Genotoxicity investigation of a cyanobacterial toxin, cylindrospermopsin

Cylindrospermopsin (CYN), a potent cyanobacterial hepatotoxin produced by Cylindrospermopsis raciborskii and other cyanobacteria, is regularly found in water supplies in many parts of the world, and has been associated with the intoxication of humans and livestock. In this study, Balb/c mice were injected via the intraperitoneal (IP) route with a single dose of 0.2 mg/kg CYN. Animals were sacrificed at 6, 12, 24, 48 and 72 It. DNA was isolated from the mouse livers, and examined for strand breakage by alkaline gel electrophoresis (pH 12). Significant DNA strand breakage was observed in the mouse liver exposed to CYN, suggesting that induction of DNA strand breakage is probably one of the key mechanisms for CYN genotoxicity. (C) 2002 Elsevier Science Ltd. All rights reserved.

A pilot study of the manual force levels required to produce manipulation induced hypoalgesia

Objective. A pilot investigation of the influence of different force levels on a treatment technique's hypoalgesic effect. Design. Randomised single blind repeated measures. Background. Optimisation of such biomechanical treatment variables as the point of force application, direction of force application and the level of applied manual force is classically regarded as the basis of best practice manipulative therapy. Manipulative therapy is frequently used to alleviate pain, a treatment effect that is often studied directly in the neurophysiological, paradigm and seldom in biomechanical research. The relationship between the level of force applied by a technique (e.g. biomechanics) and its hypoalgesic effect was the focus of this study. Method. The experiment involved the application of a lateral glide mobilisation with movement treatment technique to the symptomatic elbow of six subjects with lateral epicondylalgia. Four different levels of force, which were measured with a flexible pressure-sensing mat, were randomly applied while the subject performed a pain free grip strength test. Results. Standardised manual force data varied from 0.76 to 4.54 N/cm, lower-upper limits 95 Cl, respectively. Pain free grip strength expressed as a percentage change from pre-treatment values was significantly greater with manual forces beyond 1.9 N/cm (P = 0.014). Conclusions. This study, albeit a pilot, provides preliminary evidence that in terms of the hypoalgesic effect of a mobilisation with movement treatment technique, there may be an optimal level of applied manual force.

A four-stage index 2 Diagonally Implicit Runge-Kutta method

High index Differential Algebraic Equations (DAEs) force standard numerical methods to lower order. Implicit Runge-Kutta methods such as RADAU5 handle high index problems but their fully implicit structure creates significant overhead costs for large problems. Singly Diagonally Implicit Runge-Kutta (SDIRK) methods offer lower costs for integration. This paper derives a four-stage, index 2 Explicit Singly Diagonally Implicit Runge-Kutta (ESDIRK) method. By introducing an explicit first stage, the method achieves second order stage calculations. After deriving and solving appropriate order conditions., numerical examples are used to test the proposed method using fixed and variable step size implementations. (C) 2001 IMACS. Published by Elsevier Science B.V. All rights reserved.

Investigation of hip abductor activation in subject with clinical unilateral hip osteoarthritis

Objectives: (a) To compare the magnitude of gluteus medius and tensor fascia lata activation between a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults. (b) To compare the magnitude of activation of the gluteus medius and tensor fascia lata between sides in a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults. Methods: 19 subjects with clinical unilateral hip osteoarthritis and 19 healthy controls were investigated. The subjects performed a stepping task during which recordings were obtained using surface electromyograms from the hip abductors, and kinetic data were obtained from a dual force platform. Results: Subjects with clinical hip osteoarthritis had higher gluteus medius activation than the healthy older adults (p=0.037). In addition, there were no differences in the magnitude of gluteus medius activation between the sides (p=0.733). There was no difference in the force platform data between the groups (p=0.078). Conclusions: The increased magnitude of gluteus medius activation in the group with hip osteoarthritis is evidence of a muscular dysfunction associated with hip disease. This has implications for the progressive nature of the disease and for its conservative management.

Application of a simplified method based on regular regime approach to determine the effective moisture diffusivity of mixture of low molecular weight sugars and maltodextrin during desorption

The binary diffusivities of water in low molecular weight sugars; fructose, sucrose and a high molecular weight carbohydrate; maltodextrin (DE 11) and the effective diffusivities of water in mixtures of these sugars (sucrose, glucose, fructose) and maltodextrin (DE 11) were determined using a simplified procedure based on the Regular Regime Approach. The effective diffusivity of these mixtures exhibited both the concentration and molecular weight dependence. Surface stickiness was observed in all samples during desorption, with fructose exhibiting the highest and maltodextrin the lowest. (C) 2002 Elsevier Science Ltd. All rights reserved.

