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Determination of the temperature dependence of water solubilities of polycyclic aromatic hydrocarbons by a generator column-on-line solid-phase extraction-liquid chromatographic method.

An improved dynamic coupled column liquid chromatographic (DCCLC) technique for determining water solubility data of hydrophobic compounds is presented. The technique is based on pumping water through a thermostated generator column in order to generate emulsion-free, saturated aqueous solutions of the compound under study. Through a switching valve system the solute in the aqueous solution is extracted and concentrated by an on-line solid-phase extraction process and subsequently eluted and analyzed by high performance liquid chromatography (fluorescence detection coupled to photodiode array detection). The improvements carried out to the original DCCLC technique have given rise to savings in time for the experimental work and increased sensitivity during the detection and quantification stage. Applicability of the method for studying highly hydrophobic substances is demonstrated by determining water solubility of anthracene and pyrene in the temperature range of 8.9-49.9 and 8.5-32.2 degrees C, respectively. The measured water solubilities are in good agreement with the best available literature data. The method has also been applied to the determination of water solubility of m-terphenyl, 9, 10-dihydrophenanthrene and guaiazulene, in the temperature range of 4.8-49.9, 4.8-25.0, and 4.5-29.9 degrees C, respectively. The uncertainty in the Sw values determined in this work ranged from 0.7% to 4.6%. The experimental water solubility data, as a function of temperature, are fitted to the equation In Sw = A + B/T; where Sw and T are given in mole fraction and Kelvin, respectively.

Chemistry Techniques, Analytical↗

The validation of three human reliability quantification techniques--THERP, HEART and JHEDI: Part III--Practical aspects of the usage of the techniques.

This is the third paper in a series of three dealing with the detailed investigation of the empirical validity of three human reliability assessment (HRA) techniques. The first paper introduced the need for validation and specified the three techniques most requiring validation. The second paper detailed the results of an extensive independent validation experiment. This experimental validation involved 30 UK assessors using the techniques THERP, HEART and JHEDI (10 assessors per technique) to estimate the human error probabilities (HEPs) for 30 nuclear power and reprocessing (NP&R) tasks. The results for all three techniques were positive in terms of significant correlations, and general precision levels of 72% of all HEP estimates within a factor of 10 of the true value (unknown to the assessors). These results lend support to the empirical validity of these techniques in particular, and to HRA in general. However, the results were not all positive. In particular the consistency of usage of the techniques was variable. Additionally, subjects were generally not good at knowing their own uncertainty, i.e. they were not able to accurately predict when they were accurate nor when they were inaccurate. This desirable parameter is known as calibration, and the results from the validation suggested that subjects were not well-calibrated. This paper aims to determine how consistency of usage can be improved and to discern whether certain task types are, in practice, not well-assessed by the techniques, and hence are effectively currently beyond these techniques' abilities. Such information is aimed at aiding the HRA practitioner, or the ergonomist, interested in using these techniques. Recommendations for improving calibration are also discussed in this paper. A subsidiary but important focus of this paper is of a more fundamental nature, and of more general interest to the ergonomist. It concerns the validity of the techniques from an error reduction perspective. Currently these techniques may be used to identify how to reduce error probability, which is generally (in the qualitative sense) within the domain of ergonomics. One major mechanism for HRA-based error reduction is the utilisation of Performance Shaping Factor (PSF) information. This paper considers the validity of these PSF as ergonomics constructs. Drawing results from the validation exercise, it is seen how different PSF can be applied to the same scenario and can result in the same error probability, but will result in different error reduction guidance. It is therefore recommended that error reduction guidance must be based on a composite analysis of the results of the task, error identification and quantification analyses, with most weighting given to the qualitative analyses.

Evaluation Studies as Topic↗

Quantification of airway diameters and 3D airway tree rendering from dynamic hyperpolarized 3He magnetic resonance imaging.

As another step toward extracting quantitative information from hyperpolarized 3He MRI, airway diameters in humans were measured from projection images and multislice images of the lungs. Values obtained were in good agreement with the Weibel lung morphometry model. The measurement of airway caliber can now be achieved without the use of ionizing radiation. Furthermore, it was demonstrated that 3D airway tree renderings could be constructed from the multislice data. Both the measurement of airway diameters and the rendering of 3D airway information hold promise for the clinical assessment of bronchoconstrictive diseases such as asthma and the associated evaluation of treatment effectiveness. Work is being done to address the uncertainties of the manually intensive methods we have developed.

