Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli Sand Rat)

Background and AimsA major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat).MethodsP. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat) or a standard rodent diet supplemented with 2% cholesterol (w/w) for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR.ResultsP. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export.ConclusionsP. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.

Categorization of disaster decision support needs for the development of an integrated model for DMDSS

The wide variety of disasters and the large number of activities involved have resulted in the demand for separate Decision Support System (DSS) models to manage different requirements. The modular approach to model management is to provide a framework in which to focus multidisciplinary research and model integration. A broader view of our approach is to provide the flexibility to organize and adapt a tailored DSS model (or existing modular subroutines) according to the dynamic needs of a disaster. For this purpose, the existing modular subroutines of DSS models are selected and integrated to produce a dynamic integrated model focussed on a given disaster scenario. In order to facilitate the effective integration of these subroutines, it is necessary to select the appropriate modular subroutine beforehand. Therefore, subroutine selection is an important preliminary step towards model integration in developing Disaster Management Decision Support Systems (DMDSS). The ability to identify a modular subroutine for a problem is an important feature before performing model integration. Generally, decision support needs are combined, and encapsulate different requirements of decision-making in the disaster management area. Categorization of decision support needs can provide the basis for such model selection to facilitate effective and efficient decision-making in disaster management. Therefore, our focus in this paper is on developing a methodology to help identify subroutines from existing DSS models developed for disaster management on the basis of needs categorization. The problem of the formulation and execution of such modular subroutines are not addressed here. Since the focus is on the selection of the modular subroutines from the existing DMDSS models on basis of a proposed needs classification scheme.

Copper and lactational hormones influence the CTR1 copper transporter in PMC42-LA mammary epithelial cell culture models

Adequate amounts of copper in milk are critical for normal neonatal development, however the mechanisms regulating copper supply to milk have not been clearly defined. PMC42-LA cell cultures representative of resting, lactating and suckled mammary epithelia were used to investigate the regulation of the copper uptake protein, CTR1. Both the degree of mammary epithelial differentiation (functionality) and extracellular copper concentration greatly impacted upon CTR1 expression and its plasma membrane association. In all three models (resting, lactating and suckling) there was an inverse correlation between extracellular copper concentration and the level of CTR1. Cell surface biotinylation studies demonstrated that as extracellular copper concentration increased membrane associated CTR1 was reduced. There was a significant increase in CTR1 expression (total and membrane associated) in the suckled gland model in comparison to the resting gland model, across all copper concentrations investigated (0-50 μM). Regulation of CTR1 expression was entirely post-translational, as quantitative real-time PCR analyses showed no change to CTR1 mRNA between all models and culture conditions. X-ray fluorescence microscopy on the differentiated PMC42-LA models revealed that organoid structures distinctively accumulated copper. Furthermore, as PMC42-LA cell cultures became progressively more specialised, successively more copper accumulated in organoids (resting

Drought and desalination: Melbourne water supply and development choices in the twenty-first century

Sharply reduced catchment inflows across Australia around the end of the twentieth century led to a sequence of water restrictions followed, as the drought persisted, by approximately $10 billion of investments in desalination plants near Perth, Adelaide, Melbourne, Sydney and Brisbane. This Deakin University project jointly with Griffith University, for the National Centre of Excellence in Desalination (NCEDA), follows these new investments. We ask how best to manage bulk water supply and retail supply given the facts and fears of uncertain rainfall, modelled over a 100 year simulation period. We use Monte Carlo style studies aiming to capture the new tensions and trade-offs regarding uncertain climate, rainfall and water supply. There are presently no comprehensive life-cycle approaches to model city water balances that incorporate economic feedbacks, such as tariff adjustment, which can in turn create a financing capacity for such investment responses to low catchment levels, models that could provide significant policy implications for water planners. This project addresses the gap, and presents excerpts from a system dynamics model that augments the usual water utility representation of the physical linkages and water grids. We add inter-connected feedback loops in tariff structures, demand levels and financing capacity. Tariffs are reset in association with drought and the modelling of responses both in terms of reduced consumption and increased revenue to the utility, depending on the elasticities of demand responses to higher tariffs, both short and long term, while also allowing effects from any transitional restrictions. Before reporting on parts of the simulations applied to Melbourne, this paper will first review the general issues surrounding whether desalination is or can be a “game changer” for economic development that hinges on secure water supply. We then explore options in bulk water supply management when desalination augments the choices, including catchments, dams, recycling, pipelines from rivers and savings in irrigation. Finally, the paper addresses the intriguing and important question of the value and cost of providing water for environmental uses.

