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The effects of supplementation of the diet with highly palatable foods upon energy balance in the rat.

Full energy balance studies have been performed for 9 weeks on four groups of four adult female rats housed in a continuously running indirect calorimeter; for four weeks two of the groups received highly palatable foods in addition to a standard pelleted diet. A further sixteen groups, of which eight received the palatable foods, provided additional carcass composition data. All practicable precautions were taken to measure energy exchange accurately. Comparison of 'start-to-finish' apparent energy balance with carcass composition changes showed a systematic error of approx. +3% of energy throughput. This was most probably caused by losses of energy in food and excreta, which led to over-estimation of energy intake. Variations among individual balance periods added a standard error of approx. +/- 1%: the source of error here was probably imperfect matching of animals analysed at intermediate stages. The rats offered the palatable foods increased their metabolizable energy (m.e.) intake by 106 kJ/day, 51% of the control groups' intake, in the first week of supplementation. Over the whole 4 weeks of supplementation the increase was 64 kJ/day, or 31%. Withdrawal of the palatable foods led to an immediate fall in intake to about two-thirds of control level, and a return to control level over the next 2-3 weeks. Energy expenditure rose more slowly than intake, reaching a fairly steady level ca. 5 days after introduction of the palatable foods. Expenditure was then ca. 22 kJ/day above control level; an increase of 12% above control expenditure or, allowing for systematic and random errors, 33-37% of the additional m.e. intake. Expenditure returned to control level over the 2 weeks after ceasing supplementation. The experimental groups gained weight at a declining rate throughout the period of supplementation. The gain in live body weight at the end was ca. 32 g, but this comprised a carcass weight gain of 37 g and a loss of 5 g gastrointestinal tract contents. The carcass weight gain comprised 27 g fat (i.e. ca. 70% of the weight gained), 9 g lean tissue and 1 g additional water. The gain of carcass energy was 1100 kJ. There was a small increase in body length, an increase in liver weight, and an increase in the weight of the interscapular brown adipose tissue pad. Regression analysis showed that the increase in the weight of the interscapular brown adipose tissue pad reflected the increase in total body fat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Water flux in animals: analysis of potential errors in the tritiated water method.

Laboratory studies indicate that tritiated water measurements of water flux are accurate to within -7 to +4% in mammals, but errors are larger in some reptiles. However, under conditions that can occur in field studies, errors may be much greater. Influx of environmental water vapor via lungs and skin can cause errors exceeding +/- 50% in some circumstances. If water flux rates in an animal vary through time, errors approach +/- 15% in extreme situations, but are near +/- 3% in more typical circumstances. Errors due to fractional evaporation of tritiated water may approach -9%. This error probably varies between species. Use of an inappropriate equation for calculating water flux from isotope data can cause errors exceeding +/- 100%. The following sources of error are either negligible or avoidable: use of isotope dilution space as a measure of body water volume, loss of nonaqueous tritium bound to excreta, binding of tritium with nonaqueous substances in the body, radiation toxicity effects, and small analytical errors in isotope measurements. Water flux rates measured with tritiated water may be expected to be within +/- 10% of actual flux rates in most situations.

Animals↗

Statistical power in the detection of matrix effects.

Matrix-induced bias can adversely affect the performance evaluation a clinical laboratory receives on proficiency testing results. Therefore, it is vital that matrix effects from a matrix-biased system are detected and that laboratories using these systems are not falsely penalized on their proficiency testing results. The College of American Pathologists has developed an experimental protocol to test whether an observed bias is, in fact, due to the proficiency testing sample matrix rather than true performance or calibration problems. The probability of detecting a matrix effect using this protocol given a matrix-biased system is defined as statistical power. Five parameters are known to affect the probability of detection: (1) size of the bias in the proficiency testing material, (2) lack of fit coefficient of variation-natural variation in patient samples used to define the relationship between the test and reference methods, (3) pure error coefficient of variation-random variation in the test method, (4) the number of fresh patient samples, and (5) the number of replicates for each sample. The level of significance of the statistical test will also affect the probability of detection. Power curves are generated to show the effect these five parameters have on the determination of power. With the exception of bias, power is most influenced by the components of variance, lack of fit (nonlinear), and pure (random) error. Of these two components, the lack of fit error, which represents an uncontrollable source of error, is usually more influential than pure error, which can be reduced by a larger number of replicates. A large increase in power will result from an increase of fresh patient samples from 10 to 20, and a moderate increase in power will result from an increase of fresh patient samples from 20 to 40; no noticeable increase in power is seen with greater than 40 fresh patient samples. Large increases in power were observed for increases in the number of replicates per sample from one to two, two to three, and three to five. To markedly increase power further, 10 replicates would have to be assayed.

