A dedicated animal model for mechanical thrombectomy in acute stroke

BACKGROUND: Recent studies have focused on mechanical thrombectomy as a means to reduce the time required for revascularization and increase the revascularization rate in acute stroke. To date no systematic evaluation has been made of the different mechanical devices in this novel and fast-developing field of endovascular interventions. To facilitate such evaluations, we developed a specific in vivo model for mechanical thrombectomy that allows visualization of dislocation or fragmentation of the thrombus during angiographic manipulation. METHODS: Angiography and embolization with a preformed thrombus was performed in 8 swine. The thrombus was generated by mixing 25 IU bovine thrombin and 10 mL autologous blood. For visualization during angiography, 1 g barium sulfate was added. RESULTS: The preformed thrombus exhibited mechanical stability, reproducibility, and high radiographic absorption, providing excellent visibility during angiography. The setting allowed selective embolization of targeted vessels without thrombus fragmentation. Despite the application of barium sulfate no local or systemic reaction occurred. Histologic evaluation revealed no intimal damage caused by the thrombus or contrast agent washout. CONCLUSION: The model presented here allows selective and reliable thromboembolization of vessels that reproduce the anatomic and hemodynamic situation in acute cerebrovascular stroke. It permits visualization of the thrombus during angiography and intervention, providing unique insight into the behavior of both thrombus and device, which is potentially useful in the development and evaluation of mechanical clot retrieval in acute cerebrovascular stroke.

Posterior Simulation in the Generalized Linear Model with Semiparmetric Random Effects

Generalized linear mixed models with semiparametric random effects are useful in a wide variety of Bayesian applications. When the random effects arise from a mixture of Dirichlet process (MDP) model, normal base measures and Gibbs sampling procedures based on the Pólya urn scheme are often used to simulate posterior draws. These algorithms are applicable in the conjugate case when (for a normal base measure) the likelihood is normal. In the non-conjugate case, the algorithms proposed by MacEachern and Müller (1998) and Neal (2000) are often applied to generate posterior samples. Some common problems associated with simulation algorithms for non-conjugate MDP models include convergence and mixing difficulties. This paper proposes an algorithm based on the Pólya urn scheme that extends the Gibbs sampling algorithms to non-conjugate models with normal base measures and exponential family likelihoods. The algorithm proceeds by making Laplace approximations to the likelihood function, thereby reducing the procedure to that of conjugate normal MDP models. To ensure the validity of the stationary distribution in the non-conjugate case, the proposals are accepted or rejected by a Metropolis-Hastings step. In the special case where the data are normally distributed, the algorithm is identical to the Gibbs sampler.

Multilevel Latent Class Models with Dirichlet Mixing Distribution

Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we develop multilevel latent class model, in which subpopulation mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when either the number of classes or the cluster size is large. We propose a maximum pairwise likelihood (MPL) approach via a modified EM algorithm for this case. We also show that a simple latent class analysis, combined with robust standard errors, provides another consistent, robust, but less efficient inferential procedure. Simulation studies suggest that the three methods work well in finite samples, and that the MPL estimates often enjoy comparable precision as the ML estimates. We apply our methods to the analysis of comorbid symptoms in the Obsessive Compulsive Disorder study. Our models' random effects structure has more straightforward interpretation than those of competing methods, thus should usefully augment tools available for latent class analysis of multilevel data.

Diesel spray mixing limited vaporization with non-ideal and multi-component fuel thermophysical property effects

