Intracranial pressure pulse amplitude during changes in head elevation: a new parameter for determining optimum cerebral perfusion pressure?

During short-term postural changes, the factors determining the amplitude of intracranial pulse pressure (ICPPA) remain constant, except for cerebrovascular resistance (CVR). Therefore, it may be possible to draw conclusions from the ICPPA onto the cerebrovascular resistance (CVR) and thus the relative change in cerebral perfusion pressure (CPP).

Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients

In colorectal cancer, tumor budding at the invasive front (peritumoral budding) is an established prognostic parameter and decreased in mismatch repair-deficient tumors. In contrast, the clinical relevance of tumor budding within the tumor center (intratumoral budding) is not yet known. The aim of the study was to determine the correlation of intratumoral budding with peritumoral budding and mismatch repair status and the prognostic impact of intratumoral budding using 2 independent patient cohorts. Following pancytokeratin staining of whole-tissue sections and multiple-punch tissue microarrays, 2 independent cohorts (group 1: n = 289; group 2: n = 222) with known mismatch repair status were investigated for intratumoral budding and peritumoral budding. In group 1, intratumoral budding was strongly correlated to peritumoral budding (r = 0.64; P < .001) and less frequent in mismatch repair-deficient versus mismatch repair-proficient cases (P = .177). Sensitivity and specificity for lymph node positivity were 72.7% and 72.1%. In mismatch repair-proficient cancers, high-grade intratumoral budding was associated with right-sided location (P = .024), advanced T stage (P = .001) and N stage pN (P < .001), vascular invasion (P = .041), infiltrating tumor margin (P = .003), and shorter survival time (P = .014). In mismatch repair-deficient cancers, high intratumoral budding was linked to higher tumor grade (P = .004), vascular invasion (P = .009), infiltrating tumor margin (P = .005), and more unfavorable survival time (P = .09). These associations were confirmed in group 2. High-grade intratumoral budding was a poor prognostic factor in univariate (P < .001) and multivariable analyses (P = .019) adjusting for T stage, N stage distant metastasis, and adjuvant therapy. These preliminary results on 511 patients show that intratumoral budding is an independent prognostic factor, supporting the future investigation of intratumoral budding in larger series of both preoperative and postoperative rectal and colon cancer specimens.

Planetary Gear Modal Vibration Experiments and Correlation against Lumped-Parameter and Finite Element Models

Experimental modal analysis techniques are applied to characterize the planar dynamic behavior of two spur planetary gears. Rotational and translational vibrations of the sun gear, carrier, and planet gears are measured. Experimentally obtained natural frequencies, mode shapes, and dynamic response are compared to the results from lumped-parameter and finite element models. Two qualitatively different classes of mode shapes in distinct frequency ranges are observed in the experiments and confirmed by the lumped-parameter model, which considers the accessory shafts and fixtures in the system to capture all of the natural frequencies and modes. The finite element model estimates the high-frequency modes that have significant tooth mesh deflection without considering the shafts and fixtures. The lumped-parameter and finite element models accurately predict the natural frequencies and modal properties established by experimentation. Rotational, translational, and planet mode types presented in published mathematical studies are confirmed experimentally. The number and types of modes in the low-frequency and high-frequency bands depend on the degrees of freedom in the central members and planet gears, respectively. The accuracy of natural frequency prediction is improved when the planet bearings have differing stiffnesses in the tangential and radial directions, consistent with the bearing load direction. (C) 2012 Elsevier Ltd. All rights reserved.

Tumour budding: a promising parameter in colorectal cancer

In 2011, the Tumour Node Metastasis (TNM) staging system still remains the gold standard for stratifying colorectal cancer (CRC) patients into prognostic subgroups, and is considered a solid basis for treatment management. Nevertheless, there is still a challenge with regard to therapeutic strategy; stage II patients are not typically selected for postoperative adjuvant chemotherapy, although some stage II patients have a comparable outcome to stage III patients who, themselves do receive such treatment. Consequently, there has been an inundation of 'prognostic biomarker' studies aiming to improve the prognostic stratification power of the TNM staging system. Most proposed biomarkers are not implemented because of lack of reproducibility, validation and standardisation. This problem can be partially resolved by following the REMARK guidelines. In search of novel prognostic factors for patients with CRC, one might glance at a table in the book entitled 'Prognostic Factors in Cancer' published by the International Union against Cancer (UICC) in 2006, in which TNM stage, L and V classifications are considered 'essential' prognostic factors, whereas tumour grade, perineural invasion, tumour budding and tumour-border configuration among others are proposed as 'additional' prognostic factors. Histopathology reports normally include the 'essential' features and are accompanied by tumour grade, histological subtype and information on perineural invasion, but interestingly, the tumour-border configuration (i.e., growth pattern) and especially tumour budding are rarely reported. Although scoring systems such as the 'BRE' in breast and 'Gleason' in prostate cancer are solidly based on histomorphological features and used in daily practice, no such additional scoring system to complement TNM staging is available for CRC. Regardless of differences in study design and methods for tumour-budding assessment, the prognostic power of tumour budding has been confirmed by dozens of study groups worldwide, suggesting that tumour budding may be a valuable candidate for inclusion into a future prognostic scoring system for CRC. This mini-review therefore attempts to present a short and concise overview on tumour budding, including morphological, molecular and prognostic aspects underlining its inter-disciplinary relevance.

