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Sample records for confounding effect modification

  1. Effects of heat waves on mortality: effect modification and confounding by air pollutants.

    PubMed

    Analitis, Antonis; Michelozzi, Paola; D'Ippoliti, Daniela; De'Donato, Francesca; Menne, Bettina; Matthies, Franziska; Atkinson, Richard W; Iñiguez, Carmen; Basagaña, Xavier; Schneider, Alexandra; Lefranc, Agnès; Paldy, Anna; Bisanti, Luigi; Katsouyanni, Klea

    2014-01-01

    Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood. We explored the role of air pollution in modifying the effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990-2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results. The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75-84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75-84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15-30%) after adjustment for ozone or PM10. The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.

  2. Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events.

    PubMed

    Follmann, Dean; Huang, Chiung-Yu; Gabriel, Erin

    2016-10-30

    Unmeasured confounding is the fundamental obstacle to drawing causal conclusions about the impact of an intervention from observational data. Typically, covariates are measured to eliminate or ameliorate confounding, but they may be insufficient or unavailable. In the special setting where a transient intervention or exposure varies over time within each individual and confounding is time constant, a different tack is possible. The key idea is to condition on either the overall outcome or the proportion of time in the intervention. These measures can eliminate the unmeasured confounding either by conditioning or by use of a proxy covariate. We evaluate existing methods and develop new models from which causal conclusions can be drawn from such observational data even if no baseline covariates are measured. Our motivation for this work was to determine the causal effect of Streptococcus bacteria in the throat on pharyngitis (sore throat) in Indian schoolchildren. Using our models, we show that existing methods can be badly biased and that sick children who are rarely colonized have a high probability that the Streptococcus bacteria are causing their disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex

    PubMed Central

    Wells, Ellen M.; Herbstman, Julie B.; Lin, Yu Hong; Jarrett, Jeffery; Verdon, Carl P.; Ward, Cynthia; Caldwell, Kathleen L.; Hibbeln, Joseph R.; Witter, Frank R.; Halden, Rolf U.; Goldman, Lynn R.

    2015-01-01

    evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies. Citation Wells EM, Herbstman JB, Lin YH, Jarrett J, Verdon CP, Ward C, Caldwell KL, Hibbeln JR, Witter FR, Halden RU, Goldman LR. 2016. Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: potential confounding and effect modification by omega-3 fatty acids, selenium, and sex. Environ Health Perspect 124:373–379; http://dx.doi.org/10.1289/ehp.1408596 PMID:26115160

  4. Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex.

    PubMed

    Wells, Ellen M; Herbstman, Julie B; Lin, Yu Hong; Jarrett, Jeffery; Verdon, Carl P; Ward, Cynthia; Caldwell, Kathleen L; Hibbeln, Joseph R; Witter, Frank R; Halden, Rolf U; Goldman, Lynn R

    2016-03-01

    Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). Geometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n

  5. Confounding Effect in Clinical Research of Otolaryngology and Its Control.

    PubMed

    Yu, Yong-qiang; Huang, Dong-yan; Armijo Olivo, Susan; Yang, Huai-an; Bambanini, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Constantinescu, Gabriela; Qian Yu, Jason; Zhang, Ming

    2015-06-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.

  6. Distinguishing Selection Bias and Confounding Bias in Comparative Effectiveness Research.

    PubMed

    Haneuse, Sebastien

    2016-04-01

    Comparative effectiveness research (CER) aims to provide patients and physicians with evidence-based guidance on treatment decisions. As researchers conduct CER they face myriad challenges. Although inadequate control of confounding is the most-often cited source of potential bias, selection bias that arises when patients are differentially excluded from analyses is a distinct phenomenon with distinct consequences: confounding bias compromises internal validity, whereas selection bias compromises external validity. Despite this distinction, however, the label "treatment-selection bias" is being used in the CER literature to denote the phenomenon of confounding bias. Motivated by an ongoing study of treatment choice for depression on weight change over time, this paper formally distinguishes selection and confounding bias in CER. By formally distinguishing selection and confounding bias, this paper clarifies important scientific, design, and analysis issues relevant to ensuring validity. First is that the 2 types of biases may arise simultaneously in any given study; even if confounding bias is completely controlled, a study may nevertheless suffer from selection bias so that the results are not generalizable to the patient population of interest. Second is that the statistical methods used to mitigate the 2 biases are themselves distinct; methods developed to control one type of bias should not be expected to address the other. Finally, the control of selection and confounding bias will often require distinct covariate information. Consequently, as researchers plan future studies of comparative effectiveness, care must be taken to ensure that all data elements relevant to both confounding and selection bias are collected.

  7. Distinguishing selection bias and confounding bias in comparative effectiveness research

    PubMed Central

    Haneuse, Sebastien

    2014-01-01

    Comparative effectiveness research (CER) aims to provide patients and physicians with evidence-based guidance on treatment decisions. As researchers conduct CER they face myriad challenges. While inadequate control of confounding is the most-often cited source of potential bias, selection bias which arises when patients are differentially excluded from analyses is a distinct phenomenon with distinct consequences: confounding bias compromises internal validity while selection bias compromises external validity. Despite this distinction, however, the label “treatment-selection bias” is being used in the CER literature to denote the phenomenon of confounding bias. Motivated by an on-going study of treatment choice for depression on weight change over time, we formally distinguish confounding and selection bias in CER. By formally distinguishing selection and confounding bias we clarify important scientific, design and analysis issues relevant to ensuring validity. First is that the two types of bias may arise simultaneously in any given study; even if confounding bias is completely controlled, a study may nevertheless suffer from selection bias so that the results are not generalizable to the patient population of interest. Second is that statistical methods used to mitigate the two biases are themselves distinct; methods developed to control one type of bias should not be expected to address the other. Finally, the control of selection and confounding bias will often require distinct covariate information. Consequently, as researchers plan future studies of comparative effectiveness, care must be taken to ensure that all data elements relevant to both confounding and selection bias are collected. PMID:24309675

  8. Bayesian modeling of cost-effectiveness studies with unmeasured confounding: a simulation study.

    PubMed

    Stamey, James D; Beavers, Daniel P; Faries, Douglas; Price, Karen L; Seaman, John W

    2014-01-01

    Unmeasured confounding is a common problem in observational studies. Failing to account for unmeasured confounding can result in biased point estimators and poor performance of hypothesis tests and interval estimators. We provide examples of the impacts of unmeasured confounding on cost-effectiveness analyses using observational data along with a Bayesian approach to correct estimation. Assuming validation data are available, we propose a Bayesian approach to correct cost-effectiveness studies for unmeasured confounding. We consider the cases where both cost and effectiveness are assumed to have a normal distribution and when costs are gamma distributed and effectiveness is normally distributed. Simulation studies were conducted to determine the impact of ignoring the unmeasured confounder and to determine the size of the validation data required to obtain valid inferences.

  9. Does exposure prediction bias health-effect estimation?: The relationship between confounding adjustment and exposure prediction.

    PubMed

    Cefalu, Matthew; Dominici, Francesca

    2014-07-01

    In environmental epidemiology, we are often faced with 2 challenges. First, an exposure prediction model is needed to estimate the exposure to an agent of interest, ideally at the individual level. Second, when estimating the health effect associated with the exposure, confounding adjustment is needed in the health-effects regression model. The current literature addresses these 2 challenges separately. That is, methods that account for measurement error in the predicted exposure often fail to acknowledge the possibility of confounding, whereas methods designed to control confounding often fail to acknowledge that the exposure has been predicted. In this article, we consider exposure prediction and confounding adjustment in a health-effects regression model simultaneously. Using theoretical arguments and simulation studies, we show that the bias of a health-effect estimate is influenced by the exposure prediction model, the type of confounding adjustment used in the health-effects regression model, and the relationship between these 2. Moreover, we argue that even with a health-effects regression model that properly adjusts for confounding, the use of a predicted exposure can bias the health-effect estimate unless all confounders included in the health-effects regression model are also included in the exposure prediction model. While these results of this article were motivated by studies of environmental contaminants, they apply more broadly to any context where an exposure needs to be predicted.

  10. Unobserved time effects confound the identification of climate change impacts.

    PubMed

    Auffhammer, Maximilian; Vincent, Jeffrey R

    2012-07-24

    A recent study by Feng et al. [Feng S, Krueger A, Oppenheimer M (2010) Proc Natl Acad Sci USA 107:14257-14262] in PNAS reported statistical evidence of a weather-driven causal effect of crop yields on human migration from Mexico to the United States. We show that this conclusion is based on a different statistical model than the one stated in the paper. When we correct for this mistake, there is no evidence of a causal link.

  11. Unobserved time effects confound the identification of climate change impacts

    PubMed Central

    Auffhammer, Maximilian; Vincent, Jeffrey R.

    2012-01-01

    A recent study by Feng et al. [Feng S, Krueger A, Oppenheimer M (2010) Proc Natl Acad Sci USA 107:14257–14262] in PNAS reported statistical evidence of a weather-driven causal effect of crop yields on human migration from Mexico to the United States. We show that this conclusion is based on a different statistical model than the one stated in the paper. When we correct for this mistake, there is no evidence of a causal link. PMID:22783021

  12. Confounding Effects of Phase Delays on Causality Estimation

    PubMed Central

    Vakorin, Vasily A.; Mišić, Bratislav; Krakovska, Olga; Bezgin, Gleb; McIntosh, Anthony R.

    2013-01-01

    Linear and non-linear techniques for inferring causal relations between the brain signals representing the underlying neuronal systems have become a powerful tool to extract the connectivity patterns in the brain. Typically these tools employ the idea of Granger causality, which is ultimately based on the temporal precedence between the signals. At the same time, phase synchronization between coupled neural ensembles is considered a mechanism implemented in the brain to integrate relevant neuronal ensembles to perform a cognitive or perceptual task. Phase synchronization can be studied by analyzing the effects of phase-locking between the brain signals. However, we should expect that there is no one-to-one mapping between the observed phase lag and the time precedence as specified by physically interacting systems. Specifically, phase lag observed between two signals may interfere with inferring causal relations. This could be of critical importance for the coupled non-linear oscillating systems, with possible time delays in coupling, when classical linear cross-spectrum strategies for solving phase ambiguity are not efficient. To demonstrate this, we used a prototypical model of coupled non-linear systems, and compared three typical pipelines of inferring Granger causality, as established in the literature. Specifically, we compared the performance of the spectral and information-theoretic Granger pipelines as well as standard Granger causality in their relations to the observed phase differences for frequencies at which the signals become synchronized to each other. We found that an information-theoretic approach, which takes into account different time lags between the past of one signal and the future of another signal, was the most robust to phase effects. PMID:23349720

  13. Examining the Error of Mis-Specifying Nonlinear Confounding Effect with Application on Accelerometer-Measured Physical Activity

    ERIC Educational Resources Information Center

    Lee, Paul H.

    2017-01-01

    Purpose: Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. Methods: We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the…

  14. ADDRESSING CONFOUNDING WHEN ESTIMATING THE EFFECTS OF LATENT CLASSES ON A DISTAL OUTCOME.

    PubMed

    Schuler, Megan S; Leoutsakos, Jeannie-Marie S; Stuart, Elizabeth A

    2014-12-01

    Confounding is widely recognized in settings where all variables are fully observed, yet recognition of and statistical methods to address confounding in the context of latent class regression are slowly emerging. In this study we focus on confounding when regressing a distal outcome on latent class; extending standard confounding methods is not straightforward when the treatment of interest is a latent variable. We describe a recent 1-step method, as well as two 3-step methods (modal and pseudoclass assignment) that incorporate propensity score weighting. Using simulated data, we compare the performance of these three adjusted methods to an unadjusted 1-step and unadjusted 3-step method. We also present an applied example regarding adolescent substance use treatment that examines the effect of treatment service class on subsequent substance use problems. Our simulations indicated that the adjusted 1-step method and both adjusted 3-step methods significantly reduced bias arising from confounding relative to the unadjusted 1-step and 3-step approaches. However, the adjusted 1-step method performed better than the adjusted 3-step methods with regard to bias and 95% CI coverage, particularly when class separation was poor. Our applied example also highlighted the importance of addressing confounding - both unadjusted methods indicated significant differences across treatment classes with respect to the outcome, yet these class differences were not significant when using any of the three adjusted methods. Potential confounding should be carefully considered when conducting latent class regression with a distal outcome; failure to do so may results in significantly biased effect estimates or incorrect inferences.

  15. ADDRESSING CONFOUNDING WHEN ESTIMATING THE EFFECTS OF LATENT CLASSES ON A DISTAL OUTCOME

    PubMed Central

    Schuler, Megan S; Leoutsakos, Jeannie-Marie S; Stuart, Elizabeth A

    2014-01-01

    Confounding is widely recognized in settings where all variables are fully observed, yet recognition of and statistical methods to address confounding in the context of latent class regression are slowly emerging. In this study we focus on confounding when regressing a distal outcome on latent class; extending standard confounding methods is not straightforward when the treatment of interest is a latent variable. We describe a recent 1-step method, as well as two 3-step methods (modal and pseudoclass assignment) that incorporate propensity score weighting. Using simulated data, we compare the performance of these three adjusted methods to an unadjusted 1-step and unadjusted 3-step method. We also present an applied example regarding adolescent substance use treatment that examines the effect of treatment service class on subsequent substance use problems. Our simulations indicated that the adjusted 1-step method and both adjusted 3-step methods significantly reduced bias arising from confounding relative to the unadjusted 1-step and 3-step approaches. However, the adjusted 1-step method performed better than the adjusted 3-step methods with regard to bias and 95% CI coverage, particularly when class separation was poor. Our applied example also highlighted the importance of addressing confounding – both unadjusted methods indicated significant differences across treatment classes with respect to the outcome, yet these class differences were not significant when using any of the three adjusted methods. Potential confounding should be carefully considered when conducting latent class regression with a distal outcome; failure to do so may results in significantly biased effect estimates or incorrect inferences. PMID:25530706

  16. Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies.

    PubMed

    Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W; Tremlett, Helen

    2016-09-21

    In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008).

  17. EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE TREATMENT EFFECT

    PubMed Central

    Handorf, Elizabeth A.; Bekelman, Justin E.; Heitjan, Daniel F.; Mitra, Nandita

    2014-01-01

    Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general adjustment formula for loglinear models of mean cost and explore special cases under plausible assumptions about the distribution of the unmeasured confounder. We assess the performance of the adjustment by simulation, in particular, examining robustness to a key assumption of conditional independence between the unmeasured and measured covariates given the treatment indicator. We apply our method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder cancer cohort. We evaluate the costs for radical cystectomy vs. combined radiation/chemotherapy, and find that the significance of the treatment effect is sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders. PMID:24587844

  18. Guided Bayesian imputation to adjust for confounding when combining heterogeneous data sources in comparative effectiveness research.

    PubMed

    Antonelli, Joseph; Zigler, Corwin; Dominici, Francesca

    2017-03-03

    In comparative effectiveness research, we are often interested in the estimation of an average causal effect from large observational data (the main study). Often this data does not measure all the necessary confounders. In many occasions, an extensive set of additional covariates is measured for a smaller and non-representative population (the validation study). In this setting, standard approaches for missing data imputation might not be adequate due to the large number of missing covariates in the main data relative to the smaller sample size of the validation data. We propose a Bayesian approach to estimate the average causal effect in the main study that borrows information from the validation study to improve confounding adjustment. Our approach combines ideas of Bayesian model averaging, confounder selection, and missing data imputation into a single framework. It allows for different treatment effects in the main study and in the validation study, and propagates the uncertainty due to the missing data imputation and confounder selection when estimating the average causal effect (ACE) in the main study. We compare our method to several existing approaches via simulation. We apply our method to a study examining the effect of surgical resection on survival among 10 396 Medicare beneficiaries with a brain tumor when additional covariate information is available on 2220 patients in SEER-Medicare. We find that the estimated ACE decreases by 30% when incorporating additional information from SEER-Medicare.

  19. Multi-locus Test and Correction for Confounding Effects in Genome-Wide Association Studies.

    PubMed

    Chen, Donglai; Liu, Chuanhai; Xie, Jun

    2016-11-01

    Genome-wide association studies (GWAS) examine a large number of genetic variants, e. g., single nucleotide polymorphisms (SNP), and associate them with a disease of interest. Traditional statistical methods for GWASs can produce spurious associations, due to limited information from individual SNPs and confounding effects. This paper develops two statistical methods to enhance data analysis of GWASs. The first is a multiple-SNP association test, which is a weighted chi-square test derived for big contingency tables. The test assesses combinatorial effects of multiple SNPs and improves conventional methods of single SNP analysis. The second is a method that corrects for confounding effects, which may come from population stratification as well as other ambiguous (unknown) factors. The proposed method identifies a latent confounding factor, using a profile of whole genome SNPs, and eliminates confounding effects through matching or stratified statistical analysis. Simulations and a GWAS of rheumatoid arthritis demonstrate that the proposed methods dramatically remove the number of significant tests, or false positives, and outperforms other available methods.

  20. Multi-locus Test and Correction for Confounding Effects in Genome-Wide Association Studies

    PubMed Central

    Chen, Donglai; Liu, Chuanhai; Xie, Jun

    2016-01-01

    Genome-wide association studies (GWAS) examine a large number of genetic variants, e.g., single nucleotide polymorphisms (SNP), and associate them with a disease of interest. Traditional statistical methods for GWASs can produce spurious associations, due to limited information from individual SNPs and confounding effects. This paper develops two statistical methods to enhance data analysis of GWASs. The first is a multiple-SNP association test, which is a weighted chi-square test derived for big contingency tables. The test assesses combinatorial effects of multiple SNPs and improves conventional methods of single SNP analysis. The second is a method that corrects for confounding effects, which may come from population stratification as well as other ambiguous (unknown) factors. The proposed method identifies a latent confounding factor, using a profile of whole genome SNPs, and eliminates confounding effects through matching or stratified statistical analysis. Simulations and a GWAS of rheumatoid arthritis demonstrate that the proposed methods dramatically remove the number of significant tests, or false positives, and outperforms other available methods. PMID:27232635

  1. Effect of omitted confounders on the analysis of correlated binary data.

    PubMed

    Chao, W H; Palta, M; Young, T

    1997-06-01

    Marginal analysis using the generalized estimating equation approach is widely applied to correlated observations, as occur in studies with clusters and in longitudinal follow-up of individuals. In this article, we investigate the effect of confounding in such models. We assume that a risk factor x and a confounder z are related by a generalized linear model to the outcome y, which can be binary or ordinal. In order to investigate confounding arising from the omission of z, a joint structure for x and z must be specified. Modeling normally distributed (x,z) as sums of between- and within-individual (or cluster) components allows us to incorporate different degrees of between- and within-individual correlation. Such a structure includes, as special cases, cohort and period effects in longitudinal settings and random intercept models. The latter situation corresponds to allowing z to vary only on the between-individual (or cluster) level and to be uncorrelated with x, and leads to attenuation of the coefficient of x in marginal models with the logit and probit links. More complex situations occur when z is allowed to also vary on the within-individual (or cluster) level and when z is correlated with x. We examine the model specification and the expected bias when fitting a marginal model in the presence of the omitted confounder z. We derive general formulas and interpret the parameters and results in an ongoing cohort study. Testing for omitted covariates is also discussed.

