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Oxygen supplementation for chronic obstructive pulmonary disease patients during air travel.

PURPOSE OF REVIEW: By 2008 it is projected that over two billion people will be travelling by commercial aircraft each year. With an ageing population and treatment improvements, many of these travellers will have lung disease, particularly chronic obstructive pulmonary disease. Current guidelines as to whether a patient requires supplemental oxygen during the flight are based on limited research evidence. Awareness of the increased risk has resulted in recent scientific interest in this area. RECENT FINDINGS: Studies have demonstrated a lack of consistency in international guideline recommendations when performing assessments within the respiratory laboratory. This has led to more specific analysis of patients, including in-flight assessments, the inclusion of exercise stress and more interest in actual cabin pressure conditions. SUMMARY: Commercial air travel is generally safe for patients with chronic obstructive pulmonary disease when their disease is stable. All current guidelines reflect the considerable uncertainty in relation to the clinical circumstances when oxygen prescription during flight is essential. Currently planned flight outcome studies will provide more precise risk quantification.

Aircraft↗

Comparison of seven different scales used to quantify severity of cervical spondylotic myelopathy and post-operative improvement.

Considerable uncertainty exists over the benefit that patients receive from surgical decompressive treatment for cervical spondylotic myelopathy (CSM). Such difficulties might be addressed by accurate quantification of CSM severity as part of a trial determining the outcome of surgery in different patient groups. This study compares the applicability of various existing quantitative severity scales to measurement of CSM severity and the effects on severity of surgical decompression. Scores on the following scales were determined on 100 patients with CSM preoperatively and then again six months following surgical decompression: Odom's Criteria, Nurick grade, Ranawat grade, Myelopathy Disability Index (MDI), Japanese Orthopaedic Association (JOA) Score, European Myelopathy Score (EMS) and Short Form-36 Health Survey (SF36). All the scales showed significant improvement following surgery. However, each had differing qualities of reliability, validity and responsiveness that made them more or less suitable. The MDI showed the greatest sensitivity between different severity levels, sensitivity to operative change and reliability. However, analysis of all the questionnaire scales into components that looked at different aspects of function revealed potential problems with redundancy and a lack of consistency. This prospective observational study provides a rational basis for determining the advantages and disadvantages of different existing scales in measurement of CSM severity and for making adaptations to develop a scale more specifically suited to a comprehensive surgical trial.

Cervical Vertebrae↗

Determination of pesticides and some metabolites in different kinds of milk by solid-phase microextraction and low-pressure gas chromatography-tandem mass spectrometry.

A new analytical method is proposed to determine more than 40 multiclass pesticides in different kinds of processed (whole, skimmed and powdered) and unprocessed (goat and human) milk samples using solid-phase microextraction (SPME). A comparative study between headspace (HS) and direct immersion (DI) was carried out. The effect of milk dilution and the use of acid to reduce the influence of the matrix in DI-SPME mode were also evaluated. DI of the SPME fiber into previously diluted and acidified milk samples achieved the best sensitivity results. Pesticides were determined using low-pressure gas chromatography-tandem mass spectrometry (LP-GC-MS/MS). Both of the selected techniques have been shown to be effective at reduce fat interference and can determine analytes present at very low concentrations (limits of quantification between 0.02 and 1.00 microg L(-1)). Performance characteristics such as linearity, recovery, precision, and lower limits, together with an estimation of the measurement uncertainty using validation data, are presented for each pesticide. All of the pesticides presented recovery rates of between 81 and 110% and precision values lower than 12% (expressed as the relative standard deviation). The overall uncertainty of the method was estimated at three different concentrations (10, 25 and 50 microg L(-1)) and was lower than 25.5% in all cases. The proposed analytical methodology was applied to the analysis of target pesticides in 35 samples: 15 commercial, 3 human and 17 goat milk samples. The metabolite p,p'-DDE was the compound most frequently found in both the breast and goat milk samples, at concentration levels < 20 microg L(-1). However, pesticide residues were not found in any of the other 15 commercial milk samples (skimmed, powdered and whole milk) analyzed.

Animals↗

New developments in automated cytogenetic imaging: unattended scoring of dicentric chromosomes, micronuclei, single cell gel electrophoresis, and fluorescence signals.

