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PubMed2006

From IMRT to IGRT: frontierland or neverland?

The recent enthusiasm for real-time image guidance in radiotherapy (IGRT) is in part due to the commercial availability of advanced on-line imaging technologies. Perhaps more important than its potential to improve conventional radiotherapy, IGRT may lead to a paradigm shift in facilitating hypo-fractionated or single-dose treatment. However, there are uncertainty regarding features and approaches of competing IGRT systems and as to whether a sub-set of the features of an ideal IGRT system would suffice for specific disease sites and clinical applications. Clinical studies are necessary for the quantification of benefit needed for evidence-based medicine.

Dose Fractionation, Radiation↗

PubMed2005

Resolution, quantification and confirmation of betamethasone and dexamethasone in equine plasma by liquid chromatography/tandem mass spectrometry.

This method describes the simultaneous separation, identification, quantification and confirmation of betamethasone (BTM) and dexamethasone (DXM) in equine plasma by liquid chromatography (LC) integrated with multidimensional tandem mass spectrometry. Analytes were directly extracted from equine plasma by methyl tert-butyl ether (MTBE). The residues were reconstituted with sample solvent. LC separation of the analytes was performed on a Hypercarb column using acetonitrile/water/formic acid (95:5:0.5, v/v/v) as the mobile phase. Sample screening, quantification and confirmation were performed in multiple reaction monitoring (MRM) mode. The method was linear over the concentration range of 0.1-75 ng/mL for both analytes. Limit of detection (LOD) was 50 pg/mL and that of quantification (LOQ) was 100 pg/mL for both analytes. The limit of confirmation (LOC) for the presence of BTM or DXM by MRM was 0.5 ng/mL. The intra-and inter-day precisions expressed as coefficient of variation (CV) for quantification of DXM and BTM from 0.1 to 50 ng/mL were less than 7% and the accuracy was in the range of 97-105%. This method is capable of distinguishing BTM from DXM when both analytes are simultaneously present in equine plasma. Measurement uncertainty for both analytes was estimated at less than 16%. The method is rapid, specific, selective, sensitive, simple and reliable. The importance of this method is its usefulness in directly identifying and differentiating BTM from DXM without derivatization.

Animals↗

PubMed2002

Determination of quinolones and fluoroquinolones in fish tissue and seafood by high-performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection.

A reversed-phase high-performance liquid chromatographic method with tandem mass-spectrometric detection was developed and validated for the simultaneous analysis of eight quinolones and fluoroquinolones (oxolinic acid, flumequine, piromidic acid, enrofloxacin, ciprofloxacin, danofloxacin, sarafloxacin and orbifloxacin) in trout tissue, prawns and abalone. The analytes were extracted from homogenised tissue using acetonitrile and the extracts subjected to an automated two-stage solid-phase extraction process involving polymeric reversed-phase and anion-exchange cartridges. Good recoveries were obtained for all analytes and the limit of quantification was 5 microg/kg (10 microg/kg for ciprofloxacin). The limit of detection was 1-3 microg/kg, depending on the analyte and matrix. Confirmation of the identity of a residue was achieved by further tandem mass-spectrometric analysis. A procedure for estimating the uncertainty associated with the measurement is presented.

4-Quinolones↗

PubMed2005

Real-time, fluorescence-based quantitative PCR: a snapshot of current procedures and preferences.

Real-time fluorescence-based quantitative PCR has become established as the benchmark technology for the quantification of nucleic acids, offering an immense choice of protocols, chemistries and instruments. However, whilst there are comparatively few technical problems associated with DNA-targeted quantitative PCR, this is not the case for real-time reverse transcription PCR assays, and there is considerable uncertainty regarding biological or clinical relevance of many real-time reverse transcription PCR results. A survey of working practices of nearly 100 delegates carried out prior to the Third qPCR Symposium held in London, UK, April 25-26, 2005, reveals some of the reasons underlying the variability of reported real-time reverse transcription PCR results. Specifically, the survey reveals extensive interlaboratory variation in assay design, validation and analysis that, together with other dubious practices, are the likely cause for the publication of variable results. These results emphasize the urgent need for the establishment of best practice guidelines for this technology, particularly in the context of its mounting adaptation as a high-throughput clinical diagnostic assay.

