Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND: Paediatric multidrug-resistant (MDR) tuberculosis is a public health challenge of growing concern, accounting for an estimated 15% of all global cases of MDR tuberculosis. Clinical management is especially challenging, and recommendations are based on restricted evidence. We aimed to assess existing evidence for the treatment of MDR tuberculosis in children. METHODS: We did a systematic review and meta-analysis of published and unpublished studies reporting treatment outcomes for children with MDR tuberculosis. We searched PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up to Oct 31, 2011. Eligible studies included five or more children (aged ≤16 years) with MDR tuberculosis within a defined treatment cohort. The primary outcome was treatment success, defined as a composite of cure and treatment completion. RESULTS: We identified eight studies, which reported treatment outcomes for a total of 315 patients. We recorded much variation in the characteristics of patients and programmes. Time to appropriate treatment varied from 2 days to 46 months. Average duration of treatment ranged from 6 months to 34 months, and duration of follow-up ranged from 12 months to 37 months. The pooled estimate for treatment success was 81·67% (95% CI 72·54-90·80). Across all studies, 5·9% (95% CI 1·3-10·5) died, 6·2% (2·3-10·2) defaulted, and 39·1% (28·7-49·4) had an adverse event. The most common drug-related adverse events were nausea and vomiting. Other serious adverse events were hearing loss, psychiatric effects, and hypothyroidism. INTERPRETATION: The treatment of paediatric MDR tuberculosis has been neglected, but when children are treated outcomes can be achieved that are at least as good as those reported for adults. Programmes should be encouraged to report outcomes in children to improve the knowledge base for care, especially as new drugs become available. FUNDING: None

Elastic turbulence in two-dimensional Taylor-Couette flows

We report the onset of elastic turbulence in a two-dimensional Taylor-Couette geometry using numerical solutions of the Oldroyd-B model, also performed at high Weissenberg numbers with the program OpenFOAM. Beyond a critical Weissenberg number, an elastic instability causes a supercritical transition from the laminar Taylor-Couette to a turbulent flow. The order parameter, the time average of secondary-flow strength, follows the scaling law $\Phi \propto (\mathrm{Wi} -\mathrm{Wi}_c)^{\gamma}$ with $\mathrm{Wi}_c=10$ and $\gamma = 0.45$. The power spectrum of the velocity fluctuations shows a power-law decay with a characteristic exponent, which strongly depends on the radial position. It is greater than two, which we relate to the dimension of the geometry

Thomas-Fermi Calculations of Atoms and Matter in Magnetic Neutron Stars II: Finite Temperature Effects

We present numerical calculations of the equation of state for dense matter in high magnetic fields, using a temperature dependent Thomas-Fermi theory with a magnetic field that takes all Landau levels into account. Free energies for atoms and matter are also calculated as well as profiles of the electron density as a function of distance from the atomic nucleus for representative values of the magnetic field strength, total matter density, and temperature. The Landau shell structure, which is so prominent in cold dense matter in high magnetic fields, is still clearly present at finite temperature as long as it is less than approximately one tenth of the cyclotron energy. This structure is reflected in an oscillatory behaviour of the equation of state and other thermodynamic properties of dense matter and hence also in profiles of the density and pressure as functions of depth in the surface layers of magnetic neutron stars. These oscillations are completely smoothed out by thermal effects at temperatures of the order of the cyclotron energy or higher.Comment: 37 pages, 17 figures included, submitted to Ap

Development and Evaluation of an Adaptive Digital Module on Enzyme Kinetics

An adaptive module on basic enzyme kinetics was developed for first- and second-year university students. The module offers more assignments to students who have less knowledge of the theory than to more advanced students. The aim of the research was to investigate what influence students’ backgrounds have on their use and appreciation of this module. Both freshmen and second-year students showed a large variation in the number of assignments they needed to perform in order to finish the module, indicating that the module’s adaptive feature was exploited by all the students. Findings indicated that the prior knowledge was of influence of students’ motivation and perception of difficulty of the modul

Astrophysical Supercomputing with GPUs: Critical Decisions for Early Adopters

General purpose computing on graphics processing units (GPGPU) is dramatically changing the landscape of high performance computing in astronomy. In this paper, we identify and investigate several key decision areas, with a goal of simplyfing the early adoption of GPGPU in astronomy. We consider the merits of OpenCL as an open standard in order to reduce risks associated with coding in a native, vendor-specific programming environment, and present a GPU programming philosophy based on using brute force solutions. We assert that effective use of new GPU-based supercomputing facilities will require a change in approach from astronomers. This will likely include improved programming training, an increased need for software development best-practice through the use of profiling and related optimisation tools, and a greater reliance on third-party code libraries. As with any new technology, those willing to take the risks, and make the investment of time and effort to become early adopters of GPGPU in astronomy, stand to reap great benefits.Comment: 13 pages, 5 figures, accepted for publication in PAS

Adaptable Radiative Transfer Innovations for Submillimeter Telescopes (ARTIST)

Submillimeter observations are a key for answering many of the big questions in modern-day astrophysics, such as how stars and planets form, how galaxies evolve, and how material cycles through stars and the interstellar medium. With the upcoming large submillimeter facilities ALMA and Herschel a new window will open to study these questions. ARTIST is a project funded in context of the European ASTRONET program with the aim of developing a next generation model suite for comprehensive multi-dimensional radiative transfer calculations of the dust and line emission, as well as their polarization, to help interpret observations with these groundbreaking facilities.Comment: 4 pages, 1 figure; to appear in "IAU Symposium 270: Computational Star formation", Eds. J. Alves, B. Elmegreen, J. Girart, V. Trimbl

APECS - The Atacama Pathfinder Experiment Control System

APECS is the distributed control system of the new Atacama Pathfinder EXperiment (APEX) telescope located on the Llano de Chajnantor at an altitude of 5107 m in the Atacama desert in northern Chile. APECS is based on Atacama Large Millimeter Array (ALMA) software and employs a modern, object-oriented design using the Common Object Request Broker Architecture (CORBA) as the middleware. New generic device interfaces simplify adding instruments to the control system. The Python based observer command scripting language allows using many existing software libraries and facilitates creating more complex observing modes. A new self-descriptive raw data format (Multi-Beam FITS or MBFITS) has been defined to store the multi-beam, multi-frequency data. APECS provides an online pipeline for initial calibration, observer feedback and a quick-look display. APECS is being used for regular science observations in local and remote mode since August 2005.Comment: 4 pages, A&A, accepte

Preventive Therapy for Child Contacts of Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

BACKGROUND: Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome. METHODS: In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause. RESULTS: One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age <1 year (rate ratio [RR], 10.1; 95% confidence interval [CI], 1.65-105.8; P = .009), HIV-positive status (RR, 10.6; 95% CI, 1.01-64.9; P = .049), exposure to multiple source cases (RR, 6.75; 95% CI, 1.11-70.9; P = .036) and poor adherence (RR, 7.50; 95% CI, 1.23-78.7; P = .026). CONCLUSIONS: This 3-drug preventive therapy regimen was well tolerated and few children developed tuberculosis or died if adherent to therapy. The provision of preventive therapy to vulnerable children following exposure to MDR tuberculosis should be considered

Retooling existing tuberculosis drugs for children.

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Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks