Preventative medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

MIDDLESEX HOUSE,34-42 CLEVELAND ST, LONDON, ENGLAND, W1T 4L

Human brain mapping: a systematic comparison of parcellation methods for the human cerebral cortex

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously

Cost analysis of employing general practitioners within residential aged care facilities based on a prospective, stepped-wedge, cluster randomised trial

Objective: To assess the impacts of changing a model of care and employing general practitioners (GPs) within residential aged care facilities (RACFs) on costs to the aged care provider (ACP) and state and federal governments of Australia. Methods: This study was a cost analysis of a prospective, stepped-wedge, cluster randomised trial. All financial data from the ACP for every RACF involved, before and after implementation of the new model were obtained. Costs of hospital transfers, admissions, ambulance usage and GP consultations were calculated. Costs of new infrastructure, recruiting and training new staff were accounted for. Costs were standardised to 2019 Australian Dollars per occupied bed day (OBD). Results: Implementation of the new model of care resulted in overall cost savings of $9.7 per OBD to the ACP, with increased salary costs offset by increased federal government subsidies and Medicare claims income. Costs to the federal government increased by$19.6 per OBD, driven by increases in subsides. Costs savings of $3.0 per OBD to state governments were seen, driven by decreased costs of hospital transfers. Conclusions: Implementation of a model of care including GPs employed at RACFs had a mixed impact on costs depending on perspective, with overall savings to the ACP and state government perspective

A Hierarchical Model for the Ages of Galactic Halo White Dwarfs

In astrophysics, we often aim to estimate one or more parameters for each member object in a population and study the distribution of the fitted parameters across the population. In this paper, we develop novel methods that allow us to take advantage of existing software designed for such case-by-case analyses to simultaneously fit parameters of both the individual objects and the parameters that quantify their distribution across the population. Our methods are based on Bayesian hierarchical modelling which is known to produce parameter estimators for the individual objects that are on average closer to their true values than estimators based on case-by-case analyses. We verify this in the context of estimating ages of Galactic halo white dwarfs (WDs) via a series of simulation studies. Finally, we deploy our new techniques on optical and near-infrared photometry of ten candidate halo WDs to obtain estimates of their ages along with an estimate of the mean age of Galactic halo WDs of 12.11 +0.85-0.86 Gyr. Although this sample is small, our technique lays the ground work for large-scale studies using data from the Gaia mission

Bayesian Hierarchical Modelling of Initial-Final Mass Relations Across Star Clusters

The initial-final mass relation (IFMR) of white dwarfs (WDs) plays an important role in stellar evolution. To derive precise estimates of IFMRs and explore how they may vary among star clusters, we propose a Bayesian hierarchical model that pools photometric data from multiple star clusters. After performing a simulation study to show the benefits of the Bayesian hierarchical model, we apply this model to five star clusters: the Hyades, M67, NGC 188, NGC 2168, and NGC 2477, leading to reasonable and consistent estimates of IFMRs for these clusters. We illustrate how a cluster-specific analysis of NGC 188 using its own photometric data can produce an unreasonable IFMR since its WDs have a narrow range of zero-age main sequence (ZAMS) masses. However, the Bayesian hierarchical model corrects the cluster-specific analysis by borrowing strength from other clusters, thus generating more reliable estimates of IFMR parameters. The data analysis presents the benefits of Bayesian hierarchical modelling over conventional cluster-specific methods, which motivates us to elaborate the powerful statistical techniques in this article

Bayesian Hierarchical Modelling of Initial-Final Mass Relations Across Star Clusters

The initial-final mass relation (IFMR) of white dwarfs (WDs) plays an important role in stellar evolution. To derive precise estimates of IFMRs and explore how they may vary among star clusters, we propose a Bayesian hierarchical model that pools photo- metric data from multiple star clusters. After performing a simulation study to show the benefits of the Bayesian hierarchical model, we apply this model to five star clus- ters: the Hyades, M67, NGC 188, NGC 2168, and NGC 2477, leading to reasonable and consistent estimates of IFMRs for these clusters. We illustrate how a cluster-specific analysis of NGC 188 using its own photometric data can produce an unreasonable IFMR since its WDs have a narrow range of zero-age main sequence (ZAMS) masses. However, the Bayesian hierarchical model corrects the cluster-specific analysis by bor- rowing strength from other clusters, thus generating more reliable estimates of IFMR parameters. The data analysis presents the benefits of Bayesian hierarchical modelling over conventional cluster-specific methods, which motivates us to elaborate the pow- erful statistical techniques in this article.Comment: 29 pages, 12 figure

