Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience.

BACKGROUND AND OBJECTIVE: Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade. METHODS: Among 2228 consecutive lung specimens from 1999 to 2011, 226 cases (10.1%) were positive for GLD. One hundred ninety patients were retrospectively reviewed and diagnoses were assigned based on availability of histological/clinical/microbiological correlation. RESULTS: A confident, probable and uncertain diagnosis was made in 68.4%, 13.2% and 18.4% patients. The aetiologies comprised infectious, non-infectious and uncertain in 54.7%, 26.8% and 18.4% patients. Mycobacterial infections constituted 27% of all patients, and included atypical, tuberculous and unclassified mycobacteria in order of frequency. Acid-fast bacilli (AFB) were visualized in tissue sections in 29% cases and cultured in 73% cases. Fungal infections comprised 27% of all cases, which included Coccidioides, Cryptococcus, Aspergillus and Histoplasma in order of frequency. Fungi were visualized in tissue sections with Gomori methenamine silver (GMS) stain in 83% patients and cultured in 52% cases. Sarcoidosis was the major non-infectious aetiology, constituting 21% of all patients. Necrosis in granulomas was associated with the presence of infection (P < 0.001). CONCLUSIONS: The aetiology in necrotizing GLD with negative AFB and GMS stains is most likely infectious due to atypical mycobacteria. Coccidioidomycosis was the most common fungal infection. The aetiology in non-necrotizing GLD is most likely non-infectious, probably sarcoidosis.

Comparison of Molecular Dynamics with Classical Density Functional and Poisson-Boltzmann Theories of the Electric Double Layer in Nanochannels.

Comparisons are made among Molecular Dynamics (MD), Classical Density Functional Theory (c-DFT), and Poisson-Boltzmann (PB) modeling of the electric double layer (EDL) for the nonprimitive three component model (3CM) in which the two ion species and solvent molecules are all of finite size. Unlike previous comparisons between c-DFT and Monte Carlo (MC), the present 3CM incorporates Lennard-Jones interactions rather than hard-sphere and hard-wall repulsions. c-DFT and MD results are compared over normalized surface charges ranging from 0.2 to 1.75 and bulk ion concentrations from 10 mM to 1 M. Agreement between the two, assessed by electric surface potential and ion density profiles, is found to be quite good. Wall potentials predicted by PB begin to depart significantly from c-DFT and MD for charge densities exceeding 0.3. Successive layers are observed to charge in a sequential manner such that the solvent becomes fully excluded from each layer before the onset of the next layer. Ultimately, this layer filling phenomenon results in fluid structures, Debye lengths, and electric surface potentials vastly different from the classical PB predictions.

Optimization of charged species separation by autogenous electric field-flow fractionation in nano-scale channels.

Numerical methods are employed to examine the resolution and optimization of a relatively new technique for charged species separation that is based on flow along nano-scale channels having an electric double-layer thickness comparable to the channel size. In such channels, the electric field inherent to the double-layer produces transverse species distributions that depend on the species charge. Flow along the channel thus yields mean axial species speeds that also depend on the species charge, enabling species separation and identification. Building on earlier work describing retention and plate heights, here we characterize this new type of field-flow fractionation via the classic metric of resolution. Sample results are presented and discussed for a wide range of conditions for both pressure-driven and electroosmotic flows. Optimum design and operating conditions are also examined. We find that resolution is maximized for optimum values of the zeta potential and Debye layer thickness and that these optima depend strongly on the species charge or range of charges of interest. Under optimum conditions, acceptable resolution can be obtained over a wide range of species charges for pressure-driven flows. This separable range of charges is much smaller for electroosmotic flows. Finally, sample calculations are presented showing that all species in the range of charge between -8 to 10 can be separated simultaneously with resolutions above unity, and this is possible in less than 6 s under optimum conditions that are readily achievable.

Hierarchical transport networks optimizing dynamic response of permeable energy-storage materials.

Channel widths and spacing in latticelike hierarchical transport networks are optimized to achieve maximum extraction of gas or electrical charge from nanoporous energy-storage materials during charge and discharge cycles of specified duration. To address a range of physics, the effective transport diffusivity is taken to vary as a power, m , of channel width. Optimal channel widths and spacing in all levels of the hierarchy are found to increase in a power-law manner with normalized system size, facilitating the derivation of closed-form approximations for the optimal dimensions. Characteristic response times and ratios of channel width to spacing are both shown to vary by the factor 2/m between successive levels of any optimal hierarchy. This leads to fractal-like self-similar geometry, but only for m=2 . For this case of quadratic dependence of diffusivity on channel width, the introduction of transport channels permits increases in system size on the order of 10;{4} , 10;{8} , and 10;{10} , without any reduction in extraction efficiency, for hierarchies having 1, 2 and, 8 levels, respectively. However, we also find that for a given system size there is an optimum number of hierarchical levels that maximizes extraction efficiency.

Optimizing transient transport in materials having two scales of porosity.