Administration, Inhalation↗

Optical tomographic mapping of cerebral haemodynamics by means of time-domain detection: methodology and phantom validation.

One of the primary applications of diffuse optical imaging is to localize and quantify the changes in the cerebral oxygenation during functional brain activation. Up to now, data from an optical imager are simply presented as a two-dimensional (2D) topographic map using the modified Beer-Lambert law that assumes homogeneous optical properties beneath each optode. Due to the highly heterogeneous nature of the optical properties in the brain, the assumption is evidently invalid, leading to both low spatial resolution and inaccurate quantification in the assessment of haemodynamic changes. To cope with these difficulties, we propose a nonlinear tomographic image reconstruction algorithm for a two-layered slab geometry that uses time-resolved reflected light. The algorithm is based on the previously developed generalized pulse spectrum technique, and implemented within a semi-three-dimensional (3D) framework to conform to the topographic visualization and to reduce computational load. We demonstrate the advantages of the algorithm in quantifying simulated changes in haemoglobin concentrations and investigate its robustness to the uncertainties in the cortical structure and optical properties, as well as the effects of random noises on image quality. The methodology is also validated by experiments using a solid layered phantom.

Algorithms↗

Use of mammography in screening for breast cancer.

Recognizing the enormous impact that quality breast screening mammography can have on reducing breast cancer deaths, we need to determine when women's and physician's perceived restrictions for mammography examination impede the progress of its use for early cancer detection. A uniform system should emphasize valid communication and education between women and their physicians. Women seek to have a voice in their medical treatment. Yet that responsibility has an emotional price. Physicians and patients must decide together on the most appropriate strategies to enhance communication and adopt specific guidelines they will adhere to, to detect and cure early breast cancer. Women must be educated about breast screening mammography, and physicians must increase their efforts to proclaim its importance. Women need be assured the trend is toward using the most modern mammographic techniques. Quality medical care is medicine's purpose and in women's best interest. At present, no other diagnostic method is equivalent to mammography and capable of providing an equivalent impact on improving the detection and cure rate of breast cancer. Despite medical activities designed to reduce uncertainty in medicine, scientific evidence has not provided systematic answers as to the "best" way to approach issues of quality, cost, accessibility, or communication for breast screening mammography. No particular expert opinion or preference prevails for breast screening protocols. What is needed is adoption of a multidisciplinary approach, educating and motivating women and physicians to participate in breast screening activities. With trends directed toward high-volume breast screening operations, low-cost, quality mammography must be available and be impeccably performed. Some activities are natural subjects for financial quantification. It is objectionable to assume, however, that we can accurately place and agree on dollar amounts alone to represent the costs and benefits of screening mammography. The gaps between practices and attitudes about the benefits, risks, and costs of screening mammography suggest that people are not satisfied with the way physicians, women, influential groups, or regulatory agencies are balancing all of the elements. Better communication must exist between physicians and their peer groups involved in performing responsible mammography. Better communication must be achieved between physicians and women to take advantage of the usefulness of quality breast screening mammography. High-quality screening programs must be linked to third-party reimbursement and to legislation, if we are to make a difference. Screening mammography deserves our medical, economic, social, and political attention and action.

Adult↗

Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 2. Emissions.

