Using fathers as a negative control exposure: Implications of measurement bias

2019 ◽  
Vol 48 (6) ◽  
pp. 674-675
Author(s):  
Lekshmi Rita Venugopal ◽  
Tom Varghese M
Keyword(s):  
Epidemiological Studies ◽  
Negative Control ◽  
Measurement Bias ◽  
Time Varying ◽  
Recall Bias ◽  
Unmeasured Confounding ◽  
Differential Measurement ◽  
Exposure Analysis ◽  
Differential Measurement Error ◽  
Negative Controls

Negative control exposure analysis is a very effective tool in evaluating the effect of unmeasured confounding in observational epidemiological studies. Several biases, including recall bias, time-varying confounding factors, measurement bias and so on, can affect the credibility of negative control exposure analysis for causal interpretations. The article focuses on the implications of differential measurement error across exposed group and negative controls to causal interpretations on negative control exposure analysis.

scholarly journals Assessing The Effectiveness of Empirical Calibration Under Different Bias Scenarios

2021 ◽  
Author(s):  
Hon Hwang ◽  
Juan C Quiroz ◽  
Blanca Gallego
Keyword(s):  
Confidence Interval ◽  
Confidence Intervals ◽  
Observational Studies ◽  
Treatment Effects ◽  
Model Misspecification ◽  
Calibration Procedure ◽  
Negative Control ◽  
Unmeasured Confounding ◽  
Empirical Calibration ◽  
Negative Controls

Abstract Background: Estimations of causal effects from observational data are subject to various sources of bias. These biases can be adjusted by using negative control outcomes not affected by the treatment. The empirical calibration procedure uses negative controls to calibrate p-values and both negative and positive controls to calibrate coverage of the 95% confidence interval of the outcome of interest. Although empirical calibration has been used in several large observational studies, there is no systematic examination of its effect under different bias scenarios. Methods: The effect of empirical calibration of confidence intervals was analyzed using simulated datasets with known treatment effects. The simulations were for binary treatment and binary outcome, with simulated biases resulting from unmeasured confounder, model misspecification, measurement error, and lack of positivity. The performance of empirical calibration was evaluated by determining the change of the confidence interval coverage and bias of the outcome of interest. Results: Empirical calibration increased coverage of the outcome of interest by the 95% confidence interval under most settings but was inconsistent in adjusting the bias of the outcome of interest. Empirical calibration was most effective when adjusting for unmeasured confounding bias. Suitable negative controls had a large impact on the adjustment made by empirical calibration, but small improvements in the coverage of the outcome of interest was also observable when using unsuitable negative controls. Conclusions: This work adds evidence to the efficacy of empirical calibration on calibrating the confidence intervals of treatment effects in observational studies. We recommend empirical calibration of confidence intervals, especially when there is a risk of unmeasured confounding.

scholarly journals Mendelian randomisation for mediation analysis: current methods and challenges for implementation

2021 ◽  
Author(s):  
Alice R. Carter ◽  
Eleanor Sanderson ◽  
Gemma Hammerton ◽  
Rebecca C. Richmond ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Measurement Error ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Instrumental Variable ◽  
Real Data ◽  
Mendelian Randomisation ◽  
Differential Measurement ◽  
Individual Level ◽  
Differential Measurement Error ◽  
Summary Data

AbstractMediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

scholarly journals Evaluation of ionic degradation and slot corrosion of metallic brackets by the action of different dentifrices

2013 ◽  
Vol 18 (1) ◽  
pp. 86-93
Author(s):  
Gustavo Antônio Martins Brandão ◽  
Rafael Menezes Simas ◽  
Leandro Moreira de Almeida ◽  
Juliana Melo da Silva ◽  
Marcelo de Castro Meneghim ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Artificial Saliva ◽  
Positive Control ◽  
Negative Control ◽  
Sem Analysis ◽  
Wilcoxon Test ◽  
Surface Polishing ◽  
Aluminium Ion ◽  
Negative Controls

