On the spectrum of the Page and the Chen-LeBrun-Weber metrics

We give bounds on the first non-zero eigenvalue of the scalar Laplacian for both the Page and the Chen-LeBrun-Weber Einstein metrics. One notable feature is that these bounds are obtained without explicit knowledge of the metrics or numerical approximation to them. Our method also allows the calculation of the invariant part of the spectrum for both metrics. We go on to discuss an application of these bounds to the linear stability of the metrics. We also give numerical evidence to suggest that the bounds for both metrics are extremely close to the actual eigenvalue.Comment: 15 pages, v2 substantially rewritten, section on linear stability added; v3 updated to reflect referee's comments, v4 final version to appear in Ann. Glob. Anal. Geo

Numerical Hermitian Yang-Mills Connections and Kahler Cone Substructure

We further develop the numerical algorithm for computing the gauge connection of slope-stable holomorphic vector bundles on Calabi-Yau manifolds. In particular, recent work on the generalized Donaldson algorithm is extended to bundles with Kahler cone substructure on manifolds with h^{1,1}>1. Since the computation depends only on a one-dimensional ray in the Kahler moduli space, it can probe slope-stability regardless of the size of h^{1,1}. Suitably normalized error measures are introduced to quantitatively compare results for different directions in Kahler moduli space. A significantly improved numerical integration procedure based on adaptive refinements is described and implemented. Finally, an efficient numerical check is proposed for determining whether or not a vector bundle is slope-stable without computing its full connection.Comment: 38 pages, 10 figure

Improving adherence to surveillance and screening recommendations for people with colorectal cancer and their first degree relatives: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is among the leading causes of cancer-related morbidity and mortality worldwide. Despite clinical practice guidelines to guide surveillance care for those who have completed treatment for this disease as well as screening for first degree relatives of people with CRC, the level of uptake of these recommendations remains uncertain. If outcomes for both patients and their families are to be improved, it is important to establish systematic and cost-effective interventions to improve adherence to guideline recommendations for CRC surveillance and screening.</p> <p>Methods/Design</p> <p>A randomized controlled trial will be used to test the effectiveness of a print-based intervention to improve adherence to colonoscopy surveillance among people with CRC and adherence to CRC screening recommendations among their first degree relatives (FDRs). People diagnosed with CRC in the past 10 months will be recruited through a population-based cancer registry. Consenting participants will be asked if their first degree relatives might also be willing to participate in the trial. Information on family history of CRC will be obtained from patients at baseline. Patients and their families will be randomized to either minimal ethical care or the print-based intervention. The print-based intervention for FDRs will be tailored to the participant's level of risk of CRC as determined by the self-reported family history assessment. Follow up data on surveillance and screening participation will be collected from patients and their FDRs respectively at 12, 24 and 36 months' post recruitment. The primary analyses will relate to comparing levels of guideline adherence in usual care group versus print-based group in the patient sample and the FDR sample respectively.</p> <p>Discussion</p> <p>Results of this study will provide contribute to the evidence base about effective strategies to a) improve adherence to surveillance recommendation for people with CRC; and b) improve adherence to screening recommendation for FDRs of people with CRC. The use of a population-based cancer registry to access the target population may have significant advantages in increasing the reach of the intervention.</p> <p>Trial registration</p> <p>This trial is registered with the Australian and New Zealand Clinical Trials Registry Registration Number (ACTRN): <a href="http://www.anzctr.org.au/ACTRN12609000628246">ACTRN12609000628246</a>.</p

