Beatbox - a computer simulation environment for computational biology of the heart

Despite over a century’s study, the trigger mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace the development of fibrillation in samples of cardiac tissue, not to mention the heart in vivo. Advances in human genetics provide information on the impact of certain genes on cellular activity, but do not explain the resultant mechanisms by which fibrillation arises. Thus, for some genetic cardiac diseases, the first presenting symptom is death. Computer simulations of electrical activity in cardiac tissue offer increasingly detailed insight into these phenomena, providing a view of cellular-level activity on the scale of a whole tissue wall. Already, advances in this field have led to developments in our understanding of heart fibrillation and sudden cardiac death and their impact is expected to increase significantly as we approach the ultimate goal of whole-heart modelling. Modelling the propagation of Action Potential through cardiac tissue is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. The complexity of the problem encompasses the description of ionic currents underlying excitation of a single cell through the inhomogeneity of the tissue to the complex geometry of the whole heart. The timely running of computational models of cardiac tissue is increasingly dependant on the effective use of High Performance Computing (HPC), i.e. systems with parallel processors. Current state of the art cardiac simulation tools are limited either by the availability of modern, detailed models, or by their hardware portability or ease of use. The miscellany of current model implementations leads many researchers to develop their own ad-hoc software, preventing them from both utilising the power of HPC effectively, and from collaborating fluidly. It is, arguably, impeding scientific progress. This paper presents a roadmap for the development of Beatbox, a computer simulation environment for computational biology of the heart—an adaptable and extensible framework with which High Performance Computing may be harnessed by researchers

Amblyrhiza and the Vertebrate Paleontology of Anguillean Caves

Recorded interest in the caves of Anguilla dates back to the second half of the nineteenth century. The earliest explorations were concerned with the locating phosphatic cave earths, and resulted in the mining of several sites. Incidental to this work, the bones of the largest island rodent ever discovered were collected from Aguillan caves. Whereas the phosphate mining operations were short-lived, the remains of the giant rodent Amblyrhiza have catalyzed a continued interest in the caves of Anguilla. The most recent series of explorations have provided the first adequate documentation of Amhlyrhiza fossil sites, and have started to yield radiometric dates

High-performance computing for computational biology of the heart

This thesis describes the development of Beatbox — a simulation environment for computational biology of the heart. Beatbox aims to provide an adaptable, approachable simulation tool and an extensible framework with which High Performance Computing may be harnessed by researchers. Beatbox is built upon the QUI software package, which is studied in Chapter 2. The chapter discusses QUI’s functionality and common patterns of use, and describes its underlying software architecture, in particular its extensibility through the addition of new software modules called ‘devices’. The chapter summarises good practice for device developers in the Laws of Devices. Chapter 3 discusses the parallel architecture of Beatbox and its implementation for distributed memory clusters. The chapter discusses strategies for domain decomposition, halo swapping and introduces an efficient method for exchange of data with diagonal neighbours called Magic Corners. The development of Beatbox’s parallel Input/Output facilities is detailed, and its impact on scaling performance discussed. The chapter discusses the way in which parallelism can be hidden from the user, even while permitting the runtime execution user-defined functions. The chapter goes on to show how QUI’s extensibility can be continued in a parallel environment by providing implicit parallelism for devices and defining Laws of Parallel Devices to guide third-party developers. Beatbox’s parallel performance is evaluated and discussed. Chapter 4 describes the extension of Beatbox to simulate anatomically realistic tissue geometry. Representation of irregular geometries is described, along with associated user controls. A technique to compute no-flux boundary conditions on irregular boundaries is introduced. The Laws of Devices are further developed to include irregular geometries. Finally, parallel performance of anatomically realistic meshes is evaluated

Enabling Indigenous education success beyond regional borders

Higher education is a powerful tool for reducing social and economic disadvantage. But access to higher education can be difficult, particularly for Indigenous Australians who face multiple levels of social, economic and geographical isolation. While enabling programs can support Indigenous students to gain university entry, the experience at Central Queensland University (CQUniversity) suggests that their past success has been limited. In this paper, the authors describe the enabling program available to Indigenous students at CQUniversity. They suggest that the newly developed, flexible, online version of the program is helping to address geographical and social isolation and improve successful outcomes for Indigenous Australians