Internal combustion engines are, and will continue to be, a primary mode of power generation for ground transportation. Challenges exist in meeting fuel consumption regulations and emission standards while upholding performance, as fuel prices rise, and resource depletion and environmental impacts are of increasing concern. Diesel engines are advantageous due to their inherent efficiency advantage over spark ignition engines; however, their NOx and soot emissions can be difficult to control and reduce due to an inherent tradeoff. Diesel combustion is spray and mixing controlled providing an intrinsic link between spray and emissions, motivating detailed, fundamental studies on spray, vaporization, mixing, and combustion characteristics under engine relevant conditions. An optical combustion vessel facility has been developed at Michigan Technological University for these studies, with detailed tests and analysis being conducted. In this combustion vessel facility a preburn procedure for thermodynamic state generation is used, and validated using chemical kinetics modeling both for the MTU vessel, and institutions comprising the Engine Combustion Network international collaborative research initiative. It is shown that minor species produced are representative of modern diesel engines running exhaust gas recirculation and do not impact the autoignition of n-heptane. Diesel spray testing of a high-pressure (2000 bar) multi-hole injector is undertaken including non-vaporizing, vaporizing, and combusting tests, with sprays characterized using Mie back scatter imaging diagnostics. Liquid phase spray parameter trends agree with literature. Fluctuations in liquid length about a quasi-steady value are quantified, along with plume to plume variations. Hypotheses are developed for their causes including fuel pressure fluctuations, nozzle cavitation, internal injector flow and geometry, chamber temperature gradients, and turbulence. These are explored using a mixing limited vaporization model with an equation of state approach for thermopyhysical properties. This model is also applied to single and multi-component surrogates. Results include the development of the combustion research facility and validated thermodynamic state generation procedure. The developed equation of state approach provides application for improving surrogate fuels, both single and multi-component, in terms of diesel spray liquid length, with knowledge of only critical fuel properties. Experimental studies are coupled with modeling incorporating improved thermodynamic non-ideal gas and fuel

Mixing-cell boundary conditions and apparent mass balance errors for advective-dispersive solute transport

In many field or laboratory situations, well-mixed reservoirs like, for instance, injection or detection wells and gas distribution or sampling chambers define boundaries of transport domains. Exchange of solutes or gases across such boundaries can occur through advective or diffusive processes. First we analyzed situations, where the inlet region consists of a well-mixed reservoir, in a systematic way by interpreting them in terms of injection type. Second, we discussed the mass balance errors that seem to appear in case of resident injections. Mixing cells (MC) can be coupled mathematically in different ways to a domain where advective-dispersive transport occurs: by assuming a continuous solute flux at the interface (flux injection, MC-FI), or by assuming a continuous resident concentration (resident injection). In the latter case, the flux leaving the mixing cell can be defined in two ways: either as the value when the interface is approached from the mixing-cell side (MC-RT -), or as the value when it is approached from the column side (MC-RT +). Solutions of these injection types with constant or-in one case-distance-dependent transport parameters were compared to each other as well as to a solution of a two-layer system, where the first layer was characterized by a large dispersion coefficient. These solutions differ mainly at small Peclet numbers. For most real situations, the model for resident injection MC-RI + is considered to be relevant. This type of injection was modeled with a constant or with an exponentially varying dispersion coefficient within the porous medium. A constant dispersion coefficient will be appropriate for gases because of the Eulerian nature of the usually dominating gaseous diffusion coefficient, whereas the asymptotically growing dispersion coefficient will be more appropriate for solutes due to the Lagrangian nature of mechanical dispersion, which evolves only with the fluid flow. Assuming a continuous resident concentration at the interface between a mixing cell and a column, as in case of the MC-RI + model, entails a flux discontinuity. This flux discontinuity arises inherently from the definition of a mixing cell: the mixing process is included in the balance equation, but does not appear in the description of the flux through the mixing cell. There, only convection appears because of the homogeneous concentration within the mixing cell. Thus, the solute flux through a mixing cell in close contact with a transport domain is generally underestimated. This leads to (apparent) mass balance errors, which are often reported for similar situations and erroneously used to judge the validity of such models. Finally, the mixing cell model MC-RI + defines a universal basis regarding the type of solute injection at a boundary. Depending on the mixing cell parameters, it represents, in its limits, flux as well as resident injections. (C) 1998 Elsevier Science B.V. All rights reserved.

