Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Access and Quality of Heart Failure Management Programs in Australia

Background/aim In response to the high burden of disease associated with chronic heart failure (CHF), in particular the high rates of hospital admissions, dedicated CHF management programs (CHF-MP) have been developed. Over the past five years there has been a rapid growth of CHF-MPs in Australia. Given the apparent mismatch between the demand for, and availability of CHF-MPs, this paper has been designed to discuss the accessibility to and quality of current CHF-MPs in Australia. Methods The data presented in this report has been combined from the research of the co-authors, in particular a review of the inequities in access to chronic heart failure which utilised geographical information systems (GIS) and the survey of heterogeneity in quality and service provision in Australian. Results Of the 62 CHF-MPs surveyed in this study 93% (58) centres had been located areas that are rated as Highly Accessible. This result indicated that most of the CHF-MPs have been located in capital cities or large regional cities. Six percent (4 CHF-MPs) had been located in Accessible areas which were country towns or cities. No CHF-MPs had been established outside of cities to service the estimated 72,000 individuals with CHF living in rural and remote areas. 16% of programs recruited NYHA Class I patients and of these 20% lacked confirmation (echocardiogram) of their diagnosis. Conclusion Overall, these data highlight the urgent need to provide equitable access to CHF-MP's. When establishing CHF-MPs consideration of current evidence based models to ensure quality in practice.

A new control-volume finite-element scheme for heterogeneous porous media : application to the drying of softwood

An improved mesoscopic model is presented for simulating the drying of porous media. The aim of this model is to account for two scales simultaneously: the scale of the whole product and the scale of the heterogeneities of the porous medium. The innovation of this method is the utilization of a new mass-conservative scheme based on the Control-Volume Finite-Element (CV-FE) method that partitions the moisture content field over the individual sub-control volumes surrounding each node within the mesh. Although the new formulation has potential for application across a wide range of transport processes in heterogeneous porous media, the focus here is on applying the model to the drying of small sections of softwood consisting of several growth rings. The results conclude that, when compared to a previously published scheme, only the new mass-conservative formulation correctly captures the true moisture content evolution in the earlywood and latewood components of the growth rings during drying.

The causes and consequences of corruption

This thesis comprehensively studies the causes and consequences of corruption in both crosscountry and within-country contexts, mainly focusing on China. The thesis commences by extensively investigating the causes of corruption. Using the standard economic approach, this study finds that in China regions with more anti-corruption efforts, higher education attainment, Anglo-American historic influence, higher openness, more access to media, higher relative wages of government employees, and a greater representation of women in legislature are markedly less corrupt; while the social heterogeneity, deregulation and abundance of resources, substantially breed regional corruption. Moreover, fiscal decentralization is discovered to depress corruption significantly. This study also observes a positive relationship between corruption and the economic development in current China that is mainly driven by the transition to a market economy. Focusing on the influence of political institutions on corruption, the thesis then provides evidence that a high level of political interest helps to reduce corruption within a society, while the effect of democracy upon corruption depends on property rights protection and income distribution. With the social economic approach, however, the thesis presents both cross-country and within-country evidence that the social interaction plays an important role in determining corruption. The thesis then continues by comprehensively evaluating the consequences of corruption in China. The study provides evidence that corruption can simultaneously have both positive and negative effects on economic development. And it also observes that corruption considerably increases the income inequality in China. Furthermore this study finds that corruption in China significantly distorts public expenditures. Local corruption is also observed to substantially reduce FDI in Chinese regions. Finally the study documents that corruption substantially aggravates pollution probably through a loosening of the environmental regulation, and that it also modifies the effects of trade openness and FDI on the stringency of environmental policy. Overall, this thesis adds to the current literature by a number of novel findings concerning both the causes and the consequences of corruption.