Body Size in Amblyrhiza inundata (Rodentia, Caviomorpha), an Extinct Megafaunal Rodent From the Anguilla Bank, West Indies: Estimates and Implications

Rodent species typically evolve larger mean body sizes when isolated on islands, but the extinct caviomorph Amblyrhiza inundata, known only from Quaternary cave deposits on the islands of Anguilla and St. Martin (northern Lesser Antilles), provides an unusually dramatic example of insular gigantism. Here we report on a series of body mass estimates for Amblyrhiza using predictive equations based on anteroposterior diameters and cortical cross-sectional areas of humeral and femoral diaphyses. Analyses of 14 isolated specimens (5 femoral, 9 humeral), all representing adult or near adult animals, yield body mass estimates ranging from slightly less than 50 kg to more than 200 kg. Body size estimates derived from humeral measurements are lower than those derived from femoral measurements, but the significance of this will remain unclear until matched limb bones (i.e., specimens from the same animal) are recovered. Incisor measurements are also highly variable, but in this case the distribution is demonstrably bimodal. Presence of multiple coeval species, temporal variation, limb heterogeneity, and sexual dimorphism all qualify as possible explanations of the variation encountered in Amblyrhiza data sets, but available samples are not adequate for making a robust choice among them. Body size affects many life history variables, including demography. Population estimates derived from empirical data and predictive equations suggest that only a few thousand individuals of Amblyrhiza could have occupied the islands of the Anguilla Bank at any one time during the Late Quaternary. At certain times-for example, during the last interglacial (Sangamonian) highstand-population numbers might have sunk to only a few hundred. Absolutely small population sizes of Amblyrhiza and severe fluctuations in island area during the late Quaternary surely affected its susceptibility to extinction, whether or not humans were ultimately responsible for the event (for which there is as yet no direct evidence)

A Second Pre-Wisconsinan Locality for the Extinct Jamaican Rodent, Clidomys (Rodentia: Heptaxodontidae)

Clidomys is the most distinctive but least well known member of the late Quaternary terrestrial mammal fauna of Jamaica. Here we report the second dated locality for this genus. The Illinoisan age we report further strengthens arguments we have made elsewhere, that Clidomys represents an early - probably pre-Wisconsinan - extinction that contrasts with the growing record of Holocene extinctions in the Antilles

Deadly Partners: Interdependence of Alcohol and Trauma in the Clinical Setting

Trauma is the leading cause of death for Americans aged 1 to 45. Over a third of all fatal motor vehicle collisions and nearly eighty percent of completed suicides involve alcohol. Alcohol can be both a cause of traumatic injury as well as a confounding factor in the diagnosis and treatment of the injured patient. Fortunately, brief interventions after alcohol-related traumatic events have been shown to decrease both trauma recidivism and long-term alcohol use. This review will address the epidemiology of alcohol-related trauma, the influence of alcohol on mortality and other outcomes, and the role of prevention in alcohol-related trauma, within the confines of the clinical setting

Differential impact of low birth weight on PPAR and leptin expression in perirenal fat in male and female lambs

Scientific Abstract 93. Objective: Epidemiological studies have shown that a low birth weight coupled with a rapid postnatal growth rate is associated with an increased adiposity in adult life. We have investigated the impact of low birth weight and gender on the expression of genes that regulate the differentiation (PPARy, RXRa), insulin sensitivity (adiponectin) and lipid metabolism (leptin, LPL, G3PDH) of perirenal adipocytes in lambs at 21d of life. Methods: Lambs were separated into low birth weight (LBW, 4.5kg, n=15) groups. An Insulin RIA and competitive ELISA for leptin were used for plasma analyses. The relative quantity of PPARy, RXRa, leptin, adiponectin, LPL, and G3PDH mRNA in the perirenal fat depot was determined by qRT-PCR, and the mean size of adipocytes was determined using standard image analysis. Results: There was no difference between LBW and ABW lambs in the relative perirenal adipose tissue (PAT) mass at 21d. Plasma insulin concentrations during the first 24h after birth were strongly correlated with size of perirenal adipocytes at 21d (r²=0.57,

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field