OBJECTIVE: To evaluate the in vitro ionic degradation and slot base corrosion of metallic brackets subjected to brushing with dentifrices, through analysis of chemical composition by Energy Dispersive Spectroscopy (EDS) and qualitative analysis by Scanning Electron Microscopy (SEM). METHODS: Thirty eight brackets were selected and randomly divided into four experimental groups (n = 7). Two groups (n = 5) worked as positive and negative controls. Simulated orthodontic braces were assembled using 0.019 x 0.025-in stainless steel wires and elastomeric rings. The groups were divided according to surface treatment: G1 (Máxima Proteção Anticáries®); G2 (Total 12®); G3 (Sensitive®); G4 (Branqueador®); Positive control (artificial saliva) and Negative control (no treatment). Twenty eight brushing cycles were performed and evaluations were made before (T0) and after (T1) experiment. RESULTS: The Wilcoxon test showed no difference in ionic concentrations of titanium (Ti), chromium (Cr), iron (Fe) and nickel (Ni) between groups. G2 presented significant reduction (p < 0.05) in the concentration of aluminium ion (Al). Groups G3 and G4 presented significant increase (p < 0.05) in the concentration of aluminium ion. The SEM analysis showed increased characteristics indicative of corrosion on groups G2, G3 and G4. CONCLUSION: The EDS analysis revealed that control groups and G1 did not suffer alterations on the chemical composition. G2 presented degradation in the amount of Al ion. G3 and G4 suffered increase in the concentration of Al. The immersion in artificial saliva and the dentifrice Máxima Proteção Anticáries® did not alter the surface polishing. The dentifrices Total 12®, Sensitive® and Branqueador® altered the surface polishing.

slowly growing natural populations. Various approaches have been adopted in order to improve the sensitivity. These have included the use of multiple probes labelled with a single fluor (Lee et al. 1993); or labelled with multiple fluors (Trebesius et al. 1994) and enzyme-linked probes or detection systems that allow signal amplification (Lebaron et al. 1997, Schonhuber et al. 1999). The latter indirect approach not only has the potential for signal amplification, but may also be used in natural samples showing high levels of autofluorescence. Any thorough identification method has to include positive and negative controls. False-positive results may either be caused by cells emitting autofluorescence upon excitation or by nonspecific binding of the probe to nontarget cells. Samples should therefore be checked for autofluorescence before hybridization and a negative control with a fluorescent oligonucleotide not complementary to rRNA has to be applied to check for sequence-independent nonspecific binding. Such non-specific binding may be due to interaction of the dye compound of the probe with hydrophobic cell components. Failures to detect cells containing target sequences (false-negatives) may originate from cells with either low cellular ribosome content or limited permeability of the cell periphery for the fluorescent probe (Manz et al. 1992). With the rapidly expanding database of 16S rRNA sequences, the problem of probe specificity has become more apparent and the design of probes is becoming increasingly difficult. These problems are also applicable to PCR and other oligonucleotide-dependent techniques. The problem of probe specificity may be overcome by using multiple specific oligonucleotide probes targeting different sites on the rRNA molecule and labelled with different fluorochromes. While a single oligonucleotide target sequence may be found in a number of related taxa, the probability that target sites for three designed oligonucleotides are found in a nontarget organism is, however, much reduced.

2003 ◽  
pp. 232-232
Keyword(s):  
Signal Amplification ◽  
Specific Binding ◽  
Natural Populations ◽  
Negative Control ◽  
Target Sequence ◽  
Cell Periphery ◽  
Nonspecific Binding ◽  
Detection Systems ◽  
Cell Components ◽  
Negative Controls

scholarly journals Mendelian randomisation for mediation analysis: current methods and challenges for implementation

2019 ◽  
Author(s):  
Alice R Carter ◽  
Eleanor Sanderson ◽  
Gemma Hammerton ◽  
Rebecca C Richmond ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Measurement Error ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Real Data ◽  
Mendelian Randomisation ◽  
Reverse Causality ◽  
Differential Measurement ◽  
Individual Level ◽  
Differential Measurement Error ◽  
Summary Data

AbstractMediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Mediation analysis experiences a number of methodological difficulties, including bias due to confounding and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable Mendelian randomisation (MVMR) and two-step Mendelian randomisation. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although Mendelian randomisation relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our examples demonstrate that it is unlikely to be affected by confounders of the exposure or mediator and the outcome, reverse causality and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR, and can improve causal inference in mediation analysis.

