Reverse Mathematics, Computability, and Partitions of Trees

We examine the reverse mathematics and computability theory of a form of Ramsey’s theorem in which the linear n-tuples of a binary tree are colored

Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling

Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0–healthy tissue, 5–dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison. Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in fibrotic regions. The rotors propagated slowly around the border zones of patchy fibrosis (levels 3–4), failing to spread into inner areas of dense fibrosis. Conclusion: Rotors stabilize in the border zones of patchy fibrosis in 3D atria, where slow conduction enable the development of circuits within relatively small regions. Our results can provide a mechanistic explanation for the clinical efficacy of ablation around fibrotic regions

Comparison of three methods for measuring psoriasis severity in clinical studies (Part 1 of 2): change during therapy in Psoriasis Area and Severity Index, Static Physician's Global Assessment and Lattice System Physician's Global Assessment

BackgroundAccurate and reliable assessment of changes in psoriasis severity is critical in clinical trials of therapies.ObjectiveTo compare Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), and the Lattice System Physician's Global Assessment (LS‐PGA) in a trial of systemic treatments for plaque psoriasis vulgaris and to assess whether they measure change in psoriasis induced by therapy.MethodsPatients were randomized to voclosporin or cyclosporine for 24 weeks (the ‘24‐week‐treatment’ group, n = 366), or placebo for 12 weeks followed by voclosporin for 12 weeks (the ‘initial‐placebo’ group, n = 89).ResultsAll scoring systems changed in concert and were sensitive enough to detect reductions in severity during placebo therapy as well as with active therapy (P < 0.01 for each measurement). At study onset, there were poorer correlations of sPGA with PASI (r = 0.45) and LS‐PGA (r = 0.39) than between PASI and LS‐PGA (r = 0.68). After therapy, all correlations were stronger, but sPGA continued to be less well correlated (with PASI, r = 0.85; with LS‐PGA, r = 0.79) than LS‐PGA with PASI (r = 0.90). Two‐ or three‐step improvements in LS‐PGA showed very good to excellent accuracy in corresponding to PASI‐50 and PASI‐75, respectively, and were more accurate than comparable changes in sPGA.ConclusionPASI, sPGA and LS‐PGA are responsive to the varying degrees of improvement in psoriasis induced by either placebo or active therapy. While the three systems capture similar information, each has different reasons for use in a clinical trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111966/1/jdv13132.pd

Hypertonic saline solution for signal transmission and steering in MRI-guided intravascular catheterisation

© Springer International Publishing AG, part of Springer Nature 2018. Use of traditional low-impedance sensor leads is highly undesirable in intravascular catheters to be used with MRI guidance; thermal safety and quality of imaging are particularly impacted by these components. In this paper, we are showing that hypertonic saline solution, a high-impedance body-like fluid, could be a compatible and effective signal transmission medium when used in MRI-compatible catheters. We also propose a simple type of catheter design that can be steered hydraulically using the same saline solution. Integration of hydraulic steering is not required for MRI-compatibility; however efficient design can bring advantages in terms of structural simplicity and miniaturisation. Manufacturing of proof-of-concept prototypes using 3D printing is underway

Evaluation of Open Geospatial Consortium Standards fur Use In LLNL Geographic Information Systems (GIS)

The objective of this project is to evaluate existing and emerging Open Geospatial Consortium (OGC) standards for use in LLNL programs that rely heavily on geographic data. OGC standards are intended to facilitate interoperability between geospatial processing systems to avoid duplication of effort, lower development costs, and encourage competition based on improved capability and performance rather than vendor lock-in. Some of these standards appear to be gaining traction in the geospatial data community, the Federal government, DOE and DHS. A serious evaluation of this technology is appropriate at this time due to increasing interest and mandated compliance in the Federal government in some situations. A subset of OGC standards is identified and reviewed with a focus on applications to LLNL programs. Each standard or recommendation reviewed was evaluated in general terms. In addition, for specific programs such as Gen&amp;SIS and NARAC, a specific evaluation was made of several of the standards and how they could be used most effectively. It is also important to evaluate the acceptance of these standards in the commercial arena. The implementation of OGC standards by the largest GIS vendor (ESRI) was reviewed. At present, OGC standards are primary useful in specific situations. More generally, many of the standards are immature and their impact on the government and commercial sectors is unclear. Consequently, OGC and related developments need to be observed. As specific standards or groups of standards mature and establish their relevance, these can also be incorporated in LLNL programs as requirements dictate, especially if open implementations and commercial products are available

School performance in Australia: is there a role for quasi-markets?

