Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease.

In diffusion tensor imaging (DTI), an improvement in the signal-to-noise ratio (SNR) of the fractional anisotropy (FA) maps can be obtained when the number of recorded gradient directions (GD) is increased. Vice versa, elimination of motion-corrupted or noisy GD leads to a more accurate characterization of the diffusion tensor. We previously suggest a slice-wise method for artifact detection in FA maps. This current study applies this approach to a cohort of 18 premanifest Huntington's disease (pHD) subjects and 23 controls. By 2-D voxelwise statistical comparison of original FA-maps and FA-maps with a reduced number of GD, the effect of eliminating GD that were affected by motion was demonstrated.We present an evaluation metric that allows to test if the computed FA-maps (with a reduced number of GD) still reflect a "true" FA-map, as defined by simulations in the control sample. Furthermore, we investigated if omitting data volumes affected by motion in the pHD cohort could lead to an increased SNR in the resulting FA-maps.A high agreement between original FA maps (with all GD) and corrected FA maps (i.e. without GD corrupted by motion) were observed even for numbers of eliminated GD up to 13. Even in one data set in which 46 GD had to be eliminated, the results showed a moderate agreement

Have the Olympics outgrown cities? A longitudinal comparative analysis of the growth and planning of the Olympics and former host cities

This paper examines the growth of the Olympic Games against that of former host cities to understand whether this mega-event may have ‘outgrown’ its hosts. The increasing hosting requirements and governments’ expansive use of mega-events as tools for urban development would suggest that the ‘Olympic city’ – a term we use for describing the size of the Olympics as hosted in different cities over the decades – has grown at a faster rate than former host cities. The analysis contrasts historical indicators that capture the evolving size of planning for the event based on four dimensions – sport, spectators, marketing and costs – as well as the urban dimension of hosting experiences (venues and infrastructure) with city trajectories based on demographic and economic indicators. This is done through a longitudinal analysis of former Olympic host cities from the 1960s and 1970s and from which continuous longitudinal data are available: Tokyo, Munich, and Montreal. The findings indicate that the Olympic city has grown more strongly than these former host cities, although not uniformly across trajectories. This gives evidence for the need to review the size of mega-event impacts if they ought to continue to generate interest in hosting them in the future

A management architecture for active networks

In this paper we present an architecture for network and applications management, which is based on the Active Networks paradigm and shows the advantages of network programmability. The stimulus to develop this architecture arises from an actual need to manage a cluster of active nodes, where it is often required to redeploy network assets and modify nodes connectivity. In our architecture, a remote front-end of the managing entity allows the operator to design new network topologies, to check the status of the nodes and to configure them. Moreover, the proposed framework allows to explore an active network, to monitor the active applications, to query each node and to install programmable traps. In order to take advantage of the Active Networks technology, we introduce active SNMP-like MIBs and agents, which are dynamic and programmable. The programmable management agents make tracing distributed applications a feasible task. We propose a general framework that can inter-operate with any active execution environment. In this framework, both the manager and the monitor front-ends communicate with an active node (the Active Network Access Point) through the XML language. A gateway service performs the translation of the queries from XML to an active packet language and injects the code in the network. We demonstrate the implementation of an active network gateway for PLAN (Packet Language for Active Networks) in a forty active nodes testbed. Finally, we discuss an application of the active management architecture to detect the causes of network failures by tracing network events in time

Technical performance and diagnostic utility of the new Elecsys (R) neuron-specific enolase enzyme immunoassay

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (interlaboratory median: 1.3%) and from 1.3 to 8.5 (interlaboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and interassay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n=723) and in patients with lung cancer (n=333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n=183), the cutoff value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n=188) and was significantly higher (p<0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n=374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturers declaration up to 370 ng/ml) and a short incubation time of 18 min

Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness – Evaluation of Predicting Parameters

PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to Maternally Inherited Diabetes and Deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by two independent readers. A linear mixed effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, p<0.001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design

A 120-Mpc Periodicity in the Three-Dimensional Distribution of Galaxy Superclusters

Using a new compilation of available data on galaxy clusters and superclusters we present evidence for a quasiregular three-dimensional network of rich superclusters and voids, with the regions of high density separated by about 120 Mpc. We calculate the power spectrum for clusters of galaxies; it has a peak on the wavelength equal to the step of the network; the excess in the amplitude of the spectrum over that of the cold dark matter model is by a factor of 1.4. The probability that the spectrum can be formed within the framework of the standard cosmogony is very small. If the cluster distribution reflects the distribution of all matter (luminous and dark), then there must exists some hithero unknown process that produces regular structure on large scales.Comment: Tex, 6 pages, 2 PostScript figures embedded, accepted by Nature on November 19, 199

High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

Integrating Equity Considerations into Agent-Based Modeling: A Conceptual Framework and Practical Guidance

Advancing equity is a complex challenge for society, science, and policy. Agent-based models are increasingly used as scientific tools to advance understanding of systems, inform decision-making, and share knowledge. Yet, equity has not received due attention within the agent-based modeling (ABM) literature. In this paper, we develop a conceptual framework and provide guidance for integrating equity considerations into ABM research and modeling practice. The framework conceptualizes ABM as interfacing with equity outcomes at two levels (the science-society interface and within the model itself) and the modeler as a filter and lens that projects knowledge between the target system and the model. Within the framework, we outline three complementary, equity-advancing action pathways: (1) engage stakeholders, (2) acknowledge positionality and bias, and (3) assess equity with agent-based models. For Pathway 1, we summarize existing guidance within the participatory modeling literature. For Pathway 2, we introduce the positionality and bias document as a tool to promote modeler and stakeholder reflexivity throughout the modeling process. For Pathway 3, we synthesize a typology of approaches for modeling equity and ffer a set of preliminary suggestions for best practice. By engaging with these action pathways, modelers both reduce the risks of inadvertently perpetuating inequity and harness the opportunities for ABM to play a larger role in creating a more equitable future

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS