Fast and sensitive supercritical fluid chromatography - tandem mass spectrometry multi-class screening method for the determination of doping agents in urine.

This study shows the possibility offered by modern ultra-high performance supercritical fluid chromatography combined with tandem mass spectrometry in doping control analysis. A high throughput screening method was developed for 100 substances belonging to the challenging classes of anabolic agents, hormones and metabolic modulators, synthetic cannabinoids and glucocorticoids, which should be detected at low concentrations in urine. To selectively extract these doping agents from urine, a supported liquid extraction procedure was implemented in a 48-well plate format. At the tested concentration levels ranging from 0.5 to 5 ng/mL, the recoveries were better than 70% for 48-68% of the compounds and higher than 50% for 83-87% of the tested substances. Due to the numerous interferences related to isomers of steroids and ions produced by the loss of water in the electrospray source, the choice of SFC separation conditions was very challenging. After careful optimization, a Diol stationary phase was employed. The total analysis time for the screening assay was only 8 min, and interferences as well as susceptibility to matrix effect (ME) were minimized. With the developed method, about 70% of the compounds had relative ME within the range ±20%, at a concentration of 1 and 5 ng/mL. Finally, limits of detection achieved with the above-described strategy including 5-fold preconcentration were below 0.1 ng/mL for the majority of the tested compounds. Therefore, LODs were systematically better than the minimum required performance levels established by the World anti-doping agency, except for very few metabolites.

Using computational fluid dynamics to predict head losses in the auxiliary elements of a microirrigation sand filter

It is often assumed that total head losses in a sand filter are solely due to the filtration media and that there are analytical solutions, such as the Ergun equation, to compute them. However, total head losses are also due to auxiliary elements (inlet and outlet pipes and filter nozzles), which produce undesirable head losses because they increase energy requirements without contributing to the filtration process. In this study, ANSYS Fluent version 6.3, a commercial computational fluid dynamics (CFD) software program, was used to compute head losses in different parts of a sand filter. Six different numerical filter models of varying complexities were used to understand the hydraulic behavior of the several filter elements and their importance in total head losses. The simulation results show that 84.6% of these were caused by the sand bed and 15.4% were due to auxiliary elements (4.4% in the outlet and inlet pipes, and 11.0% in the perforated plate and nozzles). Simulation results with different models show the important role of the nozzles in the hydraulic behavior of the sand filter. The relationship between the passing area through the nozzles and the passing area through the perforated plate is an important design parameter for the reduction of total head losses. A reduced relationship caused by nozzle clogging would disproportionately increase the total head losses in the sand filter

Threshold Selection Criteria for Quantification of Lumbosacral Cerebrospinal Fluid and Root Volumes from MRI

BACKGROUND AND PURPOSE: The high variability of CSF volumes partly explains the inconsistency of anesthetic effects, but may also be due to image analysis itself. In this study, criteria for threshold selection are anatomically defined. METHODS: T2 MR images (n = 7 cases) were analyzed using 3-dimentional software. Maximal-minimal thresholds were selected in standardized blocks of 50 slices of the dural sac ending caudally at the L5-S1 intervertebral space (caudal blocks) and middle L3 (rostral blocks). Maximal CSF thresholds: threshold value was increased until at least one voxel in a CSF area appeared unlabeled and decreased until that voxel was labeled again: this final threshold was selected. Minimal root thresholds: thresholds values that selected cauda equina root area but not adjacent gray voxels in the CSF-root interface were chosen. RESULTS: Significant differences were found between caudal and rostral thresholds. No significant differences were found between expert and nonexpert observers. Average max/min thresholds were around 1.30 but max/min CSF volumes were around 1.15. Great interindividual CSF volume variability was detected (max/min volumes 1.6-2.7). CONCLUSIONS: The estimation of a close range of CSF volumes which probably contains the real CSF volume value can be standardized and calculated prior to certain intrathecal procedures

Most of the Abundant Protein Fractions of Embryonic Cerebrospinal Fluid are Produced Out of the Brain Anlagen