Social norms in the development of adolescent substance use: a longitudinal analysis of the International Youth Development Study.

Identifying specific aspects of peer social norms that influence adolescent substance use may assist international prevention efforts. This study examines two aggregated measures of social norms in the school setting and their predictive association with substance (alcohol, tobacco and marijuana) use 2 years later in a large cross-national population-based cohort of adolescents. The primary hypothesis is that in Grade 7 both "injunctive" school norms (where students associate substance use with "coolness") and "descriptive" norms (where student substance use is common) will predict Grade 9 substance use. Data come from the International Youth Development Study, including 2,248 students (51.2% female) in the US and Australia attending 121 schools in Grade 7. Independent variables included injunctive norms (aggregating measures of school-wide coolness ratings of each substance use) and descriptive norms (aggregating the prevalence of school substance use) in Grade 7. Dependent variables included binge drinking and current use of alcohol, tobacco and marijuana in Grade 9. Associations between each type of school-wide social norm and substance use behaviors in Grade 9 were tested using multilevel logistic regression, adjusting for covariates. In unadjusted models, both injunctive and descriptive norms each significantly predicted subsequent substance use. In fully adjusted models, injunctive norms were no longer significantly associated with Grade 9 use, but descriptive norms remained significantly associated with tobacco and marijuana use in the expected direction. The findings identify descriptive social norms in the school context as a particularly important area to address in adolescent substance use prevention efforts.

Development aid and growth in transition countries

Empirical studies normally analyze diverse and heterogeneous groups of countries, producing very mixed evidence on the effectiveness of development aid in promoting growth. We focus on whether aid promotes economic growth in transitional economies. We find that aid, on average, has had a positive impact on growth for this specific group of countries. This result is robust to samples, estimators, and the use of alternate instruments to address endogeneity. Aid effectiveness is not conditional on good policy and there is little evidence of non-linear growth effects arising from aid.

ZebRA: an overview of retinoic acid signaling during zebrafish development

Retinoic acid (RA), the main active vitamin A derivative, is crucial for embryo development, regulating cellular processes, embryo patterning and organogenesis. Many studies performed in mammalian or avian models have successfully undertaken the investigation of the role played by RA during embryogenesis. Since the early 1980s, the zebrafish (Danio rerio) has emerged as a powerful developmental model to study the in vivo role of RA during embryogenesis. Unlike mammalian models, zebrafish embryogenesis is external, not only allowing the observation of the translucent embryo from the earliest steps but also providing an easily accessible system for pharmacological treatment or genetic approaches. Therefore, zebrafish research largely participates in deciphering the role of RA during development. This review aims at illustrating different concepts of RA signaling based on the research performed on zebrafish. Indeed, RA action relies on a multitude of cross-talk with other signaling pathways and requires a coordinated, dynamic and fine-regulation of its level and activity in both temporal and spatial dimensions. This review also highlights major advances that have been discovered using zebrafish such as the observation of the RA gradient in vivo for the first time, the effects of RA signaling in brain patterning, its role in establishing left-right asymmetry and its effects on the development of a variety of organs and tissues including the heart, blood, bone and fat. This review demonstrates that the zebrafish is a convenient and powerful model to study retinoic acid signaling during vertebrate embryogenesis. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

Validation and development of a clinical prediction rule in clinically suspected community-acquired pneumonia

To develop a mathematical model to predict the probability of having community-acquired pneumonia and to evaluate an already developed prediction rule that has not been validated in a clinical scenario.