  2. Assessing the impact of unmeasured confounding for binary outcomes using confounding functions.

    PubMed

    Kasza, Jessica; Wolfe, Rory; Schuster, Tibor

    2017-03-03

    A critical assumption of causal inference is that of no unmeasured confounding: for estimated exposure effects to have valid causal interpretations, a sufficient set of predictors of exposure and outcome must be adequately measured and correctly included in the respective inference model(s). In an observational study setting, this assumption will often be unsatisfied, and the potential impact of unmeasured confounding on effect estimates should be investigated. The confounding function approach allows the impact of unmeasured confounding on estimates to be assessed, where unmeasured confounding may be due to unmeasured confounders and/or biases such as collider bias or information bias. Although this approach is easy to implement and pertains to the sum of all bias, its use has not been widespread, and discussion has typically been limited to continuous outcomes. In this paper, we consider confounding functions for use with binary outcomes and illustrate the approach with an example. We note that confounding function choice encodes assumptions about effect modification: some choices encode the belief that the true causal effect differs across exposure groups, whereas others imply that any difference between the true causal parameter and the estimate is entirely due to imbalanced risks between exposure groups. The confounding function approach is a useful method for assessing the impact of unmeasured confounding, in particular when alternative approaches, e.g. external adjustment or instrumental variable approaches, cannot be applied. We provide Stata and R code for the implementation of this approach when the causal estimand of interest is an odds or risk ratio.

  3. Examining the Error of Mis-Specifying Nonlinear Confounding Effect With Application on Accelerometer-Measured Physical Activity.

    PubMed

    Lee, Paul H

    2017-06-01

    Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the estimation of a causal relationship between the exposure and outcome in 3 ways: using a linear term, binning into 5 equal-size categories, or using a restricted cubic spline of the confounder. Continuous, binary, and survival outcomes were simulated. We examined the confounder across varying measurement error. In addition, we performed a real data analysis examining the 3 strategies to handle the nonlinear effects of accelerometer-measured physical activity in the National Health and Nutrition Examination Survey 2003-2006 data. The mis-specification of a nonlinear confounder had little impact on causal effect estimation for continuous outcomes. For binary and survival outcomes, this mis-specification introduced bias, which could be eliminated using spline adjustment only when there is small measurement error of the confounder. Real data analysis showed that the associations between high blood pressure, high cholesterol, and diabetes and mortality adjusted for physical activity with restricted cubic spline were about 3% to 11% larger than their counterparts adjusted with a linear term. For continuous outcomes, confounders with nonlinear effects can be adjusting with a linear term. Spline adjustment should be used for binary and survival outcomes on confounders with small measurement error.

  4. Confounder Summary Scores When Comparing the Effects of Multiple Drug Exposures

    PubMed Central

    Cadarette, Suzanne M.; Gagne, Joshua J.; Solomon, Daniel H.; Katz, Jeffrey N.; Stürmer, Til

    2009-01-01

    Purpose Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS) and disease risk score (DRS). Methods Each method was applied to a dataset (2000–2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin and raloxifene in preventing nonvertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Results Less than 5 percent deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in −7% to +13% deviation from our base estimate. Conclusions With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings. PMID:19757416

  5. Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

    PubMed Central

    Chiba, Yasutaka

    2014-01-01

    Questions of mediation are often of interest in reasoning about mechanisms, and methods have been developed to address these questions. However, these methods make strong assumptions about the absence of confounding. Even if exposure is randomized, there may be mediator-outcome confounding variables. Inference about direct and indirect effects is particularly challenging if these mediator-outcome confounders are affected by the exposure because in this case these effects are not identified irrespective of whether data is available on these exposure-induced mediator-outcome confounders. In this paper, we provide a sensitivity analysis technique for natural direct and indirect effects that is applicable even if there are mediator-outcome confounders affected by the exposure. We give techniques for both the difference and risk ratio scales and compare the technique to other possible approaches. PMID:25580387

  6. Accounting for uncertainty in confounder and effect modifier selection when estimating average causal effects in generalized linear models.

    PubMed

    Wang, Chi; Dominici, Francesca; Parmigiani, Giovanni; Zigler, Corwin Matthew

    2015-09-01

    Confounder selection and adjustment are essential elements of assessing the causal effect of an exposure or treatment in observational studies. Building upon work by Wang et al. (2012, Biometrics 68, 661-671) and Lefebvre et al. (2014, Statistics in Medicine 33, 2797-2813), we propose and evaluate a Bayesian method to estimate average causal effects in studies with a large number of potential confounders, relatively few observations, likely interactions between confounders and the exposure of interest, and uncertainty on which confounders and interaction terms should be included. Our method is applicable across all exposures and outcomes that can be handled through generalized linear models. In this general setting, estimation of the average causal effect is different from estimation of the exposure coefficient in the outcome model due to noncollapsibility. We implement a Bayesian bootstrap procedure to integrate over the distribution of potential confounders and to estimate the causal effect. Our method permits estimation of both the overall population causal effect and effects in specified subpopulations, providing clear characterization of heterogeneous exposure effects that may vary considerably across different covariate profiles. Simulation studies demonstrate that the proposed method performs well in small sample size situations with 100-150 observations and 50 covariates. The method is applied to data on 15,060 US Medicare beneficiaries diagnosed with a malignant brain tumor between 2000 and 2009 to evaluate whether surgery reduces hospital readmissions within 30 days of diagnosis.

  7. Magnitude and direction of missing confounders had different consequences on treatment effect estimation in propensity score analysis.

    PubMed

    Nguyen, Tri-Long; Collins, Gary S; Spence, Jessica; Fontaine, Charles; Daurès, Jean-Pierre; Devereaux, Philip J; Landais, Paul; Le Manach, Yannick

    2017-07-01

    Propensity score (PS) analysis allows an unbiased estimate of treatment effects but assumes that all confounders are measured. We assessed the impact of omitting confounders from a PS analysis on clinical decision making. We conducted Monte Carlo simulations on hypothetical observational studies based on virtual populations and on the population from a large randomized trial (CRASH-2). In both series of simulations, PS analysis was conducted with all confounders and with omitted confounders, which were defined to have different strengths of association with the outcome and treatment exposure. After inverse probability of treatment weighting, we calculated the absolute risk differences and numbers needed to treat (NNT). In both series of simulations, omitting a confounder that was moderately associated with the outcome and exposure led to negligible bias on the NNT scale. The bias induced by omitting strongly positive confounding variables remained less than 15 patients to treat. Major bias and reversed effects were found only when omitting highly prevalent, strongly negative confounders that were similarly associated with the outcome and exposure with odds ratios greater than 4.00 (or <0.25). This omission was accompanied by a substantial decrease in analysis power. The omission of strongly negative confounding variables from a PS analysis can lead to incorrect clinical decision making. However, omitting these variables also decreases the analysis power, which may prevent the reporting of significant but misleading effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Overcoming confounding plate effects in differential expression analyses of single-cell RNA-seq data.

    PubMed

    Lun, Aaron T L; Marioni, John C

    2017-02-06

    An increasing number of studies are using single-cell RNA-sequencing (scRNA-seq) to characterize the gene expression profiles of individual cells. One common analysis applied to scRNA-seq data involves detecting differentially expressed (DE) genes between cells in different biological groups. However, many experiments are designed such that the cells to be compared are processed in separate plates or chips, meaning that the groupings are confounded with systematic plate effects. This confounding aspect is frequently ignored in DE analyses of scRNA-seq data. In this article, we demonstrate that failing to consider plate effects in the statistical model results in loss of type I error control. A solution is proposed whereby counts are summed from all cells in each plate and the count sums for all plates are used in the DE analysis. This restores type I error control in the presence of plate effects without compromising detection power in simulated data. Summation is also robust to varying numbers and library sizes of cells on each plate. Similar results are observed in DE analyses of real data where the use of count sums instead of single-cell counts improves specificity and the ranking of relevant genes. This suggests that summation can assist in maintaining statistical rigour in DE analyses of scRNA-seq data with plate effects.

  9. The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders

    PubMed Central

    Hayes, Richard D.; Downs, Johnny; Chang, Chin-Kuo; Jackson, Richard G.; Shetty, Hitesh; Broadbent, Matthew; Hotopf, Matthew; Stewart, Robert

    2015-01-01

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007–2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2–0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes. PMID:25154620

  10. Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

    PubMed Central

    Sheikh, Mashhood Ahmed

    2017-01-01

    The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the

  11. Formulating tightest bounds on causal effects in studies with unmeasured confounders.

    PubMed

    Kuroki, Manabu; Cai, Zhihong

    2008-12-30

    This paper considers the problem of evaluating the causal effect of an exposure on an outcome in observational studies with both measured and unmeasured confounders between the exposure and the outcome. Under such a situation, MacLehose et al. (Epidemiology 2005; 16:548-555) applied linear programming optimization software to find the minimum and maximum possible values of the causal effect for specific numerical data. In this paper, we apply the symbolic Balke-Pearl linear programming method (Probabilistic counterfactuals: semantics, computation, and applications. Ph.D. Thesis, UCLA Cognitive Systems Laboratory, 1995; J. Amer. Statist. Assoc. 1997; 92:1172-1176) to derive the simple closed-form expressions for the lower and upper bounds on causal effects under various assumptions of monotonicity. These universal bounds enable epidemiologists and medical researchers to assess causal effects from observed data with minimum computational effort, and they further shed light on the accuracy of the assessment. Copyright 2008 John Wiley & Sons, Ltd.

  12. On the Confounding Effect of Temperature on Chemical Shift-Encoded Fat Quantification

    PubMed Central

    Hernando, Diego; Sharma, Samir D.; Kramer, Harald; Reeder, Scott B.

    2014-01-01

    Purpose To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. Methods The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat–water signals at various temperatures and echo time combinations. Oil–water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat–water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. Results In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. Conclusion Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions. PMID:24123362

  13. Spectral cytopathology: new aspects of data collection, manipulation and confounding effects.

    PubMed

    Miljković, Miloš; Bird, Benjamin; Lenau, Kathleen; Mazur, Antonella I; Diem, Max

    2013-07-21

    This paper presents a short review on the improvements in data processing for spectral cytopathology, the diagnostic method developed for large scale diagnostic analysis of spectral data of individual dried and fixed cells. This review is followed by the analysis of the confounding effects introduced by utilizing reflecting "low-emissivity" (low-e) slides as sample substrates in infrared micro-spectroscopy of biological samples such as individual dried cells or tissue sections. The artifact introduced by these substrates, referred to as the "standing electromagnetic wave" artifact, indeed, distorts the spectra noticeably, as postulated recently by several research groups. An analysis of the standing wave effect reveals that careful data pre-processing can reduce the spurious effects to a level where they are not creating a major problem for spectral cytopathology and spectral histopathology.

  14. Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia.

    PubMed

    Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

    2016-01-01

    Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent "time effects" in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.

  15. Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

    PubMed Central

    Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

    2015-01-01

    Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

  16. Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

    PubMed

    Charron, L; Geffard, O; Chaumot, A; Coulaud, R; Queau, H; Geffard, A; Dedourge-Geffard, O

    2013-12-01

    The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

  17. A causal examination of the effects of confounding factors on multimetric indices

    USGS Publications Warehouse

    Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

    2013-01-01

    The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

  18. A comparison of confounding adjustment methods for assessment of asthma controller medication effectiveness.

    PubMed

    Li, Lingling; Vollmer, William M; Butler, Melissa G; Wu, Pingsheng; Kharbanda, Elyse O; Wu, Ann Chen

    2014-03-01

    We compared the impact of 3 confounding adjustment procedures-covariate-adjusted regression, propensity score regression, and high-dimensional propensity score regression-to assess the effects of selected asthma controller medication use (leukotriene antagonists and inhaled corticosteroids) on the following 4 asthma-related adverse outcomes: emergency department visits, hospitalizations, oral corticosteroid use, and the composite outcome of these. We examined a cohort of 24,680 new users who were 4-17 years of age at the incident dispensing from the Population-Based Effectiveness in Asthma and Lung Diseases (PEAL) Network of 5 commercial health plans and TennCare, the Tennessee Medicaid program, during the period January 1, 2004, to December 31, 2010. The 3 methods yielded similar results, indicating that pediatric patients treated with leukotriene antagonists were no more likely than those treated with inhaled corticosteroids to experience adverse outcomes. Children in the TennCare population who had a diagnosis of allergic rhinitis and who then initiated the use of leukotriene antagonists were less likely to experience an asthma-related emergency department visit. A plausible explanation is that our data set is large enough that the 2 advanced propensity score-based analyses do not have advantages over the traditional covariate-adjusted regression approach. We provide important observations on how to correctly apply the methods in observational data analysis and suggest statistical research areas that need more work to guide implementation.

  19. Batch effect confounding leads to strong bias in performance estimates obtained by cross-validation.

    PubMed

    Soneson, Charlotte; Gerster, Sarah; Delorenzi, Mauro

    2014-01-01

    With the large amount of biological data that is currently publicly available, many investigators combine multiple data sets to increase the sample size and potentially also the power of their analyses. However, technical differences ("batch effects") as well as differences in sample composition between the data sets may significantly affect the ability to draw generalizable conclusions from such studies. The current study focuses on the construction of classifiers, and the use of cross-validation to estimate their performance. In particular, we investigate the impact of batch effects and differences in sample composition between batches on the accuracy of the classification performance estimate obtained via cross-validation. The focus on estimation bias is a main difference compared to previous studies, which have mostly focused on the predictive performance and how it relates to the presence of batch effects. We work on simulated data sets. To have realistic intensity distributions, we use real gene expression data as the basis for our simulation. Random samples from this expression matrix are selected and assigned to group 1 (e.g., 'control') or group 2 (e.g., 'treated'). We introduce batch effects and select some features to be differentially expressed between the two groups. We consider several scenarios for our study, most importantly different levels of confounding between groups and batch effects. We focus on well-known classifiers: logistic regression, Support Vector Machines (SVM), k-nearest neighbors (kNN) and Random Forests (RF). Feature selection is performed with the Wilcoxon test or the lasso. Parameter tuning and feature selection, as well as the estimation of the prediction performance of each classifier, is performed within a nested cross-validation scheme. The estimated classification performance is then compared to what is obtained when applying the classifier to independent data.

  20. Batch Effect Confounding Leads to Strong Bias in Performance Estimates Obtained by Cross-Validation

    PubMed Central

    Delorenzi, Mauro

    2014-01-01

    Background With the large amount of biological data that is currently publicly available, many investigators combine multiple data sets to increase the sample size and potentially also the power of their analyses. However, technical differences (“batch effects”) as well as differences in sample composition between the data sets may significantly affect the ability to draw generalizable conclusions from such studies. Focus The current study focuses on the construction of classifiers, and the use of cross-validation to estimate their performance. In particular, we investigate the impact of batch effects and differences in sample composition between batches on the accuracy of the classification performance estimate obtained via cross-validation. The focus on estimation bias is a main difference compared to previous studies, which have mostly focused on the predictive performance and how it relates to the presence of batch effects. Data We work on simulated data sets. To have realistic intensity distributions, we use real gene expression data as the basis for our simulation. Random samples from this expression matrix are selected and assigned to group 1 (e.g., ‘control’) or group 2 (e.g., ‘treated’). We introduce batch effects and select some features to be differentially expressed between the two groups. We consider several scenarios for our study, most importantly different levels of confounding between groups and batch effects. Methods We focus on well-known classifiers: logistic regression, Support Vector Machines (SVM), k-nearest neighbors (kNN) and Random Forests (RF). Feature selection is performed with the Wilcoxon test or the lasso. Parameter tuning and feature selection, as well as the estimation of the prediction performance of each classifier, is performed within a nested cross-validation scheme. The estimated classification performance is then compared to what is obtained when applying the classifier to independent data. PMID:24967636

  1. The confounded effects of age and exposure history in response to influenza vaccination

    PubMed Central

    Höpping, Ana Mosterín; McElhaney, Janet; Fonville, Judith M.; Powers, Douglas C.; Beyer, Walter E.P.; Smith, Derek J.

    2016-01-01

    Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence – the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly. PMID:26667611

  2. The confounded effects of age and exposure history in response to influenza vaccination.

    PubMed

    Mosterín Höpping, Ana; McElhaney, Janet; Fonville, Judith M; Powers, Douglas C; Beyer, Walter E P; Smith, Derek J

    2016-01-20

    Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence-the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly.

  3. [Bias in observational research: 'confounding'].

    PubMed

    Groenwold, Rolf H H

    2012-01-01

    Confounding is an important and common issue in observational (non-randomized) research on the effects of pharmaceuticals or exposure to etiologic factors (determinants). Confounding is present when a third factor, related to both the determinant and the outcome, distorts the causal relation between these two. There are different methods to control for confounding. The most commonly used are restriction, stratification, multivariable regression models, and propensity score methods. With these methods it is only possible to control for variables for which data is known: measured confounders. Research in the area of confounding is currently directed at the incorporation of external knowledge on unmeasured confounders, the evaluation of instrumental variables, and the impact of time-dependent confounding.

  4. Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

    PubMed Central

    Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

    2015-01-01

    We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

  5. Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

    PubMed

    Blanes-Vidal, Victoria; Schwartz, Joel

    2016-01-01

    Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias.

  6. Doubly robust estimators of causal exposure effects with missing data in the outcome, exposure or a confounder.

    PubMed

    Williamson, E J; Forbes, A; Wolfe, R

    2012-12-30

    We consider the estimation of the causal effect of a binary exposure on a continuous outcome. Confounding and missing data are both likely to occur in practice when observational data are used to estimate this causal effect. In dealing with each of these problems, model misspecification is likely to introduce bias. We present augmented inverse probability weighted (AIPW) estimators that account for both confounding and missing data, with the latter occurring in a single variable only. These estimators have an element of robustness to misspecification of the models used. Our estimators require two models to be specified to deal with confounding and two to deal with missing data. Only one of each of these models needs to be correctly specified. When either the outcome or the exposure of interest is missing, we derive explicit expressions for the AIPW estimator. When a confounder is missing, explicit derivation is complex, so we use a simple algorithm, which can be applied using standard statistical software, to obtain an approximation to the AIPW estimator.

  7. Controlling confounding by frailty when estimating influenza vaccine effectiveness using predictors of dependency in activities of daily living.

    PubMed

    Zhang, Henry T; McGrath, Leah J; Wyss, Richard; Ellis, Alan R; Stürmer, Til

    2017-08-24

    To improve control of confounding by frailty when estimating the effect of influenza vaccination on all-cause mortality by controlling for a published set of claims-based predictors of dependency in activities of daily living (ADL). Using Medicare claims data, a cohort of beneficiaries >65 years of age was followed from September 1, 2007, to April 12, 2008, with covariates assessed in the 6 months before follow-up. We estimated Cox proportional hazards models of all-cause mortality, with influenza vaccination as a time-varying exposure. We controlled for common demographics, comorbidities, and health care utilization variables and then added 20 ADL dependency predictors. To gauge residual confounding, we estimated pre-influenza season hazard ratios (HRs) between September 1, 2007 and January 5, 2008, which should be 1.0 in the absence of bias. A cohort of 2 235 140 beneficiaries was created, with a median follow-up of 224 days. Overall, 52% were vaccinated and 4% died during follow-up. During the pre-influenza season period, controlling for demographics, comorbidities, and health care use resulted in a HR of 0.66 (0.64, 0.67). Adding the ADL dependency predictors moved the HR to 0.68 (0.67, 0.70). Controlling for demographics and ADL dependency predictors alone resulted in a HR of 0.68 (0.66, 0.70). Results were consistent with those in the literature, with significant uncontrolled confounding after adjustment for demographics, comorbidities, and health care use. Adding ADL dependency predictors moved HRs slightly closer to the null. Of the comorbidities, health care use variables, and ADL dependency predictors, the last set reduced confounding most. However, substantial uncontrolled confounding remained. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Lung cancer gene associated with COPD: triple whammy or possible confounding effect?

