30 research outputs found

    Creating regional crime statistics from administrative data

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    Abstract: The only publicly-available information on the geographical distribution of crime in New Zealand is offence statistics for police administrative units. We investigate whether existing data can be used to construct geographical crime statistics that correspond to regional councils, territorial authorities, and urban areas. Methods We build experimental output geographies from police stations, the smallest administrative unit for which there are long time series of offence statistics. We develop three rules for assigning police stations to the new geographies: one based on population, one based on land area, and one based on both. We assess the performance of these rules by calculating the proportion of national land area and population that is misclassified, and the number of target units that do not receive at least one police station. We also look at whether regional statistics on serious assaults are sensitive to the choice of allocation rule. Findings The new output geographies approximate the target geographies well. For instance, our preferred rule assigns 96 percent of the national population to the correct territorial authority. Moreover, a case study of serious assaults suggests that most regional crime statistics are not sensitive to the choice of rule. Conclusion The new output geographies perform sufficiently well that they could, if required, be used to produce regional crime statistics

    Estimating Earth's temporal gravity field from GRACE observations: Mitigation of thermal errors and the interplay between orbital characteristics, basis functions and spatial resolution

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    The Gravity Recovery and Climate Experiment (GRACE) mission measured the combined effect of the Earth's static and time-variable gravity fields globally and near-continuously over 15 years at unprecedented accuracy. Launched in 2002, the GRACE mission used a unique low-Earth orbit satellite-to-satellite tracking mission design. The time-variable gravity field is influenced by the movement of masses within the hydrosphere and the solid Earth. By directly monitoring mass balance changes due to flood, drought, groundwater extraction, ocean circulation, ocean mass increase and ice mass loss, results from the GRACE mission have increased understanding of the impacts of human activity, natural variation and climate change. The accuracy of GRACE estimates of the time-variable gravity field and the associated mass anomaly time series is affected by several factors. These include orbital characteristics, quality of the observations and background forcing models and the processing strategies used for precise orbit determination and temporal gravity field estimation. This study aims to improve GRACE-based estimates of the time-variable gravity field to analyse mass anomalies by mitigating measurement errors and optimising the choices of processing strategies. The precise calculation of GRACE satellite orbits is reliant on knowledge of accurate non-gravitational forces acting on the spacecraft. Optimal performance of the accelerometers requires a highly stable thermally controlled environment which was not maintained throughout the mission. In this study, I developed pre-processing and calibration strategies to account for thermally-induced errors in the non-gravitational acceleration measurements. Accurate time-variable gravity models could then be estimated from GRACE data even in the presence of thermally-induced error. Some mathematical form, or basis function, must be assumed to parameterise the temporal gravity field on the surface of Earth. The choice of the inter-satellite observation and basis functions can also improve the recovery of the gravity field by better localising the mass variations. This study demonstrates how mass concentration (mascon) tiles can reduce signal leakage and intra-mascon variability (the variations of mass change signals within a mascon). I identified the optimal mascon parameterisation through simulation, subsequently used to generate the ANU GRACE mass anomaly time series. Improved localisation of the mass variation signals was achieved using the range acceleration as the inter-satellite observation rather than the conventional approach of using range rate observations. The GRACE processing strategies chosen to optimise the accuracy of the temporal gravity solutions tend to be used - without change - across the mission's duration. However, as the geometry of the orbits of the twin spacecraft vary throughout the mission, the ability of the observations to recover high-frequency spatial signals also varies. Through simulation, I assessed the impact of the changing orbital elements on the spatial resolution of the GRACE mascon solutions as a function of altitude and ground track density. With appropriate regularisation, mascons as small as ∼\sim150 ×\times 150 km yield the most accurate solutions even during periods of orbit resonance. Under realistic simulation conditions, the temporal gravity field solutions are significantly improved with decreased orbit altitude. Many components of my work have been implemented into the ANU GRACE software, including pre-processing and calibration strategies that account for thermally-induced errors in the accelerometer measurements, filtering to mitigate high-frequency inter-satellite range acceleration noise, protocols to create mascon grids and the iteration procedure used to generate the ANU GRACE mass anomaly estimates. The results show substantial seasonal variations, ice sheet mass loss and global mean sea level increase consistent with previous studies