scholarly journals Effect of Sodium Carboxymethylcellulose and Sorbitol on Anti-Peptic Ulcer Activity of Anredera cordifolia Leaves Extract

2019 ◽  
Vol 4 (1) ◽  
pp. 16
Author(s):  
Maria Ulfah ◽  
Revika Rachmaniar ◽  
Egi MR. Sudrajat ◽  
Rida W. Fadla ◽  
Hary S. Pinuji
Keyword(s):  
Body Weight ◽  
Peptic Ulcer ◽  
Normal Control ◽  
Wistar Rat ◽  
Positive Control ◽  
Negative Control ◽  
Sodium Carboxymethylcellulose ◽  
Freeze Dried ◽  
Male Wistar Rats ◽  
Negative Controls

Anredera cordifolia or binahong is one of the Indonesian medicinal plants that is used to treat peptic ulcer. The purpose of this study was to evaluate the effect of the addition of sodium carboxymethylcellulose (CMC) and sorbitol on anti-peptic ulcer activity of A. cordifolia leaves extracts in male Wistar rats. The plants were extracted using decoction method and freeze dried. Three liquid formulas were used i.e., i) a combination of sodium CMC and sorbitol; ii) only sorbitol; iii) extract only. The rats were divided into 6 groups, i.e., positive control (sucralfate 35 mg/kg body weight); negative control (80% ethanol); normal control; and 3 formulas. After the administration of the liquid formula, all groups, except normal control, were given 80% ethanol (l5 ml/kg body weight) to induce peptic ulcer. Antipeptic ulcer activity was evaluated using direct observation on rats gastric mucosa, and histopathology assessment. The result showed that the strongest anti-peptic ulcer  was shown by sorbitol only (96.95% inhibition),  followed by the combination of sodium CMC and sorbitol (92.68% inhibition). The formula which only contained extract showed only  31.70% inhibition.  Statistical analysis showed significant differences between formula 1 and 2 with negative controls. In conclusion, A. cordifolia leaves extract with the addition of sorbitol showed the strongest anti-peptic ulcer activity. Keyword: Anredera cordifolia, peptic ulcer, suspense, Wistar rat.

Abstract 2819: Cross-correlation Analysis of Myocardial Velocity is Superior to Conventional Time-to-Peak Parameters for Quantifying Left Ventricular Dyssynchrony

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Brandon K Fornwalt ◽  
Takeshi Arita ◽  
Mohit Bhasin ◽  
George Voulgaris ◽  
John D Merlino ◽  
...  
Keyword(s):  
Cross Correlation ◽  
Positive Control ◽  
Negative Control ◽  
Left Ventricular ◽  
Left Ventricular Dyssynchrony ◽  
Control Group ◽  
Time To Peak ◽  
Data Points ◽  
Negative Controls ◽  
Threshold Line

Background- A recent study showed that the most commonly used Tissue Doppler imaging (TDI) parameters to diagnose left ventricular dyssynchrony agree only 50% of the time. Most of these parameters require calculation of the ``time-to-peak” myocardial velocity. This ``time-to-peak” based analysis utilizes only one of >100 data points collected per heart cycle. Methods- We developed and tested a new dyssynchrony parameter, cross-correlation delay (XCD), that utilizes all velocity data points from 3 consecutive beats (~420 points). We hypothesized that XCD would be superior to existing methods at diagnosing dyssynchrony. We tested XCD on 11 members of a positive control group (echocardiographic responders to cardiac resynchronization therapy) and 12 members of a negative control group (normal echocardiogram and 12-lead ECG). We compared XCD to septal-to-lateral delay in time-to-peak (SLD), maximum difference in the basal 2- or 4-chamber times-to-peak (MaxDiff) and standard deviation of the 12 basal and mid-wall times-to-peak (Ts-SD). Results- An XCD threshold of 31ms discriminated between positive and negative controls with 100% sensitivity and specificity (Figure 1 ). SLD, MaxDiff and Ts-SD showed sensitivities of 36, 55 and 100% and specificities of 50, 42 and 50%, respectively. ROC analysis showed XCD and Ts-SD were superior to SLD and MaxDiff in discriminating between positive and negative controls (p<0.01). XCD was the only parameter which decreased after resynchronization in the positive controls (from 160±88ms to 69±61ms, p=0.003). Conclusion- XCD is superior to existing parameters at discriminating patients with LV dyssynchrony from those with normal function. Figure 1. XCD shows the greatest discrimination between positive and negative controls. Dyssynchrony values for each positive control are shown as x’s and values for each negative control are shown as circels. Different dyssynchrony parameters are shown in each subplot (A-D). Threshold values to diagnose dyssynchrony are plotted as horizontal lines in each figure. Note that x’s above the threshold line represent false positives while circles below the threshold line represent false negatives.

