Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors

© 2014 Acta Materialia Inc.Commercially available implantable needle-type glucose sensors for diabetes management are robust analytically but can be unreliable clinically primarily due to tissue-sensor interactions. Here, we present the physical, drug release and bioactivity characterization of tubular, porous dexamethasone (Dex)-releasing polyurethane coatings designed to attenuate local inflammation at the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy and micro-computed tomography (micro-CT) showed controlled porosity and coating thickness. In vitro drug release from coatings monitored over 2 weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture. Acute animal studies were used to determine the appropriate Dex payload for the implanted porous coatings. Pilot short-term animal studies showed that Dex released from porous coatings implanted in rat subcutis attenuated the initial inflammatory response to sensor implantation. These results suggest that deploying sensors with the porous, Dex-releasing coatings is a promising strategy to improve glucose sensor performance.

Suppression of conformational heterogeneity at a protein-protein interface.

Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein-protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study.

Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.

Tuberculin skin test versus blood immunologic diagnosis of latent mycobacterium tuberclosis infection among old subjects

info:eu-repo/semantics/published

Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.

The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients.

Análisis estadístico de un test de conocimientos previos de matemáticas para ingresantes universitarios

En este trabajo presentamos un análisis estadístico del Test de Conocimientos Previos de Matemáticas (TCPM) diseñado para medir el estado inicial de destrezas y conocimientos básicos en matemáticas de los alumnos ingresantes a carreras científico-tecnológicas de la Facultad de Ciencias Físico, Matemáticas y Naturales de la Universidad Nacional de San Luis. El objetivo de la investigación está centrado en observar el diagnóstico utilizado, con miras a una eventual utilización posterior. Para determinar la bondad de la prueba realizamos un análisis de la calidad, discriminación e índice de dificultad de los ítems, así como de la validez y confiabilidad del diagnóstico, para este análisis estadístico empleamos los programas TestGraf y SPSS. El test se aplicó a 698 estudiantes ingresantes a la Universidad en el ciclo lectivo 2002. De la investigación pudimos inferir que el diagnóstico resultó: difícil para la población de aplicación; de confiabilidad aceptable, y de buena calidad de items, con variada dificultad y aceptable discriminación.

Simulating one of the CIB W14 round robin test cases using the SMARTFIRE fire field model

Numerical predictions produced by the SMARTFIRE fire field model are compared with experimental data. The predictions consist of gas temperatures at several locations within the compartment over a 60 min period. The test fire, produced by a burning wood crib attained a maximum heat release rate of approximately 11MW. The fire is intended to represent a nonspreading fire (i.e. single fuel source) in a moderately sized ventilated room. The experimental data formed part of the CIB Round Robin test series. Two simulations are produced, one involving a relatively coarse mesh and the other with a finer mesh. While the SMARTFIRE simulations made use of a simple volumetric heat release rate model, both simulations were found capable of reproducing the overall qualitative results. Both simulations tended to overpredict the measured temperatures. However, the finer mesh simulation was better able to reproduce the qualitative features of the experimental data. The maximum recorded experimental temperature (12141C after 39 min) was over-predicted in the fine mesh simulation by 12%. (C) 2001 Elsevier Science Ltd. All rights reserved.

The development of a CFD based simulator for water mist suppression systems: the development of the fire submodel

The FIRE Detection and Suppression Simulation (FIREDASS) project was concerned with the development of water misting systems as a possible replacement for halon based fire suppression systems currently used in aircraft cargo holds and ship engine rooms. As part of this program of work, a computational model was developed to assist engineers optimize the design of water mist suppression systems. The model is based on Computational Fluid Dynamics (CFD) and comprised of the following components: fire model; mist model; two-phase radiation model; suppression model; detector/activation model. In this paper the FIREDASS software package is described and the theory behind the fire and radiation sub-models is detailed. The fire model uses prescribed release rates for heat and gaseous combustion products to represent the fire load. Typical release rates have been determined through experimentation. The radiation model is a six-flux model coupled to the gas (and mist) phase. As part of the FIREDASS project, a detailed series of fire experiments were conducted in order to validate the fire model. Model predictions are compared with data from these experiments and good agreement is found.