    PubMed

    Young, R P; Hopkins, R J; Hay, B A; Epton, M J; Black, P N; Gamble, G D

    2008-11-01

    Recently, several large genome-wide association studies have identified a putative "lung cancer" locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%). The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the alpha5 subunit of the nAChR gene cluster between three matched smoking cohorts. The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively. These findings suggest that the association between the alpha5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.

  9. Some effects of dust on photometry of high-z galaxies: Confounding the effects of evolution

    NASA Technical Reports Server (NTRS)

    Thronson, H. A., Jr.; Witt, A. N.; Capuano, J.

    1993-01-01

    Photometric observations of very distant galaxies--e.g., color vs. z or magnitude vs. z, have been used over the past decade or so in investigations into the evolution of the stellar component. Numerous studies have predicted significant color variations as a result of evolution, in addition to the shifting of different rest wavelengths into the band of observation. Although there is significant scatter, the data can be fit with relatively straightforward, plausible models for galaxian evolution. In very few cases are the effects of dust extinction included in the models. This is due in a large part to the uncertainty about the distribution and optical properties of the grains, and even whether or not they are present in significant numbers in some types of galaxies such as ellipticals. It is likely that the effects of dust on broadband observations are the greatest uncertainty in studies of very distant galaxies. We use a detailed Monte Carlo radiative transfer model within a spherical geometry for different star/dust distributions to examine the effects of dust on the broadband colors of galaxies as a function of redshift. The model fully accounts for absorption and angular redistribution in scattering. In this summary, we consider only the effects on color vs. redshift for three simple geometries each with the same total dust optical depth. Elsewhere at this conference, Capuano, Thronson, & Witt consider other effects of altering the relative dust/star distribution.

  10. Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications

    PubMed Central

    Hak, E; Verheij, T.; Grobbee, D; Nichol, K; Hoes, A

    2002-01-01

    Randomised allocation of vaccine or placebo is the preferred method to assess the effects of the vaccine on clinical outcomes relevant to the individual patient. In the absence of phase 3 trials using clinical end points, notably post-influenza complications, alternative non-experimental designs to evaluate vaccine effects or safety are often used. The application of these designs may, however, lead to invalid estimates of vaccine effectiveness or safety. As patients with poor prognosis are more likely to be immunised, selection for vaccination is confounded by patient factors that are also related to clinical end points. This paper describes several design and analytical methods aimed at limiting or preventing this confounding by indication in non-experimental studies. In short, comparison of study groups with similar prognosis, restriction of the study population, and statistical adjustment for dissimilarities in prognosis are important tools and should be considered. Only if the investigator is able to show that confounding by indication is sufficiently controlled for, results of a non-experimental study may be of use to direct an evidence based vaccine policy. PMID:12461118

  11. Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

    PubMed

    Ogna, Adam; Forni Ogna, Valentina; Bochud, Murielle; Guessous, Idris; Paccaud, Fred; Burnier, Michel; Wuerzner, Gregoire

    2016-04-01

    Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

  12. Measuring oxidative stress: the confounding effect of lipid concentration in measures of lipid peroxidation.

    PubMed

    Pérez-Rodríguez, Lorenzo; Romero-Haro, Ana A; Sternalski, Audrey; Muriel, Jaime; Mougeot, Francois; Gil, Diego; Alonso-Alvarez, Carlos

    2015-01-01

    Lipid peroxidation products are widely used as markers of oxidative damage in the organism. To properly interpret the information provided by these markers, it is necessary to know potential sources of bias and control confounding factors. Here, we investigated the relationship between two indicators of lipid mobilization (circulating levels of triglycerides and cholesterol) and two common markers of oxidative damage (plasma levels of malondialdehyde and hydroperoxides; the latter estimated from the d-ROMs assay kit). The following five avian species were studied: red-legged partridge (Alectoris rufa), zebra finch (Taeniopygia guttata), spotless starling (Sturnus unicolor), marsh harrier (Circus aeroginosus), and Montagu's harrier (Circus pygargus). In all cases, plasma triglyceride levels positively and significantly correlated with lipid peroxidation markers, explaining between 8% and 34% of their variability. Plasma cholesterol, in contrast, showed a significant positive relationship only among spotless starling nestlings and a marginally significant association in zebra finches. These results indicate that lipid peroxidation marker levels covary with circulating lipid levels. We discuss the potential causes and implications of this covariation and recommend that future studies that measure oxidative damage using lipid peroxidation markers report both raw and relative levels (i.e., corrected for circulating triglycerides). Whether the observed pattern also holds for other tissues and in other taxa would deserve further research.

  13. An apparent-motion confound causes the negative exogenous cuing effect at SOAs with larger numbers of target locations.

    PubMed

    Chen, Peii; Mordkoff, J Toby

    2012-01-01

    Salient but irrelevant stimuli seem to cause an automatic orienting of covert attention, facilitating the detection of targets at the cued location for a brief period of time. However, this finding is highly dependent on the number of possible target locations, at least when the simple detection of targets is all that the task requires. Whereas small numbers of possible target locations (e.g., 2 or 3) produce the well-known advantage in response time for valid cue trials (i.e., a positive cuing effect), larger numbers of possible target locations (e.g., 6 or 8) produce a negative cuing effect. If not explained in terms of a nonattentional mechanism, this latter finding raises serious questions about the standard interpretation of positive cuing effects. The present experiment tested a particular nonattentional mechanism: that a confound between target presence and apparent motion, which occurs only on invalid cue trials, is responsible for negative cuing effect. We reduced or eliminated this confound by the use of a new type of catch trial and eliminated the negative cuing effect with large numbers of target locations.

  14. Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study.

    PubMed

    Blanco, María Encarnación; González, Oskar; Albóniga, Oihane Elena; Alonso, María Luz; Alonso, Rosa María

    2017-09-01

    A pilot study for the investigation of the maturation grade of children has been carried out using plasma samples already analyzed in a previous pharmacokinetic study. By using a meticulous data treatment, possible confounding factors that may hinder the obtained results were identified. By doing so, it was possible to obtain enough evidence to support the feasibility of performing a larger study eluding some unwanted variability and minimizing not only the number of subjects involved but also the time and money spent on the study. In the pilot study the metabolic profiles obtained using UHPLC-TOF-MS technique of plasma samples from 14 newborn piglets (<5 days) were compared with the plasma profiles of 16 infant piglets (8 weeks). The type of anaesthesia administered, gender, vein or artery of blood extraction and time of sampling were studied as possible confounding factors. Unsupervised analysis by principal component analysis (PCA) clearly differentiated between neonates and children. During the data treatment and the statistical analysis, the effect of confounding factors such as the anaesthetic regimen was identified and removed, while the effect of the rest of studied factors was not considered relevant, and the discrimination between the two groups based on the age was maintained. This allowed extracting relevant conclusions for a future study design while avoiding the unnecessary sacrifice of animals. Furthermore, the results obtained demonstrate the utility of metabolomics in the discovery of novel putative plasma biomarkers such as carnitines that can be correlated with the maturation state of paediatric patients. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Prior event rate ratio adjustment for hidden confounding in observational studies of treatment effectiveness: a pairwise Cox likelihood approach.

    PubMed

    Lin, Nan Xuan; Henley, William Edward

    2016-12-10

    Observational studies provide a rich source of information for assessing effectiveness of treatment interventions in many situations where it is not ethical or practical to perform randomized controlled trials. However, such studies are prone to bias from hidden (unmeasured) confounding. A promising approach to identifying and reducing the impact of unmeasured confounding is prior event rate ratio (PERR) adjustment, a quasi-experimental analytic method proposed in the context of electronic medical record database studies. In this paper, we present a statistical framework for using a pairwise approach to PERR adjustment that removes bias inherent in the original PERR method. A flexible pairwise Cox likelihood function is derived and used to demonstrate the consistency of the simple and convenient alternative PERR (PERR-ALT) estimator. We show how to estimate standard errors and confidence intervals for treatment effect estimates based on the observed information and provide R code to illustrate how to implement the method. Assumptions required for the pairwise approach (as well as PERR) are clarified, and the consequences of model misspecification are explored. Our results confirm the need for researchers to consider carefully the suitability of the method in the context of each problem. Extensions of the pairwise likelihood to more complex designs involving time-varying covariates or more than two periods are considered. We illustrate the application of the method using data from a longitudinal cohort study of enzyme replacement therapy for lysosomal storage disorders. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  16. Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

    NASA Astrophysics Data System (ADS)

    Chaibub Neto, Elias

    2016-11-01

    Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

  17. Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

    PubMed Central

    Chaibub Neto, Elias

    2016-01-01

    Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials. PMID:27869205

  18. A principal stratification approach for evaluating natural direct and indirect effects in the presence of treatment-induced intermediate confounding.

    PubMed

    Taguri, Masataka; Chiba, Yasutaka

    2015-01-15

    Recently, several authors have shown that natural direct and indirect effects (NDEs and NIEs) can be identified under the sequential ignorability assumptions, as long as there is no mediator-outcome confounder that is affected by the treatment. However, if such a confounder exists, NDEs and NIEs will generally not be identified without making additional identifying assumptions. In this article, we propose novel identification assumptions and estimators for evaluating NDEs and NIEs under the usual sequential ignorability assumptions, using the principal stratification framework. It is assumed that the treatment and the mediator are dichotomous. We must impose strong assumptions for identification. However, even if these assumptions were violated, the bias of our estimator would be small under typical conditions, which can be easily evaluated from the observed data. This conjecture is confirmed for binary outcomes by deriving the bounds of the bias terms. In addition, the advantage of our estimator is illustrated through a simulation study. We also propose a method of sensitivity analysis that examines what happens when our assumptions are violated. We apply the proposed method to data from the National Center for Health Statistics.

  19. Removing the confounding effect of habitat specialization reveals the stabilizing contribution of diversity to species variability.

    PubMed Central

    Kolasa, Jurek; Li, Bai-Lian

    2003-01-01

    Earlier studies have found that diversity, S, stabilizes the relative variability of combined biomass or abundance of species making up a community. However, the effect of S on variability of constituent species has been elusive. We hypothesize that the proportion of specialists increases with S and, because specialists are more variable, this shift in composition will mask the stabilizing effect of S on populations of species making up a community. The test uses data on variability and ecological specialization of species in 49 natural rock pool invertebrate communities. Initial analyses produced inconclusive results similar to earlier studies. However, when variability owing to species' specialization was factored out, S reduced species' abundance variability, although not in all communities. Our study explains why the stabilizing effect of diversity on populations has not been found earlier. PMID:14667382

  20. Disentangling the confounding effects of PAR and air temperature on net ecosystem exchange in time and scale

    NASA Astrophysics Data System (ADS)

    yang, Z.; Chen, J.; Becker, R.; Chu, H.; Xie, J.; Shao, C.

    2013-12-01

    Net ecosystem exchange of CO2 (NEE) in temperate forests is modulated by microclimatic factors. The effects of those factors differ at different time scales and during different time periods. Some of them are correlated across a number of time scales, so their effects on NEE are confounded by each other. PAR and air temperature (Ta) are among the two most important drivers of NEE in temperate forests, and among the two most correlated microclimatic factors. PAR and Ta have similar daily, seasonal, and annual cycles. Their influence on NEE is confounded by each other and entangled together especially at those scales. In this study, we tried to disentangle the confounding effects of them on NEE at different time scales and during different time periods. To accomplish this objective, we applied the innovative spectral analysis techniques including Continuous Wavelet Transformation (CWT), Cross Wavelet Transformation (XWT), Wavelet Coherent (WTC), and Partial Wavelet Coherence (PWC) on seven years time series (2004-2010) of PAR, Ta and NEE from the Ohio Oak Openings site (N 41.5545°, W 83.8438°), USA for spectral analysis. We found that PAR is the major driver at short time scales (e.g. semidiurnal and daily) and Ta is the major driver at long time scales (e.g. seasonal and annual). At daily scale during growing seasons, PAR is anti-phase with NEE with no time delay while Ta lagged PAR about 2-3 hours, which could be explained by the strong dependence of photosynthesis on PAR and a 2-3 hours lags of the daily course of Ta to PAR. At daily scale during non-growing season, NEE has little variation and thus neither Ta nor PAR has high common wavelet power and significant coherence with NEE. At annual scale, Ta is anti-phase with NEE and PAR leads NEE about 34 days, which could be explained by the strong dependence of LAI dynamics on Ta and the lag between the LAI/biomass development and the progress of sunlight. We also found that NEE distributes most of its variation

  1. Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

    PubMed Central

    Olesen, Charlotte; de Vries, Corinne S; Thrane, Nana; MacDonald, Tom M; Larsen, Helle; Sørensen, Henrik Toft

    2001-01-01

    Aims The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. Results Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. Conclusions Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings. PMID:11259987

  2. Prawns, barnacles, and nonsteroidal anti-inflammatory drugs: effect modifiers or diagnostic confounders [corrected].

    PubMed

    Vidal, C; Bartolomé, B; González-Quintela, A; Rodríguez, V; Armisén, M

    2007-01-01

    A 42-year-old woman with no history of atopy reported several episodes of generalized urticaria and shortness of breath after eating shellfish (prawns and barnacles) but with good tolerance of the same foods between episodes. Skin prick tests (SPTs), serum enzyme allergosorbent tests (EAST) for specific immunoglobulin (Ig) E, Western blot and inhibition assays, and oral challenge tests with prawns, barnacles, nonsteroidal anti-inflammatory drugs (NSAIDs), and alcohol as potential effect modifiers were performed. Specific IgE to both barnacle and prawn were detected by SPTs and EAST. Results from a Western blot of raw prawn revealed an IgE binding band of 37 kDa and IgE binding bands of 143, 83, 38, 32, and 20 kDa appeared in the raw barnacle assay. Oral challenge tests were positive with prawns and prawn extract only if preceded by NSAIDs. Oral challenges with NSAIDs alone, prawns alone, barnacles with or without NSAIDs and alcohol led to no reaction. A synergistic effect of NSAIDs in inducing anaphylaxis after prawn intake was confirmed. No similar effect was achieved with barnacles despite the presence of specific IgE. Additional factors needed to elicit a clinical reaction in food allergy may not be obvious and several oral challenge protocols are mandatory in such cases.

  3. Idiosyncratic species effects confound size-based predictions of responses to climate change

    PubMed Central

    Twomey, Marion; Brodte, Eva; Jacob, Ute; Brose, Ulrich; Crowe, Tasman P.; Emmerson, Mark C.

    2012-01-01

    Understanding and predicting the consequences of warming for complex ecosystems and indeed individual species remains a major ecological challenge. Here, we investigated the effect of increased seawater temperatures on the metabolic and consumption rates of five distinct marine species. The experimental species reflected different trophic positions within a typical benthic East Atlantic food web, and included a herbivorous gastropod, a scavenging decapod, a predatory echinoderm, a decapod and a benthic-feeding fish. We examined the metabolism–body mass and consumption–body mass scaling for each species, and assessed changes in their consumption efficiencies. Our results indicate that body mass and temperature effects on metabolism were inconsistent across species and that some species were unable to meet metabolic demand at higher temperatures, thus highlighting the vulnerability of individual species to warming. While body size explains a large proportion of the variation in species' physiological responses to warming, it is clear that idiosyncratic species responses, irrespective of body size, complicate predictions of population and ecosystem level response to future scenarios of climate change. PMID:23007085

  4. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies

    PubMed Central

    Austin, Peter C.

    2011-01-01

    The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses. PMID:21818162

  5. Confounding effects of aqueous-phase impinger chemistry on apparent oxidation of mercury in flue gases.

    PubMed

    Cauch, Brydger; Silcox, Geoffrey D; Lighty, JoAnn S; Wendt, Jost O L; Fry, Andrew; Senior, Constance L

    2008-04-01

    Gas-phase reactions between elemental mercury and chlorine are a possible pathway to producing oxidized mercury species such as mercuric chloride in combustion systems. This study examines the effect of the chemistry of a commonly used sample conditioning system on apparent and actual levels of mercury oxidation in a methane-fired, 0.3 kW, quartz-lined reactor in which gas composition (HCl, Cl2, NOx, SO2) and quench rate were varied. The sample conditioning system included two impingers in parallel: one containing an aqueous solution of KCl to trap HgCl2, and one containing an aqueous solution of SnCl2 to reduce HgCl2 to elemental mercury (Hg0). Gas-phase concentrations of Cl2 as low as 1.5 ppmv were sufficient to oxidize a significant fraction of the elemental mercury in the KCl impinger via the hypochlorite ion. Furthermore, these low, but interfering levels of Cl2 appeared to persist in flue gases from several doped rapidly mixed flames with varied post flame temperature quench rates. The addition of 0.5 wt% sodium thiosulfate to the KCl solution completely prevented the oxidation from occurring in the impinger. The addition of thiosulfate did not inhibit the KCl impinger's ability to capture HgCl2. The effectiveness of the thiosulfate was unchanged by NO or SO2. These results bring into question laboratory scale experimental data on mercury oxidation where wet chemistry was used to partition metallic and oxidized mercury without the presence of sufficient levels of SO2.

  6. Confounding effects of aqueous-phase impinger chemistry on apparent oxidation of mercury in flue gases

    SciTech Connect

    Brydger Cauch; Geoffrey D. Silcox; Joann S. Lighty; Jost O.L. Wendt; Andrew Fry; Constance L. Senior

    2008-04-01

    Gas-phase reactions between elemental mercury and chlorine are a possible pathway to producing oxidized mercury species such as mercuric chloride in combustion systems. This study examines the effect of the chemistry of a commonly used sample conditioning system on apparent and actual levels of mercury oxidation in a methane-fired, 0.3 kW, quartz-lined reactor in which gas composition (HCl, Cl{sub 2}, NOx, SO{sub 2}) and quench rate were varied. The sample conditioning system included two impingers in parallel: one containing an aqueous solution of KCl to trap HgCl{sub 2}, and one containing an aqueous solution of SnCl{sub 2} to reduce HgCl{sub 2} to elemental mercury (Hg{sup 0}). Gas-phase concentrations of Cl{sub 2} as low as 1.5 ppmv were sufficient to oxidize a significant fraction of the elemental mercury in the KCl impinger via the hypochlorite ion. Furthermore, these low, but interfering levels of Cl{sub 2} appeared to persist in flue gases from several doped rapidly mixed flames with varied post flame temperature quench rates. The addition of 0.5 wt% sodium thiosulfate to the KCl solution completely prevented the oxidation from occurring in the impinger. The addition of thiosulfate did not inhibit the KCl impinger's ability to capture HgCl{sub 2}. The effectiveness of the thiosulfate was unchanged by NO or SO{sub 2}. These results bring into question laboratory scale experimental data on mercury oxidation where wet chemistry was used to partition metallic and oxidized mercury without the presence of sufficient levels of SO{sub 2}. 23 refs., 5 figs., 1 tab.

  7. Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.

    PubMed

    Khalil, Hussein; Ecke, Frauke; Evander, Magnus; Hörnfeldt, Birger

    2016-06-01

    It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health.

  8. Severity grading of chronic obstructive pulmonary disease: the confounding effect of phenotype and thoracic gas compression.

    PubMed

    Pellegrino, Riccardo; Crimi, Emanuele; Gobbi, Alessandro; Torchio, Roberto; Antonelli, Andrea; Gulotta, Carlo; Baroffio, Michele; Papa, Giuseppe Francesco Sferrazza; Dellacà, Raffaele; Brusasco, Vito

    2015-04-01

    Current guidelines recommend severity of chronic obstructive pulmonary disease be graded by using forced expiratory volume in 1 s (FEV1). But this measurement is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis because of larger lung volumes, and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity, and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution toward less severe classes in dominant emphysema more than chronic bronchitis. The body mass, obstruction, dyspnea, and exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis, but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended. Copyright © 2015 the American Physiological Society.

  9. Environment- and eye-centered inhibitory cueing effects are both observed after a methodological confound is eliminated.

    PubMed

    He, Tao; Ding, Yun; Wang, Zhiguo

    2015-11-13

    Inhibition of return (IOR), typically explored in cueing paradigms, is a performance cost associated with previously attended locations and has been suggested as a crucial attentional mechanism that biases orientation towards novelty. In their seminal IOR paper, Posner and Cohen (1984) showed that IOR is coded in spatiotopic or environment-centered coordinates. Recent studies, however, have consistently reported IOR effects in both spatiotopic and retinotopic (eye-centered) coordinates. One overlooked methodological confound of all previous studies is that the spatial gradient of IOR is not considered when selecting the baseline for estimating IOR effects. This methodological issue makes it difficult to tell if the IOR effects reported in previous studies were coded in retinotopic or spatiotopic coordinates, or in both. The present study addresses this issue with the incorporation of no-cue trials to a modified cueing paradigm in which the cue and target are always intervened by a gaze-shift. The results revealed that a) IOR is indeed coded in both spatiotopic and retinotopic coordinates, and b) the methodology of previous work may have underestimated spatiotopic and retinotopic IOR effects.

  10. Environment- and eye-centered inhibitory cueing effects are both observed after a methodological confound is eliminated

    PubMed Central

    He, Tao; Ding, Yun; Wang, Zhiguo

    2015-01-01

    Inhibition of return (IOR), typically explored in cueing paradigms, is a performance cost associated with previously attended locations and has been suggested as a crucial attentional mechanism that biases orientation towards novelty. In their seminal IOR paper, Posner and Cohen (1984) showed that IOR is coded in spatiotopic or environment-centered coordinates. Recent studies, however, have consistently reported IOR effects in both spatiotopic and retinotopic (eye-centered) coordinates. One overlooked methodological confound of all previous studies is that the spatial gradient of IOR is not considered when selecting the baseline for estimating IOR effects. This methodological issue makes it difficult to tell if the IOR effects reported in previous studies were coded in retinotopic or spatiotopic coordinates, or in both. The present study addresses this issue with the incorporation of no-cue trials to a modified cueing paradigm in which the cue and target are always intervened by a gaze-shift. The results revealed that a) IOR is indeed coded in both spatiotopic and retinotopic coordinates, and b) the methodology of previous work may have underestimated spatiotopic and retinotopic IOR effects. PMID:26565380

  11. Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn's disease in the Ryukyu Islands.

    PubMed

    Nakagome, Shigeki; Chinen, Hiroshi; Iraha, Atsushi; Hokama, Akira; Takeyama, Yasuaki; Sakisaka, Shotaro; Matsui, Toshiyuki; Kidd, Judith R; Kidd, Kenneth K; Said, Heba S; Suda, Wataru; Morita, Hidetoshi; Hattori, Masahira; Hanihara, Tsunehiko; Kimura, Ryosuke; Ishida, Hajime; Fujita, Jiro; Kinjo, Fukunori; Mano, Shuhei; Oota, Hiroki

    2017-04-01

    Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella.

  12. Effect of confounding variables on hemodynamic response function estimation using averaging and deconvolution analysis: An event-related NIRS study.

    PubMed

    Aarabi, Ardalan; Osharina, Victoria; Wallois, Fabrice

    2017-07-15

    Slow and rapid event-related designs are used in fMRI and functional near-infrared spectroscopy (fNIRS) experiments to temporally characterize the brain hemodynamic response to discrete events. Conventional averaging (CA) and the deconvolution method (DM) are the two techniques commonly used to estimate the Hemodynamic Response Function (HRF) profile in event-related designs. In this study, we conducted a series of simulations using synthetic and real NIRS data to examine the effect of the main confounding factors, including event sequence timing parameters, different types of noise, signal-to-noise ratio (SNR), temporal autocorrelation and temporal filtering on the performance of these techniques in slow and rapid event-related designs. We also compared systematic errors in the estimates of the fitted HRF amplitude, latency and duration for both techniques. We further compared the performance of deconvolution methods based on Finite Impulse Response (FIR) basis functions and gamma basis sets. Our results demonstrate that DM was much less sensitive to confounding factors than CA. Event timing was the main parameter largely affecting the accuracy of CA. In slow event-related designs, deconvolution methods provided similar results to those obtained by CA. In rapid event-related designs, our results showed that DM outperformed CA for all SNR, especially above -5 dB regardless of the event sequence timing and the dynamics of background NIRS activity. Our results also show that periodic low-frequency systemic hemodynamic fluctuations as well as phase-locked noise can markedly obscure hemodynamic evoked responses. Temporal autocorrelation also affected the performance of both techniques by inducing distortions in the time profile of the estimated hemodynamic response with inflated t-statistics, especially at low SNRs. We also found that high-pass temporal filtering could substantially affect the performance of both techniques by removing the low-frequency components of

  13. Causal diagrams and multivariate analysis III: confound it!

    PubMed

    Jupiter, Daniel C

    2015-01-01

    This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Global climate change in large European rivers: long-term effects on macroinvertebrate communities and potential local confounding factors.

    PubMed

    Floury, Mathieu; Usseglio-Polatera, Philippe; Ferreol, Martial; Delattre, Cecile; Souchon, Yves

    2013-04-01

    Aquatic species living in running waters are widely acknowledged to be vulnerable to climate-induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple-stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long-term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979-2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979-1988 and 1999-2008) and to a lesser extent discharge reduction (-80 m(3) s(-1) ) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution-sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects.

  15. A new automated method for rat sleep deprivation with minimal confounding effects on corticosterone and locomotor activity.

    PubMed

    Leenaars, Cathalijn H C; Dematteis, Maurice; Joosten, Ruud N J M A; Eggels, Leslie; Sandberg, Hans; Schirris, Mischa; Feenstra, Matthijs G P; Van Someren, Eus J W

    2011-03-15

    The function of sleep in physiology, behaviour and cognition has become a primary focus of neuroscience. Its study inevitably includes experimental sleep deprivation designs. However, concerns exist regarding confounds like stress, increased locomotor activity levels, and decreased motivation to perform operant tasks induced by the methods employed. We here propose a novel procedure for sleep deprivation in rats and evaluate how it affects sleep, corticosterone concentration profiles, locomotor activity levels, and motivation to perform an operant task. Before, during and after 12h of total sleep deprivation by means of gradually increasing the rotation variability and the speed of a novel automated, two-compartment sleep deprivation device, sleep-wake states were assessed by electroencephalography (n=21), brain extracellular corticosterone concentrations using microdialysis (n=11), locomotor activity by infrared measurements (n=8), and operant performance using a fixed-interval-fixed-ratio task (n=16). Sleep was effectively prevented during the procedure; rats on average slept less than 1% of the time (0.8±0.2%, mean±standard error). Brain corticosterone concentrations were mildly increased during the procedure, but did not exceed normal peak concentrations. Locomotor activity was not only increased during the procedure, but also did not exceed the peak levels found during undisturbed wakefulness. Food restriction to 12 g/rat/day prevented sleep deprivation from reducing the motivation to perform an operant task. This novel procedure can be applied to sleep deprive rats in a highly effective way, while keeping corticosterone and locomotor activity within the normal range.

  16. Issues Relating to Confounding and Meta-analysis When Including Non-Randomized Studies in Systematic Reviews on the Effects of Interventions

    ERIC Educational Resources Information Center

    Valentine, Jeffrey C.; Thompson, Simon G.

    2013-01-01

    Background: Confounding caused by selection bias is often a key difference between non-randomized studies (NRS) and randomized controlled trials (RCTs) of interventions. Key methodological issues: In this third paper of the series, we consider issues relating to the inclusion of NRS in systematic reviews on the effects of interventions. We discuss…

  17. Issues Relating to Confounding and Meta-analysis When Including Non-Randomized Studies in Systematic Reviews on the Effects of Interventions

    ERIC Educational Resources Information Center

    Valentine, Jeffrey C.; Thompson, Simon G.

    2013-01-01

    Background: Confounding caused by selection bias is often a key difference between non-randomized studies (NRS) and randomized controlled trials (RCTs) of interventions. Key methodological issues: In this third paper of the series, we consider issues relating to the inclusion of NRS in systematic reviews on the effects of interventions. We discuss…

  18. Relations between verbal and nonverbal memory performance: evidence of confounding effects particularly in patients with right temporal lobe epilepsy.

    PubMed

    Helmstaedter, C; Pohl, C; Elger, C E

    1995-06-01

    Confounding left hemisphere verbalization strategies can be suggested as being a major problem in the evaluation of the assumed involvement of right temporo-limbic structures in "nonverbal" visual/figural memory processing. We addressed this issue by evaluating the easily-verbalized Benton-visual-retention-test in 60 patients with either left (LTLE) or right temporal lobe epilepsy (RTLE) and 30 healthy controls. We formally estimated the informational (verbal) content of each item which hypothetically would be needed to solely retain the item from verbal memory. The results indicated confounding of verbal learning and figural memory only in the presence of right temporal lobe dysfunctions. Selective visual/figural learning deficits in RTLE patients became obvious when the verbal load of the figural material exceeded their verbal learning capacity. Instead of excluding verbalization by the use of abstract figural items, its inclusion provides a possibility to control compensatory strategies which overshadow the presence of visual/figural memory deficits.

  19. Effects of categorization method, regression type, and variable distribution on the inflation of Type-I error rate when categorizing a confounding variable.

    PubMed

    Barnwell-Ménard, Jean-Louis; Li, Qing; Cohen, Alan A

    2015-03-15

    The loss of signal associated with categorizing a continuous variable is well known, and previous studies have demonstrated that this can lead to an inflation of Type-I error when the categorized variable is a confounder in a regression analysis estimating the effect of an exposure on an outcome. However, it is not known how the Type-I error may vary under different circumstances, including logistic versus linear regression, different distributions of the confounder, and different categorization methods. Here, we analytically quantified the effect of categorization and then performed a series of 9600 Monte Carlo simulations to estimate the Type-I error inflation associated with categorization of a confounder under different regression scenarios. We show that Type-I error is unacceptably high (>10% in most scenarios and often 100%). The only exception was when the variable categorized was a continuous mixture proxy for a genuinely dichotomous latent variable, where both the continuous proxy and the categorized variable are error-ridden proxies for the dichotomous latent variable. As expected, error inflation was also higher with larger sample size, fewer categories, and stronger associations between the confounder and the exposure or outcome. We provide online tools that can help researchers estimate the potential error inflation and understand how serious a problem this is. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Effectiveness of decanter modifications on organic removal

    SciTech Connect

    Lambert, D.P.

    1992-08-20

    A series of runs were planned in the Precipitate Hydrolysis Experimental Facility (PHEF) at the Savannah River Plant to determine the effectiveness of equipment and process modifications on the PHEF decanter organic removal efficiency. Runs 54-59 were planned to test the effectiveness of spray recirculation, a new decanter, heated organic recirculation and aqueous drawoff on organic removal efficiency in the revised HAN flowsheet. Runs 60-63 were planned to provide a comparison of the original and new decanter designs on organic removal efficiency in the late wash flowsheet without organic recirculation. Operational problems were experienced in both the PHEF and IDMS pilot facilities because of the production of high boiling organics and the low organic removal efficiency of the PHEF decanters. To prevent these problems in the DWPF Salt and Chemical Cells, modifications were proposed to the decanter and flowsheet to maximize the organic removal efficiency and minimize production of high boiling organics.

  1. On the definition of a confounder

    PubMed Central

    VanderWeele, Tyler J.; Shpitser, Ilya

    2014-01-01

    Summary The causal inference literature has provided a clear formal definition of confounding expressed in terms of counterfactual independence. The causal inference literature has not, however, produced a clear formal definition of a confounder, as it has given priority to the concept of confounding over that of a confounder. We consider a number of candidate definitions arising from various more informal statements made in the literature. We consider the properties satisfied by each candidate definition, principally focusing on (i) whether under the candidate definition control for all “confounders” suffices to control for “confounding” and (ii) whether each confounder in some context helps eliminate or reduce confounding bias. Several of the candidate definitions do not have these two properties. Only one candidate definition of those considered satisfies both properties. We propose that a “confounder” be defined as a pre-exposure covariate C for which there exists a set of other covariates X such that effect of the exposure on the outcome is unconfounded conditional on (X, C) but such that for no proper subset of (X, C) is the effect of the exposure on the outcome unconfounded given the subset. A variable that helps reduce bias but not eliminate bias we propose referring to as a “surrogate confounder.” PMID:25544784

  2. Introduction to causal diagrams for confounder selection.

    PubMed

    Williamson, Elizabeth J; Aitken, Zoe; Lawrie, Jock; Dharmage, Shyamali C; Burgess, John A; Forbes, Andrew B

    2014-04-01

    In respiratory health research, interest often lies in estimating the effect of an exposure on a health outcome. If randomization of the exposure of interest is not possible, estimating its effect is typically complicated by confounding bias. This can often be dealt with by controlling for the variables causing the confounding, if measured, in the statistical analysis. Common statistical methods used to achieve this include multivariable regression models adjusting for selected confounding variables or stratification on those variables. Therefore, a key question is which measured variables need to be controlled for in order to remove confounding. An approach to confounder-selection based on the use of causal diagrams (often called directed acyclic graphs) is discussed. A causal diagram is a visual representation of the causal relationships believed to exist between the variables of interest, including the exposure, outcome and potential confounding variables. After creating a causal diagram for the research question, an intuitive and easy-to-use set of rules can be applied, based on a foundation of rigorous mathematics, to decide which measured variables must be controlled for in the statistical analysis in order to remove confounding, to the extent that is possible using the available data. This approach is illustrated by constructing a causal diagram for the research question: 'Does personal smoking affect the risk of subsequent asthma?'. Using data taken from the Tasmanian Longitudinal Health Study, the statistical analysis suggested by the causal diagram approach was performed.

  3. Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds.

    PubMed

    Bedi, G; Redman, J

    2008-09-01

    Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds. A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed. It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1-6% of variance in cognitive scores. Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

  4. Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

    PubMed Central

    Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

    2015-01-01

    Background: This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. Aims: To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. Methods: A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. Results: We report suggestive evidence of an association with vitamin D status in established psychosis (ßstandardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ2=91.7; 2 degrees of freedom (df); P=1.2×1020). Conclusions: The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect. PMID:27336042

  5. On quantifying the magnitude of confounding

    PubMed Central

    Janes, Holly; Dominici, Francesca; Zeger, Scott

    2010-01-01

    When estimating the association between an exposure and outcome, a simple approach to quantifying the amount of confounding by a factor, Z, is to compare estimates of the exposure–outcome association with and without adjustment for Z. This approach is widely believed to be problematic due to the nonlinearity of some exposure-effect measures. When the expected value of the outcome is modeled as a nonlinear function of the exposure, the adjusted and unadjusted exposure effects can differ even in the absence of confounding (Greenland , Robins, and Pearl, 1999); we call this the nonlinearity effect. In this paper, we propose a corrected measure of confounding that does not include the nonlinearity effect. The performances of the simple and corrected estimates of confounding are assessed in simulations and illustrated using a study of risk factors for low birth–weight infants. We conclude that the simple estimate of confounding is adequate or even preferred in settings where the nonlinearity effect is very small. In settings with a sizable nonlinearity effect, the corrected estimate of confounding has improved performance. PMID:20203259

  6. Are the effects of psychosocial exposures attributable to confounding? Evidence from a prospective observational study on psychological stress and mortality

    PubMed Central

    Macleod, J; Davey, S; Heslop, P; Metcalfe, C; Carroll, D; Hart, C

    2001-01-01

    .69 (95% CI 0.44, 1.09), p for trend 0.12, fully adjusted 0.76 (95% CI 0.48, 1.21), p for trend 0.25; increased compared with decreased stress, age adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.09, fully adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.08.
CONCLUSIONS—This implausible protective relation between higher levels of stress, which were associated with increased smoking, and mortality from smoking related cancers, was probably a product of confounding. Plausible reported associations between psychosocial exposures and disease, in populations where such exposures are associated with material disadvantage, may be similarly produced by confounding, and of no causal significance.


Keywords: socioeconomic differentials; psychosocial factors; mortality PMID:11707481

  7. How to ask about patient satisfaction? The visual analogue scale is less vulnerable to confounding factors and ceiling effect than a symmetric Likert scale.

    PubMed

    Voutilainen, Ari; Pitkäaho, Taina; Kvist, Tarja; Vehviläinen-Julkunen, Katri

    2016-04-01

    To study the effects of scale type (visual analogue scale vs. Likert), item order (systematic vs. random), item non-response and patient-related characteristics (age, gender, subjective health, need for assistance with filling out the questionnaire and length of stay) on the results of patient satisfaction surveys. Although patient satisfaction is one of the most intensely studied issues in the health sciences, research information about the effects of possible instrument-related confounding factors on patient satisfaction surveys is scant. A quasi-experimental design was employed. A non-randomized sample of 150 surgical patients was gathered to minimize possible alterations in care quality. Data were collected in May-September 2014 from one tertiary hospital in Finland using the Revised Humane Caring Scale instrument. New versions of the instrument were created for the present purposes. In these versions, items were either in a visual analogue format or Likert-scaled, in systematic or random order. The data were analysed using an analysis of covariance and a paired samples t-test. The visual analogue scale items were less vulnerable to bias from confounding factors than were the Likert-scaled items. The visual analogue scale also avoided the ceiling effect better than Likert and the time needed to complete the visual analogue scale questionnaire was 28% shorter than that needed to complete the Likert-scaled questionnaire. The present results supported the use of visual analogue scale rather than Likert scaling in patient satisfaction surveys and stressed the need to account for as many potential confounding factors as possible. © 2015 John Wiley & Sons Ltd.

  8. Semiparametric regression models for detecting effect modification in matched case-crossover studies.

    PubMed

    Kim, Inyoung; Cheong, Hae-Kwan; Kim, Ho

    2011-07-10

    In matched case-crossover studies, it is generally accepted that covariates on which a case and associated controls are matched cannot exert a confounding effect on independent predictors included in the conditional logistic regression model because any stratum effect is removed by the conditioning on the fixed number of sets of a case and controls in the stratum. Hence, the conditional logistic regression model is not able to detect any effects associated with the matching covariates by stratum. In addition, the matching covariates may be effect modification and the methods for assessing and characterizing effect modification by matching covariates are quite limited. In this article, we propose a unified approach in its ability to detect both parametric and nonparametric relationships between the predictor and the relative risk of disease or binary outcome, as well as potential effect modifications by matching covariates. Two methods are developed using two semiparametric models: (1) the regression spline varying coefficients model and (2) the regression spline interaction model. Simulation results show that the two approaches are comparable. These methods can be used in any matched case-control study and extend to multilevel effect modification studies. We demonstrate the advantage of our approach using an epidemiological example of a 1-4 bi-directional case-crossover study of childhood aseptic meningitis associated with drinking water turbidity. Copyright © 2011 John Wiley & Sons, Ltd.