Understanding the performance of the FLake model over two African Great Lakes

The ability of the one-dimensional lake model FLake to represent the mixolimnion temperatures for tropical conditions was tested for three locations in East Africa: Lake Kivu and Lake Tanganyika's northern and southern basins. Meteorological observations from surrounding automatic weather stations were corrected and used to drive FLake, whereas a comprehensive set of water temperature profiles served to evaluate the model at each site. Careful forcing data correction and model configuration made it possible to reproduce the observed mixed layer seasonality at Lake Kivu and Lake Tanganyika (northern and southern basins), with correct representation of both the mixed layer depth and water temperatures. At Lake Kivu, mixolimnion temperatures predicted by FLake were found to be sensitive both to minimal variations in the external parameters and to small changes in the meteorological driving data, in particular wind velocity. In each case, small modifications may lead to a regime switch, from the correctly represented seasonal mixed layer deepening to either completely mixed or permanently stratified conditions from similar to 10 m downwards. In contrast, model temperatures were found to be robust close to the surface, with acceptable predictions of near-surface water temperatures even when the seasonal mixing regime is not reproduced. FLake can thus be a suitable tool to parameterise tropical lake water surface temperatures within atmospheric prediction models. Finally, FLake was used to attribute the seasonal mixing cycle at Lake Kivu to variations in the near-surface meteorological conditions. It was found that the annual mixing down to 60m during the main dry season is primarily due to enhanced lake evaporation and secondarily to the decreased incoming long wave radiation, both causing a significant heat loss from the lake surface and associated mixolimnion cooling.

A Model Study of the Circulation in the Pearl River Estuary (PRE) and Its Adjacent Coastal Waters: 1. Simulations and Comparison with Observations

The Princeton Ocean Model is used to study the circulation features in the Pearl River Estuary and their responses to tide, river discharge, wind, and heat flux in the winter dry and summer wet seasons. The model has an orthogonal curvilinear grid in the horizontal plane with variable spacing from 0.5 km in the estuary to 1 km on the shelf and 15 sigma levels in the vertical direction. The initial conditions and the subtidal open boundary forcing are obtained from an associated larger-scale model of the northern South China Sea. Buoyancy forcing uses the climatological monthly heat fluxes and river discharges, and both the climatological monthly wind and the realistic wind are used in the sensitivity experiments. The tidal forcing is represented by sinusoidal functions with the observed amplitudes and phases. In this paper, the simulated tide is first examined. The simulated seasonal distributions of the salinity, as well as the temporal variations of the salinity and velocity over a tidal cycle are described and then compared with the in situ survey data from July 1999 and January 2000. The model successfully reproduces the main hydrodynamic processes, such as the stratification, mixing, frontal dynamics, summer upwelling, two-layer gravitational circulation, etc., and the distributions of hydrodynamic parameters in the Pearl River Estuary and coastal waters for both the winter and the summer season.

Daily ozone cycle in the stratosphere: global, regional and seasonal behaviour modelled with the Whole Atmosphere Community Climate Model

The Whole Atmosphere Community Climate Model (WACCM) is utilised to study the daily ozone cycle and underlying photochemical and dynamical processes. The analysis is focused on the daily ozone cycle in the middle stratosphere at 5 hPa where satellite-based trend estimates of stratospheric ozone are most biased by diurnal sampling effects and drifting satellite orbits. The simulated ozone cycle shows a minimum after sunrise and a maximum in the late afternoon. Further, a seasonal variation of the daily ozone cycle in the stratosphere was found. Depending on season and latitude, the peak-to-valley difference of the daily ozone cycle varies mostly between 3 and 5% (0.4 ppmv) with respect to the midnight ozone volume mixing ratio. The maximal variation of 15% (0.8 ppmv) is found at the polar circle in summer. The global pattern of the strength of the daily ozone cycle is mainly governed by the solar zenith angle and the sunshine duration. In addition, we find synoptic-scale variations in the strength of the daily ozone cycle. These variations are often anti-correlated to regional temperature anomalies and are due to the temperature dependence of the rate coefficients k2 and k3 of the Chapman cycle reactions. Further, the NOx catalytic cycle counteracts the accumulation of ozone during daytime and leads to an anti-correlation between anomalies in NOx and the strength of the daily ozone cycle. Similarly, ozone recombines with atomic oxygen which leads to an anti-correlation between anomalies in ozone abundance and the strength of the daily ozone cycle. At higher latitudes, an increase of the westerly (easterly) wind cause a decrease (increase) in the sunshine duration of an air parcel leading to a weaker (stronger) daily ozone cycle.

