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Systematic Bias (systematic + bias)
Selected AbstractsSystematic Bias Introduced by the Informed Consent Process in a Diagnostic Research StudyACADEMIC EMERGENCY MEDICINE, Issue 3 2008Alice M. Mitchell MD Abstract Objectives:, To determine population characteristics, outcomes, and reasons for unsuccessful enrollment among potential study subjects approached for written, informed consent in a minimal-risk emergency department (ED) study. The authors hypothesized that the prevalence of venous thromboembolism (VTE) would be lower among study participants and that medical acuity and refusal to provide a blood sample would be the most common reasons for nonparticipation. Methods:, The authors requested prospective, written, informed consent for a blood sample and follow-up from consecutive ED patients undergoing evaluation for pulmonary embolism (PE) and recorded spontaneously stated reasons for refusal. VTE was diagnosed or excluded using a combination of D-dimer testing and selective computed tomography (CT) angiography of the chest with venography of the lower extremities. The primary outcome was defined by the number of CT scans positive for VTE among ED patients evaluated for PE. Results:, Over 16 weeks, 260 of 287 (91%, 95% confidence interval [CI] = 87 to 94%) eligible patients were approached and consent was obtained from 183 patients (64%, 95% CI = 58% to 69%). The prevalence of VTE was 6% among participants and 13% among nonparticipants (95% CI [of the difference] = 1% to 15%). The proportions of African Americans, uninsured, and Medicaid patients were significantly higher among nonparticipants. No significant differences were found in the proportions of nonparticipants who disliked or distrusted research or desired financial reimbursement, compared to those not enrolled due to medical acuity or refused a blood sample. Conclusions:, These data implicate the written, informed consent process as a significant source of bias on estimated disease prevalence. [source] The design of single particle laser mass spectrometers,MASS SPECTROMETRY REVIEWS, Issue 2 2007Daniel M. MurphyArticle first published online: 16 OCT 200 Abstract This review explores some of the design choices made with single particle mass spectrometers. Different instruments have used various configurations of inlets, particle sizing techniques, ionization lasers, mass spectrometers, and other components. Systematic bias against non-spherical particles probably exceeds a factor of 2 for all instruments. An ionization laser tradeoff is the relatively poor beam quality and reliability of an excimer laser versus the longer wavelengths and slower response time of an Nd-YAG laser. Single particle instruments can make special demands on the speed and dynamic range of the mass spectrometers. This review explains some of the choices made for instruments that were developed for different types of measurements in the atmosphere. Some practical design notes are also given from the author's experience with each section of the instrument. Published 2006 Wiley Periodicals, Inc., Mass Spec Rev 26:150,165, 2007 [source] Role of meta-analysis of clinical trials for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Jesús M. López Arrieta Abstract Alzheimer's disease (AD) is a growing worldwide medical, social, and economic problem. In all countries, both prevalence and incidence of this disorder increase with age. The task of translating scientific clinical research into effective interventions for dementia has proved to be a difficult challenge. Data about the effects of therapeutic interventions come from several sources of evidence, ranging from studies with little potential for systematic bias and minimal random error, such as well-designed randomized controlled trials, through controlled but nonrandomized cohort and case-control studies, all the way to opinions based on laboratory evidence or theory. Although clinical trials are widespread in AD, there is increasing recognition that the results of studies do not necessarily apply to the type of patients that are seen by clinicians because of differences in patient characteristics, comorbidities, cotherapies, severity of disease, compliance, local circumstances, and patients preferences, which may differ sufficiently from those in the trial situation to attenuate or change the benefit-to-risk ratio. There are several methods to address those issues, like pragmatic trials and n-of-1 trials. When data from randomized clinical trials do not provide clear answers from sufficiently similar studies in the magnitude of effect sizes, lack of statistical significance, or identification of subgroups, systematic reviews and meta-analysis may help to provide a better summary of the data. A major difference between a traditional review and a systematic is the systematic nature in which studies are chosen and appraised. Traditional reviews are written by experts in the field who use differing and often subjective criteria to decide what studies to include and what weight to give them, and hence the conclusions are often very diverse, depending on the reviewer. Publication and selection bias is a major concern of traditional reviews. Systematic reviews and meta-analysis are being increasingly used in dementia, propelled by the Cochrane Dementia and Cognitive Improvement Group, to make decisions about