The quantification of DNA damage, both in vivo and in vitro, can be very time consuming, since large amounts of samples need to be scored. Additional uncertainties may arise due to the lack of documentation or by scoring biases. Image analysis automation is a possible strategy to cope with these difficulties and to generate a new quality of reproducibility. In this communication we collected some recent results obtained with the automated scanning platform Metafer, covering applications that are being used in radiation research, biological dosimetry, DNA repair research and environmental mutagenesis studies. We can show that the automated scoring for dicentric chromosomes, for micronuclei, and for Comet assay cells produce reliable and reproducible results, which prove the usability of automated scanning in the above mentioned research fields.

Animals↗

[A new quantitative method for quantifying left heart jets by Doppler color imaging].

Quantification of valvular lesions by Color Doppler is based on jet measurements. The aim of this new method is to reduce some of the errors in these measurements: uncertainty in delimiting the colored areas of the jets; spontaneous beat-to-beat variations of the jets entailing interpretative difficulties. The first step was to determine the correlations between the colored areas and previously established single-gated Doppler criteria, retaining spectral criteria to define the borders of the jets, so overcoming some of the limitations of color Doppler. The association of these methods resulted in better discrimination between grades and a better correlation in 45 angiographically controlled mitral and aortic regurgitations than with color Doppler alone. In stenotic lesions, spectral criteria from single-gated associated exploration enabled localisation of the level for planimetry of the section of the jet at its origin visualised by color Doppler. Satisfactory correlations were obtained with the Gorlin surface area in a group of 43 patients with mitral and aortic stenosis. A coefficient of variation of 13 to 14 per cent was found with planimetry of the regurgitant jet in the upstream cardiac chamber. Uni-dimensional measurement decreased this variation to 6 to 11 per cent in the same patients. The largest decrease in variability (6 to 8 per cent) was observed in stenotic and regurgitant lesions with planimetry of the section of jet at its origin performed in held mid-expiration and so this would appear to be the best method. The guide lines and technological improvement associated with the physiopathological information provided by color Doppler should refine the quantification of valvular heart lesions.

Adult↗

Accurate quantification of PAHs in water in the presence of dissolved humic acids using isotope dilution mass spectrometry.

The effect of dissolved humic acids on the recovery of PAHs from water samples has been investigated using a commercially available humic acid preparation as colloid model and a mixture containing the 16 EPA PAHs. The presence of humic acid reduced the extraction efficiency down to between 10 and 75%. An analytical protocol was therefore developed for the accurate determination of PAHs in the presence of humic acids based on isotope dilution mass spectrometry. The procedure compensates for losses due to sorption of PAHs and can be used for the determination of the total PAH concentration in water, i.e. dissolved PAHs plus PAHs adsorbed on colloids. To obtain reliable estimates it is essential to allow a certain time for equilibration between the isotope spike and the aqueous matrix which may vary between 5 and 24 h, in correlation with the water solubility of PAHs. The protocol allows one to recover the 16 PAHs studied at 94 to 105%. The expanded uncertainty of the measurements was 5-7% for all PAHs. Liquid-liquid extraction and solid-phase extraction in combination with the developed isotope dilution protocol performed equally well for the quantification of PAHs from water samples rich in colloidal material.

Adsorption↗

The role of bioinformatics in two-dimensional gel electrophoresis.

Over the last two decades, two-dimensional electrophoresis (2-DE) gel has established itself as the de facto approach to separating proteins from cell and tissue samples. Due to the sheer volume of data and its experimental geometric and expression uncertainties, quantitative analysis of these data with image processing and modelling has become an actively pursued research topic. The results of these analyses include accurate protein quantification, isoelectric point and relative molecular mass estimation, and the detection of differential expression between samples run on different gels. Systematic errors such as current leakage and regional expression inhomogeneities are corrected for, followed by each protein spot in the gel being segmented and modelled for quantification. To assess differential expression of protein spots in different samples run on a series of two-dimensional gels, a number of image registration techniques for correcting geometric distortion have been proposed. This paper provides a comprehensive review of the computation techniques used in the analysis of 2-DE gels, together with a discussion of current and future trends in large scale analysis. We examine the pitfalls of existing techniques and highlight some of the key areas that need to be developed in the coming years, especially those related to statistical approaches based on multiple gel runs and image mining techniques through the use of parallel processing based on cluster computing and the grid technology.