Bias↗

Use of biomarkers in epidemiologic studies: minimizing the influence of measurement error in the study design and analysis.

The inclusion of biomarkers measured on the continuous scale, such as endogenous sex hormones or antioxidant levels, has become common in epidemiologic studies, and introduces additional sources of error that are specific to biomarkers. This includes error associated with specimen collection, processing, and storage; laboratory error (both within and between batch); and variability in the biomarker levels over time within an individual. In this review, we discuss and recommend study design and analytic strategies to deal with these sources of measurement error. In particular we describe methods to prevent or minimize some sources of error through appropriate sample collection and storage, communication with the laboratory, proper batching of samples, and participant matching. We also discuss how to quantify error related to biomarkers, focusing on issues of quality control, pilot studies, and how to measure within-person stability over time. Further, we discuss analytic issues for dealing with laboratory and within-person variability. Finally we recommend that journals standardize the reporting of biomarker assays in scientific manuscripts.

Biomarkers↗

In vitro stress shielding measurements can be affected by large errors.

Hip prostheses and other implantable devices for the proximal femur are tested experimentally to study their effects on load transfer. We report on some experimental errors (related to the load simulation) that can undermine the reliability of strain measurements. A first source of error is that of overconstraining the setup. This situation makes it impossible to control or even determine the force values. The second source of error is related to geometric alterations induced by surgery, which modify the lever arms and thus the loading system. Two options are available to compensate for a geometric alteration: either applying the same system of forces or the same resultant bending moment to the implanted femur. The errors that arise if these parameters are not controlled can make it impossible to determine if one device performs better or worse than another.

Biomechanical Phenomena↗

Human movement analysis using stereophotogrammetry. Part 4: assessment of anatomical landmark misplacement and its effects on joint kinematics.

Estimating the effects of different sources of error on joint kinematics is crucial for assessing the reliability of human movement analysis. The goal of the present paper is to review the different approaches dealing with joint kinematics sensitivity to rotation axes and the precision of anatomical landmark determination. Consistent with the previous papers in this series, the review is limited to studies performed with video-based stereophotogrammetric systems. Initially, studies dealing with estimates of precision in determining the location of both palpable and internal anatomical landmarks are reviewed. Next, the effects of anatomical landmark position uncertainty on anatomical frames are shown. Then, methods reported in the literature for estimating error propagation from anatomical axes location to joint kinematics are described. Interestingly, studies carried out using different approaches reported a common conclusion: when joint rotations occur mainly in a single plane, minor rotations out of this plane are strongly affected by errors introduced at the anatomical landmark identification level and are prone to misinterpretation. Finally, attempts at reducing joint kinematics errors due to anatomical landmark position uncertainty are reported. Given the relevance of this source of errors in the determination of joint kinematics, it is the authors' opinion that further efforts should be made in improving the reliability of the joint axes determination.

Biomechanical Phenomena↗

Optimal design of a two-sample test for assessing [125I]iothalamate plasma clearance in peritoneal dialysis.