treatment, management, and care and to guide future research. This narrative review describes the rationale for randomized clinical trials and systematic reviews in dementia, particularly AD. Drug Dev. Res. 56:401,411, 2002. © 2002 Wiley-Liss, Inc. [source] Catheterization,Doppler Discrepancies in Nonsimultaneous Evaluations of Aortic StenosisECHOCARDIOGRAPHY, Issue 5 2005Payam Aghassi M.D. Prior validation studies have established that simultaneously measured catheter (cath) and Doppler mean pressure gradients (MPG) correlate closely in evaluation of aortic stenosis (AS). In clinical practice, however, cath and Doppler are rarely performed simultaneously; which may lead to discrepant results. Accordingly, our aim was to ascertain agreement between these methods and investigate factors associated with discrepant results. We reviewed findings in 100 consecutive evaluations for AS performed in 97 patients (mean age 72 ± 10 yr) in which cath and Doppler were performed within 6 weeks. We recorded MPG, aortic valve area (AVA), cardiac output, and ejection fraction (EF) by both methods. Aortic root diameter, left ventricular end-diastolic dimension (LVIDd) and posterior wall thickness (PWT) were measured by echocardiography and gender, heart rate, and heart rhythm were also recorded. An MPG discrepancy was defined as an intrapatient difference > 10 mmHg. Mean pressure gradients by cath and Doppler were 36 ± 22 mmHg and 37 ± 20 mmHg, respectively (P = 0.73). Linear regression showed good correlation (r = 0.82) between the techniques. An MPG discrepancy was found in 36 (36%) of 100 evaluations; in 19 (53%) of 36 evaluations MPG by Doppler was higher than cath, and in 17 (47%) of 36, it was lower. In 33 evaluations, EF differed by >10% between techniques. Linear regression analyses revealed that EF difference between studies was a significant predictor of MPG discrepancy (P = 0.004). Women had significantly higher MPG than men by both cath and Doppler (43 ± 25 mmHg versus 29 ± 15 mmHg [P = 0.001]; 42 ± 23 mmHg versus 32 ± 15 mmHg [P = 0.014], respectively). Women exhibited discrepant results in 23 (47%) of 49 evaluations versus 13 (25%) of 51 evaluations in men (P = 0.037). After adjustment for women's higher MPG, there was no statistically significant difference in MPG discrepancy between genders (P = 0.22). No significant interactions between MPG and aortic root diameter, relative wall thickness (RWT), heart rate, heart rhythm, cardiac output, and time interval between studies were found. In clinical practice, significant discrepancies in MPG were common when cath and Doppler are performed nonsimultaneously. No systematic bias was observed and Doppler results were as likely yield lower as higher MPGs than cath. EF difference was a significant predictor of discrepant MPG. Aortic root diameter, relative wall thickness, heart rate, heart rhythm, cardiac output, presence or severity of coronary artery disease, and time interval between studies were not predictors of discrepant results. [source] Fossilized embryos are widespread but the record is temporally and taxonomically biasedEVOLUTION AND DEVELOPMENT, Issue 2 2006Philip C. J. Donoghue SUMMARY We report new discoveries of embryos and egg capsules from the Lower Cambrian of Siberia, Middle Cambrian of Australia and Lower Ordovician of North America. Together with existing records, embryos have now been recorded from four of the seven continents. However, the new discoveries highlight secular and systematic biases in the fossil record of embryonic stages. The temporal window within which the embryos and egg capsules are found is of relatively short duration; it ends in the Early Ordovician and is roughly coincident with that of typical "Orsten"-type faunas. The reduced occurrence of such fossils has been attributed to reducing levels of phosphate in marine waters during the early Paleozoic, but may also be owing to the increasing depth of sediment mixing by infaunal metazoans. Furthermore, most records younger than the earliest Cambrian are of a single kind,large eggs and embryos of the priapulid-like scalidophoran Markuelia. We explore alternative explanations for the low taxonomic diversity of embryos recovered thus far, including sampling, size, anatomy, ecology, and environment, concluding that the preponderance of Markuelia embryos is due to its precocious development of cuticle at an embryonic stage, predisposing it to preservation through action as a substrate on which microbially mediated precipitation of authigenic calcium phosphate may occur. The fossil record of embryos may be limited to a late Neoproterozoic to early Ordovician snapshot that is subject to dramatic systematic bias. Together, these biases must be considered seriously in attempts to use the fossil record to arbitrate between hypotheses of developmental and life history evolution implicated in the origin of metazoan clades. [source] Regional tomographic inversion of the amplitude and phase of Rayleigh waves with 2-D sensitivity kernelsGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2006Yingjie Yang SUMMARY In this study, we test the adequacy of 2-D sensitivity kernels for fundamental-mode Rayleigh waves based on the single-scattering (Born) approximation to account for the effects of heterogeneous structure on the wavefield in a regional surface wave study. The calculated phase and amplitude data using the 2-D sensitivity kernels