DNA Primers↗

PubMed2006

Technique for backward particle tracking in a flow field.

A numerical method to determine the history of particle paths is presented and its application for mixing quantification is illustrated. When more than one source exists in a flow field, the current technique can reveal the particle's identity found in any time and place in the field, by backward tracking its origin. Since the particle position at a preceding time is not known, the velocity vector is implicit. To resolve this uncertainty, a three-stage iterative procedure is developed and implemented. The current particle velocity is multiplied by the time increment and the product is used to estimate the previous time increment particle position. Two velocity matrices are generated on a mesh around the estimated position. The first matrix is the Eulerian velocity field interpolated on the mesh. The second matrix contains velocity vectors that point to the current particle position. A correlation matrix is calculated from the two velocity matrices in order to resolve the actual particle position in the previous time increment. Determination of the time increments' size is performed by checking the maximum of the correlation matrix. The new algorithm was validated using a numerical solution of the confined twin-jet flow at low Reynolds number. This flow performs a Hopf bifurcation at a Reynolds number of about 30, therefore chaotic trajectories might exist in the flow. First, the convergence of the backward particle path to the streamlines in steady flow was demonstrated. Convergence of the particle paths for various time increments was achieved also at the unsteady two-dimensional confined twin-jet flow. When the flow has more than one source, the proposed tracking method can be applied to generate complete and ordered particle source images in any desired position and time in the flow field. Maps of particle sources are used to visualize the flow patterns and the stretched interface between the two fluid sources. Those maps are demonstrated as a powerful tool for mixing quantification and can be implemented also for pollution source detection and many other fluid dynamics applications.

Journal Article↗

PubMed1983

Computer-aided assessment of receptor status in human breast cancer.

Computer-aided analysis of simulated cytosolic estradiol-17 beta receptor binding data using Scatchard and nonlinear Mass Action models showed the latter to be superior. Simulation studies of binding data, incorporating the magnitude and uncertainties associated with inefficiencies of separating free from bound hormone, nonspecific and specific binding, allowed the prediction of uncertainties associated with estimates of receptor content. Realistic values for the minimum detectable receptor concentration that can be distinguished from zero with a given probability were also obtained and may be used as a cutoff value for selection of patients for hormone therapy. This improved reliability in quantification should more clearly define the prognostic value of these receptor assays with respect to adjuvant therapy for primary cancer following surgery or anti-estrogen treatment for recurrent disease, thereby improving the management of breast cancer. Computer simulations and regression analyses were performed on a PDP11/34 using programs written in FORTRAN IV.

Breast Neoplasms↗

PubMed1986

Risk management in chemical safety: some general observations relating to the state of the art.

Risk management for chemical safety begins with judgement and produces arbitrary regulations. In between, technical risk assessment has value in clarifying the behaviour of particular chemical risk systems. Risk quantification can be useful in some cases and quite misleading in others. In no case can it alone be the decisive factor. In the public's perception, chemicals are feared most for potential insidious exposure in the general environment. Risk management then must deal with high system uncertainty and information heavily influenced by value judgements. The technical contribution to risk assessment is reduced, in real terms, as the decision-making scenario expands with its increasing exposure to system 'noise', interference and misinformation. Improved communication in the system requires the use of simplified language. The suitability of risk estimation methodologies must be assessed in terms of general comprehensibility in the management for chemical safety will remain, perhaps always, more of an art than a science, concerned with an interplay of information that can be 'rationalised' with other information that defies such rationalisation.

Communication↗

PubMed2007

Reference tissue quantification of DCE-MRI data without a contrast agent calibration.

The quantification of dynamic contrast-enhanced (DCE) MRI data conventionally requires a conversion from signal intensity to contrast agent concentration by measuring a change in the tissue longitudinal relaxation rate, R(1). In this paper, it is shown that the use of a spoiled gradient-echo acquisition sequence (optimized so that signal intensity scales linearly with contrast agent concentration) in conjunction with a reference tissue-derived vascular input function (VIF), avoids the need for the conversion to Gd-DTPA concentration. This study evaluates how to optimize such sequences and which dynamic time-series parameters are most suitable for this type of analysis. It is shown that signal difference and relative enhancement provide useful alternatives when full contrast agent quantification cannot be achieved, but that pharmacokinetic parameters derived from both contain sources of error (such as those caused by differences between reference tissue and region of interest proton density and native T(1) values). It is shown in a rectal cancer study that these sources of uncertainty are smaller when using signal difference, compared with relative enhancement (15 +/- 4% compared with 33 +/- 4%). Both of these uncertainties are of the order of those associated with the conversion to Gd-DTPA concentration, according to literature estimates.