Accurate and complete data on the global atmospheric releases (emissions) of individual PCB congeners are essential to study source-receptor relationships and contamination patterns in remote areas, such as the Arctic. Information on the anthropogenic emissions may also be useful for the interpretation of measured levels and patterns of atmospheric PCBs. This study builds upon an accompanying paper, presenting an estimate of the global historical production and consumption of 22 PCB congeners (Breivik K, Sweetman A, Pacyna JM, Jones KC. Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 1. Global production and consumption. Sci Total Environ, submitted). Here, a dynamic mass balance model is elaborated, parameterised and applied in an attempt to estimate the historical anthropogenic emissions as a direct result of the widespread usage of PCBs for a period of 70 years. This paper presents details of the mass balance approach, along with a discussion of the major uncertainties. It is shown that the diversity of historical usage, disposal and accidental release pathways makes it an extremely difficult task to bridge the gap between consumption and emissions, resulting in an equally complex and diverse true emission pattern. These results may therefore at best represent order-of-magnitude estimates only and the results in absolute terms should be treated with great caution. In spite of these uncertainties, useful information can still be gained. The results suggest that temperature is an extremely important factor controlling both emission amount as well as the emission pattern of PCBs. In particular, the emissions of the more chlorinated (and persistent) PCB congeners appear to be significantly influenced by (uncontrolled) high-temperature sources. As a consequence, it may prove warranted to undertake further measures to avoid that contaminated materials are subject to elevated temperatures and uncontrolled burning. It is furthermore suggested that efforts should be directed towards a better characterisation and quantification of these potentially important release pathways. In addition, alternative approaches to bridge the gap between consumption and emissions in quantitative terms should be considered in order to improve these estimates.

Arctic Regions↗

IsoBayes: a Bayesian approach for single-isoform proteomics inference.

MOTIVATION: Studying protein isoforms is an essential step in biomedical research; at present, the main approach for analyzing proteins is via bottom-up mass spectrometry proteomics, which return peptide identifications, that are indirectly used to infer the presence of protein isoforms. However, the detection and quantification processes are noisy; in particular, peptides may be erroneously detected, and most peptides, known as shared peptides, are associated to multiple protein isoforms. As a consequence, studying individual protein isoforms is challenging, and inferred protein results are often abstracted to the gene-level or to groups of protein isoforms. RESULTS: Here, we introduce IsoBayes, a novel statistical method to perform inference at the isoform level. Our method enhances the information available, by integrating mass spectrometry proteomics and transcriptomics data in a Bayesian probabilistic framework. To account for the uncertainty in the measurement process, we propose a two-layer latent variable approach: first, we sample if a peptide has been correctly detected (or, alternatively filter peptides); second, we allocate the abundance of such selected peptides across the protein(s) they are compatible with. This enables us, starting from peptide-level data, to recover protein-level data; in particular, we: (i) infer the presence/absence of each protein isoform (via a posterior probability), (ii) estimate its abundance (and credible interval), and (iii) target isoforms where transcript and protein relative abundances significantly differ. We benchmarked our approach in simulations, and in two multi-protease real datasets: our method displays good sensitivity and specificity when detecting protein isoforms, its estimated abundances highly correlate with the ground truth, and can detect changes between protein and transcript relative abundances. AVAILABILITY AND IMPLEMENTATION: IsoBayes is freely distributed as a Bioconductor R package, and is accompanied by an example usage vignette.

Proteomics↗

A method for measuring the size distribution of latex particles by scanning force microscopy.

A methodology has been developed to accurately determine the size distribution of latex particles using the scanning force microscope (SFM). Unlike other workers, who have generally measured the lateral dimensions of monolayers of latex particles using a global quantification method, we have measured the heights of individual latex particles located at the edges of latex monolayers that were immobilised onto mica substrates. In agreement with other work, we noted that the edges of monolayers of latex particles provided stable and reproducible scanning force imaging. Whilst SFM imaging noise, image processing artifacts, tip/sample forces and variations in the mica substrate are sources of measurement error that should not be overlooked, our experience has been that the variation over time of the sensitivity of the Z actuator is the greatest potential uncertainty in determining the heights of latex particles. The methodology that we used requires frequent calibration of the Z actuator of the SFM, typically before and after two or three images, in order to ensure that the uncertainties in the Z sensitivity are known and minimised. This methodology was developed for an SFM instrument that was equipped with open loop piezoelectric actuators following a careful study of the behaviour of those actuators. Using this methodology, we have measured the size distributions of populations of 300-400 latex particles from each of several different latex samples, with the maximum variation in the Z-actuator calibration experienced during the measurement of a sample being less than 2%, often about 1% and occasionally better still. In so doing, we have demonstrated that SFMs equipped with open loop actuators can be used for high confidence quantitative measurements of step heights.

Journal Article↗

The use of clinical trial simulation to support dose selection: application to development of a new treatment for chronic neuropathic pain.