Computational Biology↗

[Statistics and humanities].

PURPOSE: This paper introduces a series of short articles focusing on methodological tools in clinical research, and describes some of the relations existing between medical practice and clinical research. STATE OF THE ART AND MAIN POINTS: The nature of the differences between statistical, epidemiological, and clinical uncertainty, and the lack of knowledge regarding relations between in vivo and in vitro phenomenon are explored. Also, notions of precision of numbers and validity of quantification are discussed and compared with the validity of narrative description of a pathological process, such as it is supposed to actually occur. PERSPECTIVES AND PROJETS: Intrinsic limitations of analytical and observational methods being explained, the usefulness of these same methods in the understanding of a disease or the evaluation of a therapy will be progressively described in more details.

Biomedical Research↗

Interlaboratory studies to determine optimal analytical methods for measuring the oxidation index of UHMWPE.

Fourier transform infrared spectroscopy has emerged as the technique of choice for the quantification of oxidation in ultra-high molecular weight polyethylene used in orthopedic implants. We initiated interlaboratory studies to determine the method of normalization, hence quantification, that provided the highest level of reproducibility across multiple institutions. The goal of this research was to identify optimal normalization methods that minimize the experimental uncertainties associated with interlaboratory reproducibility and intralaboratory repeatability of oxidation index measurements. Test samples were prepared from GUR 4150 HP, gamma irradiated in air, and had a shelf age of two years. Samples were analyzed according to ten oxidation index test methods during two interlaboratory studies, which were conducted in accordance with ASTM E691. Variations in reproducibility and repeatability were evaluated using analysis of variance (ANOVA). The basis of the test methods (peak area-based vs. peak height-based), as well as the normalization method, were both found to be associated with significant differences in reproducibility (p = 0.0006 andp < 0.0001, respectively). Normalization techniques based on the 1370 and 2022cm(-1) peaks areas were found to be the most reproducible methods, and were associated with mean interlaboratory uncertainties of 16.5% and 24.2%, respectively. Repeatability of the test methods was not sensitive to the normalization technique; the mean intralaboratory repeatability for all of oxidation index measurements was found to be 10.2%. The results of this interlaboratory research will be a useful basis for the development of a new oxidation index standard for the orthopedics community.

Biocompatible Materials↗

Does the Rayleigh equation apply to evaluate field isotope data in contaminant hydrogeology?

Stable isotope data have been increasingly used to assess in situ biodegradation of organic contaminants in groundwater. The data are usually evaluated using the Rayleigh equation to evaluate whether isotope data follow a Rayleigh trend, to calculate the extent of contaminant biodegradation, or to estimate first-order rate constants. However, the Rayleigh equation was developed for homogeneous systems while in the subsurface, contaminants can migrate at different velocities due to physical heterogeneity. This paper presents a method to quantify the systematic effect that is introduced by applying the Rayleigh equation to field isotope data. For this purpose, the travel time distribution between source and sampling point is characterized by an analytical solution to the advection-dispersion equation. The systematic effect was evaluated as a function of the magnitude of physical heterogeneity, geometry of the contaminant plume, and degree of biodegradation. Results revealed that the systematic effect always leads to an underestimation of the actual values of isotope enrichment factors, the extent of biodegradation, or first-order rate constants, especially in the dispersion-dominant region representing a higher degree of physical heterogeneity. A substantial systematic effect occurs especially for the quantification of first-order rate constants (up to 50% underestimation of actual rate) while it is relatively small for quantification of the extent of biodegradation (< 5% underestimation of actual degree of biodegradation). The magnitude of the systematic effect is in the same range as the uncertainty due to uncertainty of the analytical data, of the isotope enrichment factor, and the average travel time.

Biodegradation, Environmental↗

The concept of probability in safety assessments of technological systems.

Safety assessments of technological systems, such as nuclear power plants, chemical process facilities, and hazardous waste repositories, require the investigation of the occurrence and consequences of rare events. The subjectivistic (Bayesian) theory of probability is the appropriate framework within which expert opinions, which are essential to the quantification process, can be combined with experimental results and statistical observations to produce quantitative measures of the risks from these systems. A distinction is made between uncertainties in physical models and state-of-knowledge uncertainties about the parameters and assumptions of these models. The proper role of past and future relative frequencies and several issues associated with elicitation and use of expert opinions are discussed.