are compared to phase and amplitude data obtained from seismic waveforms synthesized by the pseudo-spectral method for plane Rayleigh waves propagating through heterogeneous structure. We find that the kernels can accurately predict the perturbation of the wavefield even when the size of anomaly is larger than one wavelength. The only exception is a systematic bias in the amplitude within the anomaly itself due to a site response. An inversion method of surface wave tomography based on the sensitivity kernels is developed and applied to synthesized data obtained from a numerical simulation modelling Rayleigh wave propagation over checkerboard structure. By comparing recovered images to input structure, we illustrate that the method can almost completely recover anomalies within an array of stations when the size of the anomalies is larger than or close to one wavelength of the surface waves. Surface wave amplitude contains important information about Earth structure and should be inverted together with phase data in surface wave tomography. [source] Experimental studies of sequential selection and assignment with relative ranksJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 3 2006J. Neil Bearden Abstract We study a class of sequential selection and assignment problems in which a decision maker (DM) must sequentially assign applicants to positions with the objective of minimizing expected cost. In modeling this class of problems, we assume that on each period the DM is only informed of the rank of the present applicant relative to the applicants that she previously observed and assigned. We first present the optimal decision policy that we subsequently use as a normative benchmark, and then report results from three experiments designed to study sequential assignment behavior. In comparing the aggregate results from all three experiments to the optimal decision policy, we identify a systematic bias, called the middleness bias, to over-assign applicants to intermediate positions. The results also reveal a strong bias for early applicants to be over-assigned to important positions. Copyright © 2006 John Wiley & Sons, Ltd. [source] On hidden heterogeneity in directional asymmetry , can systematic bias be avoided?JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2006L. C. STIGE Abstract Directional asymmetry (DA) biases the analysis of fluctuating asymmetry (FA) mainly because among-individual differences in the predisposition for DA are difficult to detect. However, we argue that systematic bias mainly results from predictable associations between signed right,left asymmetry and other factors, i.e. from systematic variation in DA. We here demonstrate methods to test and correct for this, by analysing bilateral asymmetry in size and shape of an irregular sea urchin. Notably, in this model system, DA depended significantly on body length and geographic origin, although mean signed asymmetry (mean DA) was not significant in the sample as a whole. In contrast to the systematic variation in DA, undetectable, random variability in the underlying DA mainly leads to reduced statistical power. Using computer simulations, we show that this loss of power is probably slight in most circumstances. We recommend future studies on FA to routinely test and correct for not only as yet for mean DA, but also for systematic variation in DA. [source] Pulsed dye densitometry with two different sensor types for cardiac output measurement after cardiac surgery: a comparison with the thermodilution techniqueACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2004C. K. Hofer Background:, Assessment of cardiac output (CO) by the indocyanine green (ICG) dye dilution technique (IDD) with transcutaneous signal detection may be a less invasive alternative to the pulmonary artery catheter (PAC). The aim of this study was to determine the accuracy and reliability of the DDG2001 analyzer (Nihon Kohden Corp, Tokyo, Japan) using a finger (IDDf) and a nose (IDDn) sensor as compared with the thermodilution technique by PAC. Methods:, In 31 consecutive patients after routine cardiac surgery, CO measurements were performed by IDD compared with the thermodilution technique following postoperative haemodynamic stabilization in the intensive care unit. Repeated measurements were made at 30-min intervals. CO was determined by iced water bolus (IWB: mean of three repeated injections) and IDDf or IDDn, respectively (mean of three repeated ICG injections). Results:, Thirty-three per cent of all measurements for IDDf and 9% for IDDn failed due to a missing signal detection. Mean bias for IDDf to IWB was ,0.5 l min,1·m,2 (limits of agreement: ,1.8/0.8 l min,1·m,2) and for IDDn to IWB was ,0.1 l min,1·m,2 (limits of agreement: ,1.6/1.5 l min,1·m,2). Correlation between IDDf and IWB (r = 0.2) was found to be inferior to the correlation between IDDn and IWB (r = 0.5). Conclusion:, The IDD showed a systematic bias compared with the IWB and its performance was limited due to signal detection failure. Therefore, the DDG2001 analyzer cannot be recommended as a substitute for the PAC in routine monitoring of cardiac output after cardiac surgery. [source] The estimation of the Sunyaev,Zel'dovich effects with unbiased multifiltersMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2005D. Herranz ABSTRACT In this work we study the performance of linear multifilters for the estimation of the