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Abstract Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

Unbiased estimation of the half-life to price index convergence among U.S. cities

Estimates of the half-life to convergence of prices across a panel of cities are subject to bias from three potential sources: inappropriate cross-sectional aggregation of heterogeneous coefficients, presence of lagged dependent variables in a model with individual fixed effects, and time aggregation of commodity prices. This paper finds no evidence of heterogeneity bias in annual CPI data for 17 U.S. cities from 1918 to 2006, but correcting for the “Nickell bias” and time aggregation bias produces a half-life of 7.5 years, shorter than estimates from previous studies.

Choreographic approaches to music composition for a new musical interface : the eMic

Gesture in performance is widely acknowledged in the literature as an important element in making a performance expressive and meaningful. The body has been shown to play an important role in the production and perception of vocal performance in particular. This paper is interested in the role of gesture in creative works that seek to extend vocal performance via technology. A creative work for vocal performer, laptop computer and a Human Computer Interface called the eMic (Extended Microphone Stand Interface controller) is presented as a case study, to explore the relationships between movement, voice production, and musical expression. The eMic is an interface for live vocal performance that allows the singers’ gestures and interactions with a sensor based microphone stand to be captured and mapped to musical parameters. The creative work discussed in this paper presents a new compositional approach for the eMic by working with movement as a starting point for the composition and thus using choreographed gesture as the basis for musical structures. By foregrounding the body and movement in the creative process, the aim is to create a more visually engaging performance where the performer is able to more effectively use the body to express their musical objectives.

Least-squares congealing for large numbers of images

In this paper we pursue the task of aligning an ensemble of images in an unsupervised manner. This task has been commonly referred to as “congealing” in literature. A form of congealing, using a least-squares criteria, has been recently demonstrated to have desirable properties over conventional congealing. Least-squares congealing can be viewed as an extension of the Lucas & Kanade (LK)image alignment algorithm. It is well understood that the alignment performance for the LK algorithm, when aligning a single image with another, is theoretically and empirically equivalent for additive and compositional warps. In this paper we: (i) demonstrate that this equivalence does not hold for the extended case of congealing, (ii) characterize the inherent drawbacks associated with least-squares congealing when dealing with large numbers of images, and (iii) propose a novel method for circumventing these limitations through the application of an inverse-compositional strategy that maintains the attractive properties of the original method while being able to handle very large numbers of images.

A multi-resolution image alignment technique based on direct methods for pose estimation of aerial vehicles

In this paper, we seek to expand the use of direct methods in real-time applications by proposing a vision-based strategy for pose estimation of aerial vehicles. The vast majority of approaches make use of features to estimate motion. Conversely, the strategy we propose is based on a MR (Multi- Resolution) implementation of an image registration technique (Inverse Compositional Image Alignment ICIA) using direct methods. An on-board camera in a downwards-looking configuration, and the assumption of planar scenes, are the bases of the algorithm. The motion between frames (rotation and translation) is recovered by decomposing the frame-to-frame homography obtained by the ICIA algorithm applied to a patch that covers around the 80% of the image. When the visual estimation is required (e.g. GPS drop-out), this motion is integrated with the previous known estimation of the vehicles’ state, obtained from the on-board sensors (GPS/IMU), and the subsequent estimations are based only on the vision-based motion estimations. The proposed strategy is tested with real flight data in representative stages of a flight: cruise, landing, and take-off, being two of those stages considered critical: take-off and landing. The performance of the pose estimation strategy is analyzed by comparing it with the GPS/IMU estimations. Results show correlation between the visual estimation obtained with the MR-ICIA and the GPS/IMU data, that demonstrate that the visual estimation can be used to provide a good approximation of the vehicle’s state when it is required (e.g. GPS drop-outs). In terms of performance, the proposed strategy is able to maintain an estimation of the vehicle’s state for more than one minute, at real-time frame rates based, only on visual information.