A multi-model comparison of Atlantic multidecadal variability

A multi-model analysis of Atlantic multidecadal variability is performed with the following aims: to investigate the similarities to observations; to assess the strength and relative importance of the different elements of the mechanism proposed by Delworth et al. (J Clim 6:1993–2011, 1993) (hereafter D93) among coupled general circulation models (CGCMs); and to relate model differences to mean systematic error. The analysis is performed with long control simulations from ten CGCMs, with lengths ranging between 500 and 3600 years. In most models the variations of sea surface temperature (SST) averaged over North Atlantic show considerable power on multidecadal time scales, but with different periodicity. The SST variations are largest in the mid-latitude region, consistent with the short instrumental record. Despite large differences in model configurations, we find quite some consistency among the models in terms of processes. In eight of the ten models the mid-latitude SST variations are significantly correlated with fluctuations in the Atlantic meridional overturning circulation (AMOC), suggesting a link to northward heat transport changes. Consistent with this link, the three models with the weakest AMOC have the largest cold SST bias in the North Atlantic. There is no linear relationship on decadal timescales between AMOC and North Atlantic Oscillation in the models. Analysis of the key elements of the D93 mechanisms revealed the following: Most models present strong evidence that high-latitude winter mixing precede AMOC changes. However, the regions of wintertime convection differ among models. In most models salinity-induced density anomalies in the convective region tend to lead AMOC, while temperature-induced density anomalies lead AMOC only in one model. However, analysis shows that salinity may play an overly important role in most models, because of cold temperature biases in their relevant convective regions. In most models subpolar gyre variations tend to lead AMOC changes, and this relation is strong in more than half of the models.

Modelling Nd-isotopes with a coarse resolution ocean circulation model: Sensitivities to model parameters and source/sink distributions

The neodymium (Nd) isotopic composition (Nd) of seawater is a quasi-conservative tracer of water mass mixing and is assumed to hold great potential for paleoceanographic studies. Here we present a comprehensive approach for the simulation of the two neodymium isotopes 143Nd, and 144Nd using the Bern3D model, a low resolution ocean model. The high computational efficiency of the Bern3D model in conjunction with our comprehensive approach allows us to systematically and extensively explore the sensitivity of Nd concentrations and Nd to the parametrisation of sources and sinks. Previous studies have been restricted in doing so either by the chosen approach or by computational costs. Our study thus presents the most comprehensive survey of the marine Nd cycle to date. Our model simulates both Nd concentrations as well as Nd in good agreement with observations. Nd covaries with salinity, thus underlining its potential as a water mass proxy. Results confirm that the continental margins are required as a Nd source to simulate Nd concentrations and Nd consistent with observations. We estimate this source to be slightly smaller than reported in previous studies and find that above a certain magnitude its magnitude affects Nd only to a small extent. On the other hand, the parametrisation of the reversible scavenging considerably affects the ability of the model to simulate both, Nd concentrations and Nd. Furthermore, despite their small contribution, we find dust and rivers to be important components of the Nd cycle. In additional experiments, we systematically varied the diapycnal diffusivity as well as the Atlantic-to-Pacific freshwater flux to explore the sensitivity of Nd concentrations and its isotopic signature to the strength and geometry of the overturning circulation. These experiments reveal that Nd concentrations and Nd are comparatively little affected by variations in diapycnal diffusivity and the Atlantic-to-Pacific freshwater flux. In contrast, an adequate representation of Nd sources and sinks is crucial to simulate Nd concentrations and Nd consistent with observations. The good agreement of our results with observations paves the way for the evaluation of the paleoceanographic potential of Nd in further model studies.

Precise Measurement of the Neutrino Mixing Parameter θ₂₃ from Muon Neutrino Disappearance in an Off-Axis Beam

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter θ 23 . Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57×10 20 protons on target, T2K has fit the energy-dependent ν μ oscillation probability to determine oscillation parameters. The 68% confidence limit on sin 2 (θ 23 ) is 0.514 +0.055 −0.056 (0.511±0.055 ), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Δm 2 32 =(2.51±0.10)×10 −3   eV 2 /c 4 (inverted hierarchy: Δm 2 13 =(2.48±0.10)×10 −3   eV 2 /c 4 ). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty.