BACKGROUND: Plasma clearance of a tracer in peritoneal dialysis (PD) can be used to assess treatment adequacy without labour-intensive fluid collections. Accuracy and precision of plasma clearance estimates by the bolus injection technique depend on the estimation accuracy of the area under the concentration curve and the measurement precision of plasma concentrations. The first source of error is due to oversimplified, e.g. monoexponential, descriptions of plasma disappearance curves. The second source of error arises from the propagation of measurement errors to the parameter estimates. METHODS: The theoretical bias of parameter estimates is determined first for a monoexponential approximation of a biexponential disappearance curve and as a function of the first sampling time at which mixing is still incomplete. The precision of plasma clearance estimates, expressed as coefficient of variation, is then described as a function of the experimental variables and of the standard deviation of measurement error. This allows the determination of the optimal two-sample test that yields most precise estimates of plasma clearance. RESULTS: The optimal two-sample schedules for assessing plasma clearance of [125I]iothalamate in PD patients vary between subjects according to individual clearances and distribution volumes. Our results suggest collecting the first sample 120 min, and the second 2-4 days, after the bolus injection. CONCLUSIONS: The proposed two-sample test is suitable to be used in clinical routine for assessment of adequacy of PD treatment but requires a priori estimation of individual tracer kinetics and of laboratory measurement errors. A fixed design with the first sample taken after 120 min and the second sample collected 3 days after the bolus injection should yield the best performance.

Adult↗

Assessment of genome-wide protein function classification for Drosophila melanogaster.

The functional classification of genes on a genome-wide scale is now in its infancy, and we make a first attempt to assess existing methods and identify sources of error. To this end, we compared two independent efforts for associating proteins with functions, one implemented by FlyBase and the other by PANTHER at Celera Genomics. Both methods make inferences based on sequence similarity and the available experimental evidence. However, they differ considerably in methodology and process. Overall, assuming that the systematic error across the two methods is relatively small, we find the protein-to-function association error rate of both the FlyBase and PANTHER methods to be <2%. The primary source of error for both methods appears to be simple human error. Although homology-based inference can certainly cause errors in annotation, our analysis indicates that the frequency of such errors is relatively small compared with the number of correct inferences. Moreover, these homology errors can be minimized by careful tree-based inference, such as that implemented in PANTHER. Often, functional associations are made by one method and not the other, indicating that one of the greatest challenges lies in improving the completeness of available ontology associations.

Animals↗

Application of the complex multivariate normal distribution to crystallographic methods with insights into multiple isomorphous replacement phasing.

Probabilistic methods involving maximum-likelihood parameter estimation have become a powerful tool in computational crystallography. At the centre of these methods are the relevant probability distributions. Here, equations are developed based on the complex multivariate normal distribution that generalize the distributions currently used in maximum-likelihood model and heavy-atom refinement. In this treatment, the effects of various sources of error in the experiment are considered separately and allowance is made for correlations among sources of error. The multivariate distributions presented are closely related to the distributions previously derived in ab initio phasing and can be applied to many different aspects of a crystallographic structure-determination process including model refinement, density modification, heavy-atom phasing and refinement or combinations of them. The underlying probability distributions for multiple isomorphous replacement are re-examined using these techniques. The re-analysis requires the underlying assumptions to be made explicitly and results in a variance term that, unlike those previously used for maximum-likelihood multiple isomorphous replacement phasing, is expressed explicitly in terms of structure-factor covariances. Test cases presented show that the newly derived multiple isomorphous replacement likelihood functions perform satisfactorily compared with currently used programs.

Crystallography, X-Ray↗

Evaluation and management of upper urinary tract obstruction in infancy and childhood.

Our clinical experience over the past 5 years would suggest that both the diuretic renogram and the Whitaker study permit an objective and quantitative assessment of urinary obstruction. The diagnostic accuracy of both studies exceeds 90 per cent, although neither study has proved to be infallible. Both have potential sources of error that must be monitored carefully if their reliability is to be maximized. Potential sources of error in the diuretic renogram include the state of hydration, renal functional status, distensibility and volume of the collecting system, a filled bladder, and ability to respond to the diuretic. Its reliability can be increased if the standard testing protocol is followed, the study closely monitored, and the limitations of the test realized. Interpretation of the diuretic renogram based only upon the appearance of the washout curve without consideration of the calculated half time or the sequential analogue images is unreliable and in our experience would have been responsible for an incorrect interpretation in 40 per cent of patients. The diuretic renal scan is used as the initial testing modality because it is reliable, reproducible, noninvasive, and objective and provides important information concerning individual renal function. Over 80 per cent of children with hydronephrosis can be completely evaluated by the diuretic renogram alone without the need for more invasive testing modalities. Nevertheless, the pressure perfusion study will continue to be necessary for the evaluation of certain individuals. Because of its invasive nature, we prefer to reserve this study for very specific, well-defined circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Blood flow determination in splenorenal shunts using a dye dilution technique.