  9. 'Bigger data' on scale-dependent effects of invasive species on biodiversity cannot overcome confounded analyses: a comment on Stohlgren & Rejmánek (2014).

    PubMed

    Chase, Jonathan M; Powell, Kristin I; Knight, Tiffany M

    2015-08-01

    A recent study by Stohlgren & Rejmánek (SR: Stohlgren TJ, Rejmánek M. 2014 Biol. Lett. 10. (doi:10.1098/rsbl.2013.0939)) purported to test the generality of a recent finding of scale-dependent effects of invasive plants on native diversity; dominant invasive plants decreased the intercept and increased the slope of the species-area relationship. SR (2014) find little correlation between invasive species cover and the slopes and intercepts of SARs across a diversity of sites. We show that the analyses of SR (2014) are inappropriate because of confounding causality.

  10. Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers

    PubMed Central

    2011-01-01

    Background Associations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins. Methods We examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses. Results The medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albumin Conclusions Associations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins. PMID:21569589

  11. Structural equation modeling versus marginal structural modeling for assessing mediation in the presence of posttreatment confounding.

    PubMed

    Moerkerke, Beatrijs; Loeys, Tom; Vansteelandt, Stijn

    2015-06-01

    Inverse probability weighting for marginal structural models has been suggested as a strategy to estimate the direct effect of a treatment or exposure on an outcome in studies where the effect of mediator on outcome is subject to posttreatment confounding. This type of confounding, whereby confounders of the effect of mediator on outcome are themselves affected by the exposure, complicates mediation analyses and necessitates apt analysis strategies. In this article, we contrast the inverse probability weighting approach with the traditional path analysis approach to mediation analysis. We show that in a particular class of linear models, adjustment for posttreatment confounding can be realized via a fairly standard modification of the traditional path analysis approach. The resulting approach is simpler; by avoiding inverse probability weighting, it moreover results in direct effect estimators with smaller finite sample bias and greater precision. We further show that a particular variant of the G-estimation approach from the causal inference literature is equivalent with the path analysis approach in simple linear settings but is more generally applicable in settings with interactions and/or noncontinuous mediators and confounders. We conclude that the use of inverse probability weighting for marginal structural models to adjust for posttreatment confounding in mediation analysis is primarily indicated in nonlinear models for the outcome.

  12. Confounding and control of confounding in nonexperimental studies of medications in patients with CKD.

    PubMed

    Bradbury, Brian D; Gilbertson, David T; Brookhart, M Alan; Kilpatrick, Ryan D

    2012-01-01

    Confounding is an important source of bias in nonexperimental studies, arising when the effect of an exposure on the occurrence of an outcome is distorted by the effect of some other factor. In nonexperimental studies of patients with CKD or who are on chronic dialysis, confounding is a significant concern owing to the high burden of comorbid disease, extent of required clinical management, and high frequency of adverse clinical events in this patient population. Confounding can be addressed in both the design stage (restriction, accurate measurement of confounders) and analysis stage (stratification, multivariable adjustment, propensity scores, marginal structural models, instrumental variable) of a study. Time-dependent confounding and confounding by indication are 2 special cases of confounding that can arise in studies of treatment effects and may require more sophisticated analytic techniques to adequately address. The availability and expanded use of large health care databases have ensured greater precision and have now placed the focus on validity. Addressing the major threats to validity, such as confounding, should be a first-order concern.

  13. Chemical and structural effects of base modifications in messenger RNA

    NASA Astrophysics Data System (ADS)

    Harcourt, Emily M.; Kietrys, Anna M.; Kool, Eric T.

    2017-01-01

    A growing number of nucleobase modifications in messenger RNA have been revealed through advances in detection and RNA sequencing. Although some of the biochemical pathways that involve modified bases have been identified, research into the world of RNA modification -- the epitranscriptome -- is still in an early phase. A variety of chemical tools are being used to characterize base modifications, and the structural effects of known base modifications on RNA pairing, thermodynamics and folding are being determined in relation to their putative biological roles.

  14. A counterfactual approach to bias and effect modification in terms of response types.

    PubMed

    Suzuki, Etsuji; Mitsuhashi, Toshiharu; Tsuda, Toshihide; Yamamoto, Eiji

    2013-07-31

    The counterfactual approach provides a clear and coherent framework to think about a variety of important concepts related to causation. Meanwhile, directed acyclic graphs have been used as causal diagrams in epidemiologic research to visually summarize hypothetical relations among variables of interest, providing a clear understanding of underlying causal structures of bias and effect modification. In this study, the authors aim to further clarify the concepts of bias (confounding bias and selection bias) and effect modification in the counterfactual framework. The authors show how theoretical data frequencies can be described by using unobservable response types both in observational studies and in randomized controlled trials. By using the descriptions of data frequencies, the authors show epidemiologic measures in terms of response types, demonstrating significant distinctions between association measures and effect measures. These descriptions also demonstrate sufficient conditions to estimate effect measures in observational studies. To illustrate the ideas, the authors show how directed acyclic graphs can be extended by integrating response types and observed variables. This study shows a hitherto unrecognized sufficient condition to estimate effect measures in observational studies by adjusting for confounding bias. The present findings would provide a further understanding of the assumption of conditional exchangeability, clarifying the link between the assumptions for making causal inferences in observational studies and the counterfactual approach. The extension of directed acyclic graphs using response types maintains the integrity of the original directed acyclic graphs, which allows one to understand the underlying causal structure discussed in this study. The present findings highlight that analytic adjustment for confounders in observational studies has consequences quite different from those of physical control in randomized controlled trials. In

  15. Development of histopathological indices in the digestive gland and gonad of mussels: integration with contamination levels and effects of confounding factors.

    PubMed

    Cuevas, Nagore; Zorita, Izaskun; Costa, Pedro M; Franco, Javier; Larreta, Joana

    2015-05-01

    Bivalve histopathology has become an important tool in aquatic toxicology, having been implemented in many biomonitoring programmes worldwide. However, there are various gaps in the knowledge of many sentinel organisms and the interference of confounding factors. This work aimed (i) to develop a detailed semi-quantitative histopathological index of the digestive gland and gonad of the Mytilus galloprovincialis mussel collected from five sites contaminated with distinct patterns of organic and inorganic toxicants along the Basque coast (SE Bay of Biscay) and (ii) to investigate whether seasonal variability and parasitosis act as confounding factors. A total of twenty-three histopathological alterations were analysed in the digestive gland and gonad following a weighed condition index approach. The alterations were integrated into a single value for a better understanding of the mussels' health status. The digestive gland was consistently more damaged than the gonad. Mussels from the most impacted sites endured the most significant deleterious effects showing inflammation-related alterations together with digestive tubule atrophy and necrosis. Neoplastic diseases were scarce, with only a few cases of fibromas (benign neoplasia). In contrast, in moderately or little impacted sites, contamination levels did not cause significant tissue damage. However, parasites contributed to overestimating the values of histopathological indices (i.e. more severe tissue damage) in mussels from little impacted sites, whilst the opposite occurred in mussels from highly polluted sites. Accordingly, inter-site differences were more pronounced in autumn when natural physiological responses of advanced maturation stages did not interfere in the histological response. In conclusion, although seasonal variability and parasitosis mask the response of histopathological indices, this biomonitoring approach may provide good sensitivity for assessing the health status of mussels if fluctuations

  16. Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients.

    PubMed

    Han, Ling; Pisani, M A; Araujo, K L B; Allore, Heather G

    Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior (Induction) and posterior (Subsequent) to each treatment episode of receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for the Subsequent than the Induction intervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.

  17. The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: an illustration

    PubMed Central

    Lemire, Mathieu; Zaidi, Syed H.E.; Zanke, Brent W.; Gallinger, Steven; Hudson, Thomas J.; Cleary, Sean P.

    2016-01-01

    Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+:p=10−6; CD8+:p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced. PMID:26368860

  18. Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures

    PubMed Central

    Yashin, Anatoliy I.; Zhbannikov, Ilya; Arbeeva, Liubov; Arbeev, Konstantin G.; Wu, Deqing; Akushevich, Igor; Yashkin, Arseniy; Kovtun, Mikhail; Kulminski, Alexander M.; Stallard, Eric; Kulminskaya, Irina; Ukraintseva, Svetlana

    2016-01-01

    This paper shows that the effects of causal SNPs on lifespan, estimated through GWAS, may be confounded and the genetic structure of the study population may be responsible for this effect. Simulation experiments show that levels of linkage disequilibrium (LD) and other parameters of the population structure describing connections between two causal SNPs may substantially influence separate estimates of the effect of the causal SNPs on lifespan. This study suggests that differences in LD levels between two causal SNP loci within two study populations may contribute to the failure to replicate previous GWAS findings. The results of this paper also show that successful replication of the results of genetic association studies does not necessarily guarantee proper interpretation of the effect of a causal SNP on lifespan. PMID:27877192

  19. Identifiability, exchangeability and confounding revisited

    PubMed Central

    Greenland, Sander; Robins, James M

    2009-01-01

    In 1986 the International Journal of Epidemiology published "Identifiability, Exchangeability and Epidemiological Confounding". We review the article from the perspective of a quarter century after it was first drafted and relate it to subsequent developments on confounding, ignorability, and collapsibility. PMID:19732410

  20. Estimated effect of weight loss on risk of coronary heart disease and mortality in middle-aged or older women: sensitivity analysis for unmeasured confounding by undiagnosed disease

    PubMed Central

    Danaei, Goodarz; Robins, James M.; Young, Jessica; Hu, Frank B.; Manson, JoAnn E; Hernán, Miguel A.

    2016-01-01

    Background The evidence on the effect of weight loss on coronary heart disease (CHD) or mortality has been mixed. The effect estimates can be confounded due to undiagnosed diseases that may affect weight loss. Methods We used data from the Nurses’ Health Study to estimate the 26-year risk of CHD under several hypothetical weight loss interventions (e.g. maintain baseline weight, lose 5% of weight every 2 years if overweight/obese). We applied the parametric g-formula and implemented a novel sensitivity analysis for unmeasured confounding due to undiagnosed disease by imposing a lag time for the effect of weight loss on chronic disease. Sensitivity analyses were conducted by using only the first 16 years of follow-up, restricting the analysis to women who had reported intentional weight loss, those who were younger (<49 years old at baseline), and those who never smoked. Results The 26-year risk of CHD under no weight loss intervention was 5.0% (95% Confidence Interval 4.9, 5.3). The estimated risk did not change under hypothetical weight loss interventions using lag times from 0 to 18 years. For a 6-year lag time, the risk ratios of CHD for weight loss compared with no intervention ranged from 1.00 (0.99, 1.02) to 1.02 (0.99, 1.05) for different degrees of weight loss with and without restricting the intervention to participants with no major chronic disease. Similarly, no protective effect of weight loss was estimated for mortality risk. In contrast, we estimated a protective effect of weight loss on risk of type 2 diabetes. The estimated effect of weight loss on CHD and mortality remained null in all sensitivity analyses. Conclusion We estimated that maintaining weight or losing weight after becoming overweight or obese does not reduce the risk of CHD or death in this cohort of middle-aged US women. Unmeasured confounding, measurement error, and model misspecification are possible explanations but they did not prevent us from estimating a beneficial effect of

  1. The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors.

    PubMed

    Møller, P; Knudsen, L E; Loft, S; Wallin, H

    2000-10-01

    Within the last decade, the comet assay has been used with increasing popularity to investigate the level of DNA damage in terms of strand breaks and alkaline labile sites in biomonitoring studies. The assay is easily performed on WBCs and has been included in a wide range of biomonitoring studies of occupational exposures encompassing styrene, vinyl chloride, 1,3-butadiene, pesticides, hair dyes, antineoplastic agents, organic solvents, sewage and waste materials, wood dust, and ionizing radiation. Eleven of the occupational studies were positive, whereas seven were negative. Notably, the negative studies appeared to have less power than the positive studies. Also, there were poor dose-response relationships in many of the biomonitoring studies. Many factors have been reported to produce effects by the comet assay, e.g., age, air pollution exposure, diet, exercise, gender, infection, residential radon exposure, smoking, and season. Until now, the use of the comet assay has been hampered by the uncertainty of the influence of confounding factors. We argue that none of the confounding factors are unequivocally positive in the majority of the studies. We recommend that age, gender, and smoking status be used as criteria for the selection of populations and that data on exercise, diet, and recent infections be registered before blood sampling. Samples from exposed and unexposed populations should be collected at the same time to avoid seasonal variation. In general, the comet assay is considered a suitable and fast test for DNA-damaging potential in biomonitoring studies.

  2. Effects of anesthetic regimens and other confounding factors affecting the interpretation of motor evoked potentials during pediatric spine surgery.

    PubMed

    Balvin, Mark J; Song, Kit M; Slimp, Jefferson C

    2010-09-01

    Children undergoing corrective spine surgery are at risk of serious neurologic injury. Monitoring transcranial electric motor evoked potentials (TCeMEPs) during these procedures may identify and help prevent injury to motor pathways. The difficulty in obtaining consistent motor evoked potential (MEP) responses during pediatric spine surgery can result in part to the suppression of evoked responses caused by volatile inhalational anesthetics, elevated levels of propofol, and/or physiologic variables. Data obtained from 140 pediatric patients who underwent spine surgery with MEP monitoring were retrospectively analyzed and evaluated for age and anesthetic effects on stimulation variables. MEPs acquired under inhalational anesthetic agents required greater stimulation compared to intravenous propofol anesthesia. Additionally, the responses were more variable when inhalational agents were used. These effects were more prominent in younger age patients. The number of alerts of MEP loss or reduction related to anesthetic levels or blood pressure changes was higher under inhalational agents.

  3. Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

    PubMed Central

    McClelland, M; Nelson, M; Raschke, E

    1994-01-01

    Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

  4. Analysis of the effects of microbiome-related confounding factors on the reproducibility of the volatolomic test.

    PubMed

    Leja, Marcis; Amal, Haitham; Lasina, Ieva; Skapars, Roberts; Sivins, Armands; Ancans, Guntis; Tolmanis, Ivars; Vanags, Aigars; Kupcinskas, Juozas; Ramonaite, Rima; Khatib, Salam; Bdarneh, Shifaa; Natour, Rasha; Ashkar, Areen; Haick, Hossam

    2016-06-24

    Volatile organic compound (VOC) testing in breath has potential in gastric cancer (GC) detection. Our objective was to assess the reproducibility of VOCs in GC, and the effects of conditions modifying gut microbiome on the test results. Ten patients with GC were sampled for VOC over three consecutive days; 17 patients were sampled before and after H. pylori eradication therapy combined with a yeast probiotic; 61 patients were sampled before and after bowel cleansing (interventions affecting the microbiome). The samples were analyzed by: (1) gas chromatography linked to mass spectrometry (GC-MS), applying the non-parametric Wilcoxon test (level of significance p  <  0.05); (2) by cross-reactive nanoarrays combined with pattern recognition. Discriminant function analysis (DFA) was used to build the classification models; and leave-one-out cross-validation analysis was used to classify the findings. Exhaled VOCs profiles were stable for GC patients over a three day period. Alpha pinene (p  =  0.028) and ethyl acetate (p  =  0.030) increased after the antibiotic containing eradication regimen; acetone (p  =  0.0001) increased following bowel cleansing prior to colonoscopy. We further hypothesize that S. boulardii given with the standard eradication regimen to re-establish the gut microbiome was the source for long-term ethyl acetate production. Differences between the initial and the follow-up sample were also revealed in the DFA analysis of the sensor data. VOC measurement results are well-reproducible in GC patients indicating a useful basis for potential disease diagnostics. However, interventions with a potential effect on the gut microbiome may have an effect upon the VOC results, and therefore should be considered for diagnostic accuracy.

  5. An indicator for effects of organic toxicants on lotic invertebrate communities: Independence of confounding environmental factors over an extensive river continuum.

    PubMed

    Beketov, Mikhail A; Liess, Matthias

    2008-12-01

    Distinguishing between effects of natural and anthropogenic environmental factors on ecosystems is a fundamental problem in environmental science. In river systems the longitudinal gradient of environmental factors is one of the most relevant sources of dissimilarity between communities that could be confounded with anthropogenic disturbances. To test the hypothesis that in macroinvertebrate communities the distribution of species' sensitivity to organic toxicants is independent of natural longitudinal factors, but depends on contamination with organic toxicants, we analysed the relationship between community sensitivity SPEAR(organic) (average community sensitivity to organic toxicants) and natural and anthropogenic environmental factors in a large-scale river system, from alpine streams to a lowland river. The results show that SPEAR(organic) is largely independent of natural longitudinal factors, but strongly dependent on contamination with organic toxicants (petrochemicals and synthetic surfactants). Usage of SPEAR(organic) as a stressor-specific longitude-independent measure will facilitate detection of community disturbance by organic toxicants.

  6. Historical cohort study of US man-made vitreous fiber production workers: VI. Respiratory system cancer standardized mortality ratios adjusted for the confounding effect of cigarette smoking.

    PubMed

    Marsh, G M; Buchanich, J M; Youk, A O

    2001-09-01

    To date, the US cohort study of man-made vitreous fiber workers has provided no consistent evidence of a relationship between man-made vitreous fiber exposure and mortality from malignant or non-malignant respiratory disease. Nevertheless, there have been small, overall excesses in respiratory system cancer (RSC) among workers from the fiberglass and rock/slag wool production plants included in the study that were unexplained by estimated worker exposures to respirable fiber or other agents present in the plants. The present investigation was designed to provide a quantitative estimate of the extent to which the overall excess in RSC mortality observed at the total cohort level among male fiberglass and rock/slag wool workers is a result of the positive confounding effects of cigarette smoking. Because cigarette-smoking data were neither available nor obtainable at the individual level for all members of the fiberglass and rock/slag wool cohorts, we used the "indirect" method to adjust RSC standardized mortality ratios (SMRs) at the group (cohort and plant) level. Our adjustment suggested that cigarette smoking accounts for all of the 7% and 24% excesses in RSC observed, respectively, for the male fiberglass and rock/slag wool cohorts in the latest mortality updates. The same conclusion was reached regardless of which of several alternative formulations were used to adjust local rate-based RSC SMRs. We found that our smoking adjustments were robust with respect to several alternative characterizations and (with the exception of one fiberglass plant) produced adjusted RSC SMRs that were lower than their unadjusted counterparts. Further, all statistically significantly elevated unadjusted SMRs were reduced to not statistically significant levels. These results reaffirm that RSC SMRs based on US and local rates must take into account the potential confounding effects of cigarette smoking. They also suggest that the use of local county mortality rate-based SMRs may not

  7. Confounding compression: the effects of posture, sizing and garment type on measured interface pressure in sports compression clothing.

