Improvements in prevalence trend fitting and incidence estimation in EPP 2013

OBJECTIVE: Describe modifications to the latest version of the Joint United Nations Programme on AIDS (UNAIDS) Estimation and Projection Package component of Spectrum (EPP 2013) to improve prevalence fitting and incidence trend estimation in national epidemics and global estimates of HIV burden. METHODS: Key changes made under the guidance of the UNAIDS Reference Group on Estimates, Modelling and Projections include: availability of a range of incidence calculation models and guidance for selecting a model; a shift to reporting the Bayesian median instead of the maximum likelihood estimate; procedures for comparison and validation against reported HIV and AIDS data; incorporation of national surveys as an integral part of the fitting and calibration procedure, allowing survey trends to inform the fit; improved antenatal clinic calibration procedures in countries without surveys; adjustment of national antiretroviral therapy reports used in the fitting to include only those aged 15–49 years; better estimates of mortality among people who inject drugs; and enhancements to speed fitting. RESULTS: The revised models in EPP 2013 allow closer fits to observed prevalence trend data and reflect improving understanding of HIV epidemics and associated data. CONCLUSION: Spectrum and EPP continue to adapt to make better use of the existing data sources, incorporate new sources of information in their fitting and validation procedures, and correct for quantifiable biases in inputs as they are identified and understood. These adaptations provide countries with better calibrated estimates of incidence and prevalence, which increase epidemic understanding and provide a solid base for program and policy planning

Multi-heme Cytochromes in Shewanella oneidensis MR-1:Structures, functions and opportunities

Multi-heme cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometers. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-heme cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-heme cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward there are opportunities to engage multi-heme cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-heme cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-heme cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies

Do Staphylococcus epidermidis genetic clusters predict isolation sources?

Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital

Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method

Conditional Sampling for Max-Stable Processes with a Mixed Moving Maxima Representation

This paper deals with the question of conditional sampling and prediction for the class of stationary max-stable processes which allow for a mixed moving maxima representation. We develop an exact procedure for conditional sampling using the Poisson point process structure of such processes. For explicit calculations we restrict ourselves to the one-dimensional case and use a finite number of shape functions satisfying some regularity conditions. For more general shape functions approximation techniques are presented. Our algorithm is applied to the Smith process and the Brown-Resnick process. Finally, we compare our computational results to other approaches. Here, the algorithm for Gaussian processes with transformed marginals turns out to be surprisingly competitive.Comment: 35 pages; version accepted for publication in Extremes. The final publication is available at http://link.springer.co

What limits supercurrents in high temperature superconductors? A microscopic model of cuprate grain boundaries

The interface properties of high-temperature cuprate superconductors have been of interest for many years, and play an essential role in Josephson junctions, superconducting cables, and microwave electronics. In particular, the maximum critical current achievable in high-Tc wires and tapes is well known to be limited by the presence of grain boundaries, regions of mismatch between crystallites with misoriented crystalline axes. In studies of single, artificially fabricated grain boundaries the striking observation has been made that the critical current Jc of a grain boundary junction depends exponentially on the misorientation angle. Until now microscopic understanding of this apparently universal behavior has been lacking. We present here the results of a microscopic evaluation based on a construction of fully 3D YBCO grain boundaries by molecular dynamics. With these structures, we calculate an effective tight-binding Hamiltonian for the d-wave superconductor with a grain boundary. The critical current is then shown to follow an exponential suppression with grain boundary angle. We identify the buildup of charge inhomogeneities as the dominant mechanism for the suppression of the supercurrent.Comment: 28 pages, 12 figure

Transcriptional profiling of endobronchial ultrasound guided lymph node samples aids diagnosis of mediastinal lymphadenopathy

Background: Endobronchial ultrasound (EBUS) guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis or tuberculosis. However, improved methods for discriminating between tuberculosis and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genome-wide transcriptional profiling to aid diagnostic processes in this setting. Methods: Mediastinal lymph node samples from 88 individuals were obtained by EBUS guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were employed to evaluate the potential for using the transcriptome to distinguish between diagnostic categories. Results: Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values >0.9 for discriminating between granulomatous and non-granulomatous disease, tuberculosis and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and non-granulomatous disease, then between tuberculosis and sarcoidosis in granulomatous cases and between cancer and reactive lymphadenopathy in non-granulomatous cases achieved >90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect tuberculosis and cancer. In some diagnostically ambiguous cases computational classification predicted granulomatous disease or cancer before pathological abnormalities were evident. Conclusions: Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS guided biopsies

Sequestration of Martian CO2 by mineral carbonation

Carbonation is the water-mediated replacement of silicate minerals, such as olivine, by carbonate, and is commonplace in the Earth’s crust. This reaction can remove significant quantities of CO2 from the atmosphere and store it over geological timescales. Here we present the first direct evidence for CO2 sequestration and storage on Mars by mineral carbonation. Electron beam imaging and analysis show that olivine and a plagioclase feldspar-rich mesostasis in the Lafayette meteorite have been replaced by carbonate. The susceptibility of olivine to replacement was enhanced by the presence of smectite veins along which CO2-rich fluids gained access to grain interiors. Lafayette was partially carbonated during the Amazonian, when liquid water was available intermittently and atmospheric CO2 concentrations were close to their present-day values. Earlier in Mars’ history, when the planet had a much thicker atmosphere and an active hydrosphere, carbonation is likely to have been an effective mechanism for sequestration of CO2

Grey Literature and Professional Knowledge Making

International audienceWhat does grey literature mean? What role does it play in the production and dissemination of practitioner knowledge? How do reports, presentations and communications, working papers and other un-published material contribute to professional, extra-academic knowledge making? The following paper tries to provide some elements for a better understanding of grey literature, with examples from different collections and disciplines. Moreover, it puts the focus on critical issues like standards, identifiers and quality, and it discusses the impact of open science, i.e. the movement to make scientific research, data and dissemination accessible to all levels of an inquiring society, amateur or professional