PURPOSE: Pregabalin is being evaluated for the treatment of neuropathic pain. Two phase 2 studies were simulated to determine how precisely the dose that caused a one-point reduction in the pain score could be estimated. The likelihood of demonstrating at least a one-point change for each available dose strength was also calculated. METHODS: A pharmacokinetic-pharmacodynamic (PK/PD) model relating pain relief to gabapentin plasma concentrations was derived from a phase 3 study. The PK component of the model was modified to reflect pregabalin PK. The PD component was modified by scaling the gabapentin concentration-effect relationship to reflect pregabalin potency, which was based on preclincal data. Uncertainty about the potency difference and the steepness of the concentration-response slope necessitated simulating a distribution of outcomes for a series of PK/PD models. RESULTS: Analysis of the simulated data suggested that after accounting for the uncertainty, there was an 80% chance that the dose defining the clinical feature was within 45% of the true value. The likelihood of estimating a dose that was within an acceptable predefined precision range relative to a known value approximated 60%. The minimum dose that should be studied to have a reasonable chance of estimating the dose that caused a one-point change was 300 mg. CONCLUSIONS: Doses that identify predefined response may be imprecisely estimated, suggesting that replication of a similar outcome may be elusive in a confirmatory study. Quantification of this precision provides a rationale for phase 2 trial design and dose selection for confirmatory studies.

Acetates↗

Quantification and modeling of crop losses: a review of purposes.

This review considers the cascade of events that link injuries caused by plant pathogens on crop stands to possible (quantitative and qualitative) crop losses (damage), and to the resulting economic losses. To date, much research has focused on injury control to prevent this cascade of events from occurring. However, this cascade involves a complex succession of components and processes whereby knowledge on crop loss generates entry points for management. Proposed here is a framework linking different types of knowledge on crop loss to a range of decision categories, from tactical to strategic short- or long-term. Important advances in this field are now under way, including a probabilistic treatment of the injury-damage relationship, or analyses of the sources of uncertainty attached to some components of the decision process. Management of injury profiles, rather than individual injuries, and shifts in dimensionality of crop losses are anticipated to contribute to the design of sustainable agricultural systems, and address global issues concerning food security and food safety.

Crops, Agricultural↗

Validated procedure for simultaneous trace level determination of the anti-cancer agent gemcitabine and its metabolite in human urine by high-performance liquid chromatography with tandem mass spectrometry.

A sensitive, accurate and reproducible procedure has been developed for the quantitative determination of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and its metabolite 2',2'-difluorodeoxyuridine (2dFdU) in human urine. The samples (2 mL) were extracted by solid-phase extraction (SPE) and analyzed by reversed-phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS), operating in multiple reaction monitoring (MRM mode). This procedure was validated using 2'-deoxycytidine as internal standard (IS). The urine assay was linear over the range 0-50 microg/L, with a limit of quantification (LLOQ) of 0.2 microg/L for gemcitabine and 1.0 microg/L for the metabolite. The respective limits of detection (LODs) for dFdC and 2dFdU were 0.05 and 0.3 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 8.5 and 12.7% for gemcitabine and 2dFdU, respectively. The overall precision expressed as relative standard deviation (CVr) was always less than 7.1% for both analytes. The recovery of gemcitabine was always greater than 90% with a CVr <6.3%. The measurement uncertainty determined from the validation data assessed the possibility of determining this drug and its metabolite at trace levels in urine, considering that the combined uncertainty of the whole procedure was always less than 30%.

Antimetabolites, Antineoplastic↗

Radiation pneumonitis after breast cancer irradiation: analysis of the complication probability using the relative seriality model.