Biophysical Phenomena↗

PubMed1999

Fractal behavior in quantum statistical physics.

The properties of an ideal gas of spinless particles are investigated by using the path integral formalism. It is shown that the quantum paths exhibit a fractal character which remains unchanged in the relativistic domain provided the creation of new particles is avoided, and the Brownian motion remains the stochastic process associated with the quantum paths. These results are obtained by using a special representation of the Klein-Gordon wave equation. On the quantum paths the relation between velocity and momentum is not the usual one. The mean square value of the velocity depends on the time needed to define the velocity and its value shows the interplay between pure quantum effects and thermodynamics. The fractal character is also investigated starting from wave equations by analyzing the evolution of a Gaussian wave packet via the Hausdorff dimension. Both approaches give the same fractal character in the same limit. It is shown that the time that appears in the path integral behaves like an ordinary time, and the key quantity is the time interval needed for the thermostat to give to the particles a thermal action equal to the quantum of action. Thus, the partition function calculated via the path integral formalism also describes the dynamics of the system for short time intervals. For low temperatures, it is shown that a time-energy uncertainty relation is verified at the end of the calculations. The energy involved in this relation has not a thermodynamic meaning but results from the fact that the particles do not follow the equations of motion along the paths. The results suggest that the density matrix obtained by quantification of the classical canonical distribution function via the path integral formalism should not be totally identical to that obtained via the usual route.

Journal Article↗

PubMed2000

National Research Council report on potable reuse.

In 1998, the United States National Research Council prepared a report assessing the viability of potable reuse. The report concludes that planned indirect potable reuse is a viable application of reclaimed water but should be considered for implementation only after other alternative measures, such as development of new water sources, nonpotable reuse, and water conservation, have been evaluated and determined not to be economically or technically feasible. Although health-effects research has not indicated that there have been any adverse health effects resulting from drinking highly treated reclaimed water, those data are sparse. There are uncertainties associated with assessing the potential health risks of drinking reclaimed water. The report acknowledges that several issues remain unresolved regarding reclaimed water treatment and reliability, microbial and chemical constituents of concern, and water quality and health effects monitoring. Research needs include methods to detect emerging pathogens, identification and quantification of trace organic compounds, development of suitable in vivo toxicological methods, and evaluation of the effectiveness and reliability of multiple treatment barriers. The report also concludes that direct potable reuse is not a viable option to consider at this time.

Conservation of Natural Resources↗

PubMed1997

Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

The capacity of HIV-1 to establish latent infection of CD4+ T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus and viral RNA in plasma and of infectious virus, viral DNA and viral messenger RNA species in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4+ T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4+ T cells with replication-competent integrated provirus (<10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4+ T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4+ T cells and macrophages.

Anti-HIV Agents↗

PubMed2004

The analysis of thyroxine in human serum by an 'exact matching' isotope dilution method with liquid chromatography/tandem mass spectrometry.

A method for the analysis of thyroxine in human serum, utilising 'exact matching' isotope dilution mass spectrometry (IDMS) in combination with liquid chromatography/tandem mass spectrometry (LC/MS/MS), has been developed with a limit of quantification of 0.5 ng g(-1) of thyroxine in human serum. The extraction and clean-up of thyroxine from serum involves an efficient protein-precipitation stage followed by a solid-phase extraction procedure to produce an extract essentially free from interfering compounds. The method is reproducible, with expanded uncertainties of less than 2%, and is relatively fast to perform.

Blood Chemical Analysis↗

PubMed2006

Quantitative determination of absolute organohalogen concentrations in environmental samples by X-ray absorption spectroscopy.