    PubMed

    Brophy-Williams, Ned; Driller, Matthew William; Shing, Cecilia Mary; Fell, James William; Halson, Shona Leigh; Halson, Shona Louise

    2015-01-01

    The purpose of this investigation was to measure the interface pressure exerted by lower body sports compression garments, in order to assess the effect of garment type, size and posture in athletes. Twelve national-level boxers were fitted with sports compression garments (tights and leggings), each in three different sizes (undersized, recommended size and oversized). Interface pressure was assessed across six landmarks on the lower limb (ranging from medial malleolus to upper thigh) as athletes assumed sitting, standing and supine postures. Sports compression leggings exerted a significantly higher mean pressure than sports compression tights (P < 0.001). Oversized tights applied significantly less pressure than manufacturer-recommended size or undersized tights (P < 0.001), yet no significant differences were apparent between different-sized leggings. Standing posture resulted in significantly higher mean pressure application than a seated posture for both tights and leggings (P < 0.001 and P = 0.002, respectively). Pressure was different across landmarks, with analyses revealing a pressure profile that was neither strictly graduated nor progressive in nature. The pressure applied by sports compression garments is significantly affected by garment type, size and posture assumed by the wearer.

  8. Compounding Effects of Agricultural Land Use and Water Use in Free-Flowing Rivers: Confounding Issues for Environmental Flows.

    PubMed

    Hardie, Scott A; Bobbi, Chris J

    2017-03-03

    Defining the ecological impacts of water extraction from free-flowing river systems in altered landscapes is challenging as multiple stressors (e.g., flow regime alteration, increased sedimentation) may have simultaneous effects and attributing causality is problematic. This multiple-stressor context has been acknowledged in environmental flows science, but is often neglected when it comes to examining flow-ecology relationships, and setting and implementing environmental flows. We examined the impacts of land and water use on rivers in the upper Ringarooma River catchment in Tasmania (south-east Australia), which contains intensively irrigated agriculture, to support implementation of a water management plan. Temporal and spatial and trends in river condition were assessed using benthic macroinvertebrates as bioindicators. Relationships between macroinvertebrate community structure and environmental variables were examined using univariate and multivariate analyses, focusing on the impacts of agricultural land use and water use. Structural changes in macroinvertebrate communities in rivers in the catchment indicated temporal and spatial declines in the ecological condition of some stretches of river associated with agricultural land and water use. Moreover, water extraction appeared to exacerbate impairment associated with agricultural land use (e.g., reduced macroinvertebrate density, more flow-avoiding taxa). The findings of our catchment-specific bioassessments will underpin decision-making during the implementation of the Ringarooma water management plan, and highlight the need to consider compounding impacts of land and water use in environmental flows and water planning in agricultural landscapes.

  9. The aunt and uncle effect: an empirical evaluation of the confounding influence of full sibs of parents on pedigree reconstruction.

    PubMed

    Olsen, J B; Busack, C; Britt, J; Bentzen, P

    2001-01-01

    This study used simulations and a known two-generation pedigree of chinook salmon (Oncorhynchus tshawytscha) to evaluate the effect of full sibs of parents on pedigree reconstruction. Parentage analysis was conducted on 100 parent pair-offspring relationships from pedigrees with unrelated (simulation) and related (chinook salmon) candidate parents. Parentage assignment success for the chinook salmon was lower than in the simulated populations. For example, the six most variable loci (mean H(E) = 0.87) provided a mean of 97% unambiguous assignments in the simulated population and 67% unambiguous assignments for the chinook salmon. Estimates of the pairwise relatedness coefficient ((xy)) for most nonexcluded false parents and true parents of chinook salmon offspring exceeded 0.50. These results support the conclusion that closely related candidate parents decrease the power of genetic markers for pedigree reconstruction based on exclusion. Ambiguous parentage may be resolved using single parent- and parent pair-offspring likelihood analysis, however, these methods should be used with caution and they are not replacements for using more loci when many candidate parents are full sibs.

  10. The confounding effect of nitrite on N2O production by an enriched ammonia-oxidizing culture.

    PubMed

    Law, Yingyu; Lant, Paul; Yuan, Zhiguo

    2013-07-02

    The effect of nitrite (NO2(-)) on the nitrous oxide (N2O) production rate of an enriched ammonia-oxidizing bacteria (AOB) culture was characterized over a concentration range of 0-1000 mg N/L. The AOB culture was enriched in a nitritation system fed with synthetic anaerobic digester liquor. The N2O production rate was highest at NO2(-) concentrations of less than 50 mg N/L. At dissolved oxygen (DO) concentration of 0.55 mg O2/L, further increases in NO2(-) concentration from 50 to 500 mg N/L resulted in a gradual decrease in N2O production rate, which maintained at its lowest level of 0.20 mg N2O-N/h/g VSS in the NO2(-) concentration range of 500-1000 mg N/L. The observed NO2(-)-induced decrease in N2O production was even more apparent at increased DO concentration. At DO concentrations of 1.30 and 2.30 mg O2/L, the lowest N2O production rate (0.25 mg N2O-N/h/g VSS) was attained at a lower NO2(-) concentration of 200-250 mg N/L. These observations suggest that N2O production by the culture is diminished by both high NO2(-) and high DO concentrations. Collectively, the findings show that exceedingly high NO2(-) concentrations in nitritation systems could lead to decreased N2O production. Further studies are required to determine the extent to which the same response to NO2(-) is observed across different AOB cultures.

  11. P-wave indices in patients with pulmonary emphysema: do P-terminal force and interatrial block have confounding effects?

    PubMed

    Chhabra, Lovely; Chaubey, Vinod K; Kothagundla, Chandrasekhar; Bajaj, Rishi; Kaul, Sudesh; Spodick, David H

    2013-01-01

    Pulmonary emphysema causes several electrocardiogram changes, and one of the most common and well known is on the frontal P-wave axis. P-axis verticalization (P-axis > 60°) serves as a quasidiagnostic indicator of emphysema. The correlation of P-axis verticalization with the radiological severity of emphysema and severity of chronic obstructive lung function have been previously investigated and well described in the literature. However, the correlation of P-axis verticalization in emphysema with other P-indices like P-terminal force in V1 (Ptf), amplitude of initial positive component of P-waves in V1 (i-PV1), and interatrial block (IAB) have not been well studied. Our current study was undertaken to investigate the effects of emphysema on these P-wave indices in correlation with the verticalization of the P-vector. Unselected, routinely recorded electrocardiograms of 170 hospitalized emphysema patients were studied. Significant Ptf (s-Ptf) was considered ≥40 mm.ms and was divided into two types based on the morphology of P-waves in V1: either a totally negative (-) P wave in V1 or a biphasic (+/-) P wave in V1. s-Ptf correlated better with vertical P-vectors than nonvertical P-vectors (P = 0.03). s-Ptf also significantly correlated with IAB (P = 0.001); however, IAB and P-vector verticalization did not appear to have any significant correlation (P = 0.23). There was a very weak correlation between i-PV1 and frontal P-vector (r = 0.15; P = 0.047); however, no significant correlation was found between i-PV1 and P-amplitude in lead III (r = 0.07; P = 0.36). We conclude that increased P-tf in emphysema may be due to downward right atrial position caused by right atrial displacement, and thus the common assumption that increased P-tf implies left atrial enlargement should be made with caution in patients with emphysema. Also, the lack of strong correlation between i-PV1 and P-amplitude in lead III or vertical P-vector may suggest the predominant role of downward

  12. Chemical and structural effects of base modifications in messenger RNA

    PubMed Central

    Harcourt, Emily M.; Kietrys, Anna M.; Kool, Eric T.

    2017-01-01

    A growing number of nucleobase modifications in messenger RNA have been revealed through advances in detection and RNA sequencing. Although some of the biochemical pathways that involve modified bases have been identified, research into the world of RNA modification — the epitranscriptome — is still in an early phase. A variety of chemical tools are being used to characterize base modifications, and the structural effects of known base modifications on RNA pairing, thermodynamics and folding are being determined in relation to their putative biological roles. PMID:28102265

  13. Methodological issues of confounding in analytical epidemiologic studies.

    PubMed

    Hajian Tilaki, Karimollah

    2012-01-01

    Confounding can be thought of as mixing the effect of exposure on the risk of disease with a third factor which distorts the measure of association such as risk ratio or odds ratio. This bias arises because of complex functional relationship of confounder with both exposure and disease (outcome). In this article, we provided a conceptual framework review of confounding issues in epidemiologic studies, in particular in observational studies and nonrandomized experimental studies. We have shown in 2 by 2 tables with analytical examples how the index of association will be distorted when confounding is present. The criteria, source of confounding and several points in confounding issues have been addressed. The advantages and disadvantages of several strategies for control of confounding have been discussed.

  14. Modification by Influenza on Health Effects of Air Pollution in Hong Kong

    PubMed Central

    Wong, Chit Ming; Yang, Lin; Thach, Thuan Quoc; Chau, Patsy Yuen Kwan; Chan, King Pan; Thomas, G. Neil; Lam, Tai Hing; Wong, Tze Wai; Hedley, Anthony J.; Peiris, J.S. Malik

    2009-01-01

    Background Both influenza viruses and air pollutants have been well documented as major hazards to human health, but few epidemiologic studies have assessed effect modification of influenza on health effects of ambient air pollutants. Objectives We aimed to assess modifying effects of influenza on health effects of ambient air pollutants. Methods We applied Poisson regression to daily numbers of hospitalizations and mortality to develop core models after adjustment for potential time-varying confounding variables. We assessed modification of influenza by adding variables for concentrations of single ambient air pollutants and proportions of influenza-positive specimens (influenza intensity) and their cross-product terms. Results We found significant effect modification of influenza (p < 0.05) for effects of ozone. When influenza intensity is assumed to increase from 0% to 10%, the excess risks per 10-μg/m3 increase in concentration of O3 increased 0.24% and 0.40% for hospitalization of respiratory disease in the all-ages group and ≥ 65 year age group, respectively; 0.46% for hospitalization of acute respiratory disease in the all-ages group; and 0.40% for hospitalization of chronic obstructive pulmonary disease in the ≥ 65 group. The estimated increases in the excess risks for mortality of respiratory disease and chronic obstructive pulmonary disease in the all-ages group were 0.59% and 1.05%, respectively. We found no significant modification of influenza on effects of other pollutants in most disease outcomes under study. Conclusions Influenza activity could be an effect modifier for the health effects of air pollutants particularly for O3 and should be considered in the studies for short-term effects of air pollutants on health. PMID:19270795

  15. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    PubMed Central

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory causal indicators are controversial and little-understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning intended by a researcher. This article questions the validity of evidence used to claim that causal indicators are inherently susceptible to interpretational confounding. Further, a simulation study demonstrates that causal indicator coefficients are stable across correctly-specified models. Determining the suitability of causal indicators has implications for the way we conceptualize measurement and build and evaluate measurement models. PMID:25530730

  16. Effect modification of ozone-related mortality risks by temperature in 97 US cities.

    PubMed

    Jhun, Iny; Fann, Neal; Zanobetti, Antonella; Hubbell, Bryan

    2014-12-01

    Many time-series studies have characterized the relationship between short-term ozone exposure and adverse health outcomes, controlling for temperature as a confounder. Temperature may also modify ozone effects, though this has been largely under-investigated. In this study, we explored whether temperature modifies the effect of short-term ozone exposure on mortality. We used the database developed for the National Morbidity and Mortality Air Pollution Study to estimate ozone mortality risks in 97 US cities in May through September, 1987-2000. We treated temperature as a confounder as well as an effect modifier by estimating risks at low, moderate, and high temperature categories. When temperature was treated as a confounder, a 10-ppb increase in daily 24-h ozone was associated with a 0.47% (95% CI: 0.19%-0.76%) increase in mortality. When we assessed effect modification by temperature, the interaction between ozone and temperature was not statistically significant. However, there was a U-shaped pattern in mortality risk, which was greater at the low (<25th percentile) and high (>75th percentile) temperature levels than moderate temperature levels. At the high temperature category, a 10% increase in AC prevalence mitigated mortality risk associated with 10-ppb of ozone exposure by -0.18% (95% CI: -0.35%, -0.02%). Furthermore, ozone mortality risk in the high temperature category increased as we restricted our analyses to hotter days. On days where temperatures exceeded the 75th, 90th, and 95th percentile temperatures, a 10-ppb increase in ozone was associated with a 0.65% (95% CI: 0.20%-1.09%), 0.83% (95% CI: 0.17%-1.48%), and 1.35% (95% CI: 0.44%-2.27%) increase in mortality, respectively. These results suggested that high temperatures may exacerbate physiological responses to short-term ozone exposure.

  17. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    ERIC Educational Resources Information Center

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

  18. Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

    ERIC Educational Resources Information Center

    Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

    2016-01-01

    A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

  19. Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

    ERIC Educational Resources Information Center

    Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

    2016-01-01

    A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

  20. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    ERIC Educational Resources Information Center

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

  1. Effect Modification and Interaction Terms: It Takes Two to Tango.

    PubMed

    Jupiter, Daniel C

    2016-01-01

    In this Investigators' Corner I look more deeply into the previously discussed phenomenon of effect modification. I revisit an explanation and examples of the phenomenon and then examine how to account for it statistically. Specifically, I show, in detail, how to write a regression equation that includes interaction terms that account for the effect modification. Finally, I look at interpretation of regression coefficients both with and without the presence of effect modification, and the associated interaction terms. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Confounding in longitudinal studies in addiction treatment research

    PubMed Central

    Pierce, Matthias; Dunn, Graham; Millar, Tim

    2017-01-01

    Abstract Background: The effectiveness of treatment for people with substance use disorders is usually examined using longitudinal cohorts. In these studies, treatment is often considered as a time-varying exposure. The aim of this commentary is to examine confounding in this context, when the confounding variable is time-invariant and when it is time-varying. Method: Types of confounding are described with examples and illustrated using path diagrams. Simulations are used to demonstrate the direction of confounding bias and the extent that it is accounted for using standard regression adjustment techniques. Results: When the confounding variable is time invariant or time varying and not influenced by prior treatment, then standard adjustment techniques are adequate to control for confounding bias, provided that in the latter scenario the time-varying form of the variable is used. When the confounder is time varying and affected by prior treatment status (i.e. it is a mediator of treatment), then standard methods of adjustment result in inconsistency. Conclusions: In longitudinal cohorts where treatment exposure is time varying, confounding is an issue which should be considered, even if treatment exposure is initially randomized. In these studies, standard methods of adjustment may result be inadequate, even when all confounders have been identified. This occurs when the confounder is also a mediator of treatment. This is a likely scenario in many studies in addiction.

  3. Confounding in longitudinal studies in addiction treatment research.

    PubMed

    Pierce, Matthias; Dunn, Graham; Millar, Tim

    2017-05-04

    Background: The effectiveness of treatment for people with substance use disorders is usually examined using longitudinal cohorts. In these studies, treatment is often considered as a time-varying exposure. The aim of this commentary is to examine confounding in this context, when the confounding variable is time-invariant and when it is time-varying. Method: Types of confounding are described with examples and illustrated using path diagrams. Simulations are used to demonstrate the direction of confounding bias and the extent that it is accounted for using standard regression adjustment techniques. Results: When the confounding variable is time invariant or time varying and not influenced by prior treatment, then standard adjustment techniques are adequate to control for confounding bias, provided that in the latter scenario the time-varying form of the variable is used. When the confounder is time varying and affected by prior treatment status (i.e. it is a mediator of treatment), then standard methods of adjustment result in inconsistency. Conclusions: In longitudinal cohorts where treatment exposure is time varying, confounding is an issue which should be considered, even if treatment exposure is initially randomized. In these studies, standard methods of adjustment may result be inadequate, even when all confounders have been identified. This occurs when the confounder is also a mediator of treatment. This is a likely scenario in many studies in addiction.

  4. Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My!

    PubMed

    Vetter, Thomas R; Mascha, Edward J

    2017-09-01

    the association or treatment effect. Interaction among variables, also known as effect modification, exists when the effect of 1 explanatory variable on the outcome depends on the particular level or value of another explanatory variable. Bias and confounding are common potential explanations for statistically significant associations between exposure and outcome when the true relationship is noncausal. Understanding interactions is vital to proper interpretation of treatment effects. These complex concepts should be consistently and appropriately considered whenever one is not only designing but also analyzing and interpreting data from a randomized trial or observational study.

  5. Observed effects of “distributional learning” may not relate to the number of peaks. A test of “dispersion” as a confounding factor

    PubMed Central

    Wanrooij, Karin; Boersma, Paul; Benders, Titia

    2015-01-01

    Distributional learning of speech sounds is learning from simply being exposed to frequency distributions of speech sounds in one’s surroundings. In laboratory settings, the mechanism has been reported to be discernible already after a few minutes of exposure, in both infants and adults. These “effects of distributional training” have traditionally been attributed to the difference in the number of peaks between the experimental distribution (two peaks) and the control distribution (one or zero peaks). However, none of the earlier studies fully excluded a possibly confounding effect of the dispersion in the distributions. Additionally, some studies with a non-speech control condition did not control for a possible difference between processing speech and non-speech. The current study presents an experiment that corrects both imperfections. Spanish listeners were exposed to either a bimodal distribution encompassing the Dutch contrast /ɑ/∼/a/ or a unimodal distribution with the same dispersion. Before and after training, their accuracy of categorization of [ɑ]- and [a]-tokens was measured. A traditionally calculated p-value showed no significant difference in categorization improvement between bimodally and unimodally trained participants. Because of this null result, a Bayesian method was used to assess the odds in favor of the null hypothesis. Four different Bayes factors, each calculated on a different belief in the truth value of previously found effect sizes, indicated the absence of a difference between bimodally and unimodally trained participants. The implication is that “effects of distributional training” observed in the lab are not induced by the number of peaks in the distributions. PMID:26441719

  6. Parent-of-origin effects on genome-wide DNA methylation in the Cape honey bee (Apis mellifera capensis) may be confounded by allele-specific methylation.

    PubMed

    Remnant, Emily J; Ashe, Alyson; Young, Paul E; Buchmann, Gabriele; Beekman, Madeleine; Allsopp, Michael H; Suter, Catherine M; Drewell, Robert A; Oldroyd, Benjamin P

    2016-03-12

    Intersexual genomic conflict sometimes leads to unequal expression of paternal and maternal alleles in offspring, resulting in parent-of-origin effects. In honey bees reciprocal crosses can show strong parent-of-origin effects, supporting theoretical predictions that genomic imprinting occurs in this species. Mechanisms behind imprinting in honey bees are unclear but differential DNA methylation in eggs and sperm suggests that DNA methylation could be involved. Nonetheless, because DNA methylation is multifunctional, it is difficult to separate imprinting from other roles of methylation. Here we use a novel approach to investigate parent-of-origin DNA methylation in honey bees. In the subspecies Apis mellifera capensis, reproduction of females occurs either sexually by fertilization of eggs with sperm, or via thelytokous parthenogenesis, producing female embryos derived from two maternal genomes. We compared genome-wide methylation patterns of sexually-produced, diploid embryos laid by a queen, with parthenogenetically-produced diploid embryos laid by her daughters. Thelytokous embryos inheriting two maternal genomes had fewer hypermethylated genes compared to fertilized embryos, supporting the prediction that fertilized embryos have increased methylation due to inheritance of a paternal genome. However, bisulfite PCR and sequencing of a differentially methylated gene, Stan (GB18207) showed strong allele-specific methylation that was maintained in both fertilized and thelytokous embryos. For this gene, methylation was associated with haplotype, not parent of origin. The results of our study are consistent with predictions from the kin theory of genomic imprinting. However, our demonstration of allele-specific methylation based on sequence shows that genome-wide differential methylation studies can potentially confound imprinting and allele-specific methylation. It further suggests that methylation patterns are heritable or that specific sequence motifs are targets

  7. Modeling confounding by half-sibling regression

    PubMed Central

    Schölkopf, Bernhard; Hogg, David W.; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-01-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as “half-sibling regression,” is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  8. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-05

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application.