BACKGROUND: Toxicity of the respiratory system is quite common after radiotherapy of thoracic tumors; breast cancer patients represent one of the groups for which there is also a long expected survival. The quantification of lung tissue response to irradiation is important in designing treatments associated with a minimum of complications and maximum tumor control. METHODS: The study population consisted of 68 patients who received irradiation for breast cancer at Stage II. Radiation pneumonitis was retrospectively assessed on the basis of clinical symptoms and radiological findings. For each patient, a measure of the exposure (i.e., the lung dose-volume histogram [DVH]) and a measure of the outcome was available. Based on these data, a maximum likelihood fitting to the relative seriality model was performed. The uncertainties of the model parameters were calculated and their impact on the dose-response curve was studied. The optimum parameter set was then applied to 5 other patient groups treated for breast cancer, and the normal tissue complication probability (NTCP) was calculated. Each group was individuated by the radiotherapy treatment technique used; the dose distribution in the lung was described by a mean DVH and the incidence of radiation pneumonitis in each group was known. Lung radiosensitivity was assumed to be homogeneous through all of the calculations. RESULTS: The relative seriality model could describe the dataset. The volume effect was found to be relevant in the description of radiation pneumonitis. Age was found to be associated with increased risk of radiation pneumonitis. Two distinct dose-response curves were obtained by splitting the group according to age. The impact of the parameter uncertainties on the dose-response curve was quite large. The parameter set determined could be used predictively on 3 of the 5 patient groups. CONCLUSION: The complication data could be modeled with the relative seriality model. However, further independent datasets, classified according to the same endpoint, must be analyzed before introducing NTCP modeling in clinical practice.

Age Factors↗

Trace analysis and occurrence of anhydroerythromycin and tylosin in influent and effluent wastewater by liquid chromatography combined with electrospray tandem mass spectrometry.

Two wastewater treatment plants (WWTPs) of northern Colorado were monitored for anhydroerythromycin and tylosin. An analytical method has been developed and validated for the trace determination and confirmation of these compounds in the raw influent and final effluent water matrices. This method was used to evaluate the occurrence and fate of these compounds in WWTPs. The method uses solid-phase extraction and liquid chromatography-tandem mass spectrometry with positive electrospray ionization. Detection and quantification was performed using selected reaction monitoring, and a method detection limit of between 0.01 and 0.06 microg/L was obtained. Unequivocal confirmation analysis of analyte identity according to the criteria (based on the use of identification points) of the 2002/657/EC European Commission Decision was possible with satisfactory results. Average recoveries for the two compounds ranged from 89.2+/-9.7% for raw influent to 93.7+/-6.9% for effluent wastewaters. The within-run precision of the assay was found to be always less than 14.1% for the two analytes. The overall precision was always less than 13.7%. The relative uncertainty of the present assay was also evaluated and the combined relative uncertainty ranged from 6.4 to 15.5% over three days of the validation study. These compounds were partially removed in the WWTPs with a removal efficiency of >50%. The measured concentrations in raw influents and effluents ranged from 0.09-0.35 and 0.04-0.12 microg/L for anhydroerythromycin to 0.06-0.18 and ND-0.06 microg/L for tylosin, respectively. The results indicate that WWTP effluents are relevant point sources for residues of these compounds in the aquatic environment. These occurrence results were compared with those in WWTP wastewaters of other countries.

Anti-Bacterial Agents↗

Autoradiographical methods for the assessment of radionuclides in hot particles on filter samples.

Three different autoradiographical methods were tested for detection, localisation and quantification of radionuclides in hot particles deposited on air filters. With all methods, hot particles could successfully be localised on air filters. Two methods, a X-ray film technique and a digital autoradiography technique using a microchannel array detector, have been examined with particles of known activity and with particles on air filter samples of the Chernobyl area to be able to quantify the 90Sr activity in the hot particles consistently. The results obtained in this study suggest that the digital autoradiography system is a very useful tool having a high efficiency with a low measurement uncertainty and allowing short exposure times for extensive measurement tasks.

Air Pollution, Radioactive↗

Computer-assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain.

Magnetic resonance (MR) imaging is the principal imaging technique for the diagnosis of multiple sclerosis (MS). However, quantifying the number and extent of lesions on MR images manually is arduous. The authors have developed a computerized three-dimensional (3D) quantitative system to assist in the identification and analysis of MS lesions in proton-density (PD)- and T2-weighted volumes of the head. The system provides intuitive, interactive operations that allow flexible extraction of information from the data. Use of the system to analyze MR examinations of a phantom containing regular "lesions" showed that accurate (average error, < 0.21 cm3) and precise (10% or better for lesions > 1 cm3) measurements of objects less than 7 cm3 is possible, and that an estimate of the quantization error predicted the uncertainty in the volume. Analysis of four MR examinations of a chronic-progressive MS patient conducted over an 18-month period was performed. A two-dimensional histogram showing the frequency of voxels with particular PD- and T2-weighted intensities revealed a distinct cluster only in histograms of sections that contained lesions. Measurements and 3D volume rendering of lesions clearly showed changes in lesion shape, position, and size.