Recent changes to the organisation of Australia's education system have raised the possibility of implementing wide-ranging market reforms. In this article we discuss the scope for introducing reforms similar to the United Kingdom's 'quasi-market' model. We discuss the role of school league tables in providing signals and incentives in a quasi-market. Specifically, we compare a range of unadjusted and model-based league tables of primary school performance in Queensland's public education system. These comparisons indicate that model-based tables which account for socio-economic status and student intake quality vary significantly from the unadjusted tables

Human Macrophage Differentiation Involves an Interaction Between Integrins and Fibronectin

The authors have examined the role of the {beta}{sub 1} integrin family of adhesion receptors (VLA) and the extracellular matrix protein fibronectin (FN) in macrophage differentiation of (1) human HL-60 myeloid leukemia cells induced by phorbol 12-myristate 13-acetate (PMA) and (2) human peripheral blood monocytes induced by either PMA or macrophage-colony stimulating factor (M=CSF). Increased VLA and FN gene expression was observed as early as 4 h after PMA treatment of HL-60 cells and PMA- or M-CSF-treatment of monocytes, and it preceded the manifestation of macrophage markers. Treated HL-60 cells and monocytes also released and deposited FN on the surface of the tissue culture dishes. An HL-60 cell variant, HL-525, which is deficient in protein kinase C {beta} and resistant to PMA-induced differentiation, exhibited elevated levels of the VLA antigen but failed to express the FN gene. Incubation of HL-525 cells on dishes precoated with exogenous FN resulted in a macrophage differentiation. The macrophage phenotype induced in HL-60 cells, HL-525 cells, or monocytes was attenuated to various degrees by anti-VLA or anti-FN MAbs or by exogenous RGDS, a VLA-binding motif on FN. The authors suggest that macrophage differentiation is initiated by the activation of protein kinase C, which leads to the expression of the integrin, FN and related genes. The integrins mediate cell attachment and spreading on appropriate substrates by binding to deposited extracellular proteins such as FN. This attachment and spreading, in turn, leads to the expression of genes that code for the macrophage functions

Evaluation of OGC Standards for Use in LLNL GIS

Over the summer of 2005, the Lawrence Livermore National Laboratory (LLNL) Computer Applications and Research Department conducted a small project that examined whether Open Geospatial Consortium (OGC) standards might be useful in meeting program mission requirements more effectively. OGC standards are intended to facilitate interoperability between geospatial processing systems to lower development costs and to avoid duplication of effort and vendor lock-in. Some OGC standards appear to be gaining traction in the geospatial data community, the Federal government, Department of Energy (DOE) and Department of Homeland Security (DHS) and so an evaluation was deemed appropriate

Sources and pathways of dust during the Australian 'Millennium Drought' decade

From the late 1990s to mid-2010, Australia was affected by a prolonged period of drought, the “Millennium Drought,” during which numerous severe dust storms crossed the continent. We inspect this period to produce the first continental-scale climatology of air-parcel trajectories that is specific to dust and use it to gain new insights into dust transport dynamics over the eastern half of Australia. The analysis is based upon dust arrival times from airport meteorological observations made at nine mostly coastal cities for 2000–2009. The Hybrid Single-Particle Lagrangian Integrated Trajectory model was used to calculate 1.26 million backward trajectories from receptor cities, with only those trajectories associated with a dust storm observation considered in the analysis of dust transport. To tie dust trajectories from receptors to likely emission sources, trajectories were linked to six known major dust source regions in and around the Lake Eyre Basin. The Lake Eyre North ephemeral lake system, alluvial-dominated Channel Country, and agricultural Mallee-Riverina regions emerge as important sources for the period, providing variable contributions to different parts of the seaboard as controlled by different front-related wind systems. Our study also provides new detail regarding dust pathways from continental Australia. For the Millennium Drought we identify that the broadly established Southeast Dust Path may be more accurately subdivided into three active pathways, driven by prefrontal northerly winds and a variation in the influence of frontal westerlies. The detail of these pathways has implications for dust delivery from specific Australian sources to different marine environments