CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques.

Determinación de la producción de forraje y la calidad nutricional de diferentes secuencias de cultivos anuales invernales

El contexto actual que enfrentan los productores lecheros, caracterizado por un incremento de los costos de producción y una fuerte presión de la agricultura sobre la actividad tambo, hace que deban incrementar la productividad para poder mantener la rentabilidad de sus explotaciones. Aumentos en la productividad pueden lograrse mediante el incremento de la cantidad de forraje producido y utilizado por hectárea, por ejemplo implementando rotaciones forrajeras complementarias (CFR). Los objetivos del siguiente trabajo fueron comparar la oferta forrajera y la calidad nutricional de los cultivos anuales invernales que componen las CFR, frente a otros de mayor tradicion en la pampa húmeda. Se evaluó la cantidad de materia seca producida por hectárea (tn MS ha-1) de tres tratamientos: colza forrajera (Brassica rapa) - trebol persa (Trifolium repesinatum), avena (Avena sativa) y raigras anual (Lolium multiflorum). Se tomaron muestras de cada cultivo para la determinacion de la calidad nutricional: proteína cruda (PC), fibra detergente neutro (FDN), fibra detergente acido (FDA) y se estimó la digestibilidad de la materia seca (DMS). El diseño experimental utilizado fue de bloques completos aleatorizados con tres repeticiones. Los cultivos se sembraron a fines de marzo, se realizaron tres cortes con destino a pastoreo y un cuarto con destino a silaje para la avena y el raigras anual. En el caso de la colza forrajera, solo fue factible realizar dos cosechas debido a un pobre segundo rebrote posiblemente atribuído a la falta de precipitaciones durante ese período. Asimismo, el trébol persa intersembrado luego de la segunda cosecha de la colza, no logró germinar debido a las mismas condiciones expuestas anteriormente. Los tratamientos se analizaron estadísticamente mediante un análisis de varianza (ANOVA) y cuando correspondió, se realizó una prueba de comparaciones multiples (Tukey p . 0,05) para determinar las diferencias entre las medias. Los resultados obtenidos en el presente trabajo demostraron que la oferta forrajera total del tratamiento colza forrajera fue significativamente menor a los tratamientos avena y raigras anual (p . 0,05) debido principalmente al deficit hídrico que generó la pérdida de la tercer cosecha de colza forrajera y la falla en la siembra del trebol persa. En cuanto a la calidad forrajera, se observaron menores valores de FDN, FDA y consecuentemente mayor DMS para el tratamiento colza forrajera, sin embargo para PC no se hallaron resultados consistentes como para los casos anteriores. Los resultados han sido promisorios considerando que la oferta forrajera y calidad nutricional de los dos primeros cortes del tratamiento colza forrajera igualaron a la avena y raigras. Serán necesarias nuevas experiencias en secano y también bajo riego con el fin de generar mas informacion sobre estas especies.

An integrated modeling approach to solder joint formation

The attachment of electronic components to printed circuit boards using solder material is a complex process. This paper presents a novel modeling methodology, which integrates the governing physics taking place. Multiphysics modeling technology, imbedded into the simulation tool—PHYSICA is used to simulate fluid flow, heat transfer, solidification, and stress evolution in an integrated manner. Results using this code are presented, detailing the mechanical response of two solder materials as they cool, solidify and then deform. The shape that a solder joint takes upon melting is predicted using the SURFACE EVOLVER code. Details are given on how these predictions can be used in the PHYSICA code to provide a modeling route by which the shape, solidification history, and resulting stress profiles can be predicted.

Modeling the dynamics of Magnetic Semilevitation Melting

In semilevitation melting, a cylindrical metal ingot is melted by a coaxial a.c. induction coil. A watercooled solid base supports the ingot, while the top and side free surface is confined by the magnetic forces as the melting front progresses. The dynamic interplay between gravity, hydrodynamic stress, and the Lorentz force in the fluid determines the instantaneous free surface shape. The coupled nonstationary equations for turbulent flow, heat with phase change, and high-frequency electromagnetic field are solved numerically for the axisymmetric time-dependent domain by a continuous mesh transformation, using a pseudospectral method. Results are obtained for the two actually existing coil configurations and several validation cases.

Multiphysics modeling and its application to the casting process

A modeling strategy is presented to solve the governing equations of fluid flow, temperature (with solidification), and stress in an integrated manner. These equations are discretized using finite volume methods on unstructured grids, which provide the capability to represent complex domains. Both the cell-centered and vertex-based forms of the finite volume discretization procedure are explained, and the overall integrated solution procedure using these techniques with suitable solvers is detailed. Two industrial processes, based on the casting of metals, are used to demonstrate the capabilities of the resultant modeling framework. This manufacturing process requires a high degree of coupling between the governing physical equations to accurately predict potential defects. Comparisons between model predictions and experimental observations are given.