Group B Streptococcal β-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming beta-hemolysin/cytolysin (Bh/c) exotoxin on cardiomyocyte viability, contractility, and calcium transients. METHODOLOGY/PRINCIPAL FINDINGS: HL-1 cardiomyocytes exposed to intact wild-type (WT) or isogenic Deltabeta h/c mutant GBS, or to cell-free extracts from either strain, were assessed for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed cardiomyocytes was analyzed by visual quantitation of the rate and extent of contractility. Mitochondrial membrane polarization was measured in TMRE-loaded cells exposed to GBS beta h/c. Effects of GBS beta h/c on calcium transients were studied in fura-2AM-loaded primary rat ventricular cardiomyocytes. Exposure of HL-1 cardiomyocytes to either WT GBS or beta h/c extracts significantly reduced both rate and extent of contractility and later induced necrotic and apoptotic cell death. No effects on cardiomyocyte viability or function were observed after treatment with Deltabeta h/c mutant bacteria or extracts. The beta h/c toxin was associated with complete and rapid loss of detectable calcium transients in primary neonatal rat ventricular cardiomyocytes and induced a loss of mitochondrial membrane polarization. These effects on viability and function were abrogated by the beta h/c inhibitor, dipalmitoyl phosphatidylcholine (DPPC). CONCLUSIONS/SIGNIFICANCE: Our data show a rapid loss of cardiomyocyte viability and function induced by GBS beta h/c, and these deleterious effects are inhibited by DPPC, a normal constituent of human pulmonary surfactant.. These findings have clinical implications for the cardiac dysfunction observed in neonatal GBS infections

OntoFox: web-based support for ontology reuse

<p>Abstract</p> <p>Background</p> <p>Ontology development is a rapidly growing area of research, especially in the life sciences domain. To promote collaboration and interoperability between different projects, the OBO Foundry principles require that these ontologies be open and non-redundant, avoiding duplication of terms through the re-use of existing resources. As current options to do so present various difficulties, a new approach, MIREOT, allows specifying import of single terms. Initial implementations allow for controlled import of selected annotations and certain classes of related terms.</p> <p>Findings</p> <p>OntoFox <url>http://ontofox.hegroup.org/</url> is a web-based system that allows users to input terms, fetch selected properties, annotations, and certain classes of related terms from the source ontologies and save the results using the RDF/XML serialization of the Web Ontology Language (OWL). Compared to an initial implementation of MIREOT, OntoFox allows additional and more easily configurable options for selecting and rewriting annotation properties, and for inclusion of all or a computed subset of terms between low and top level terms. Additional methods for including related classes include a SPARQL-based ontology term retrieval algorithm that extracts terms related to a given set of signature terms and an option to extract the hierarchy rooted at a specified ontology term. OntoFox's output can be directly imported into a developer's ontology. OntoFox currently supports term retrieval from a selection of 15 ontologies accessible via SPARQL endpoints and allows users to extend this by specifying additional endpoints. An OntoFox application in the development of the Vaccine Ontology (VO) is demonstrated.</p> <p>Conclusions</p> <p>OntoFox provides a timely publicly available service, providing different options for users to collect terms from external ontologies, making them available for reuse by import into client OWL ontologies.</p

Microbial transformations of selenite by methane-oxidizing bacteria

Abstract Methane oxidizing bacteria are well known for their role in the global methane cycle and their potential for microbial transformation of wide range of hydrocarbon and chlorinated hydrocarbon pollution. Recently, it has also emerged that methane-oxidizing bacteria interact with inorganic pollutants in the environment. Here we report what we believe to be the first study of the interaction of pure strains of methane-oxidizing bacteria with selenite. Results indicate that the commonly used laboratory model strains of methane oxidizing bacteria, Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b are both able to reduce the toxic selenite (SeO32-) but not selenate (SeO42-) to red spherical nanoparticulate elemental selenium (Se0), which was characterised via EDX and EXAFS. The cultures also produced volatile selenium-containing species, which suggests that both strains may have an additional activity that can either transform Se0 or selenite into volatile methylated forms of selenium. Transmission electron microscopy (TEM) measurements and experiments with the cell fractions: cytoplasm, cell wall and cell membrane show that the nanoparticles are formed mainly on the cell wall. Collectively these results are promising for the use of methane-oxidizing bacteria for bioremediation or suggest possible uses in the production of selenium nanoparticles for biotechnology

Overcoming degradation in spatial multiplexing systems with stochastic nonlinear impairments