Comparison of an ELISA and an LC/MS/MS method for measuring tacrolimus concentrations and making dosage decisions in transplant recipients

This study compared an enzyme-linked immunosorbent assay (ELISA) to a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for measurement of tacrolimus concentrations in adult kidney and liver transplant recipients, and investigated how assay choice influenced pharmacokinetic parameter estimates and drug dosage decisions. Tacrolimus concentrations measured by both ELISA and LC/MS/MS from 29 kidney (n = 98 samples) and 27 liver (n = 97 samples) transplant recipients were used to evaluate the performance of these methods in the clinical setting. Tacrolimus concentrations measured by the two techniques were compared via regression analysis. Population pharmacokinetic models were developed independently using ELISA and LC/MS/MS data from 76 kidney recipients. Derived kinetic parameters were used to formulate typical dosing regimens for concentration targeting. Dosage recommendations for the two assays were compared. The relation between LC/MS/MS and ELISA measurements was best described by the regression equation ELISA = 1.02 . (LC/MS/MS) + 0.14 in kidney recipients, and ELISA = 1.12 . (LC/MS/MS) - 0.87 in liver recipients. ELISA displayed less accuracy than LC/MS/MS at lower tacrolimus concentrations. Population pharmacokinetic models based on ELISA and LC/MS/MS data were similar with residual random errors of 4.1 ng/mL and 3.7 ng/mL, respectively. Assay choice gave rise to dosage prediction differences ranging from 0% to 30%. ELISA measurements of tacrolimus are not automatically interchangeable with LC/MS/MS values. Assay differences were greatest in adult liver recipients, probably reflecting periods of liver dysfunction and impaired biliary secretion of metabolites. While the majority of data collected in this study suggested assay differences in adult kidney recipients were minimal, findings of ELISA dosage underpredictions of up to 25% in the long term must be investigated further.

Linguistic evaluation method for the environmental assessment of infrastructure projects

A soft linguistic evaluation method is proposed for the environmental assessment of physical infrastructure projects based on fuzzy relations. Infrastructure projects are characterized in terms of linguistic expressions of 'performance' with respect to factors or impacts and the 'importance' of those factors/impacts. A simple example is developed to illustrate the method in the context of three road infrastructure projects assessed against five factors/impacts. In addition, a means to include hard or crisp factors is presented and illustrated with respect to a sixth factor.

Assessing clinical reasoning: a method to monitor its development in a PBL curriculum

The aim of this study was to develop and trial a method to monitor the evolution of clinical reasoning in a PBL curriculum that is suitable for use in a large medical school. Termed Clinical Reasoning Problems (CRPs), it is based on the notion that clinical reasoning is dependent on the identification and correct interpretation of certain critical clinical features. Each problem consists of a clinical scenario comprising presentation, history and physical examination. Based on this information, subjects are asked to nominate the two most likely diagnoses and to list the clinical features that they considered in formulating their diagnoses, indicating whether these features supported or opposed the nominated diagnoses. Students at different levels of medical training completed a set of 10 CRPs as well as the Diagnostic Thinking Inventory, a self-reporting questionnaire designed to assess reasoning style. Responses were scored against those of a reference group of general practitioners. Results indicate that the CRPs are an easily administered, reliable and valid assessment of clinical reasoning, able to successfully monitor its development throughout medical training. Consequently, they can be employed to assess clinical reasoning skill in individual students and to evaluate the success of undergraduate medical schools in providing effective tuition in clinical reasoning.

Experimental investigation of contaminant transport in coastal groundwater

Contaminant transport in coastal aquifers is of increasing interest since, with the development of coastal areas, contaminants from surface sources may enter coastal aquifers and pollute the groundwater flow. Coastal groundwater flow is complicated because of the presence of a freshwater-saltwater diffusion zone and the tidal variation of sea level at the seaward end. This paper investigates experimentally the behaviour of contaminant plumes with different densities in an unconfined coastal aquifer. Experiments were performed in a flow tank filled with glass beads as the porous medium. Results show that the dense contaminant has a more diffusive front than the less dense one in the seaward direction towards the coastline. The plume becomes more diffusive when it travels closer to the saltwater interface. On the contrary, the less dense contaminant presents a relatively sharp outline. It tends to migrate in the upper portion of the aquifer and exits in a concentrated manner over a small discharge area at the coastline, not further seaward under the sea. Non-dimensional parameters show that instabilities occur in our experiments for a density difference of 1.2% or larger between the contaminant and the ambient water. The experimental results provide guidance for field monitoring and numerical modelling. (C) 2002 Elsevier Science Ltd. All rights reserved.

Application of the maximum entropy method to the (2 + 1)D four-fermion model

We investigate spectral functions extracted using the maximum entropy method from correlators measured in lattice simulations of the (2+1)-dimensional four-fermion model. This model is particularly interesting because it has both a chirally broken phase with a rich spectrum of mesonic bound states and a symmetric phase where there are only resonances. In the broken phase we study the elementary fermion, pion, sigma, and massive pseudoscalar meson; our results confirm the Goldstone nature of the π and permit an estimate of the meson binding energy. We have, however, seen no signal of σ→ππ decay as the chiral limit is approached. In the symmetric phase we observe a resonance of nonzero width in qualitative agreement with analytic expectations; in addition the ultraviolet behavior of the spectral functions is consistent with the large nonperturbative anomalous dimension for fermion composite operators expected in this model.