The microenvironment of the central nervous system is important for neuronal function and development. During the early stages of embryo development the cephalic vesicles are filled by embryonic cerebrospinal fluid, a complex fluid containing different protein fractions, which contributes to the regulation of the survival, proliferation and neurogenesis of neuroectodermal stem cells. The protein content of embryonic cerebrospinal fluid from chick and rat embryos at the start of neurogenesis has already been determined. Most of the identified gene products are thought to be involved in the regulation of developmental processes during embryogenesis. However, due to the crucial roles played by embryonic cerebrospinal fluid during brain development, the embryological origin of the gene products it contains remains an intriguing question. According to the literature most of these products are synthesised in embryonic tissues other than the neuroepithelium. In this study we examined the embryological origin of the most abundant embryonic cerebrospinal fluid protein fractions by means of slot-blot analysis and by using several different embryonic and extraembryonic protein extracts, immunodetected with polyclonal antibodies. This first attempt to elucidate their origin is not based on the proteins identified by proteomic methods, but rather on crude protein fractions detected by SDS-PAGE analysis and to which polyclonal antibodies were specifically generated. Despite some of the limitations of this study, i.e. that one protein fraction may contain more than one gene product, and that a specific gene product may be contained in different protein fractions depending on post-translational modifications, our results show that most of the analysed protein fractions are not produced by the cephalic neuroectoderm but are rather stored in the egg reservoir; furthermore, few are produced by embryo tissues, thus indicating that they must be transported from their production or storage sites to the cephalic cavities, most probably via embryonic serum. These results raise the question as to whether the transfer of proteins from these two embryo compartments is regulated at this early developmental stage.

The influence of a certain volume of fluid in the lower tear meniscus on intraocular pressure measurements using the non-contact tonometer

Background: Intraocular pressure (IOP) is the pressure inside the eye that helps to maintain the integrity and the suitable form of the ocular globe. Precise and accurate measures of IOP are needed for the diagnosis as well as follow-up of glaucoma. In daily clinical practice, Goldmann applanation tonometer (GAT) and Non-contact tonometer (NCT) are the most common devices for measuring IOP. A close agreement between these methods has been showed, particularly in normotensive patients and a poor agreement, especially when IOP levels are above the normal range. Ophthalmologists have noticed a poor agreement between NCT and GAT, observing that by using NCT and after comparing with GAT, there is an overestimation of IOP readings, and particularly it occurs when the eyes are tearful. Previous studies investigate the effect of tears in Non-contact tonometer readings by the instillation of artificial tears, concluding in one of the studies that the variation was less than 1mmHg and not clinically significant, in contrast with another study which the increases were sadistically significant. Tear menisci are a thin strip of tear fluid located between the bulbar conjunctiva and the eyelid margins. We think that the overestimation of IOP readings using NCT could be due to the presence of a higher volume of tear in the lower tear meniscus which might cause an optical interference in the optoelectronic applanation monitoring system of this deviceObjectives: To research the influence of a certain volume of fluid in the lower tear meniscus on IOP measurements using the NCT in healthy eyes. Moreover, to investigate the agreement between IOP readings obtained by NCT and GAT in the presence and absence of this volume of fluidMethods: The study design will be transversal for diagnostic tests of repeated measures. We will study patients with no ocular pathology and IOP<21mmHg. It will consist in the measurement of IOP using NCT before and after the instillation of COLIRCUSÍ FLUOTEST, used as a volume of fluid in the lower tear meniscus, to observe if there will be differences using the paired t-test. Moreover, we will take IOP measures by GAT in order to know the agreement between these methods after and before the application of these eyedrops, using the ICC (intraclass correlation coefficient) and the Bland-Altmann method

Extraction and isolation of dictamnine, obacunone and fraxinellone from Dictamnus dasycarpus Turcz. by supercritical fluid extraction and high-speed counter-current chromatography

Supercritical fluid extraction was used to extract active compounds from the Chinese traditional medicinal D. dasycarpus under the pressure of 30 MPa and temperature of 45 ºC. Further separation and purification was established by high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:0.8:1.3:0.9, volume ratio). The separation yielded a total of 47 mg of dictamnine, 24 mg of obacunone and 83 mg of fraxinellone from 1.0 g of the crude extract in one step separation with the purity of 99.2, 98.4 and 99.0%, respectively, as determined by HPLC. The chemical structures of these compounds were identified by ESI-MS, IR, ¹H-NMR and 13C-NMR.