Development of a morphometric magnetic resonance image parameter suitable for distinguishing between normal dogs and dogs with cerebellar atrophy

Neurodegenerative diseases affect the cerebellum of numerous dog breeds. Although subjective, magnetic resonance (MR) imaging has been used to detect cerebellar atrophy in these diseases, but there are few data available on the normal size range of the cerebellum relative to other brain regions. The purpose of this study was to determine whether the size of the cerebellum maintains a consistent ratio with other brain regions in different ages and breeds of normal dogs and to define a measurement that can be used to identify cerebellar atrophy on MR images. Images from 52 normal and 13 dogs with cerebellar degenerative diseases were obtained. Volume and mid-sagittal cross-sectional area of the forebrain, brainstem, and cerebellum were calculated for each normal dog and compared between different breeds and ages as absolute and relative values. The ratio of the cerebellum to total brain and of the brainstem to cerebellum mid-sagittal cross-sectional area was compared between normal and affected dogs and the sensitivity and specificity of these ratios at distinguishing normal from affected dogs was calculated. The percentage of the brain occupied by the cerebellum in diverse dog breeds between 1 and 5 years of age was not significantly different, and cerebellar size did not change with increasing age. Using a cut off of 89%, the ratio between the brainstem and cerebellum mid-sagittal cross-sectional area could be used successfully to differentiate affected from unaffected dogs with a sensitivity and specificity of 100%, making this ratio an effective tool for identifying cerebellar atrophy on MR images.

Investigation Of Leucine And Glutamic Acid Properties From The Nanoscale To The Macroscale

Aerosols are known to have important effects on climate, the atmosphere, and human health. The extent of those effects is unknown and largely depend on the interaction of aerosols with water in the atmosphere. Ambient aerosols are complex mixtures of both inorganic and organic compounds. The cloud condensation nuclei (CCN) activities, hygroscopic behavior and particle morphology of a monocarboxylic amino acid (leucine) and a dicarboxylic amino acid (glutamic acid) were investigated. Activation diameters at various supersaturation conditions were experimentally determined and compared with Köhler theoretical values. The theory accounts for both surface tension and the limited solubility of organic compounds. It was discovered that glutamic acid aerosols readily took on water both when relative humidity was less than 100% and when the supersaturation condition was reached, while leucine did not show any water activation at those conditions. Moreover, the study also suggests that Köhler theory describes CCN activity of organic compounds well when only surface tension of the compound is taken into account and complete solubility is assumed. Single parameter ¿ was also computed using both CCN data and hygroscopic growth factor (GF). The results of ¿ range from 0.17 to 0.53 using CCN data and 0.09 to 0.2 using GFs. Finally, the study suggests that during the water-evaporation/particle-nucleation process, crystallization from solution droplets takes place at different locations: for glutamic acid at the particles¿ center and leucine at the particles¿ boundary.

End-tidal CO(2). An important parameter for a correct interpretation in functional brain studies using speech tasks

The aim was to investigate the effect of different speech tasks, i.e. recitation of prose (PR), alliteration (AR) and hexameter (HR) verses and a control task (mental arithmetic (MA) with voicing of the result on end-tidal CO2 (PETCO2), cerebral hemodynamics and oxygenation. CO2 levels in the blood are known to strongly affect cerebral blood flow. Speech changes breathing pattern and may affect CO2 levels. Measurements were performed on 24 healthy adult volunteers during the performance of the 4 tasks. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) and PETCO2 by a gas analyzer. Statistical analysis was applied to the difference between baseline before the task, 2 recitation and 5 baseline periods after the task. The 2 brain hemispheres and 4 tasks were tested separately. A significant decrease in PETCO2 was found during all 4 tasks with the smallest decrease during the MA task. During the recitation tasks (PR, AR and HR) a statistically significant (p < 0.05) decrease occurred for StO2 during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. [O2Hb] decreased significantly during PR, AR and HR in both hemispheres. [HHb] increased significantly during the AR task in the right PFC. [tHb] decreased significantly during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased and [HHb] decreased significantly during the MA task. We conclude that changes in breathing (hyperventilation) during the tasks led to lower CO2 pressure in the blood (hypocapnia), predominantly responsible for the measured changes in cerebral hemodynamics and oxygenation. In conclusion, our findings demonstrate that PETCO2 should be monitored during functional brain studies investigating speech using neuroimaging modalities, such as fNIRS, fMRI to ensure a correct interpretation of changes in hemodynamics and oxygenation.