Algorithms↗

Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla.

A method for quantitative determination of the glutamate (Glu) concentration in human brain using PRESS-based single voxel MR spectroscopy (MRS) at 3 T has been developed and validated by repeatedly analyzing voxels comprising the anterior cingulate cortex (acc) and the left hippocampus (hc) in 40 healthy volunteer brains. At an optimum echo time of 80 ms, the C4 resonance of Glu appears well resolved and separated from major interferents, that is, glutamine and N-acetylaspartate. As a complementary method, a multiple quantum coherence filter sequence for Glu was employed. For quantification of Glu and the principal MRS-visible metabolites as well as for an estimate of the glutamine level, analysis of both types of in vivo spectra was carried out by a time domain-frequency domain method involving prior knowledge obtained from phantom spectra. Using PRESS, coefficients of variation (CV) for Glu concentration were of the order of 10%. When the concentrations were corrected by individual cerebrospinal fluid fractions obtained by segmentation using spm, CVs tended to increase and the correlation coefficients for the two MRS sessions tended to decrease, indicating that this type of correction adds uncertainty to the data. The concentrations of Glu in the two voxels studied were found to be significantly different (11.6 mmol/l in acc, 10.9 mmol/l in hc, P = 0.023) and decrease with age (P < 0.04). These concentrations agreed well with those determined using the quantum coherence filter method although the uncertainty of the latter limits reliable analysis.

Adult↗

The role of echocardiography in the assessment of mechanical dyssynchrony and its importance in predicting response to prognosis after cardiac resynchronization therapy.

The aim of this review is to synthesize the published evidence regarding the benefits of identifying mechanical asynchrony before implantation of biventricular devices, and the role of echocardiography in the identification and quantification of mechanical asynchrony. It summarizes the published studies addressing the several echocardiographic parameters of dyssynchrony that have already proven to predict response to cardiac resynchronization therapy. M-mode echocardiography, Doppler tissue imaging, strain and strain rate imaging, tissue tracking, and 3-dimensional echocardiography parameters of dyssynchrony shown to be able to identify responders are discussed. In addition, the prognostic implication of the identification of mechanical asynchrony before implantation is addressed. A summary of the published evidence of the echocardiographic parameters able to identify patients more likely to derive a prognostic benefit is provided. Finally, it mentions some of the current uncertainties and possible future applications of echocardiographic evaluation of dyssynchrony.

Cardiac Pacing, Artificial↗

High-throughput microwave-digestion procedures to monitor neurotoxic elements in body fluids by means of inductively coupled plasma mass spectrometry.

Microwave (MW) digestion procedures with high sample throughput (simultaneous digestion of 36 or 80 samples) and procedural simplicity (disposable plastic tubes, or re-usable liners with screw-cap) were investigated for their efficiency in routine analyses of biological samples. Different digestion vessel materials were tested for metal leaching/adsorption and thermal resistance: quartz, glass, polyethylene (PE) and polystyrene (PS). For the instrumental quantification of Al, Bi, Cd, Co, Cr, Hg, Mn, Mo, Ni, Pb, Sb, and Tl at ultra-trace levels in urine, serum, and whole blood, sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) was used. The different pretreatment conditions and vessels were evaluated in terms of contamination risk, effective power of detection, accuracy, and precision. Results of analyses of serum, urine and whole blood certified reference materials (CRMs) were fully satisfactory for almost all the analytes. In the case of Hg, Mo, and Tl in serum digested in plastic containers the results were just below the lower limit of uncertainty of the certified range. On the basis of the present data the following MW procedures can be suggested: 1. for urine, digestion with nitric acid at atmospheric pressure in plastic vials; 2. for serum, digestion with nitric acid at atmospheric pressure in glass vessels; and 3. for whole blood, digestion under pressure in quartz tubes. Because of the levels of the procedural blanks, Bi was not measurable at the concentrations expected in human fluids, and Al was accurately detectable in whole blood only.

Humans↗