amplitudes of the thermal and kinematic Sunyaev,Zel'dovich (SZ) effects. We show that when both effects are present, estimation of these effects with standard matched multifilters is intrinsically biased. This bias is due to the fact that both signals have basically the same spatial profile. We find a new family of multifilters related to the matched multifilters that cancel this systematic bias, hence we call them unbiased matched multifilters. We test the unbiased matched multifilters and compare them with the standard matched multifilters using simulations that reproduce the future Planck mission observations. We find that in the case of the standard matched multifilters the systematic bias in the estimation of the kinematic Sunyaev,Zel'dovich effect can be very large, even greater than the statistical error bars. Unbiased matched multifilters cancel this kind of bias effectively. In concordance with other works in the literature, our results indicate that the sensitivity and resolution of Planck will not be enough to give reliable estimations of the kinematic Sunyaev,Zel'dovich effects of individual clusters. However, as the estimation with the unbiased matched multifilters is not intrinsically biased, it can be possible to use them to study statistically any peculiar cosmological bulk flows via the kinematic SZ effect. [source] Unbiased ensemble square root filtersPROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2007S. L. Dance Ensemble square root filters are a method of data assimilation, where model forecasts are combined with observations to produce an improved state estimate, or analysis. There are a number of different algorithms in the literature and it is not clear which of these is the best for any given application. This work shows that in some implementations there can be a systematic bias in the analysis ensemble mean and consequently an accompanying shortfall in the spread of the analysis ensemble as expressed by the ensemble covariance matrix. We have established a set of necessary and sufficient conditions for the scheme to be unbiased. While these conditions are not a cure-all and cannot deal with independent sources of bias such as model and observation errors, they should be useful to designers of ensemble square root filters in the future. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Improving feature detection and analysis of surface-enhanced laser desorption/ionization-time of flight mass spectraPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2005Scott M. Carlson Abstract Discovering valid biological information from surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) depends on clear experimental design, meticulous sample handling, and sophisticated data processing. Most published literature deals with the biological aspects of these experiments, or with computer-learning algorithms to locate sets of classifying biomarkers. The process of locating and measuring proteins across spectra has received less attention. This process should be tunable between sensitivity and false-discovery, and should guarantee that features are biologically meaningful in that they represent chemical species that can be identified and investigated. Existing feature detection in SELDI-TOF MS is not optimal for acquiring biologically relevant data. Most methods have so many user-defined settings that reproducibility and comparability among studies suffer considerably. To address these issues, we have developed an approach, called simultaneous spectrum analysis (SSA), which (i) locates proteins across spectra, (ii),measures their abundance, (iii),subtracts baseline, (iv),excludes irreproducible measurements, and (v),computes normalization factors for comparing spectra. SSA uses only two key parameters for feature detection and one parameter each for quality thresholds on spectra and peaks. The effectiveness of SSA is demonstrated by identifying proteins differentially expressed in SELDI-TOF spectra from plasma of wild-type and knockout mice for plasma glutathione peroxidase. Comparing analyses by SSA and CiphergenExpress Data Manager,2.1 finds similar results for large signal peaks, but SSA improves the number and quality of differences betweens groups among lower signal peaks. SSA is also less likely to introduce systematic bias when normalizing spectra. [source] Consistency of a two clinical site sample collection: A proteomics studyPROTEOMICS - CLINICAL APPLICATIONS, Issue 8-9 2010Cedric Wiesner Abstract Purpose: We investigated the ability to perform a clinical proteomic study using samples collected at different times from two independent clinical sites. Experimental Design: Label-free 2-D-LC-MS proteomic analysis was used to differentially quantify tens of thousands of peptides from human plasma. We have asked whether samples collected from two sites, when analyzed by this type of peptide profiling, reproducibly contain detectable peptide markers that are differentially expressed in the plasma of disease (advanced renal cancer) patients relative to healthy normals. Results: We have demonstrated that plasma proteins enriched in disease patients are indeed detected reproducibly in both clinical collections. Regression analysis, unsupervised hierarchical clustering and PCA detected no systematic bias in the data related to site of sample collection and processing. Using a genetic algorithm, support vector machine