Intraspecific variability of Holostylis reniformis: concentration of lignans, as determined by maceration and supercritical fluid extraction (SFE-CO2), as a function of plant provenance and plant parts

Maceration and supercritical fluid extraction were used to prepare extracts from parts of plants (Holostylis reniformis) collected in two different regions of Brazil. ¹H NMR, HPLC-DAD-ESI/MS, HPLC-DAD, GC-MS, and chemometric techniques were used to analyse lignans in the extracts and showed that yields of SFE-CO2 were less than or equal to those of hexane maceration extracts. These analyses, in conjunction with the concentrations of aliphatic hydrocarbons, fatty acids and their methyl and ethyl derivatives in the extracts, also allowed the chemical composition of parts and provenance of the plant to be differentiated.

Super/subcritical fluid chromatography with packed columns: state of the art and applications

Separations using supercritical fluid chromatography (SFC) with packed columns have been re-discovered and explored in recent years. SFC enables fast and efficient separations and, in some cases, gives better results than high performance liquid chromatography (HPLC). This paper provides an overview of recent advances in SFC separations using packed columns for both achiral and chiral separations. The most important types of stationary phases used in SFC are discussed as well as the most critical parameters involved in the separations and some recent applications.

Pulsatile Blood Flow Simulations in Computed Tomography(CT) Scan-Based and Idealized Geometries of Human Aorta

Blood flow in human aorta is an unsteady and complex phenomenon. The complex patterns are related to the geometrical features like curvature, bends, and branching and pulsatile nature of flow from left ventricle of heart. The aim of this work was to understand the effect of aorta geometry on the flow dynamics. To achieve this, 3D realistic and idealized models of descending aorta were reconstructed from Computed Tomography (CT) images of a female patient. The geometries were reconstructed using medical image processing code. The blood flow in aorta was assumed to be laminar and incompressible and the blood was assumed to be Newtonian fluid. A time dependent pulsatile and parabolic boundary condition was deployed at inlet. Steady and unsteady blood flow simulations were performed in real and idealized geometries of descending aorta using a Finite Volume Method (FVM) code. Analysis of Wall Shear Stress (WSS) distribution, pressure distribution, and axial velocity profiles were carried out in both geometries at steady and unsteady state conditions. The results obtained in thesis work reveal that the idealization of geometry underestimates the values of WSS especially near the region with sudden change of diameter. However, the resultant pressure and velocity in idealized geometry are close to those in real geometry

Simulating Fluid Flow in a Compressed Valve

The objective of the work is to study fluid flow behavior through a pinch valve and to estimate the flow coefficient (KV ) at different opening positions of the valve. The flow inside a compressed valve is more complex than in a straight pipe, and it is one of main topics of interest for engineers in process industry. In the present work, we have numerically simulated compressed valve flow at different opening positions. In order to simulate the flow through pinch valve, several models of the elastomeric valve tube (pinch valve tube) at different opening positions were constructed in 2D-axisymmetric and 3D geometries. The numerical simulations were performed with the CFD packages; ANSYS FLUENT and ANSYS CFX by using parallel computing. The distributions of static pressure, velocity and turbulent kinetic energy have been studied at different opening positions of the valve in both 2D-axisymmetric and 3D experiments. The flow coefficient (KV ) values have been measured at different valve openings and are compared between 2D-axisymmetric and 3D simulation results.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

From Fluid Dynamics to Human Psychology.What Drives Financial Markets Towards Extreme Events