    Molecular Imaging to Target Transplanted Muscle Progenitor Cells

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    Duchenne muscular dystrophy (DMD) is a severe genetic neuromuscular disorder that affects 1 in 3,500 boys, and is characterized by progressive muscle degeneration(1, 2). In patients, the ability of resident muscle satellite cells (SCs) to regenerate damaged myofibers becomes increasingly inefficient(4). Therefore, transplantation of muscle progenitor cells (MPCs)/myoblasts from healthy subjects is a promising therapeutic approach to DMD. A major limitation to the use of stem cell therapy, however, is a lack of reliable imaging technologies for long-term monitoring of implanted cells, and for evaluating its effectiveness. Here, we describe a non-invasive, real-time approach to evaluate the success of myoblast transplantation. This method takes advantage of a unified fusion reporter gene composed of genes (firefly luciferase [fluc], monomeric red fluorescent protein [mrfp] and sr39 thymidine kinase [sr39tk]) whose expression can be imaged with different imaging modalities(9, 10). A variety of imaging modalities, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and high frequency 3D-ultrasound are now available, each with unique advantages and limitations(11). Bioluminescence imaging (BLI) studies, for example, have the advantage of being relatively low cost and high-throughput. It is for this reason that, in this study, we make use of the firefly luciferase (fluc) reporter gene sequence contained within the fusion gene and bioluminescence imaging (BLI) for the short-term localization of viable C2C12 myoblasts following implantation into a mouse model of DMD (muscular dystrophy on the X chromosome [mdx] mouse) (12-14). Importantly, BLI provides us with a means to examine the kinetics of labeled MPCs post-implantation, and will be useful to track cells repeatedly over time and following migration. Our reporter gene approach further allows us to merge multiple imaging modalities in a single living subject; given the tomographic nature, fine spatial resolution and ability to scale up to larger animals and humans(10,11), PET will form the basis of future work that we suggest may facilitate rapid translation of methods developed in cells to preclinical models and to clinical applications

    Changes in the cardiac GHSR1a-ghrelin system correlate with myocardial dysfunction in diabetic cardiomyopathy in mice

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    Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5 after birth. In group 1, mild fasting hyperglycemia (11 mM) was first detected 8 weeks after the last injection, and in group 2, severe fasting hyperglycemia (20 mM) was first detected 1 to 3 weeks after the last injection. In group 1, left ventricular function was slightly impaired as measured by echocardiography, and Western blot analysis showed a significant decrease in myocardial GHSR1a. In group 2, GHSR1a levels were also decreased as assessed by Cy5-ghrelin(1-19) fluorescence microscopy, and there was a significant negative correlation between GHSR1a levels and glucose tolerance. There were significant positive correlations between GHSR1a and ghrelin and between GHSR1a and sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), a marker for contractility, but not between GHSR1a and B-type natriuretic peptide, a marker for heart failure. We conclude that the subclinical stage of DCM is accompanied by alterations in the myocardial ghrelin-GHSR1a system, suggesting the possibility of a biomarker for DCM

    Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

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    Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

    MagA expression attenuates iron export activity in undifferentiated multipotent P19 cells

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    © 2019 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Magnetic resonance imaging (MRI) is a non-invasive imaging modality used in longitudinal cell tracking. Previous studies suggest that MagA, a putative iron transport protein from magnetotactic bacteria, is a useful gene-based magnetic resonance contrast agent. Hem-agglutinin-tagged MagA was stably expressed in undifferentiated embryonic mouse teratocarcinoma, multipotent P19 cells to provide a suitable model for tracking these cells during differentiation. Western blot and immunocytochemistry confirmed the expression and membrane localization of MagA in P19 cells. Surprisingly, elemental iron analysis using inductively-coupled plasma mass spectrometry revealed significant iron uptake in both parental and MagA-expressing P19 cells, cultured in the presence of iron-supplemented medium. Withdrawal of this extracellular iron supplement revealed unexpected iron export activity in P19 cells, which MagA expression attenuated. The influence of iron supplementation on parental and MagA-expressing cells was not reflected by longitudinal relaxation rates. Measurement of transverse relaxation rates (R2* and R2) reflected changes in total cellular iron content but did not clearly distinguish MagA-expressing cells from the parental cell type, despite significant differences in the uptake and retention of total cellular iron. Unlike other cell types, the reversible component R20 (R2* – R2) provided only a moderately strong correlation to amount of cellular iron, normalized to amount of protein. This is the first report to characterize MagA expression in a previously unrecognized iron exporting cell type. The interplay between contrast gene expression and systemic iron metabolism substantiates the potential for diverting cellular iron toward the formation of a novel iron compartment, however rudimentary when using a single magnetotactic bacterial gene expression system like magA. Since relatively few mammalian cells export iron, the P19 cell line provides a tractable model of ferroportin activity, suitable for magnetic resonance analysis of key iron-handling activities and their influence on gene-based MRI contrast
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