classification method, we were able to correctly classify disease samples at 88% sensitivity and 94% specificity using the second site as an independent validation set. Conclusions and clinical relevance: We conclude that multiple site collection, when analyzed by label-free 2-D-LC-MS, generates data that are sufficiently reproducible to guide reliable biomarker discovery. [source] Reliability of the anaerobic threshold in cardiopulmonary exercise testing of patients with abdominal aortic aneurysms,ANAESTHESIA, Issue 1 2009E. Kothmann Summary Anaerobic threshold (AT), determined by cardiopulmonary exercise testing (CPET), is a well-documented measure of pre-operative fitness, although its reliability in patient populations is uncertain. Our aim was to assess the reliability of AT measurement in patients with abdominal aortic aneurysms. Eighteen patients were recruited. CPET was performed four times over a 6-week period. We examined shifts in the mean AT to evaluate systematic bias with random measurement error assessed using typical within-patient error and intraclass correlation coefficient (ICC, 3,1) statistics. There was no significant or clinically substantial change in mean AT across the tests (p = 0.68). The typical within-patient error expressed as a percentage coefficient of variation was 10% (95% CI, 8,13%), with an ICC of 0.74 (95% CI, 0.55,0.89). We consider the reliability of the AT to be acceptable, supporting its clinical validity and utility as an objective marker of pre-operative fitness in this population. [source] The Time Course of New T-Wave ECG Descriptors Following Single- and Double-Dose Administration of Sotalol in Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Fabrice Extramiana M.D., Ph.D. Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R2= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26,35 [source] The role of subjective time in identity regulationAPPLIED COGNITIVE PSYCHOLOGY, Issue 8 2009Anne E. Wilson We explore the function of subjective perceptions of time in regulating personal identity. Events that reflect favourably on the self feel more recent than events that reflect negatively on the self. We propose that this systematic bias in subjective time judgment serves an identity regulation function: These biases allow people to maintain a favourable evaluation of current self. Recent events are likely to be judged as ,belonging' to the current self and thus incorporated into current identity. Distant events are more likely to be viewed as belonging to a former self who is quite distinct from the today's self. Therefore, by perceiving past positive experiences as more recent than negative ones, people are able to continue to take credit for former glories while reducing the threat of past failings on present identity. We discuss evidence for both the motivational account of subjective distancing and its role in regulating and maintaining a desired current identity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Accounting for Executive Stock Options: A Case Study in Avoiding Tough DecisionsAUSTRALIAN ACCOUNTING REVIEW, Issue 26 2002Jeff Coulton We review the development of accounting requirements for executive stock options (ESOs) and find that the standard-setting process has been susceptible to pressure groups including the corporate sector, politicians and even the accounting profession itself. The failure of Australian and overseas accounting regulators to take tough decisions may have created a systematic bias towards the use of ESOs which can result in grossly inefficient compensation structures motivated by a desire to maximise reported profits rather than to create optimal managerial incentives. We conclude that most of the arguments against recognition of stock option expense can be dismissed as blatant self-interest at worst, or remarkably muddled thinking at best. [source] Prediction of human clearance of therapeutic proteins: simple allometric scaling method revisitedBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2010Weirong Wang Abstract In this report, the utility of a commonly used interspecies scaling method to predict the systemic clearance (CL) of therapeutic proteins in humans was evaluated. Based on analysis of a pharmacokinetic data set of 34 therapeutic proteins, including 12 monoclonal antibodies (mAbs) and Fc fusion proteins, human CL can generally be predicted reasonably well with simple allometric scaling and a fixed exponent of 0.8:,95% of the cases predicted values within 2-fold of the observed values when using CL data from multiple species, or,90% simply using CL from monkeys. Specific to mAbs/Fc fusion proteins, scaling from monkey CL using a fixed exponent of 0.8 gave an excellent prediction; all predicted CL values were within 2-fold of the corresponding observed values. Compared with the simple allometric scaling method that uses a fitted exponent from CL data of ,3 preclinical species, the fixed exponent approach with 1,2 preclinical species is simple, resource-saving and minimizes systematic bias. Together with its overall satisfactory prediction accuracy, especially in the absence of non-linear pharmacokinetics and species-specific clearance mechanisms, this fixed exponent method affords a viable alternative to other published allometric methods, including the Rule of Exponents (ROE). Copyright © 2010 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||