Equipment Design↗

Frequency of depression after stroke: a systematic review of observational studies.

BACKGROUND AND PURPOSE: Although depression is an important sequelae of stroke, there is uncertainty regarding its frequency and outcome. METHODS: We undertook a systematic review of all published nonexperimental studies (to June 2004) with prospective consecutive patient recruitment and quantification of depressive symptoms/illness after stroke. RESULTS: Data were available from 51 studies (reported in 96 publications) conducted between 1977 and 2002. Although frequencies varied considerably across studies, the pooled estimate was 33% (95% confidence interval, 29% to 36%) of all stroke survivors experiencing depression. Differences in case mix and method of mood assessment could explain some of the variation in estimates across studies. The data also suggest that depression resolves spontaneously within several months of onset in the majority of stroke survivors, with few receiving any specific antidepressant therapy or active management. CONCLUSIONS: Depression is common among stroke patients, with the risks of occurrence being similar for the early, medium, and late stages of stroke recovery. There is a pressing need for further research to improve clinical practice in this area of stroke care.

Antidepressive Agents↗

Acid-induced phase separation of anionic surfactants for the extraction of 1,4-dichlorobenzene from honey prior to liquid chromatography.

The acid-induced liquid-liquid phase separation of anionic surfactants in aqueous solutions and its applicability to cloud point extraction methodology were applied as a tool for the extraction of 1,4-dichlorobenzene (p-DCB) from aqueous samples. p-DCB is extracted into the micelles of sodium dodecane sulfonate (SDSA) in a 4.2 M HCl solution. The micellar phase is separated from the bulk aqueous solution after centrifugation and collected from the surface of the suspension. The micellar extracts are injected into a high-performance liquid chromatographic apparatus and quantified at 225 nm with a reference wavelength of 280 nm. Following the proposed methodology, a preconcentration factor of ca. 160 is achieved (starting from 50 mL solutions) allowing for detection limits at the low microg/L level. Application to honey samples produced detection limits of 2.5 microg/kg with quantification limits of 7.5 microg/kg, while the recoveries of the method ranged from 85% at high concentrations to 95% at lower concentrations of p-DCB. The combined uncertainty of the entire analytical procedure was 4.5% at the concentration level of 30 microg/kg allowing for reliable and reproducible results for the determination of p-DCB at the concentration levels considered as thresholds for EU and U.S. legislation (10 microg/kg).

Analysis of Variance↗

A new automated method for the quantification of mitral regurgitant volume and dynamic regurgitant orifice area based on a normalized centerline velocity distribution using color M-mode and continuous wave Doppler imaging.

Previous echocardiographic techniques for quantifying valvular regurgitation (PISA) are limited by factors including uncertainties in orifice location and hemispheric convergence assumption. Using computational fluid dynamics simulations, we developed a new model for the estimation of orifice diameter and regurgitant volume without the aforementioned assumptions of the PISA technique. Using experimental data obtained from the in vitro flow model we successfully validated our new model. The model output (y) and reference (x) values were in close agreement (y = 0.95x + 0.38, r = 0.96, error = 1.68 +/- 7.54% for the orifice diameter and y = 1.18x - 4.72, r = 0.93, error = 6.48 +/- 16.81% for the regurgitant volume).

Aortic Valve Insufficiency↗

An epidemiologic critique of current microbial risk assessment practices: the importance of prevalence and test accuracy data.