A thermodynamic model for di-trioctahedral chlorite from experimental and natural data in the system MgO-FeO-Al2O3-SiO2-H2O. Applications to P-T sections and geothermometry

We present a new thermodynamic activity-composition model for di-trioctahedral chlorite in the system FeO–MgO–Al2O3–SiO2–H2O that is based on the Holland–Powell internally consistent thermodynamic data set. The model is formulated in terms of four linearly independent end-members, which are amesite, clinochlore, daphnite and sudoite. These account for the most important crystal-chemical substitutions in chlorite, the Fe–Mg, Tschermak and di-trioctahedral substitution. The ideal part of end-member activities is modeled with a mixing-on-site formalism, and non-ideality is described by a macroscopic symmetric (regular) formalism. The symmetric interaction parameters were calibrated using a set of 271 published chlorite analyses for which robust independent temperature estimates are available. In addition, adjustment of the standard state thermodynamic properties of sudoite was required to accurately reproduce experimental brackets involving sudoite. This new model was tested by calculating representative P–T sections for metasediments at low temperatures (<400 °C), in particular sudoite and chlorite bearing metapelites from Crete. Comparison between the calculated mineral assemblages and field data shows that the new model is able to predict the coexistence of chlorite and sudoite at low metamorphic temperatures. The predicted lower limit of the chloritoid stability field is also in better agreement with petrological observations. For practical applications to metamorphic and hydrothermal environments, two new semi-empirical chlorite geothermometers named Chl(1) and Chl(2) were calibrated based on the chlorite + quartz + water equilibrium (2 clinochlore + 3 sudoite = 4 amesite + 4 H2O + 7 quartz). The Chl(1) thermometer requires knowledge of the (Fe3+/ΣFe) ratio in chlorite and predicts correct temperatures for a range of redox conditions. The Chl(2) geothermometer which assumes that all iron in chlorite is ferrous has been applied to partially recrystallized detrital chlorite from the Zone houillère in the French Western Alps.

Gas transport in firn: multiple-tracer characterisation and model intercomparison for NEEM, Northern Greenland

Air was sampled from the porous firn layer at the NEEM site in Northern Greenland. We use an ensemble of ten reference tracers of known atmospheric history to characterise the transport properties of the site. By analysing uncertainties in both data and the reference gas atmospheric histories, we can objectively assign weights to each of the gases used for the depth-diffusivity reconstruction. We define an objective root mean square criterion that is minimised in the model tuning procedure. Each tracer constrains the firn profile differently through its unique atmospheric history and free air diffusivity, making our multiple-tracer characterisation method a clear improvement over the commonly used single-tracer tuning. Six firn air transport models are tuned to the NEEM site; all models successfully reproduce the data within a 1σ Gaussian distribution. A comparison between two replicate boreholes drilled 64 m apart shows differences in measured mixing ratio profiles that exceed the experimental error. We find evidence that diffusivity does not vanish completely in the lock-in zone, as is commonly assumed. The ice age- gas age difference (1 age) at the firn-ice transition is calculated to be 182+3−9 yr. We further present the first intercomparison study of firn air models, where we introduce diagnostic scenarios designed to probe specific aspects of the model physics. Our results show that there are major differences in the way the models handle advective transport. Furthermore, diffusive fractionation of isotopes in the firn is poorly constrained by the models, which has consequences for attempts to reconstruct the isotopic composition of trace gases back in time using firn air and ice core records.

Tuberculosis in Cape Town: An age-structured transmission model.

BACKGROUND Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. METHODS We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. RESULTS The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. CONCLUSION The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.

Effects of Surface Forcing on Interannual Variability of the Fall Phytoplankton Bloom in the Gulf of Maine Revealed Using a Process-Oriented Model

SeaWiFS (Sea-viewing Wide Field-of-view Sensor) chlorophyll data revealed strong interannual variability in fall phytoplankton dynamics in the Gulf of Maine, with 3 general features in any one year: (1) rapid chlorophyll increases in response to storm events in fall; (2) gradual chlorophyll increases in response to seasonal wind-and cooling-induced mixing that gradually deepens the mixed layer; and (3) the absence of any observable fall bloom. We applied a mixed-layer box model and a 1-dimensional physical-biological numerical model to examine the influence of physical forcing (surface wind, heat flux, and freshening) on the mixed-layer dynamics and its impact on the entrainment of deep-water nutrients and thus on the appearance of fall bloom. The model results suggest that during early fall, the surface mixed-layer depth is controlled by both wind-and cooling-induced mixing. Strong interannual variability in mixed-layer depth has a direct impact on short-and long-term vertical nutrient fluxes and thus the fall bloom. Phytoplankton concentrations over time are sensitive to initial pre-bloom profiles of nutrients. The strength of the initial stratification can affect the modeled phytoplankton concentration, while the timing of intermittent freshening events is related to the significant interannual variability of fall blooms.