Investigation of ultrasonic properties of PAG and MAGIC polymer gel dosimeters

Ultrasonic speed of propagation and attenuation were investigated as a function of absorbed radiation dose in PAG and MAGIC polymer gel dosimeters. Both PAG and MAGIC gel dosimeters displayed a dependence of ultrasonic parameters on absorbed dose with attenuation displaying significant changes in the dose range investigated. The ultrasonic attenuation dose sensitivity at 4 MHz in MAGIC gels was determined to be 4.7 +/- 0.3 dB m(-1) Gy(-1) and for PAG 3.9 +/- 0.3 dB m(-1) Gy(-1). Ultrasonic speed dose sensitivities were 0.178 +/- 0.006 m s(-1) Gy(-1) for MAGIC gel and -0.44 +/- 0.02 m s(-1) Gy(-1) for PAG. Density and compressional elastic modulus were investigated to explain the different sensitivities of ultrasonic speed to radiation for PAG and MAGIC gels. The different sensitivities were found to be due to differences in the compressional elastic modulus as a function of dose for the two formulations. To understand the physical phenomena underlying the increase in ultrasonic attenuation with dose, the viscoelastic properties of the gels were studied. Results suggest that at ultrasonic frequencies, attenuation in polymer gel dosimeters is primarily due to volume viscosity. It is concluded that ultrasonic attenuation significantly increases with absorbed dose. Also, the ultrasonic speed in polymer gel dosimeters is affected by changes in dosimeter elastic modulus that are likely to be a result of polymerization. It is suggested that ultrasound is a sufficiently sensitive technique for polymer gel dosimetry.

MR image-based measurement of rates of change in volumes of brain structures. Part 1: Method and validation

A detailed analysis procedure is described for evaluating rates of volumetric change in brain structures based on structural magnetic resonance (MR) images. In this procedure, a series of image processing tools have been employed to address the problems encountered in measuring rates of change based on structural MR images. These tools include an algorithm for intensity non-uniforniity correction, a robust algorithm for three-dimensional image registration with sub-voxel precision and an algorithm for brain tissue segmentation. However, a unique feature in the procedure is the use of a fractional volume model that has been developed to provide a quantitative measure for the partial volume effect. With this model, the fractional constituent tissue volumes are evaluated for voxels at the tissue boundary that manifest partial volume effect, thus allowing tissue boundaries be defined at a sub-voxel level and in an automated fashion. Validation studies are presented on key algorithms including segmentation and registration. An overall assessment of the method is provided through the evaluation of the rates of brain atrophy in a group of normal elderly subjects for which the rate of brain atrophy due to normal aging is predictably small. An application of the method is given in Part 11 where the rates of brain atrophy in various brain regions are studied in relation to normal aging and Alzheimer's disease. (C) 2002 Elsevier Science Inc. All rights reserved.

A design method for superconducting MRI magnets with ferromagnetic material

The emphasis of this work is on the optimal design of MRI magnets with both superconducting coils and ferromagnetic rings. The work is directed to the automated design of MRI magnet systems containing superconducting wire and both `cold' and `warm' iron. Details of the optimization procedure are given and the results show combined superconducting and iron material MRI magnets with excellent field characteristics. Strong, homogeneous central magnetic fields are produced with little stray or external field leakage. The field calculations are performed using a semi-analytical method for both current coil and iron material sources. Design examples for symmetric, open and asymmetric clinical MRI magnets containing both superconducting coils and ferromagnetic material are presented.

Finite difference time domain (FDTD) method for modeling the effect of switched gradients on the human body in MRI

Numerical modeling of the eddy currents induced in the human body by the pulsed field gradients in MRI presents a difficult computational problem. It requires an efficient and accurate computational method for high spatial resolution analyses with a relatively low input frequency. In this article, a new technique is described which allows the finite difference time domain (FDTD) method to be efficiently applied over a very large frequency range, including low frequencies. This is not the case in conventional FDTD-based methods. A method of implementing streamline gradients in FDTD is presented, as well as comparative analyses which show that the correct source injection in the FDTD simulation plays a crucial rule in obtaining accurate solutions. In particular, making use of the derivative of the input source waveform is shown to provide distinct benefits in accuracy over direct source injection. In the method, no alterations to the properties of either the source or the transmission media are required. The method is essentially frequency independent and the source injection method has been verified against examples with analytical solutions. Results are presented showing the spatial distribution of gradient-induced electric fields and eddy currents in a complete body model.