For decades researchers have been trying to build models that would help understand price performance in financial markets and, therefore, to be able to forecast future prices. However, any econometric approaches have notoriously failed in predicting extreme events in markets. At the end of 20th century, market specialists started to admit that the reasons for economy meltdowns may originate as much in rational actions of traders as in human psychology. The latter forces have been described as trading biases, also known as animal spirits. This study aims at expressing in mathematical form some of the basic trading biases as well as the idea of market momentum and, therefore, reconstructing the dynamics of prices in financial markets. It is proposed through a novel family of models originating in population and fluid dynamics, applied to an electricity spot price time series. The main goal of this work is to investigate via numerical solutions how well theequations succeed in reproducing the real market time series properties, especially those that seemingly contradict standard assumptions of neoclassical economic theory, in particular the Efficient Market Hypothesis. The results show that the proposed model is able to generate price realizations that closely reproduce the behaviour and statistics of the original electricity spot price. That is achieved in all price levels, from small and medium-range variations to price spikes. The latter were generated from price dynamics and market momentum, without superimposing jump processes in the model. In the light of the presented results, it seems that the latest assumptions about human psychology and market momentum ruling market dynamics may be true. Therefore, other commodity markets should be analyzed with this model as well.

Predictors of fluid intravasation during operative hysteroscopy: a preplanned prospective observational study with 200 cases

PURPOSE: To verify the predictors of intravasation rate during hysteroscopy.METHODS: Prospective observational study (Canadian Task Force classification II-1). All cases (n=200 women; 22 to 86 years old) were treated in an operating room setting. Considering respective bag overfill to calculate water balance, we tested two multiple linear regression models: one for total intravasation (mL) and the other for absorption rate (mL.min-1). The predictors tested (independent variables) were energy (mono/bipolar), tube patency (with/without tubal ligation), hysterometry (cm), age≤50 years, body surface area (m2), surgical complexity (with/without myomectomy) and duration (min).RESULTS: Mean intravasation was significantly higher when myomectomy was performed (442±616 versus 223±332 mL; p<0.01). In the proposed multiple linear regression models for total intravasation (adjusted R2=0.44; p<0.01), the only significant predictors were myomectomy and duration (p<0.01).In the proposed model for intravasation rate (R2=0.39; p<0.01), only myomectomy and hysterometry were significant predictors (p=0.02 and p<0.01, respectively).CONCLUSIONS: Not only myomectomy but also hysterometry were significant predictors of intravasation rate during operative hysteroscopy.

Peritoneal fluid changes in horses subjected to small colon distension

Intestinal devitalization in cases of small colon obstruction may be difficult to detect based only in clinical signs. The purpose was to serially evaluate blood and peritoneal fluid of horses subjected to small colon distension. Seventeen adult horses were allotted in three groups. In the small colon-distended group (DG, n=7) a surgically-implanted latex balloon was inflated to promote intraluminal small colon distension. In the shamoperated group (SG, n=5), the balloon was implanted but not inflated, and no surgery was done in the control group (CG, n=5). Blood and peritoneal fluid were sampled before and after (6 samples with a 30-minute interval) intestinal obstruction for cytological and biochemical analyses. No significant changes in clinical signs occurred within groups or across time during the experimental period. There were no statistical differences among SG and SG groups in hematologic and blood chemistry variables. Although total protein concentration and lactate dehydrogenase (LDH) activity in peritoneal fluid remained most of the time within reference values during the experimental period in all groups, increases from baseline values were detected in SG and DG groups. Such increases occurred earlier, progressively and with greater magnitude in the DG when compared with the SG (P<0.05). Increases from baselines values were also observed in total nucleated cells and neutrophils counts in the DG (P<0.05). In conclusion, distension of the equine small colon induced progressive subtle increases in total protein and LDH concentrations in the peritoneal fluid during the first hours. Serial evaluation of these variables in peritoneal fluid may be useful for early detection of intestinal devitalization in clinical cases of equine small colon obstruction.