An in situ procedure for quantifying total organic and inorganic Cl concentrations in environmental samples based on X-ray absorption near-edge structure (XANES) spectroscopy has been developed. Cl 1s XANES spectra reflect contributions from all Cl species present in a sample, providing a definitive measure of total Cl concentration in chemically heterogeneous samples. Spectral features near the Cl K-absorption edge provide detailed information about the bonding state of Cl, whereas the absolute fluorescence intensity of the spectra is directly proportional to total Cl concentration, allowing for simultaneous determination of Cl speciation and concentration in plant, soil, and natural water samples. Absolute Cl concentrations are obtained from Cl 1s XANES spectra using a series of Cl standards in a matrix of uniform bulk density. With the high sensitivity of synchrotron-based X-ray absorption spectroscopy, Cl concentration can be reliably measured down to the 5-10 ppm range in solid and liquid samples. Referencing the characteristic near-edge features of Cl in various model compounds, we can distinguish between inorganic chloride (Cl(inorg)) and organochlorine (Cl(org)), as well as between aliphatic Cl(org) and aromatic Cl(org), with uncertainties in the range of approximately 6%. In addition, total organic and inorganic Br concentrations in sediment samples are quantified using a combination of Br 1s XANES and X-ray fluorescence (XRF) spectroscopy. Br concentration is detected down to approximately 1 ppm by XRF, and Br 1s XANES spectra allow quantification of the Br(inorg) and Br(org) fractions. These procedures provide nondestructive, element-specific techniques for quantification of Cl and Br concentrations that preclude extensive sample preparation.

Bromine↗

PubMed1999

Quantifying stenosis in renal arteriograms: a fuzzy syntactic analysis.

The introduction of fuzzy logic improves a system for the automatic quantification of renal artery lesions seen in digital subtraction angiograms. A two-step approach has been followed. An earlier system based on non-fuzzy syntactic analysis provided a clear symbolic description of the stenotic lesions. Although this system worked correctly, it did not take into account the variability and uncertainty inherent to image processing and to knowledge on the reference diameter. This system has been improved by the introduction of fuzzy logic in the representation of the reference diameter. It provides a description of the stenosis in terms of fuzzy quantities. To illustrate the benefits of the fuzzy approach, the results of the two systems have been compared by plotting the differences of an index of variability. It appears that the differences are statistically different when using a two-tailed paired t-test (t = 2.37; p = 0.025). The result shows that the fuzzy approach is better than a non-fuzzy approach in the sense that the index of variability is reduced significantly.

Angiography, Digital Subtraction↗

PubMed2006

Estimation of sucrose esters (E473) in foods using gas chromatography-mass spectrometry.

A method was developed for estimating the content in foods of the emulsifying additive E473, sucrose esters of fatty acids. The analytical approach taken to estimate the complex mixtures that comprise this additive involved, selective solvent extraction of the intact esters using a mixture of tetrahydrofuran and ethyl acetate, alkaline hydrolysis of the esters to liberate sucrose, and then GC-MS measurement of the liberated sucrose using GC-MS after acidic hydrolysis to glucose and fructose and then silylation. The method was developed to aid future estimates of intake of this food additive. The method determines the total sucrose esters content of a food sample and does not attempt to discrimination between individual sucrose esters when present as a mixture in a food sample. A single (average) factor is used to convert the liberated sucrose content into sucrose ester content. The method was applied to analysis of eight different food types (including bakery wares, sugar confectionery, dairy product, margarine, meat pies and a sauce) spiked with 0.5-1% of a mixture of three sucrose esters that spanned the hydrophilic/lipophilic balance (HLB) range 1-16. The limit of quantification was around 50 mg kg-1, which is more than adequate for these additives. The analytical recovery rate was 73-106% with an average of 91%. The precision of the method (RSD) was 6-18% (n = 3-20 for each food type) with an average RSD of 11%. The main analytical uncertainty is the conversion factor used to express sucrose ester content from the amount of sucrose liberated. The method is also applicable to sucroglycerides (E474).

Animals↗

PubMed2004

Modeling expected solute concentration in randomly heterogeneous flow systems with multicomponent reactions.