Analysis of productive performance of crop and animal production systems : an integrated analytical framework

This article presents a two-stage analytical framework that integrates ecological crop (animal) growth and economic frontier production models to analyse the productive efficiency of crop (animal) production systems. The ecological crop (animal) growth model estimates "potential" output levels given the genetic characteristics of crops (animals) and the physical conditions of locations where the crops (animals) are grown (reared). The economic frontier production model estimates "best practice" production levels, taking into account economic, institutional and social factors that cause farm and spatial heterogeneity. In the first stage, both ecological crop growth and economic frontier production models are estimated to calculate three measures of productive efficiency: (1) technical efficiency, as the ratio of actual to "best practice" output levels; (2) agronomic efficiency, as the ratio of actual to "potential" output levels; and (3) agro-economic efficiency, as the ratio of "best practice" to "potential" output levels. Also in the first stage, the economic frontier production model identifies factors that determine technical efficiency. In the second stage, agro-economic efficiency is analysed econometrically in relation to economic, institutional and social factors that cause farm and spatial heterogeneity. The proposed framework has several important advantages in comparison with existing proposals. Firstly, it allows the systematic incorporation of all physical, economic, institutional and social factors that cause farm and spatial heterogeneity in analysing the productive performance of crop and animal production systems. Secondly, the location-specific physical factors are not modelled symmetrically as other economic inputs of production. Thirdly, climate change and technological advancements in crop and animal sciences can be modelled in a "forward-looking" manner. Fourthly, knowledge in agronomy and data from experimental studies can be utilised for socio-economic policy analysis. The proposed framework can be easily applied in empirical studies due to the current availability of ecological crop (animal) growth models, farm or secondary data, and econometric software packages. The article highlights several directions of empirical studies that researchers may pursue in the future.

Birds of a feather get lost together : new venture team composition and performance

This study explores the relationship between new venture team composition and new venture persistence and performance over time. We examine the team characteristics of a 5-year panel study of 202 new venture teams and new venture performance. Our study makes two contributions. First, we extend earlier research concerning homophily theories of the prevalence of homogeneous teams. Using structural event analysis we demonstrate that team members’ start-up experience is important in this context. Second, we attempt to reconcile conflicting evidence concerning the influence of team homogeneity on performance by considering the element of time. We hypothesize that higher team homogeneity is positively related to short term outcomes, but is less effective in the longer term. Our results confirm a difference over time. We find that more homogeneous teams are less likely to be higher performing in the long term. However, we find no relationship between team homogeneity and short-term performance outcomes.

Improving self-report measures of speeding

There is continuing debate regarding the psychometric properties of self-report measures of behaviour, particularly in road safety research. Practical considerations often preclude the use of objective assessments, leading to reliance on self-report measures. Acknowledging that such measures are likely to remain commonly used, this pilot project sought not to argue whether self-report measures should continue to be used, but to explore factors associated with how individuals respond to self-reported speeding measures. This paper reports preliminary findings from a qualitative study (focus groups and in-depth interviews) conducted with licensed drivers to explore the operational utility of self-reported speeding behaviour measures. Drawing upon concepts from the Theory of Planned Behaviour (TPB; Ajzen, 1991) and Agency Theory (Bandura, 2001), we identified four dimensions of self-reported speeding: including timeframe, speed zone, degree over the speed limit and, overall frequency of the behaviour, and examined participants’ perceptions of the operational utility of these factors. Issues related to comprehensibility, perceived accuracy, response format and layout were also explored. Results indicated that: heterogeneity in the timeframe of behavioural reflections suggests a need to provide a set timeframe for participants to consider when thinking about their previous speeding behaviour; response categories and formats should be carefully considered to ensure the most accurate representations of the frequency and degree of speeding are captured; the need to clearly articulate “low-level” speeding on self-report measures; and, that self-reports of speeding behaviour are typically context-irrelevant unless stipulated in the question. Limitations and directions for further research are discussed.