Evaluation of diagnostic accuracy of 10 serological assays for detection of SARS-CoV-2 antibodies.

2020 ◽  
Author(s):  
MD. ◽  
Sara Gómez de Frutos ◽  
Diego Domingo García PharmD ◽  
Eva Navarro Lara ◽  
Ayla Yarci Carrión ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Gold Standard ◽  
Epidemiological Studies ◽  
Antibody Detection ◽  
Diagnostic Tools ◽  
Sensitivity Range ◽  
Sensitivity Specificity ◽  
Negative Controls ◽  
Ig G ◽  
Positive Controls

Abstract BackgroundAntibody detection is essential to establish exposure, infection and immunity to SARS-CoV-2, as well as to perform epidemiological studies. The worlwide urge for new diagnostic tools to control the pandemic has led to a quick in- corporation in clinical practice of the recently developed serological assays.MethodsWe evaluated the diagnostic accuracy to detect Ig G, Ig M+A and/or IgA anti SARS-CoV-2 of 10 different assays: 3 Lateral Flow card inmunoassays, 4 en- zyme-linked inmunoabsorbent assay (ELISA) and 3 chemiluminescent particle immunoassays (CMIA). Using PCR for COVID-19 as gold standard, sensitivity, specificity, PPV, and NPV were determined. Each assay was tested in 2 groups: Positive Controls, formed by 50 sera from 50 patients with SARS-CoV-2 pneu- monia with positive PCR; Negative Controls, formed by 50 sera from 50 pa- tients with respiratory infection non-COVID-19.ResultsSensitivity range of the 10 assays evaluated for patients with positive COVID-19 PCR was 40-77% (65-81% considering IgG plus IgM). Specificity ranged 83-100%. VPP and VPN were respectively 81-100% and 61.6-81%.ConclusionsResults obtained varied widely among the assays evaluated.Highest diagnostic accuracy was obtained with ELISA and CMIAs, but they last much longer.

scholarly journals Malaria serology: performance of six Plasmodium falciparum antigen extracts and of three ways of determining serum titers in IgG and IgM-ELISA

1993 ◽  
Vol 35 (6) ◽  
pp. 495-502 ◽  
Author(s):  
Maria Carmen Arroyo Sanchez ◽  
Sandra do Lago Moraes de Avila ◽  
Vera de Paula Quartier-Oliveira ◽  
Antonio Walter Ferreira
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Diagnosis ◽  
Sodium Deoxycholate ◽  
Epidemiological Studies ◽  
Negative Control ◽  
Igg Antibody ◽  
Direct Titration ◽  
Antibody Titers ◽  
Constant Slope ◽  
Better Than

The study evaluated six Plasmodium falciparum antigen extracts to be used in the IgG and IgM enzyme-linked immunosorbent assays (ELISA), for malaria diagnosis and epidemiological studies. Results obtained with eighteen positive and nine negative control sera indicated that there were statistically significant differences among these antigen extracts (Multifactor ANOVA, p< 0.0001). Urea, sodium deoxycholate and Zwittergent antigen extracts performed better than did the three others, their features being very similar for the detection of IgG antibodies. Urea, alkaline and sodium deoxycholate antigen extracts proved to be better than the others for the detection of IgM antibodies. A straight line relationship was found between the optical densities (or their respective log 10) and the log 10 of antibody dilutions, with a very constant slope. Thus serum titers could be determined by direct titration and by two different equations, needing only one serum dilution. For IgM antibody detections, log 10 expression gave results that better correlated with direct titration (95% Bonferroni). For IgG antibody detections, the titer differences were not significant. The reproducibility of antibody titers and antigen batches was also evaluated, giving satisfactory results.

Sign in / Sign up

Export Citation Format

Share Document