanism being used as a secondary tool to bring conscious deliberation to stimuli that fails to match up against expectations. In schizophrenia, the predictive mode is over-stimulated, while the bottom-up feedback mechanism atrophies. The dysfunctional distribution pattern effectively confines dopamine activity to the striatum, thereby stimulating the structural components of thought and behaviour: well-learned routines, narrative structures, lexica, grammar, schemata, archetypes, and other procedural resources. Meanwhile, the loss of activity in the frontal complex reduces the capacity for declarative awareness and for processing anything that fails to meet expectations.

Support for an auto-associative model of spoken cued recall: Evidence from fMRI

Cued recall and item recognition are considered the standard episodic memory retrieval tasks. However, only the neural correlates of the latter have been studied in detail with fMRI. Using an event-related fMRI experimental design that permits spoken responses, we tested hypotheses from an auto-associative model of cued recall and item recognition [Chappell, M., & Humphreys, M. S. (1994). An auto-associative neural network for sparse representations: Analysis and application to models of recognition and cued recall. Psychological Review, 101, 103-128]. In brief, the model assumes that cues elicit a network of phonological short term memory (STM) and semantic long term memory (LTM) representations distributed throughout the neocortex as patterns of sparse activations. This information is transferred to the hippocampus which converges upon the item closest to a stored pattern and outputs a response. Word pairs were learned from a study list, with one member of the pair serving as the cue at test. Unstudied words were also intermingled at test in order to provide an analogue of yes/no recognition tasks. Compared to incorrectly rejected studied items (misses) and correctly rejected (CR) unstudied items, correctly recalled items (hits) elicited increased responses in the left hippocampus and neocortical regions including the left inferior prefrontal cortex (LIPC), left mid lateral temporal cortex and inferior parietal cortex, consistent with predictions from the model. This network was very similar to that observed in yes/no recognition studies, supporting proposals that cued recall and item recognition involve common rather than separate mechanisms.

The use of embodiments in distributed collaborative business process modelling

Remote networked collaboration with business model documentation has many communication problems. The aim of this project is to solve some of these communication problems by using digital 3D representations of human visual cues. Results from this project increased our understanding of the role and effects of visual cues in remote collaboration, specifically for validating business process models. Technology designs to support such cues across a distance have been proposed in this thesis with qualitative and quantitative methods of analysis being combined to analyse the impact of these cues on the communication, coordination and performance of a team collaborating remotely.

A model to explain specific cellular communications and cellular harmony: - a hypothesis of coupled cells and interactive coupling molecules

Background The various cell types and their relative numbers in multicellular organisms are controlled by growth factors and related extracellular molecules which affect genetic expression pathways. However, these substances may have both/either inhibitory and/or stimulatory effects on cell division and cell differentiation depending on the cellular environment. It is not known how cells respond to these substances in such an ambiguous way. Many cellular effects have been investigated and reported using cell culture from cancer cell lines in an effort to define normal cellular behaviour using these abnormal cells. A model is offered to explain the harmony of cellular life in multicellular organisms involving interacting extracellular substances. Methods A basic model was proposed based on asymmetric cell division and evidence to support the hypothetical model was accumulated from the literature. In particular, relevant evidence was selected for the Insulin-Like Growth Factor system from the published data, especially from certain cell lines, to support the model. The evidence has been selective in an attempt to provide a picture of normal cellular responses, derived from the cell lines. Results The formation of a pair of coupled cells by asymmetric cell division is an integral part of the model as is the interaction of couplet molecules derived from these cells. Each couplet cell will have a receptor to measure the amount of the couplet molecule produced by the other cell; each cell will be receptor-positive or receptor-negative for the respective receptors. The couplet molecules will form a binary complex whose level is also measured by the cell. The hypothesis is heavily supported by selective collection of circumstantial evidence and by some direct evidence. The basic model can be expanded to other cellular interactions. Conclusions These couplet cells and interacting couplet molecules can be viewed as a mechanism that provides a controlled and balanced division-of-labour between the two progeny cells, and, in turn, their progeny. The presence or absence of a particular receptor for a couplet molecule will define a cell type and the presence or absence of many such receptors will define the cell types of the progeny within cell lineages.

Evaluation of a skin self examination attitude scale using an item response theory model approach

Introduction The Skin Self-Examination Attitude Scale (SSEAS) is a brief measure that allows for the assessment of attitudes in relation to skin self-examination. This study evaluated the psychometric properties of the SSEAS using Item Response Theory (IRT) methods in a large sample of men ≥ 50 years in Queensland, Australia. Methods A sample of 831 men (420 intervention and 411 control) completed a telephone assessment at the 13-month follow-up of a randomized-controlled trial of a video-based intervention to improve skin self-examination (SSE) behaviour. Descriptive statistics (mean, standard deviation, item–total correlations, and Cronbach’s alpha) were compiled and difficulty parameters were computed with Winsteps using the polytomous Rasch Rating Scale Model (RRSM). An item person (Wright) map of the SSEAS was examined for content coverage and item targeting. Results The SSEAS have good psychometric properties including good internal consistency (Cronbach’s alpha = 0.80), fit with the model and no evidence for differential item functioning (DIF) due to experimental trial grouping was detected. Conclusions The present study confirms the SSEA scale as a brief, useful and reliable tool for assessing attitudes towards skin self-examination in a population of men 50 years or older in Queensland, Australia. The 8-item scale shows unidimensionality, allowing levels of SSE attitude, and the item difficulties, to be ranked on a single continuous scale. In terms of clinical practice, it is very important to assess skin cancer self-examination attitude to identify people who may need a more extensive intervention to allow early detection of skin cancer.

Histopathological features of bone regeneration in a canine segmental ulnar defect model

Background Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopaedic surgeions and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. The present study has been designed in vivo to evaluate the effects of cellular auto-transplantation of tail vertebrae on healing of experimental critical bone defect in a dog model. Methods Six indigenous breeds of dog with 32 ± 3.6 kg average weight from both sexes (5 males and 1 female) received bilateral critical-sized ulnar segmental defects. After determining the health condition, divided to 2 groups: The Group I were kept as control I (n = 1) while in Group II (experimental group; n = 5) bioactive bone implants were inserted. The defects were implanted with either autogeneic coccygeal bone grafts in dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. Animals were euthanized at 16 weeks and analyzed by histopathology. Results Histological evaluation of this new bone at sixteen weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. And also reformation cortical compartment and reconstitution of marrow space were observed at the graft-host interface together with graft resorption and necrosis responses. Finally, our data were consistent with the osteoconducting function of the tail autograft. Conclusions Our results suggested that the tail vertebrae autograft seemed to be a new source of autogenous cortical bone in order to supporting segmental long bone defects in dogs. Furthermore, cellular autotransplantation was found to be a successful replacement for the tail vertebrae allograft bone at 3-4 cm segmental defects in the canine mid- ulna. Clinical application using graft expanders or bone autotransplantation should be used carefully and requires further investigation.