Liquid metal turbulent flow dynamics in a cylindrical container with free surface: experiment and numerical analysis

The liquid metal flow in induction crucible models is known to be unstable, turbulent and difficult to predict in the regime of medium frequencies when the electromagnetic skin-layer is of considerable extent. We present long term turbulent flow measurements by a permanent magnet incorporated potential difference velocity probe in a cylindrical container filled with eutectic melt In-Ga-Sn. The parallel numerical simulation of the long time scale development of the turbulent average flow is presented. The numerical flow model uses an implicit pseudo-spectral code and k-w turbulence model, which was recently developed for the transitional flow modelling. The results compare reasonably to the experiment and demonstrate the time development of the turbulent flow field and the turbulence energy.

A computational model for defect prediction in shape castings based on the interaction of free surface flow, heat transfer, and solidification phenomena

High-integrity castings require sophisticated design and manufacturing procedures to ensure they are essentially macrodefect free. Unfortunately, an important class of such defects—macroporosity, misruns, and pipe shrinkage—are all functions of the interactions of free surface flow, heat transfer, and solidication in complex geometries. Because these defects arise as an interaction of the preceding continuum phenomena, genuinely predictive models of these defects must represent these interactions explicitly. This work describes an attempt to model the formation of macrodefects explicitly as a function of the interacting continuum phenomena in arbitrarily complex three-dimensional geometries. The computational approach exploits a compatible set of finite volume procedures extended to unstructured meshes. The implementation of the model is described together with its testing and a measure of validation. The model demonstrates the potential to predict reliably shrinkage macroporosity, misruns, and pipe shrinkage directly as a result of interactions among free-surface fluid flow, heat transfer, and solidification.

The recovery mechanism of platinum group metals from catalytic converters in spent automotive exhaust systems

The recovery of platinum group metals (PGMs) from catalytic converters of spent exhaust systems is considered in this paper. To be cost-effective, recovery processes must be well over 90% efficient and so the optimisation of their operation is vital. Effective optimisation requires a sound understanding of the operation and the underlying process mechanisms. This paper focuses on pyrometallurgical recovery operations used and typified by the Johnson–Matthey process. Analysis of this process reveals that it cannot be simply explained by the gravity model that is normally assumed. The analysis reveals that the affinity of PGM particles for the melted collector metal is a key factor in the behaviour of the process. A rational explanation of the key issues that govern the process behaviour is proposed and shown to be consistent with available operational data. The results generated would be applicable to other similar processes.

Collector-metal behaviour in the recovery of platinum-group metals from catalytic converters

A commercial pyrometallurgical process for the extraction of platinum-group metals (PGM) from a feedstock slag was analysed with the use of a model based on computational fluid dynamics. The results of the modelling indicate that recovery depends on the behaviour of the collector phase. A possible method is proposed for estimation of the rate at which PGM particles in slag are absorbed into an iron collector droplet that falls through it. Nanoscale modelling techniques (for particle migration or capture) are combined with a diffusion-controlled mass-transfer model to determine the iron collector droplet size needed for >95% PGM recovery in a typical process bath (70 mm deep) in a realistic time-scale (<1 h). The results show that an iron droplet having a diameter in the range 0.1–0.3 mm gives good recovery (>90%) within a reasonable time. This finding is compatible with published experimental data. Pyrometallurgical processes similar to that investigated should be applicable to other types of waste that contain low levels of potentially valuable metals.

An experimental and numerical CFD study of turbulence in a tundish container

This paper describes work performed at IRSID/USINOR in France and the University of Greenwich, UK, to investigate flow structures and turbulence in a water-model container, simulating aspects typical of metal tundish operation. Extensive mean and fluctuating velocity measurements were performed at IRSID using LDA to determine the flow field and these form the basis for a numerical model validation. This apparently simple problem poses several difficulties for the CFD modelling. The flow is driven by the strong impinging jet at the inlet. Accurate description of the jet is most important and requires a localized fine grid, but also a turbulence model that predicts the correct spreading rates of jet and impinging wall boundary layers. The velocities in the bulk of the tundish tend to be (indeed need to be) much smaller than those of the jet, leading to damping of turbulence, or even laminar flow. The authors have developed several low-Reynolds number (low-Re) k–var epsilon model variants to compute this flow and compare against measurements. Best agreement is obtained when turbulence damping is introduced to account not only for walls, but also for low-Re regions in the bulk – the k–var epsilon model otherwise allows turbulence to accumulate in the container due to the restricted outlet. Several damping functions are tested and the results reported here. The k–ω model, which is more suited to transitional flow, also seems to perform well in this problem.

Coupled 3-D finite difference time domain and finite volume methods for solving microwave heating in porous media

Computational results for the microwave heating of a porous material are presented in this paper. Combined finite difference time domain and finite volume methods were used to solve equations that describe the electromagnetic field and heat and mass transfer in porous media. The coupling between the two schemes is through a change in dielectric properties which were assumed to be dependent both on temperature and moisture content. The model was able to reflect the evolution of temperature and moisture fields as the moisture in the porous medium evaporates. Moisture movement results from internal pressure gradients produced by the internal heating and phase change.