  9. Iron metabolism in children: Confounding factors

    PubMed Central

    Brittenham, Gary M.

    2011-01-01

    Characterization of iron metabolism in infants and children may be confounded by the diverse effects of developmental, genetic, and acquired influences on iron metabolism and laboratory measurements of iron status, especially in areas with intense perennial transmission of Plasmodium falciparum malaria. In the Pemba iron and folic acid supplementation trial, the coadministration of folic acid with iron is a further confounding factor. Because the design of the Pemba iron and folic acid supplementation study did not include a group that received iron supplementation without folic acid, the observed increase in serious adverse events cannot be ascribed unequivocally to iron alone, to folic acid alone, or to the combination of the two. In interpreting the results from the Pemba iron and folic acid supplementation trial, additional analyses of existing data from the trial and from earlier studies in the area could help clarify the roles of iron and folic acid. PMID:18297889

  10. The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding.

    PubMed

    Smith, Eric G

    2014-01-01

      Nonrandomized studies typically cannot account for confounding from unmeasured factors.    A method is presented that exploits the recently-identified phenomenon of  "confounding amplification" to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome.   Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method's requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding.   Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method's estimates (although bootstrapping is one plausible approach).   To this author's knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is straightforward.  The method's routine usefulness, however, has

  11. Confounding factors to predict the awakening effect-site concentration of propofol in target-controlled infusion based on propofol and fentanyl anesthesia.

    PubMed

    Chan, Shun-Ming; Lee, Meei-Shyuan; Lu, Chueng-He; Cherng, Chen-Hwan; Huang, Yuan-Shiou; Yeh, Chun-Chang; Kuo, Chan-Yang; Wu, Zhi-Fu

    2015-01-01

    We conducted a large retrospective study to investigate the confounding factors that predict Ce ROC under propofol-based TIVA with TCI. We recorded sex, age, height, weight, Ce LOC, Ce ROC, total propofol and fentanyl consumption dose, and anesthetic time. Simple linear regression models were used to identify potential predictors of Ce ROC, and multiple linear regression models were used to identify the confounding predictors of Ce ROC. We found that Ce ROC correlated with age, sex, Ce LOC, and both total fentanyl and propofol consumption dose. The prediction formula was: Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC + 0.04 (if fentanyl consumption > 150 μg; if not, ignore this value) + 0.07 × (1 or 2, according to the total propofol consumption dose, 1 for a propofol amount 1000-2000 mg and 2 for a propofol amount > 2000 mg). We simplified the formula further as Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC. In conclusion, Ce ROC can be predicted under TCI with propofol- and fentanyl-based TIVA. The confounding factors that predicted propofol Ce ROC are age, sex, Ce LOC, and total consumption dose of propofol and fentanyl.

  12. Disparity modifications and the emotional effects of stereoscopic images

    NASA Astrophysics Data System (ADS)

    Kawai, Takashi; Atsuta, Daiki; Tomiyama, Yuya; Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Häkkinen, Jukka

    2014-03-01

    This paper describes a study that focuses on disparity changes in emotional scenes of stereoscopic (3D) images, in which an examination of the effects on pleasant and arousal was carried out by adding binocular disparity to 2D images that evoke specific emotions, and applying disparity modification based on the disparity analysis of famous 3D movies. From the results of the experiment, for pleasant, a significant difference was found only for the main effect of the emotions. On the other hand, for arousal, there was a trend of increasing the evaluation values in the order 2D condition, 3D condition and 3D condition applied the disparity modification for happiness, surprise, and fear. This suggests the possibility that binocular disparity and the modification affect arousal.

  13. Protective effects in radiation modification of elastomers

    NASA Astrophysics Data System (ADS)

    Głuszewski, Wojciech; Zagórski, Zbigniew P.; Rajkiewicz, Maria

    2014-12-01

    Saturated character of ethylene/octene thermoplastic elastomers demands an application of nonconventional methods of crosslinking connections between chains of molecules. These are organic peroxides, usually in the presence of coagents or an application of ionizing radiation. Several approaches (radiation, peroxide, peroxide/plus radiation and radiation/plus peroxide) were applied in crosslinking of elastomere Engage 8200. Attention was directed to the protection effects by aromatic peroxides and by photo- and thermostabilizers on radiolysis of elastomers. Role of dose of radiation, dose rate of radiation as well as the role of composition of elastomere on the radiation yield of hydrogen and absorbtion of oxygen was investigated. DRS method was used to follow postirradiation degradation. Influence of crosslinking methods on properties of elastomers is described. Results were interpreted from the point of view of protective actions of aromatic compounds.

  14. Graphical presentation of confounding in directed acyclic graphs.

    PubMed

    Suttorp, Marit M; Siegerink, Bob; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

    2015-09-01

    Since confounding obscures the real effect of the exposure, it is important to adequately address confounding for making valid causal inferences from observational data. Directed acyclic graphs (DAGs) are visual representations of causal assumptions that are increasingly used in modern epidemiology. They can help to identify the presence of confounding for the causal question at hand. This structured approach serves as a visual aid in the scientific discussion by making underlying relations explicit. This article explains the basic concepts of DAGs and provides examples in the field of nephrology with and without presence of confounding. Ultimately, these examples will show that DAGs can be preferable to the traditional methods to identify sources of confounding, especially in complex research questions.

  15. Effects of Cognitive Bias Modification Training via Smartphones.

    PubMed

    Yang, Ranming; Cui, Lixia; Li, Feng; Xiao, Jing; Zhang, Qin; Oei, Tian P S

    2017-01-01

    Background and Objectives: Negative cognitive biases have been linked to anxiety and mood problems. Accumulated data from laboratory studies show that positive and negative interpretation styles with accompanying changes in mood can be induced through cognitive bias modification (CBM) paradigms. Despite the therapeutic potential of positive training effects, few studies have explored training paradigms administered via smartphones. The current study aimed to compare the effectiveness of three different types of training programmes (cognitive bias modification-attention, CBM-A; cognitive bias modification-interpretation, CBM-I; attention and interpretation modification, AIM) administered via smart-phones by using a control condition (CC). Methods:Seventy-six undergraduate participants with high social anxiety (Liebowitz Social Anxiety Scale, LSAS ≥ 30) were randomly assigned to four groups: CBM-A (n = 20), CBM-I (n = 20), AIM (n = 16), and CC (n = 20). Results: The results showed that the effects of CBM training, CBM-I training, or AIM training vs. CC for attention yielded no significant differences in dot-probe attention bias scores. The CBM-I group showed significantly less threat interpretation and more benign interpretation than the CC group on interpretation bias scores. Conclusions: The present results supported the feasibility of delivering CBM-I via smartphones, but the effectiveness of CBM-A and AIM training via smartphones was limited.

  16. Learner Interaction Using Email: The Effects of Task Modification

    ERIC Educational Resources Information Center

    Knight, Paul

    2005-01-01

    This paper outlines the findings of a research project studying the effects of task modification on learner interaction when using email. Taking as its starting point interactionalist theories of SLA, it argues that if those interactional features characteristic of negotiation of meaning which have been identified as promoting SLA are to be…

  17. The missing cause approach to unmeasured confounding in pharmacoepidemiology.

    PubMed

    Abrahamowicz, Michal; Bjerre, Lise M; Beauchamp, Marie-Eve; LeLorier, Jacques; Burne, Rebecca

    2016-03-30

    Unmeasured confounding is a major threat to the validity of pharmacoepidemiological studies of medication safety and effectiveness. We propose a new method for detecting and reducing the impact of unobserved confounding in large observational database studies. The method uses assumptions similar to the prescribing preference-based instrumental variable (IV) approach. Our method relies on the new 'missing cause' principle, according to which the impact of unmeasured confounding by (contra-)indication may be detected by assessing discrepancies between the following: (i) treatment actually received by individual patients and (ii) treatment that they would be expected to receive based on the observed data. Specifically, we use the treatment-by-discrepancy interaction to test for the presence of unmeasured confounding and correct the treatment effect estimate for the resulting bias. Under standard IV assumptions, we first proved that unmeasured confounding induces a spurious treatment-by-discrepancy interaction in risk difference models for binary outcomes and then simulated large pharmacoepidemiological studies with unmeasured confounding. In simulations, our estimates had four to six times smaller bias than conventional treatment effect estimates, adjusted only for measured confounders, and much smaller variance inflation than unbiased but very unstable IV estimates, resulting in uniformly lowest root mean square errors. The much lower variance of our estimates, relative to IV estimates, was also observed in an application comparing gastrointestinal safety of two classes of anti-inflammatory drugs. In conclusion, our missing cause-based method may complement other methods and enhance accuracy of analyses of large pharmacoepidemiological studies.

  18. Confounding and causation in the epidemiology of lead.

    PubMed

    Wilson, Ian Harold; Wilson, Simon Barton

    2016-01-01

    The National Health and Medical Research Council recently reported that there were not enough high-quality studies to conclude that associations between health effects and blood lead levels <10 μg/dL were caused by lead. It identified uncontrolled confounding, measurement error and other potential causal factors as common weaknesses. This paper supports those findings with evidence of uncontrolled confounding by parental education, intelligence or household management from several papers. It suggests that inappropriate statistical tests and aggregation of data representing different exposure routes partly explain why confounding has been overlooked. Inadequate correction of confounding has contributed to incorrect conclusions regarding causality at low levels of lead. Linear or log-linear regression models have tended to mask any threshold. While the effects of higher levels of lead exposure are not disputed, overestimation of health effects at low lead exposures has significant implications for policy-makers endeavouring to protect public health through cost-effective regulations.

  19. Methodological problems with population cancer studies: The forgotten confounding factors.

    PubMed

    Blaylock, Russell L

    2015-01-01

    Among clinical physicians it is the population study that is considered to be the "gold standard" of medical evidence concerning acceptable treatments. As new information comes to light concerning the many variables and confounding factors that can affect such studies, many older studies lose much of their original impact. While newer population studies take into consideration a far greater number of confounding factors many are still omitted and a number of these omitted factors can have profound effects on interpretation and validity of the study. In this editorial, I will discuss some of the omitted confounding factors and demonstrate how they can alter the interpretation of these papers and their clinical application.

  20. Effect of surface modification on semiconductor nanocrystal fluorescence lifetime.

    PubMed

    Ruedas-Rama, Maria J; Orte, Angel; Hall, Elizabeth A H; Alvarez-Pez, Jose M; Talavera, Eva M

    2011-04-04

    Semiconductor nanocrystals, namely, quantum dots (QDs), present a set of unique photoluminescence properties, which has led to increased interest in using them as advantageous alternatives to conventional organic dyes. Many applications of QDs involve surface modification to enhance the solubility or biocompatibility of the QDs. One of the least exploited properties of QDs is the very long photoluminescence lifetime that usually has complex kinetics owing to the effect of quantum confinement. Herein, we describe the effect of different surface modifications on the photoluminescence decay kinetics of QDs. The different surface modifications were carefully chosen to provide lipophilic or water-soluble QDs with either positive or negative surface net charges. We also survey the effect on the QD lifetime of several ligands that interact with the QD surface, such as organic chromophores or fluorescent proteins. The results obtained demonstrate that time-resolved fluorescence is a useful tool for QD-based sensing to set the basis for the development of time-resolved-based nanosensors.

  1. The effects of inlet flow modification on cavitating inducer performance

    NASA Technical Reports Server (NTRS)

    Del Valle, J.; Braisted, D. M.; Brennen, C. E.

    1992-01-01

    This paper explores the effect of inlet flow modification on the cavitating and noncavitating performance of two cavitating inducers, one of simple helical design and the other a model of the low-pressure LOX pump in the Space Shuttle Main Engine. The modifications were generated by sections of honeycomb, both uniform and nonuniform. Significant improvement in the performance over a wide range of flow coefficients resulted from the use of either honeycomb section. Measurements of the axial and swirl velocity profiles of the flows entering the inducers were made in order to try to understand the nature of the inlet flow and the manner in which it is modified by the honeycomb sections.

  2. Using an instrumental variable to test for unmeasured confounding.

    PubMed

    Guo, Zijian; Cheng, Jing; Lorch, Scott A; Small, Dylan S

    2014-09-10

    An important concern in an observational study is whether or not there is unmeasured confounding, that is, unmeasured ways in which the treatment and control groups differ before treatment, which affect the outcome. We develop a test of whether there is unmeasured confounding when an instrumental variable (IV) is available. An IV is a variable that is independent of the unmeasured confounding and encourages a subject to take one treatment level versus another, while having no effect on the outcome beyond its encouragement of a certain treatment level. We show what types of unmeasured confounding can be tested for with an IV and develop a test for this type of unmeasured confounding that has correct type I error rate. We show that the widely used Durbin-Wu-Hausman test can have inflated type I error rates when there is treatment effect heterogeneity. Additionally, we show that our test provides more insight into the nature of the unmeasured confounding than the Durbin-Wu-Hausman test. We apply our test to an observational study of the effect of a premature infant being delivered in a high-level neonatal intensive care unit (one with mechanical assisted ventilation and high volume) versus a lower level unit, using the excess travel time a mother lives from the nearest high-level unit to the nearest lower-level unit as an IV.

  3. Environmental confounding in gene-environment interaction studies.

    PubMed

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  4. Using an instrumental variable to test for unmeasured confounding

    PubMed Central

    Guo, Zijian; Cheng, Jing; Lorch, Scott A.; Small, Dylan S.

    2014-01-01

    An important concern in an observational study is whether or not there is unmeasured confounding, that is, unmeasured ways in which the treatment and control groups differ before treatment which affect the outcome. We develop a test of whether there is unmeasured confounding when an instrumental variable (IV) is available. An IV is a variable that is independent of the unmeasured confounding and encourages a subject to take one treatment level versus another, while having no effect on the outcome beyond its encouragement of a certain treatment level. We show what types of unmeasured confounding can be tested for with an IV and develop a test for this type of unmeasured confounding that has correct type I error rate. We show that the widely used Durbin–Wu–Hausman test can have inflated type I error rates when there is treatment effect heterogeneity. Additionally, we show that our test provides more insight into the nature of the unmeasured confounding than the Durbin–Wu–Hausman test. We apply our test to an observational study of the effect of a premature infant being delivered in a high-level neonatal intensive care unit (one with mechanical assisted ventilation and high volume) versus a lower level unit, using the excess travel time a mother lives from the nearest high-level unit to the nearest lower-level unit as an IV. PMID:24930696

  5. [Application of directed acyclic graphs in control of confounding].

    PubMed

    Xiang, R; Dai, W J; Xiong, Y; Wu, X; Yang, Y F; Wang, L; Dai, Z H; Li, J; Liu, A Z

    2016-07-01

    Observational study is a method most commonly used in the etiology study of epidemiology, but confounders, always distort the true causality between exposure and outcome when local inferencing. In order to eliminate these confounding, the determining of variables which need to be adjusted become a key issue. Directed acyclic graph(DAG)could visualize complex causality, provide a simple and intuitive way to identify the confounding, and convert it into the finding of the minimal sufficient adjustment for the control of confounding. On the one hand, directed acyclic graph can choose less variables, which increase statistical efficiency of the analysis. On the other hand, it could help avoiding variables that is not measured or with missing values. In a word, the directed acyclic graph could facilitate the reveal of the real causality effectively.

  6. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

    PubMed

    Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B

    2015-06-01

    In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task

  7. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

    PubMed Central

    Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

    2015-01-01

    Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

  8. The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

    PubMed Central

    Smith, Eric G.

    2015-01-01

    Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is

  9. The effectiveness of workplace dietary modification interventions: a systematic review.

    PubMed

    Geaney, F; Kelly, C; Greiner, B A; Harrington, J M; Perry, I J; Beirne, P

    2013-11-01

    To evaluate the effectiveness of workplace dietary modification interventions alone or in combination with nutrition education on employees' dietary behaviour, health status, self-efficacy, perceived health, determinants of food choice, nutrition knowledge, co-worker support, job satisfaction, economic cost and food-purchasing patterns. Data sources included PubMed, Medline, Embase, Psych Info., Web of Knowledge and Cochrane Library (November 2011). This review was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were randomised controlled trials and controlled studies. Interventions were implemented for at least three months. Cochrane Collaboration's risk of bias tool measured potential biases. Heterogeneity precluded meta-analysis. Results were presented in a narrative summary. Six studies conducted in Brazil, the USA, Netherlands and Belgium met the inclusion criteria. Four studies reported small increases in fruit and vegetable consumption (≤half serving/day). These studies involved workplace dietary modifications and three incorporated nutrition education. Other outcomes reported included health status, co-worker support, job satisfaction, perceived health, self-efficacy and food-purchasing patterns. All studies had methodological limitations that weakened confidence in the results. Limited evidence suggests that workplace dietary modification interventions alone and in combination with nutrition education increase fruit and vegetable intakes. These interventions should be developed with recommended guidelines, workplace characteristics, long-term follow-up and objective outcomes for diet, health and cost. © 2013.

  10. Infection with parasitic nematodes confounds vaccination efficacy.

    PubMed

    Urban, Joseph F; Steenhard, Nina R; Solano-Aguilar, Gloria I; Dawson, Harry D; Iweala, Onyinye I; Nagler, Cathryn R; Noland, Gregory S; Kumar, Nirbhay; Anthony, Robert M; Shea-Donohue, Terez; Weinstock, Joel; Gause, William C

    2007-08-19

    T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-gamma, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide

  11. Ecological Effects of Weather Modification: A Problem Analysis.

    ERIC Educational Resources Information Center

    Cooper, Charles F.; Jolly, William C.

    This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

  12. Confounding and bias in the attributable fraction.

    PubMed

    Darrow, Lyndsey A; Steenland, N Kyle

    2011-01-01

    Inappropriate methods are frequently used to calculate the population attributable fraction (AF) for a given exposure of interest. This commonly occurs when authors use adjusted relative risks (RRs) reported in the literature (the "source" data), without access to the original data. In this analysis, we examine the relationship between the direction and magnitude of confounding in the source data and resulting bias in the attributable fraction when incorrect methods are used. We assess confounding by the confounding risk ratio, which is the ratio of the crude RR to the adjusted RR. We assess bias in the AF by the ratio of the incorrectly calculated AF to the correctly calculated AF. Using generated data, we examine the relationship between confounding and AF bias under various scenarios of population prevalence of exposure and strength of the exposure-disease association. For confounding risk ratios greater than 1.0 (ie, crude RR >adjusted RR), the AF is underestimated; for confounding risk ratios less than 1.0 (ie, crude RR confounding increases, and is dependent on the prevalence of exposure in the total population, with bias greatest at the lowest prevalence of exposure. Bias in the AF is also higher when the exposure-disease association is weaker. Results of these analyses can assist interpretation of incorrectly calculated attributable fraction estimates commonly reported in the epidemiologic literature.

  13. Imaging the neural effects of cognitive bias modification training.

    PubMed

    Wiers, Corinde E; Wiers, Reinout W

    2017-05-01

    Cognitive bias modification (CBM) was first developed as an experimental tool to examine the causal role of cognitive biases, and later developed into complementary interventions in experimental psychopathology research. CBM involves the "re-training" of implicit biases by means of multiple trials of computerized tasks, and has been demonstrated to change anxious, depressive and drug-seeking behavior, including clinically relevant effects. Recently, the field has progressed by combining CBM with neuroimaging techniques, which provides insight into neural mechanisms underlying how CBM affects implicit biases in anxiety, depression, and addiction, and potentially other pathologies. This narrative literature review summarizes the state of the art of studies on the neural effects of CBM and provides directions for future research in the field. A total of 13 published studies were found and discussed: n=9 in anxiety, n=2 in depressive behavior, and n=2 in addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effect of epigenetic modification of maspin on extravillous trophoblastic function.