Data deficiencies are impeding the development and validation of microbial risk assessment models. One such deficiency is the failure to adjust test-based (apparent) prevalence estimates to true prevalence estimates by correcting for the imperfect accuracy of tests that are used. Such adjustments will facilitate comparability of data from different populations and from the same population over time as tests change and the unbiased quantification of effects of mitigation strategies. True prevalence can be estimated from apparent prevalence using frequentist and Bayesian methods, but the latter are more flexible and can incorporate uncertainty in test accuracy and prior prevalence data. Both approaches can be used for single or multiple populations, but the Bayesian approach can better deal with clustered data, inferences for rare events, and uncertainty in multiple variables. Examples of prevalence inferences based on results of Salmonella culture are presented. The opportunity to adjust test-based prevalence estimates is predicated on the availability of sensitivity and specificity estimates. These estimates can be obtained from studies using archived gold standard (reference) samples, by screening with the new test and follow-up of test-positive and test-negative samples with a gold standard test, and by use of latent class methods, which make no assumptions about the true status of each sampling unit. Latent class analysis can be done with maximum likelihood and Bayesian methods, and an example of their use in the evaluation of tests for Toxoplasma gondii in pigs is presented. Guidelines are proposed for more transparent incorporation of test data into microbial risk assessments.

Bayes Theorem↗

On the parameterization of the biological effect in a mixed radiation field.

The exposure of astronauts and electronics to the cosmic radiation especially to the particle component pose a major risk to all space flights. Up to now it is not possible to quantify this risk within acceptable limits of accuracy. This uncertainty is not only caused by difficulties in the more or less exact prediction of the incidence of the cosmic radiation but depends also on the problem of the quantification of the radiation field and the correlation of the biological effect. Usually the biological action of a mixed radiation field is estimated as product of the measured dose with an average quality factor, the relative biological efficiency. Because of the large variation in energy and atomic number of the cosmic particles, average values of the quality factor are not precise for risk estimation. A more appropriate way to treat the biological effects of mixed radiation is the concept of particle fluence and action cross section.

Animals↗

Improved diagnostic approaches to infection/sepsis detection.

Sepsis is a major healthcare problem from the perspective of mortality and economics. Advances in diagnostic detection of infection and sepsis have been slow, but recent advances in both soluble biomarker detection and quantitative cellular measurements promise the availability of improved diagnostic techniques. Though the promise of cytokine measurements reaching clinical practice have not matured, procalcitonin levels are currently available in many countries and appear to offer enhanced diagnostic distinction between bacterial and viral etiologies. Cellular diagnostics is poised to enter clinical laboratory practice in the form of neutrophil CD64 measurements, which offer superior sensitivity and specificity to conventional laboratory assessment of sepsis. Neutrophil CD64 expression is negligible in the healthy state. However, it increases as part of the systemic response to severe infection or sepsis. The combination of cellular proteomics, as in the case of neutrophil CD64 quantification, and selected soluble biomarkers of the inflammatory response, such as procalcitonin or triggering receptor expressed on myeloid cells (TREM)-1, is predicted to remove the current subjectivity and uncertainty in the diagnosis and therapeutic monitoring of infection and sepsis.

Biomarkers↗

Estimate of uncertainty of measurement from a single-laboratory validation study: application to the determination of lead in blood.

BACKGROUND: Lead is an environmental pollutant, and human exposure is assessed by monitoring lead concentrations in blood. Because the main source of environmental exposure has been the use of leaded gasoline, its phase-out has led to decreased lead concentrations in the general population. Therefore, validated analytical methods for the determination of lower lead concentrations in blood (<150 microg/L) are needed. In addition, new ISO standards require that laboratories determine and specify the uncertainty of their results. METHODS: We validated a method to determine lead in blood at concentrations up to 150 microg/L by electrothermal atomic absorption spectrometry with Zeeman background correction according to EURACHEM guidelines. Blood samples were diluted (1:1 by volume) with 2 mL/L Triton X-100. NH4H2PO4 (5 g/L) and Mg(NO3)2 (0.5 g/L) were used as modifiers. Matrix-matched standards were used for calibration. RESULTS: We determined the limits of detection (3.1 microg/L) and quantification (9.4 microg/L). Repeatability and intermediate imprecision within the range 35-150 microg/L were <5.5% and <6.0%, respectively. We assessed trueness by use of certified reference materials, by recovery tests, and by comparison with target values of other reference materials (candidate external quality assessment samples). The expanded uncertainty ranged from 20% to 16% (with a confidence level of 95%) depending on concentration. CONCLUSIONS: This study provides a working example of the estimate of uncertainty from method performance data according to the EURACHEM/CITAC guidelines. The estimated uncertainty is compatible with quality specifications for the analysis of lead in blood adopted in the US and the European Union.

Environmental Pollutants↗