Influence of physical and chemical properties of solids on heavy metal adsorption

Partition of heavy metals between particulate and dissolve fraction of stormwater primarily depends on the adsorption characteristics of solids particles. Moreover, the bioavailability of heavy metals is also influenced by the adsorption behaviour of solids. However, due to the lack of fundamental knowledge in relation to the heavy metals adsorption processes of road deposited solids, the effectiveness of stormwater management strategies can be limited. The research study focused on the investigation of the physical and chemical parameters of solids on urban road surfaces and, more specifically, on heavy metal adsorption to solids. Due to the complex nature of heavy metal interaction with solids, a substantial database was generated through a series of field investigations and laboratory experiments. The study sites for the build-up pollutant sample collection were selected from four urbanised suburbs located in a major river catchment. Sixteen road sites were selected from these suburbs and represented typical industrial, commercial and residential land uses. Build-up pollutants were collected using a wet and dry vacuum collection technique which was specially designed to improve fine particle collection. Roadside soil samples were also collected from each suburb for comparison with the road surface solids. The collected build-up solids samples were separated into four particle size ranges and tested for a range of physical and chemical parameters. The solids build-up on road surfaces contained a high fraction (70%) of particles smaller than 150ìm, which are favourable for heavy metal adsorption. These solids particles predominantly consist of soil derived minerals which included quartz, albite, microcline, muscovite and chlorite. Additionally, a high percentage of amorphous content was also identified in road deposited solids. In comparing the mineralogical data of surrounding soil and road deposited solids, it was found that about 30% of the solids consisted of particles generated from traffic related activities on road surfaces. Significant difference in mineralogical composition was noted in different particle sizes of build-up solids. Fine solids particles (<150ìm) consisted of a clayey matrix and high amorphous content (in the region of 40%) while coarse particles (>150ìm) consisted of a sandy matrix at all study sites, with about 60% quartz content. Due to these differences in mineralogical components, particles larger than and smaller than 150ìm had significant differences in their specific surface area (SSA) and effective cation exchange capacity (ECEC). These parameters, in turn, exert a significant influence on heavy metal adsorption. Consequently, heavy metal content in >150ìm particles was lower than in the case of fine particles. The particle size range <75ìm had the highest heavy metal content, corresponding with its high clay forming minerals, high organic matter and low quartz content which increased the SSA, ECEC and the presence of Fe, Al and Mn oxides. The clay forming minerals, high organic matter and Fe, Al and Mn oxides create distinct groups of charge sites on solids surfaces and exhibit different adsorption mechanisms and bond strength, between heavy metal elements and charge sites. Therefore, the predominance of these factors in different particle sizes leads to different heavy metal adsorption characteristics. Heavy metals show preference for association with clay forming minerals in fine solids particles, whilst in coarse particles heavy metals preferentially associate with organic matter. Although heavy metal adsorption to amorphous material is very low, the heavy metals embedded in traffic related materials have a potential impact on stormwater quality.Adsorption of heavy metals is not confined to an individual type of charge site in solids, whereas specific heavy metal elements show preference for adsorption to several different types of charge sites in solids. This is attributed to the dearth of preferred binding sites and the inability to reach the preferred binding sites due to competition between different heavy metal species. This confirms that heavy metal adsorption is significantly influenced by the physical and chemical parameters of solids that lead to a heterogeneity of surface charge sites. The research study highlighted the importance of removal of solids particles from stormwater runoff before they enter into receiving waters to reduce the potential risk posed by the bioavailability of heavy metals. The bioavailability of heavy metals not only results from the easily mobile fraction bound to the solids particles, but can also occur as a result of the dissolution of other forms of bonds by chemical changes in stormwater or microbial activity. Due to the diversity in the composition of the different particle sizes of solids and the characteristics and amount of charge sites on the particle surfaces, investigations using bulk solids are not adequate to gain an understanding of the heavy metal adsorption processes of solids particles. Therefore, the investigation of different particle size ranges is recommended for enhancing stormwater quality management practices.