The Optimal Confidence Region for a Random Parameter

Under a two-level hierarchical model, suppose that the distribution of the random parameter is known or can be estimated well. Data are generated via a fixed, but unobservable realization of this parameter. In this paper, we derive the smallest confidence region of the random parameter under a joint Bayesian/frequentist paradigm. On average this optimal region can be much smaller than the corresponding Bayesian highest posterior density region. The new estimation procedure is appealing when one deals with data generated under a highly parallel structure, for example, data from a trial with a large number of clinical centers involved or genome-wide gene-expession data for estimating individual gene- or center-specific parameters simultaneously. The new proposal is illustrated with a typical microarray data set and its performance is examined via a small simulation study.

Automation of shear-wave splitting parameter determination of local earthquakes at Yellowstone : application as indicator of crustal stress and temporal variation

Shear-wave splitting can be a useful technique for determining crustal stress fields in volcanic settings and temporal variations associated with activity. Splitting parameters were determined for a subset of local earthquakes recorded from 2000-2010 at Yellowstone. Analysis was automated using an unsupervised cluster analysis technique to determine optimum splitting parameters from 270 analysis windows for each event. Six stations clearly exhibit preferential fast polarization values sub-orthogonal to the direction of minimum horizontal compression. Yellowstone deformation results in a local crustal stress field differing from the regional field dominated by NE-SW extension, and fast directions reflect this difference rotating around the caldera maintaining perpendicularity to the rim. One station exhibits temporal variations concordant with identified periods of caldera subsidence and uplift. From splitting measurements, we calculated a crustal anisotropy of ~17-23% and crack density ~0.12-0.17 possibly resulting from stress-aligned fluid filled microcracks in the upper crust and an active hydrothermal system.

Parameter estimation for transformer modeling

Large Power transformers, an aging and vulnerable part of our energy infrastructure, are at choke points in the grid and are key to reliability and security. Damage or destruction due to vandalism, misoperation, or other unexpected events is of great concern, given replacement costs upward of $2M and lead time of 12 months. Transient overvoltages can cause great damage and there is much interest in improving computer simulation models to correctly predict and avoid the consequences. EMTP (the Electromagnetic Transients Program) has been developed for computer simulation of power system transients. Component models for most equipment have been developed and benchmarked. Power transformers would appear to be simple. However, due to their nonlinear and frequency-dependent behaviors, they can be one of the most complex system components to model. It is imperative that the applied models be appropriate for the range of frequencies and excitation levels that the system experiences. Thus, transformer modeling is not a mature field and newer improved models must be made available. In this work, improved topologically-correct duality-based models are developed for three-phase autotransformers having five-legged, three-legged, and shell-form cores. The main problem in the implementation of detailed models is the lack of complete and reliable data, as no international standard suggests how to measure and calculate parameters. Therefore, parameter estimation methods are developed here to determine the parameters of a given model in cases where available information is incomplete. The transformer nameplate data is required and relative physical dimensions of the core are estimated. The models include a separate representation of each segment of the core, including hysteresis of the core, λ-i saturation characteristic, capacitive effects, and frequency dependency of winding resistance and core loss. Steady-state excitation, and de-energization and re-energization transients are simulated and compared with an earlier-developed BCTRAN-based model. Black start energization cases are also simulated as a means of model evaluation and compared with actual event records. The simulated results using the model developed here are reasonable and more correct than those of the BCTRAN-based model. Simulation accuracy is dependent on the accuracy of the equipment model and its parameters. This work is significant in that it advances existing parameter estimation methods in cases where the available data and measurements are incomplete. The accuracy of EMTP simulation for power systems including three-phase autotransformers is thus enhanced. Theoretical results obtained from this work provide a sound foundation for development of transformer parameter estimation methods using engineering optimization. In addition, it should be possible to refine which information and measurement data are necessary for complete duality-based transformer models. To further refine and develop the models and transformer parameter estimation methods developed here, iterative full-scale laboratory tests using high-voltage and high-power three-phase transformer would be helpful.