Single-mode optical fibres now underpin telecommunication systems and have allowed continuous increases in traffic volume and bandwidth demand whilst simultaneously reducing cost- and energy-per-bit over the last 40 years. However, it is now recognised that such systems are rapidly approaching the limits imposed by the nonlinear Kerr effect. To address this, recent research has been carried out into mitigating Kerr nonlinearities to increase the nonlinear threshold and into spatial multiplexing to offer additional spatial pathways. However, given the complexity associated with nonlinear transmission in spatial multiplexed systems subject to random inter-spatial-path nonlinearities it is widely believed that these technologies are mutually exclusive. By investigating the linear and nonlinear crosstalk in few-mode fibres based optical communications, we numerically demonstrate, for the first time, that even in the presence of significant random mixing of signals, substantial performance benefits are possible. To achieve this, the impact of linear mixing on the Kerr nonlinearities should be taken into account using different compensation strategies for different linear mixing regimes. For the optical communication systems studied, we demonstrate that the performance may be more than doubled with the appropriate selection of compensation method for fibre characteristics which match those presented in the literature

Lipodystrophy and obesity are associated with decreased number of T cells with regulatory function and pro-inflammatory macrophage phenotype

Background/Objectives:In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity.Subjects/Methods:Blood was collected from 16 LD, 16 obese (OB, BMI&gt;30 kg m -2) and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was employed to assess the number of circulating CD4 + /CD25 hi regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs included: 1. morphological/oil-Red-O staining analyses to define two morphotypes: lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of conditioned medium from MDMs (MDMs CM) on human SGBS cells.Results:As compared to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs and iNKTs (P&lt;0.001 and P&lt;0.01 for LD and OB, respectively), higher number of LL-MDMs (P&lt;0.001 and P&lt;0.01 for LD and OB, respectively), lower number of sp-MDMs (P&lt;0.001 for both LD and OB), which correlated with increased paracrine stimulation of lipid accumulation in cells (P&lt;0.001 and P&lt;0.01 for LD and OB, respectively). LD MDMs showed decreased and increased expression for anti-inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes, respectively. Analysis of correlation indicated that Tregs are directly related with HDL (P&lt;0.01) and inversely related with LL-MDM (P&lt;0.001) and that LL-MDM are directly related with triglycerides (P&lt;0.01) and oxidized LDL (P&lt;0.01).Conclusions:LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of MDM towards lipid accumulation. Lipid profile of the patients correlates with these changes

Systematic review: Effects, design choices, and context of pay-for-performance in health care

<p>Abstract</p> <p>Background</p> <p>Pay-for-performance (P4P) is one of the primary tools used to support healthcare delivery reform. Substantial heterogeneity exists in the development and implementation of P4P in health care and its effects. This paper summarizes evidence, obtained from studies published between January 1990 and July 2009, concerning P4P effects, as well as evidence on the impact of design choices and contextual mediators on these effects. Effect domains include clinical effectiveness, access and equity, coordination and continuity, patient-centeredness, and cost-effectiveness.</p> <p>Methods</p> <p>The systematic review made use of electronic database searching, reference screening, forward citation tracking and expert consultation. The following databases were searched: Cochrane Library, EconLit, Embase, Medline, PsychINFO, and Web of Science. Studies that evaluate P4P effects in primary care or acute hospital care medicine were included. Papers concerning other target groups or settings, having no empirical evaluation design or not complying with the P4P definition were excluded. According to study design nine validated quality appraisal tools and reporting statements were applied. Data were extracted and summarized into evidence tables independently by two reviewers.</p> <p>Results</p> <p>One hundred twenty-eight evaluation studies provide a large body of evidence -to be interpreted with caution- concerning the effects of P4P on clinical effectiveness and equity of care. However, less evidence on the impact on coordination, continuity, patient-centeredness and cost-effectiveness was found. P4P effects can be judged to be encouraging or disappointing, depending on the primary mission of the P4P program: supporting minimal quality standards and/or boosting quality improvement. Moreover, the effects of P4P interventions varied according to design choices and characteristics of the context in which it was introduced.</p> <p>Future P4P programs should (1) select and define P4P targets on the basis of baseline room for improvement, (2) make use of process and (intermediary) outcome indicators as target measures, (3) involve stakeholders and communicate information about the programs thoroughly and directly, (4) implement a uniform P4P design across payers, (5) focus on both quality improvement and achievement, and (6) distribute incentives to the individual and/or team level.</p> <p>Conclusions</p> <p>P4P programs result in the full spectrum of possible effects for specific targets, from absent or negligible to strongly beneficial. Based on the evidence the review has provided further indications on how effect findings are likely to relate to P4P design choices and context. The provided best practice hypotheses should be tested in future research.</p