Porous materials having multiple scales of porosity afford the opportunity to combine the high surface area and functionality of nanopores with the superior charge/discharge characteristics of wider transport channels. However, the relative volume fractions assigned to nanopores and transport channels must be thoughtfully balanced because the introduction of transport channels reduces the volume available for nanopore functionality. In the present paper, the optimal balance between nanopore capacity and system response time is achieved by adjusting the aperture and spacing of a family of transport channels that provide access to adjacent nanopores during recharge/discharge cycles of materials intended for storage of gas or electric charge. A diffusive transport model is used to describe alternative processes of viscous gas flow, Knudsen gas flow, and ion diffusion or electromigration. The coupled transport equations for the nanopores and transport channels are linearized and solved analytically for a periodic variation in external gas pressure, ion concentration, or electric potential using a separation-of-variables approach in the complex domain. Optimization of these solutions yields closed-form expressions for channel apertures and spacing that provide maximum discharge of gas or electric charge for a fixed system volume and a desired discharge time.

Charged species transport, separation, and dispersion in nanoscale channels: autogenous electric field-flow fractionation.

Numerical methods are employed to examine the transport of charged species in pressure-driven and electroosmotic flow along nanoscale channels having an electric double-layer thickness comparable to the channel size. In such channels, the electric field inherent to the double layer produces transverse species distributions that depend on species charge. Flow along the channel thus yields mean axial species speeds that also depend on the species charge, enabling species separation and identification. Here we characterize field-flow separations of this type via the retention and plate height. For pressure-driven flows, we demonstrate that mean species speeds along the channel are uniquely associated with a single species charge, allowing species separation based on charge alone. In contrast, electroosmotic flows generally yield identical speeds for several values of the charge, and these speeds generally depend on both the species charge and electrophoretic mobility. Coefficients of dispersion for charged species in both planar and cylindrical geometries are presented as part of this analysis.

Influence of atomistic physics on electro-osmotic flow: an analysis based on density functional theory.

Molecular density profiles and charge distributions determined by density functional theory (DFT) are used in conjunction with the continuum Navier-Stokes equations to compute electro-osmotic flows in nanoscale channels. The ion species of the electrolyte are represented as centrally charged hard spheres, and the solvent is treated as a dense fluid of neutral hard spheres having a uniform dielectric constant. The model explicitly accounts for Lennard-Jones interactions among fluid and wall molecules, hard sphere repulsions, and short range electrical interactions, as well as long range Coulombic interactions. Only the last of these interactions is included in classical Poisson-Boltzmann (PB) modeling of the electric field. Although the proposed DFT approach is quite general, the sample calculations presented here are limited to symmetric monovalent electrolytes. For a prescribed surface charge, this DFT model predicts larger counterion concentrations near charged channel walls, relative to classical PB modeling, and hence smaller concentrations in the channel center. This shifting of counterions toward the walls reduces the effective thickness of the Debye layer and reduces electro-osmotic velocities as compared to classical PB modeling. Zeta potentials and fluid speeds computed by the DFT model are as much as two or three times smaller than corresponding PB results. This disparity generally increases with increasing electrolyte concentration, increasing surface charge density and decreasing channel width. The DFT results are found to be comparable to those obtained by molecular dynamics simulation, but require considerably less computing time.

The efficiency of electrokinetic pumping at a condition of maximum work.

Numerical methods are employed to examine the work, electric power input, and efficiency of electrokinetic pumps at a condition corresponding to maximum pump work. These analyses employ the full Poisson-Boltzmann equations and account for both convective and conductive electric currents, including surface conductance. We find that efficiencies at this condition of maximum work depend on three dimensionless parameters, the normalized zeta potential, normalized Debye layer thickness, and a fluid property termed the Levine number indicating the nominal ratio of convective to conductive electric currents. Efficiencies at maximum work exhibit a maximum for an optimum Debye layer thickness when the zeta potential and Levine number are fixed. This maximum efficiency increases with the square of the zeta potential when the zeta potential is small, but reaches a plateau as the zeta potential becomes large. The maximum efficiency in this latter regime is thus independent of the zeta potential and depends only on the Levine number. Simple analytical expressions describing this maximum efficiency in terms of the Levine number are provided. Geometries of a circular tube and planar channel are examined.

Design and analysis of folded channels for chip-based separations.

Analytical methods are employed to investigate band broadening in a microchannel turn and adjoining straight channel segments for species transport by electrophoresis or electroosmotic flow. On the basis of closed-form solutions, we find that turn-induced broadening is negligible relative to total broadening when the radius of the turn exceeds some minimum. This minimum radius is about six-tenths of the product of the channel width and the Peclet number. We also find that the minimum radius is significantly reduced when a straight channel segment adjoins the turn in a folded configuration. Such straight segments noticeably reduce the minimum radius even for segment lengths comparable to the turn radius. The application of these results to folded and spiral channels is discussed, and sample calculations for practical conditions are presented. New pleated and coiled geometries for the compact layout of separation channels are also presented.