Determination of flow through splenorenal shunts performed for portal hypertension was tried in 7 patients using a dye dilution technique. Varying shunt flows were obtained. The results of the flow determinations were compared with the findings at arteriography and the cause of the varying flows could be revealed. Retrograde flow through the left ovarian vein leading to incomplete mixing was the most common source of error. The employed dye dilution techniques lends itself to shunt flow determination only if sources of error can be ruled out by arteriography.

Dye Dilution Technique↗

Ecological effects in multi-level studies.

Multi-level research that attempts to describe ecological effects in themselves (for example, the effect on individual health from living in deprived communities), while also including individual level effects (for example, the effect of personal socioeconomic disadvantage), is now prominent in research on the socioeconomic determinants of health and disease. Such research often involves the application of advanced statistical multi-level methods. It is hypothesised that such research is at risk of reaching beyond an epidemiological understanding of what constitutes an ecological effect, and what sources of error may be influencing any observed ecological effect. This paper aims to present such an epidemiological understanding. Three basic types of ecological effect are described: a direct cross level effect (for example, living in a deprived community directly affects individual personal health), cross level effect modification (for example, living in a deprived community modifies the effect of individual socioeconomic status on individual health), and an indirect cross level effect (for example, living in a deprived community increases the risk of smoking, which in turn affects individual health). Sources of error and weaknesses in study design that may affect estimates of ecological effects include: a lack of variation in the ecological exposure (and health outcome) in the available data; not allowing for intraclass correlation; selection bias; confounding at both the ecological and individual level; misclassification of variables; misclassification of units of analysis and assignment of individuals to those units; model mis-specification; and multicollinearity. Identification of ecological effects requires the minimisation of these sources of error, and a study design that captures sufficient variation in the ecological exposure of interest.

Bias↗

Consistent non-cartesian off-axis MRI quality: calibrating and removing multiple sources of demodulation phase errors.

The consistency of off-axis MRI with non-Cartesian sequences across a large number of scanners is highly variable. Improper timing alignment of the gradient fields, data acquisition system, and real-time frequency demodulation reference signal, which are necessary for off-axis imaging, is an important source of this variability. In addition, eddy currents and anisotropic gradient delays cause deviations in k-space trajectories that in turn make the demodulation reference signals inaccurate. A method is presented to quickly measure the timing error in the frequency demodulation reference signal and separate it from anisotropic gradient delays. k-Space deviations, as measured with a previous gradient calibration technique, are shown to be a second source of demodulation phase errors that degrade image quality. Using the timing delay and k-space deviations, a retrospective phase correction is applied to each k-space sample before the data are regridded during reconstruction. The timing delays of four MR scanners were measured to be 4.2-7.5 micros below the manufacturer's suggested delay. Significant degradation in 3D radial (3D projection reconstruction (PR)) knee and breast images are retrospectively corrected while a partial prospective correction is applied for spiral imaging. The method allows for more consistent performance of non-Cartesian sequences across multiple scanners without operator intervention.

Algorithms↗

Evaluating the results of mail survey research.

OBJECTIVE: To present overall guidance enabling the reader to critically evaluate survey research conducted via mail questionnaire. Also considered are the sources of error that may operate during the conduct of survey research and the threats they pose to both the internal rigor of the study and the generalizability of the results. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Not applicable. CONCLUSION: Survey research has been used so commonly and for such a wide range of purposes in a large number of fields, that some people may mistakenly conclude that surveys are easy to conduct. Survey research involves much more than generating a set of questions to ask a group of subjects. To draw valid conclusions about the topic of a survey, the pharmacist must be prepared to evaluate the results in light of how well the investigators approached four sources of error--coverage, sampling, measurement, and nonresponse. The evaluation of survey administration procedures primarily concerns determining whether or not a pilot study was conducted, whether proper statistical analyses were conducted, and whether multiple mailing procedures were used. Failure to account for these sources of error, or inappropriate survey administration, could seriously affect both the generalizability and validity of the results.

Data Interpretation, Statistical↗

Statistical process control for radiotherapy quality assurance.