Many environmental problems require assessment of extensive reaction systems within natural subsurface flow systems exhibiting large physical and biogeochemical heterogeneity. We present an approach to couple stochastic advective-reactive modeling of physical solute transport (LaSAR) with the geochemical model PHREEQC for modeling solute concentrations in systems with variable flow velocity and multicomponent reactions. PHREEQC allows for general and flexible quantification of a multitude of linear and nonlinear geochemical processes, while LaSAR efficiently handles field-scale solute spreading in stochastic heterogeneous flow fields. The combined LaSAR-PHREEQC approach requires very modest computational efforts, thereby allowing a large number of reactive transport problems to be readily assessed and facilitating handling of quantifiable uncertainty in environmental model applications. Computational efficiency and explicit handling of field-scale dispersion without introduction of excessive fluid mixing that may impair model results are general advantages of the LaSAR compared with alternative solute transport modeling approaches. The LaSAR-PHREEQC approach is restricted to steady or unidirectional flow fields, and our specific application examples are limited to homogeneous reaction systems without local or transverse dispersion-diffusion, although these are not general methodological limitations. As a comprehensive application example, we simulate the spreading of acid mine drainage in a groundwater focusing on Zn2+ and including relevant, major-component geochemistry. Model results show that Zn2+ may be substantially attenuated by both sorption and precipitation, with flow heterogeneity greatly affecting expected solute concentrations downstream of the mine waste deposit in both cases.

Adsorption↗

PubMed2003

Differentiation of the halogen content of peat samples using ion chromatography after combustion (TX/TOX-IC).

The proposed method for the differential AOX analysis of water samples was tested for its applicability to differentiate the halogen content of peat samples. For determination of the total and the total organic-bound chlorine, bromine and iodine, peat samples were combusted, and the combustion gases trapped and analyzed by ion chromatography (TX/TOX-IC). The total and the organically bound chlorine, bromine and iodine, respectively, can be determined by two-fold analysis with deviations of around 10%. With respect to chlorine more than a double determination could be required. The limit of quantification is 20 mg kg(-1) for chlorine, 2 mg kg(-1) for bromine and 1 mg kg(-1) for iodine, if 25 mg of peat is combusted. The most crucial step of the analysis is the inorganic halogen removal, which is necessary if the organically bound fraction is determined. However, there are some uncertainties about the complete removal of the inorganic halides from the solid samples. Thus, the values of the organically bound fraction have to be discussed as maximal concentrations. Nevertheless, we suggest that the applied method can be useful as a tool for studying the fate of halogens in soils.

Chromatography↗

PubMed2001

The interaction between risk factors and self-regulation in the development of chronic diseases.

Most established risk factors for chronic disease incidence and mortality from cancer, such as cigarette smoke, alcohol drinking, occupational and environmental hazards and dietary factors, have been shown to vary in their importance in terms of relative risk. In studies which addressed the individual level of behaviour, but also coping and self-regulation, a strong modifying effect of long-lasting hopelessness and helplessness has been found to depend on personality. Autonomy and healthful self-regulation have been defined as the regulation of behaviour in those activities which are carried out in the physical and social environment and lead to stimulated feeling, pleasure, perception of inner and social security, and competence. Persons with such well-regulated behaviour are capable of coping with sources of listlessness, uncertainty and instability. Those individuals showing a well-regulated behaviour arrive at a psycho-neuro-physiological basis for better competence and defence against health hazards. The capability determined by the degree of self-regulation is measured with different instruments. The experience with a questionnaire for the assessment of self-regulation, its quantification and predictive value is presented here. The method of study is by prospective approach, which permits the demonstration of causal associations (promotion, co-causality) and facilitates the experimental approach through intervention. A causal association is likely if the effect of a modifier is not only found in a prospective (observational) follow-up but also if the (experimental) intervention shows an effect. The method of intervention by stimulation of self-regulation is the autonomy training developed by Grossarth-Maticek. Using several examples presenting the method, the modifying effect is shown by referring to four risk factors. If the risk factors are associated with an inhibited self-regulation, then the effect in terms of disease and pathological outcome is stronger. This was shown with the hazardous effects of smoking, alcohol drinking and dietary malnutrition as well as with automobile exhaust. It may be important, for example, whether a person feels self-determined when driving a car for hours but does not need to consume ethanol-containing drinks for feeling well. One's own capability to regulate well over time apparently modulates functions of the body and hence modifies the effects of physical factors. In epidemiological studies, which assess mostly only exogenous factors (so called established risk factors) this evidence has to be considered by including the pertinent data on the relevant questions in each field study.

Alcohol Drinking↗