Functional Mimicry of a Human Immunodeficiency Virus Type 1 Coreceptor by a Neutralizing Monoclonal Antibody

Interaction of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein with the primary receptor, CD4, promotes binding to a chemokine receptor, either CCR5 or CXCR4. The chemokine receptor-binding site on gp120 elicits CD4-induced (CD4i) antibodies in some HIV-1-infected individuals. Like CCR5 itself, the CD4i antibody 412d exhibits a preference for CCR5-using HIV-1 strains and utilizes sulfated tyrosines to achieve binding to gp120. Here, we show that 412d binding requires the gp120 β19 strand and the base of the V3 loop, elements that are important for the binding of the CCR5 N terminus. Two gp120 residues in the V3 loop base determined 412d preference for CCR5-using HIV-1 strains. A chimeric molecule in which the 412d heavy-chain third complementarity-determining loop sequence replaces the CCR5 N terminus functioned as an efficient second receptor, selectively supporting the entry of CCR5-using HIV-1 strains. Sulfation of N-terminal tyrosines contributed to the function of this chimeric receptor. These results emphasize the close mimicry of the CCR5 N terminus by the gp120-interactive region of a naturally elicited CD4i antibody

A Top-Down LC-FTICR MS-Based Strategy for Characterizing Oxidized Calmodulin in Activated Macrophages

A liquid chromatography-mass spectrometry (LC-MS)-based approach for characterizing the degree of nitration and oxidation of intact calmodulin (CaM) has been used to resolve ∼250 CaM oxiforms using only 500 ng of protein. The analysis was based on high-resolution data of the intact CaM isoforms obtained by Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) coupled with an on-line reversed-phase LC separation. Tentative identifications of post-translational modifications (PTMs), such as oxidation or nitration, have been assigned by matching observed protein mass to a database containing all theoretically predicted oxidation products of CaM and verified through a combination of tryptic peptide information (generated from bottom-up analyses) and on-line collisionally induced dissociation (CID) tandem mass spectrometry (MS/MS) at the intact protein level. The reduction in abundance and diversity of oxidatively modified CaM (i.e., nitrated tyrosines and oxidized methionines) induced by macrophage activation has been explored and semiquantified for different oxidation degrees (i.e., no oxidation, moderate, and high oxidation). This work demonstrates the power of the top-down approach to identify and quantify hundreds of combinations of PTMs for single protein target such as CaM and implicate competing repair and peptidase activities to modulate cellular metabolism in response to oxidative stress

Trapped-Ion Cell with Improved DC Potential Harmonicity for FT-ICR MS

The trapped-ion cell is a key component critical for optimal performance in Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS). To extend the performance of FT-ICR MS, we have developed a new cell design that is capable of generating a DC trapping potential which closely approaches that of an ideal Penning trap, i.e., a 3D axial quadrupolar potential distribution. The new cell design was built upon an open cylindrical geometry, supplemented with two pairs of cylindrical compensation segments. Electric potential calculations for trial cell geometries were aimed at minimizing spatial variations of the radial electric field divided by radius. The resulting cell proportions and compensation voltages delivered practically constant effective ion cyclotron frequency that was independent of ion radial and axial positions. Our customized 12 tesla FT-ICR instrument was upgraded with the new cell, and the performance was characterized for a range of ion excitation power and ion populations. Operating the compensated cell at increased postexcitation radii, ∼0.7 of the cell inner radius, resulted in improved mass measurement accuracy together with increased signal intensity. Under these same operating conditions the noncompensated open cell configuration exhibited peak splitting and reduced signal life time. Mass accuracy tests using 11 calibrants covering a wide m/z range reproducibly produced under 0.05 ppm RMS precision of the internal calibration for reduced ion populations and the optimal excitation radius. Conditions of increased ion population resulted in a twofold improvement in mass accuracy compared with the noncompensated cell, due to the larger achievable excitation radii and correspondingly lower space charge related perturbations of the calibration law