UnitingWorld : Partnership for effective involvement in mission including development

This chapter argues that, both theologically and practically, development is a form of mission and therefore dividing 'mission' and 'development' is artificial. A theological understanding of mission clearly incorporates upholding rights especially of people most excluded and vulnerable, the core task of development.One church agency involved in both development and supporting partners in communicating the gospel is UnitingWorld – the national agency of the Uniting Church in Australia responsible for international partnerships including development. The Uniting Church was formed in 1977 from the merging of three denominations, all of which had a long history of overseas engagement – for example with Fiji since 1844 and Korea since 1889. Such partnerships have endured and spread to the point where the Uniting Church now has thirty six formal partners, mainly in the Pacific and Asia.Over the past 20 years, a range of social trends, such as decolonisation, climate change, and increased global commitment to justice, as well as changes in missiological thinking, have influenced collaboration with indigenous churches as well as organisations not explicitly Christian.Recolonising approaches by international inter-government bodies and by the Australian government through promoting predominantly western neo-liberal economic values to neighbours, invites the church to collaborate in valuing partner cultures, spiritualities, values and world-views. For UnitingWorld this is most evident in its Pacific engagement, especially with programs arising from the Pacific Conference of Churches.These factors have further relativised the tensions between what was seen as “mission” and what was seen as “development”. Evangelism as communication of good news exhibits a different hue – now coming out of the natural conversations between partners and speaking of God’s life- giving alternatives to destructive social and economic models. Whilst development is inherent in mission, the major challenge faced by UnitingWorld is with Protestant partners strongly influenced by an era of church teaching that emphasised personal commitment tied to distinctive religious expressions.In this chapter we use case studies from the Pacific to show how UnitingWorld is partnering with a range of church and other organisations to support people in exercising their rights and re-engaging Australian church communities in this task.

Alternative service delivery models for families with a new speech generating device: perspectives of parents and therapists

Purpose: Research has revealed limitations in the provision of in-person services to families with a new speech generating device (SGD), both in Australia and overseas. Alternative service models such as parent training, peer support and telepractice may offer a solution, but their use with this population has not been researched to date.

Method: Using interviews and focus groups, this study explored the experiences and opinions of 13 speech-language pathologists and seven parents regarding alternatives to in-person support and training for families with a new SGD. Data were analysed using grounded theory. Themes explored in this paper include the benefits and drawbacks of alternative service models as well as participants’ suggestions for the optimal implementation of these approaches.

Result: Participants confirmed the utility of alternative service models, particularly for rural/remote and underserviced clients. Benefits of these models included reduced travel time for families and therapists, as well as enhanced information access, support and advocacy for parents.

Conclusion: Participants viewed the provision of ongoing professional support to families as critical, regardless of service modality. Additional issues arising from this study include the need for development of organizational policies, resources and training infrastructure to support the implementation of these alternative service models.

CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis

Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

Functional system maps as boundary objects in complex system development

A trend towards the provision of product-service packaging and the proliferation of service businesses introduces both tangible and intangible elements into system design. In this paper, we consider the utility of hierarchical system models as a way of flexibly combining such elements by focusing on requisite functionality. Four cases illustrate how the same approach may be used to clarify the requirements of business or socio-technical systems during system development, operation or reengineering stages. It is suggested that a suitable loosely coupled model has significant utility as a 'boundary object' - a term first coined in the study of museum artefacts. Discussion of such objects requires the use of imagination, which may support innovative system design and development. It is suggested that a well-crafted model has multiple uses - as a foundation for system development, in combining traditional and agile project management strategies and in providing a framework to facilitate the capture and organisation of project knowledge.

A review on otolith models in human perception

The vestibular system, which consists of semicircular canals and otolith, are the main sensors mammals use to perceive rotational and linear motions. Identifying the most suitable and consistent mathematical model of the vestibular system is important for research related to driving perception. An appropriate vestibular model is essential for implementation of the Motion Cueing Algorithm (MCA) for motion simulation purposes, because the quality of the MCA is directly dependent on the vestibular model used. In this review, the history and development process of otolith models are presented and analyzed. The otolith organs can detect linear acceleration and transmit information about sensed applied specific forces on the human body. The main purpose of this review is to determine the appropriate otolith models that agree with theoretical analyses and experimental results as well as provide reliable estimation for the vestibular system functions. Formulating and selecting the most appropriate mathematical model of the vestibular system is important to ensure successful human perception modelling and simulation when implementing the model into the MCA for motion analysis.

Creating High-Impact Workforce Development Programs

As communities across the nation continue to face persistent unemployment, many states are turning to community college workforce development programs to combat joblessness. However, state governments and community colleges alike are often unable to devote significant resources to building new workforce initiatives. This brief examines how community colleges in four states have worked with state governments and other partners to overcome budget constraints and create effective workforce development programs, highlighting funding models and innovative practices to make efficient use of limited resources.