Every quality assurance process uncovers random and systematic errors. These errors typically consist of many small random errors and a very few number of large errors that dominate the result. Quality assurance practices in radiotherapy do not adequately differentiate between these two sources of error. The ability to separate these types of errors would allow the dominant source(s) of error to be efficiently detected and addressed. In this work, statistical process control is applied to quality assurance in radiotherapy for the purpose of setting action thresholds that differentiate between random and systematic errors. The theoretical development and implementation of process behavior charts are described. We report on a pilot project is which these techniques are applied to daily output and flatness/symmetry quality assurance for a 10 MV photon beam in our department. This clinical case was followed over 52 days. As part of our investigation, we found that action thresholds set using process behavior charts were able to identify systematic changes in our daily quality assurance process. This is in contrast to action thresholds set using the standard deviation, which did not identify the same systematic changes in the process. The process behavior thresholds calculated from a subset of the data detected a 2% change in the process whereas with a standard deviation calculation, no change was detected. Medical physicists must make decisions on quality assurance data as it is acquired. Process behavior charts help decide when to take action and when to acquire more data before making a change in the process.

Humans↗

Rate constants from the reaction path Hamiltonian. I. Reactive flux simulations for dynamically correct rates.

As ab initio electronic structure calculations become more accurate, inherent sources of error in classical transition state theory such as barrier recrossing and tunneling may become major sources of error in calculating rate constants. This paper introduces a general method for diabatically constructing the transverse eigensystem of a reaction path Hamiltonian in systems with many degenerate transverse frequencies. The diabatically constructed reaction path Hamiltonian yields smoothly varying coupling constants that, in turn, facilitate reactive flux calculations. As an example we compute the dynamically corrected rate constant for the chair to boat interconversion of cyclohexane, a system with 48 degrees of freedom and a number of degenerate frequencies. The transmission coefficients obtained from the reactive flux simulations agree with previous results that have been calculated using an empirical potential. Furthermore, the calculated rate constants agree with experimental values. Comparison to variational transition state theory shows that, despite finding the true bottleneck along the reaction pathway, variational transition state theory only accounts for half of the rate constant reduction due to recrossing trajectories.

Journal Article↗

Three-dimensional ultrasound imaging.

Ultrasound is an inexpensive and widely used imaging modality for the diagnosis and staging of a number of diseases. In the past two decades, it has benefited from major advances in technology and has become an indispensable imaging modality, due to its flexibility and non-invasive character. In the last decade, research investigators and commercial companies have further advanced ultrasound imaging with the development of 3D ultrasound. This new imaging approach is rapidly achieving widespread use with numerous applications. The major reason for the increase in the use of 3D ultrasound is related to the limitations of 2D viewing of 3D anatomy, using conventional ultrasound. This occurs because: (a) Conventional ultrasound images are 2D, yet the anatomy is 3D, hence the diagnostician must integrate multiple images in his mind. This practice is inefficient, and may lead to variability and incorrect diagnoses. (b) The 2D ultrasound image represents a thin plane at some arbitrary angle in the body. It is difficult to localize the image plane and reproduce it at a later time for follow-up studies. In this review article we describe how 3D ultrasound imaging overcomes these limitations. Specifically, we describe the developments of a number of 3D ultrasound imaging systems using mechanical, free-hand and 2D array scanning techniques. Reconstruction and viewing methods of the 3D images are described with specific examples. Since 3D ultrasound is used to quantify the volume of organs and pathology, the sources of errors in the reconstruction techniques as well as formulae relating design specification to geometric errors are provided. Finally, methods to measure organ volume from the 3D ultrasound images and sources of errors are described.

Animals↗

[Self measurement of blood pressure: patient education].

Many patients measure their blood pressure without any instruction due to the availability of modern measuring devices. Although the technique can be mastered by most of the patients, some sources of error have to be eliminated. The aim of such an instruction is to explain these sources of error to the patients and to give them opportunity to practise the self measurement under medical supervision. An instruction sheet is handed out as a pamphlet. The patients are also directed to keep a record of all measurements which is periodically controlled by the physician. It is also advisable to reexamine the measuring technique of the patient from time to time and to check the accuracy of the patients measuring device.

Blood Pressure Determination↗