Modeling and experiments on an isothermal fatigue test for solder joints

This paper investigates an isothermal fatigue test for solder joints developed at the NPL. The test specimen is a lap joint between two copper arms. During the test the displacement at the ends of the copper are controlled and the force measured. The modeling results in the paper show that the displacement across the solder joint is not equal to the displacement applied at the end of the specimen. This is due to deformation within the copper arms. A method is described to compensate for this difference. The strain distribution in the solder was determined by finite element analysis and compared to the distribution generated by a theoretical 'ideal' test which generates an almost pure shear mode in the solder. By using a damage-based constitutive law the shape of the crack generated in the specimen has been predicted for both the actual test and the ideal pure shear test. Results from the simulations are also compared with experimental data using SnAgCu solder.

Assessment of the impact of computed and measured fire environments on building evacuation using bench and real scale test data

This study investigates the use of computer modelled versus directly experimentally determined fire hazard data for assessing survivability within buildings using evacuation models incorporating Fractionally Effective Dose (FED) models. The objective is to establish a link between effluent toxicity, measured using a variety of small and large scale tests, and building evacuation. For the scenarios under consideration, fire simulation is typically used to determine the time non-survivable conditions develop within the enclosure, for example, when smoke or toxic effluent falls below a critical height which is deemed detrimental to evacuation or when the radiative fluxes reach a critical value leading to the onset of flashover. The evacuation calculation would the be used to determine whether people within the structure could evacuate before these critical conditions develop.

The study of flow and temperature fields in conducting droplets suspended in a DC/AC combination field

Electromagnetic Levitation (EML) is a valuable method for measuring the thermo-physical properties of metals - surface tensions, viscosity, thermal/electrical conductivity, specific heat, hemispherical emissivity, etc. – beyond their melting temperature. In EML, a small amount of the test specimen is melted by Joule heating in a suspended AC coil. Once in liquid state, a small perturbation causes the liquid envelope to oscillate and the frequency of oscillation is then used to compute its surface tension by the well know Rayleigh formula. Similarly, the rate at which the oscillation is dampened relates to the viscosity. To measure thermal conductivity, a sinusoidally varying laser source may be used to heat the polar axis of the droplet and the temperature response measured at the polar opposite – the resulting phase shift yields thermal conductivity. All these theoretical methods assume that convective effects due to flow within the droplet are negligible compared to conduction, and similarly that the flow conditions are laminar; a situation that can only be realised under microgravity conditions. Hence the EML experiment is the method favoured for Spacelab experiments (viz. TEMPUS). Under terrestrial conditions, the full gravity force has to be countered by a much larger induced magnetic field. The magnetic field generates strong flow within the droplet, which for droplets of practical size becomes irrotational and turbulent. At the same time the droplet oscillation envelope is no longer ellipsoidal. Both these conditions invalidate simple theoretical models and prevent widespread EML use in terrestrial laboratories. The authors have shown in earlier publications that it is possible to suppress most of the turbulent convection generated in the droplet skin layer, through use of a static magnetic field. Using a pseudo-spectral discretisation method it is possible compute very accurately the dynamic variation in the suspended fluid envelope and simultaneously compute the time-varying electromagnetic, flow and thermal fields. The use of a DC field as a dampening agent was also demonstrated in cold crucible melting, where suppression of turbulence was achieved in a much larger liquid metal volume and led to increased superheat in the melt and reduction of heat losses to the water-cooled walls. In this paper, the authors describe the pseudo-spectral technique as applied to EML to compute the combined effects of AC and DC fields, accounting for all the flow-induced forces acting on the liquid volume (Lorentz, Maragoni, surface tension, gravity) and show example simulations.

A written assessment is an invalid test of numeracy skills

Nurses need good clinical numeracy skills to aid them in their clinical practice. There is some concern, however, that the calculation skills learned during pre-registration nurse education have little practical application to nurses. This article discusses the Fitness for Practice initiatives from the Nursing and Midwifery Council which aim to ensure new registrants are numerate. The article argues that written numeracy assessment tools are not a valid test of the numeracy skills candidates will require for clinical practice and that nurse education needs to focus on researching and examining how best to support, assess and develop the numeracy skills of nursing students within their clinical practice placements to ensure that at the point of registration they are fit for practice.