    PubMed

    Shi, Xinwei; Wu, Yuanyuan; Liu, Haiyi; Gong, Xun; Du, Hui; Li, Yuqi; Zhao, Jun; Chen, Ping; Tang, Guiju; Qiao, Fuyuan

    2012-12-01

    This study investigated the effect of epigenetic modification of maspin on extravillous trophoblastic function. The mRNA expression of maspin in placentae from normotensive and preeclamptic pregnant women was detected by RT-PCR. TEV-1 cells, a human first-trimester extravillous trophoblast cell line, were cultured and treated with CoCl(2) (300 μmol/L) to induce chemical hypoxia and with 5-aza (500 nmol/L) to induce demethylation. The mRNA expression of maspin in TEV-1 cells subjected to different treatments was determined by RT-PCR, and the proliferative and migratory abilities of TEV-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assays. Our results showed that the maspin mRNA expression level in placentae from preeclamptic women was much higher than that from normotensive women. CoCl(2) or 5-aza could up-regulate the mRNA expression of maspin and significantly suppress the proliferation and migration of TEV-1 cells. It was concluded that the epigenetic modification in promoter region of maspin contributes to incomplete trophoblast invasion, which offers a novel approach for predicting and treating placental dysfunction.

  15. Effect of thermal modification on rheological properties of polyethylene blends

    SciTech Connect

    Siriprumpoonthum, Monchai; Nobukawa, Shogo; Yamaguchi, Masayuki; Satoh, Yasuo; Sasaki, Hiroko

    2014-03-15

    We examined the effects of thermal modification under flow field on the rheological properties of linear low-density polyethylene (LLDPE) with high molecular weight, low-density polyethylene (LDPE), and their blends, without thermal stabilizer. Although structural changes during processing are not detected by size extrusion chromatography or nuclear magnetic resonance spectroscopy, linear viscoelastic properties changed greatly, especially for the LLDPE. A cross-linking reaction took place, leading to, presumably, star-shaped long-chain branches. Consequently, the modified LLDPE, having high zero-shear viscosity, became a thermorheologically complex melt. Moreover, it should be noted that the drawdown force, defined as the uniaxial elongational force at a constant draw ratio, was significantly enhanced for the blends. Enhancement of elongational viscosity was also detected. The drawdown force and elongational viscosity are marked for the thermally modified blend as compared with those for the blend of thermally modified pure components. Intermolecular cross-linking reactions between LDPE and LLDPE, yielding polymers with more than two branch points per chain, result in marked strain-hardening in the elongational viscosity behavior even at small strain. The recovery curve of the oscillatory modulus after the shear modification is further evidence of a branched structure.

  16. Opportunities for minimization of confounding in observational research.

    PubMed

    Quartey, George; Feudjo-Tepie, Maurille; Wang, Jixian; Kim, Joseph

    2011-01-01

    Observational epidemiological studies are increasingly used in pharmaceutical research to evaluate the safety and effectiveness of medicines. Such studies can complement findings from randomized clinical trials by involving larger and more generalizable patient populations by accruing greater durations of follow-up and by representing what happens more typically in the clinical setting. However, the interpretation of exposure effects in observational studies is almost always complicated by non-random exposure allocation, which can result in confounding and potentially lead to misleading conclusions. Confounding occurs when an extraneous factor, related to both the exposure and the outcome of interest, partly or entirely explains the relationship observed between the study exposure and the outcome. Although randomization can eliminate confounding by distributing all such extraneous factors equally across the levels of a given exposure, methods for dealing with confounding in observational studies include a careful choice of study design and the possible use of advanced analytical methods. The aim of this paper is to introduce some of the approaches that can be used to help minimize the impact of confounding in observational research to the reader working in the pharmaceutical industry.

  17. Methodological problems with population cancer studies: The forgotten confounding factors

    PubMed Central

    Blaylock, Russell L.

    2015-01-01

    Among clinical physicians it is the population study that is considered to be the “gold standard” of medical evidence concerning acceptable treatments. As new information comes to light concerning the many variables and confounding factors that can affect such studies, many older studies lose much of their original impact. While newer population studies take into consideration a far greater number of confounding factors many are still omitted and a number of these omitted factors can have profound effects on interpretation and validity of the study. In this editorial, I will discuss some of the omitted confounding factors and demonstrate how they can alter the interpretation of these papers and their clinical application. PMID:26097772

  18. Literature-Based Discovery of Confounding in Observational Clinical Data

    PubMed Central

    Malec, Scott A.; Wei, Peng; Xu, Hua; Bernstam, Elmer V.; Myneni, Sahiti; Cohen, Trevor

    2016-01-01

    Observational data recorded in the Electronic Health Record (EHR) can help us better understand the effects of therapeutic agents in routine clinical practice. As such data were not collected for research purposes, their reuse for research must compensate for additional information that may bias analyses and lead to faulty conclusions. Confounding is present when factors aside from the given predictor(s) affect the response of interest. However, these additional factors may not be known at the outset. In this paper, we present a scalable literature-based confounding variable discovery method for biomedical research applications with pharmacovigilance as our use case. We hypothesized that statistical models, adjusted with literature-derived confounders, will more accurately identify causative drug-adverse drug event (ADE) relationships. We evaluated our method with a curated reference standard, and found a pattern of improved performance ~ 5% in two out of three models for gastrointestinal bleeding (pre-adjusted Area Under Curve ≥ 0.6). PMID:28269951

  19. Associations of Early- and Later-Childhood Poverty With Child Cognitive Function in Indonesia: Effect Decomposition in the Presence of Exposure-Induced Mediator-Outcome Confounding.

    PubMed

    Maika, Amelia; Mittinty, Murthy N; Brinkman, Sally; Lynch, John

    2017-05-15

    The amount of family financial resources available in early life influences child health and development. Using data from the 2000 and 2007 waves of the Indonesian Family Life Survey, we estimated the associations of early-life poverty (at age <7 years) and poverty in later childhood (at age 7-14 years) with cognitive function at age 7-14 years. Our analysis provided little support for the idea that an early intervention to support household income has a larger effect than intervention later in childhood; both seemed equally important. We also decomposed the effect of poverty at age <7 years into direct and indirect effects mediated through poverty and schooling/home environment at age 7-14 years. For decomposing the effects, we used 3 approaches: 1) joint mediators, 2) path-specific, and 3) intervention analog. Being exposed to poverty before age 7 years had a larger direct effect (difference in cognitive function z score) on child cognitive function at age 7-14 years (i.e., joint mediators β = -0.07, 95% confidence interval: -0.12, -0.02) than the indirect effects mediated through later poverty at age 7-14 years (β = -0.01, 95% confidence interval: -0.04, 0.01) and school attendance/home environment at age 7-14 years. The effect of poverty on cognitive function was small; nevertheless, financial intervention may still benefit children's cognitive function. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

    ERIC Educational Resources Information Center

    Talloen, Wouter; Moerkerke, Beatrijs; Loeys, Tom; De Naeghel, Jessie; Van Keer, Hilde; Vansteelandt, Stijn

    2016-01-01

    To assess the direct and indirect effect of an intervention, multilevel 2-1-1 studies with intervention randomized at the upper (class) level and mediator and outcome measured at the lower (student) level are frequently used in educational research. In such studies, the mediation process may flow through the student-level mediator (the within…

  1. Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

    ERIC Educational Resources Information Center

    Talloen, Wouter; Moerkerke, Beatrijs; Loeys, Tom; De Naeghel, Jessie; Van Keer, Hilde; Vansteelandt, Stijn

    2016-01-01

    To assess the direct and indirect effect of an intervention, multilevel 2-1-1 studies with intervention randomized at the upper (class) level and mediator and outcome measured at the lower (student) level are frequently used in educational research. In such studies, the mediation process may flow through the student-level mediator (the within…

  2. Ground cloud related weather modification effects. [heavy lift launch vehicles

    NASA Technical Reports Server (NTRS)

    Lee, J.

    1980-01-01

    The principal concerns about inadvertent weather modification by the solar power satellite system rocket effluents are discussed, namely the possibility that the ground cloud might temporarily modify local weather and the cumulative effects of nearly 500 launches per year. These issues are discussed through the consideration of (1) the possible alteration of the microphysical processes of clouds in the general area due to rocket effluents and debris and cooling water entrained during the launch and (2) the direct dynamical and thermodynamical responses to the inputs of thermal energy and moisture from the rocket exhaust for given ambient meteorological conditions. The huge amount of thermal energy contained in the exhaust of the proposed launch vehicle would in some situations induce a saturated, wet convective cloud or enhance an existing convective activity. Nevertheless, the effects would be limited to the general area of the launch site. The observed long lasting high concentrations of cloud condensation nuclei produced during and after a rocket launch may appreciably affect the frequency of occurrence and persistence of fogs and haze. In view of the high mission frequency proposed for the vehicle launches, a potential exists for a cumulative effect.

  3. Developing hazelnut tissue culture medium free of ion confounding

    USDA-ARS?s Scientific Manuscript database

    The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

  4. Effects of positive interpretive bias modification in highly anxious individuals.

    PubMed

    Salemink, Elske; van den Hout, Marcel; Kindt, Merel

    2009-06-01

    Over the past 20 years evidence has accumulated that individuals suffering from anxiety tend to interpret ambiguous information as threatening. Considering the causal role of this interpretive bias in anxiety, it was recently established that modifying interpretive biases influences anxiety. This suggests that anxiety can be clinically treated by directly targeting this interpretive bias. The present study was designed to modify a negative interpretive bias in highly anxious individuals, and subsequently assess the hypothesized beneficial effects on clinical measures. High trait-anxious participants were randomly assigned to one of two conditions: a positive interpretational Cognitive Bias Modification (CBM-I) or a control condition (n=2 x 17). The program was offered online for eight consecutive days. Upon completing the program, participants who had followed positive CBM-I were less state and trait-anxious compared to the control group. Additionally, positively trained participants scored lower on a measure of general psychopathology (SCL-90). No effects were observed on social anxiety and stress vulnerability. The mixed pattern of findings renders them rather inconclusive, leaving interpretations of the potential therapeutic merits of CBM-I open for future research.

  5. Stability studies of plasma modification effects of polylactide and polycaprolactone surface layers

    NASA Astrophysics Data System (ADS)

    Moraczewski, Krzysztof; Stepczyńska, Magdalena; Malinowski, Rafał; Rytlewski, Piotr; Jagodziński, Bartłomiej; Żenkiewicz, Marian

    2016-07-01

    The article presents results of research on the stability of oxygen plasma modification effects of polylactide and polycaprolactone surface layers. The modified samples were aged for three, six or nine weeks. The studies were carried out using scanning electron microscopy, goniometry and Fourier transform infrared spectroscopy. Studies have shown that the plasma modification has significant impact on the geometric structure and chemical composition of the surface, wettability and surface energy of tested polymers. The modification effects are not permanent. It has been observed that over time the effects of plasma modification fade. Studies have shown that modifying effect lasts longer in the case of polycaprolactone.

  6. Task-switching cost and repetition priming: two overlooked confounds in the first-set procedure of the Sternberg paradigm and how they affect memory set-size effects.

    PubMed

    Jou, Jerwen

    2014-10-01

    Subjects performed Sternberg-type memory recognition tasks (Sternberg paradigm) in four experiments. Category-instance names were used as learning and testing materials. Sternberg's original experiments demonstrated a linear relation between reaction time (RT) and memory-set size (MSS). A few later studies found no relation, and other studies found a nonlinear relation (logarithmic) between the two variables. These deviations were used as evidence undermining Sternberg's serial scan theory. This study identified two confounding variables in the fixed-set procedure of the paradigm (where multiple probes are presented at test for a learned memory set) that could generate a MSS RT function that was either flat or logarithmic rather than linearly increasing. These two confounding variables were task-switching cost and repetition priming. The former factor worked against smaller memory sets and in favour of larger sets whereas the latter factor worked in the opposite way. Results demonstrated that a null or a logarithmic RT-to-MSS relation could be the artefact of the combined effects of these two variables. The Sternberg paradigm has been used widely in memory research, and a thorough understanding of the subtle methodological pitfalls is crucial. It is suggested that a varied-set procedure (where only one probe is presented at test for a learned memory set) is a more contamination-free procedure for measuring the MSS effects, and that if a fixed-set procedure is used, it is worthwhile examining the RT function of the very first trials across the MSSs, which are presumably relatively free of contamination by the subsequent trials.

  7. Ultrafast transient absorption spectrum of the room temperature Ionic liquid 1-hexyl-3-methylimidazolium bromide: Confounding effects of photo-degradation

    NASA Astrophysics Data System (ADS)

    Musat, Raluca M.; Crowell, Robert A.; Polyanskiy, Dmitriy E.; Thomas, Marie F.; Wishart, James F.; Katsumura, Yosuke; Takahashi, Kenji

    2015-12-01

    The photochemistry of the charge transfer (CT) band of the room temperature ionic liquid (RTIL) 1-hexyl-3-methylimidazolium bromide (HMIm+/Br-) is investigated using near-IR to vis ultrafast transient absorption (TA) and steady-state UV absorption spectroscopies. Continuous irradiation of the CT band at 266 nm results in the formation of photo-products that absorb strongly at 266 nm. It is shown that these photo-products, which are apparently very stable, adversely affect ultrafast TA measurements. Elimination of these effects reveals at least two transient species that exist within the TA detection window of 100 fs to 3 ns and 500-1250 nm. One of the components is a short-lived (<1 ps) species that absorbs at 1080 nm. The second band exhibits a multicomponent spectrum that is very broad with an absorption maximum around 600 nm and a lifetime that is longer than the 3 ns window of our TA spectrometer. Within the signal to noise ratio of the TA spectrometer little to no solvated electron is generated by the CT mechanism.

  8. Pregnancy-associated plasma protein-A predicts survival in end-stage renal disease-confounding and modifying effects of cardiovascular disease, body composition and inflammation.

    PubMed

    Nilsson, Erik; Cao, Yang; Lindholm, Bengt; Ohyama, Ayane; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Stenvinkel, Peter

    2017-07-24

    effect modifiers for the observed moderate association of PAPP-A with survival.

  9. Confounding and exposure measurement error in air pollution epidemiology.

    PubMed

    Sheppard, Lianne; Burnett, Richard T; Szpiro, Adam A; Kim, Sun-Young; Jerrett, Michael; Pope, C Arden; Brunekreef, Bert

    2012-06-01

    Studies in air pollution epidemiology may suffer from some specific forms of confounding and exposure measurement error. This contribution discusses these, mostly in the framework of cohort studies. Evaluation of potential confounding is critical in studies of the health effects of air pollution. The association between long-term exposure to ambient air pollution and mortality has been investigated using cohort studies in which subjects are followed over time with respect to their vital status. In such studies, control for individual-level confounders such as smoking is important, as is control for area-level confounders such as neighborhood socio-economic status. In addition, there may be spatial dependencies in the survival data that need to be addressed. These issues are illustrated using the American Cancer Society Cancer Prevention II cohort. Exposure measurement error is a challenge in epidemiology because inference about health effects can be incorrect when the measured or predicted exposure used in the analysis is different from the underlying true exposure. Air pollution epidemiology rarely if ever uses personal measurements of exposure for reasons of cost and feasibility. Exposure measurement error in air pollution epidemiology comes in various dominant forms, which are different for time-series and cohort studies. The challenges are reviewed and a number of suggested solutions are discussed for both study domains.

  10. The relation of collapsibility and confounding to faithfulness and stability.

    PubMed

    Mansournia, Mohammad Ali; Greenland, Sander

    2015-07-01

    A probability distribution may have some properties that are stable under a structure (e.g., a causal graph) and other properties that are unstable. Stable properties are implied by the structure and thus will be shared by populations following the structure. In contrast, unstable properties correspond to special circumstances that are unlikely to be replicated across those populations. A probability distribution is faithful to the structure if all independencies in the distribution are logical consequences of the structure. We explore the distinction between confounding and noncollapsibility in relation to the concepts of faithfulness and stability. Simple collapsibility of an odds ratio over a risk factor is unstable and thus unlikely if the exposure affects the outcome, whether or not the risk factor is associated with exposure. For a binary exposure with no effect, collapsibility over a confounder also requires unfaithfulness. Nonetheless, if present, simple collapsibility of the odds ratio limits the degree of confounding by the covariate. Collapsibility of effect measures is stable if the covariate is independent of the outcome given exposure, but it is unstable if the covariate is an instrumental variable. Understanding stable and unstable properties of distributions under causal structures, and the distinction between stability and faithfulness, yields important insights into the correspondence between noncollapsibility and confounding.

  11. 78 FR 20137 - Probable Economic Effect of Certain Modifications to the North American Free Trade Agreement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... COMMISSION Probable Economic Effect of Certain Modifications to the North American Free Trade Agreement Rules.... 3313), the Commission instituted investigation No. TA-103-027, Probable Economic Effect of Certain... provide advice on the probable economic effect of the proposed modifications on U.S. trade under the...

  12. Effect of Chemical Modifications on Aptamer Stability in Serum.

    PubMed

    Kratschmer, Christina; Levy, Matthew

    2017-09-25

    There is increasing interest in the use of aptamers for the development of therapeutics. However, as oligonucleotides, aptamers are susceptible to nuclease degradation; poor serum stability is likely to negatively affect in vivo function. Modified nucleotides have been used to thwart nuclease degradation. However, few studies report the serum stability of selected aptamers. In this study, we examined the effect of various chemical modifications (2'-deoxy, 2'-hydroxyl, 2'-fluoro, and 2'-O-methyl) on the stability of a control oligonucleotide sequence following incubation in frozen human, fresh mouse, and fresh human serum. We also assessed the effect of the 3' inverted dT cap on stability. Surprisingly, we found that fYrR (2'-fluoro RNA) is only roughly as stable as DNA (2'-deoxy). Interestingly, the inclusion of a 3' inverted dT cap had only a modest effect on serum stability, if any. In one instance, the addition of a 3' inverted dT cap rendered a molecule composed of DNA more stable than its fYrR counterpart. By far, fully modified oligonucleotides (100% 2-O-Methyl or 2'-O-methyl A, C, and U in combination with 2'-fluoro G, termed fGmH) had the longest half-lives. These compositions demonstrated little degradation in human serum even after prolonged incubation. Together these results support the need for using fully modified aptamers for in vivo applications and should encourage those in the field to exploit newer polymerase variants capable of directly generating such polymers.

  13. Polycation binding to glomerular basement membrane. Effect of biochemical modification.

    PubMed

    Bertolatus, J A; Hunsicker, L G

    1987-02-01

    The polycation hexadimethrine (HDM) binds to anionic sites in the glomerular basement membrane (GBM) and causes heavy proteinuria when infused in vivo. An in vitro assay of 3H-HDM binding to isolated dog GBM was developed, to permit further analysis of the GBM components binding HDM. 3H-HDM binding to isolated GBM was saturable, reversible in dose-dependent fashion by competing polycations, and inhibited by increasing salt concentration and low pH. The pH dependence of binding suggested that most of the HDM binds to carboxyl groups rather than to the sulfate groups of proteoglycans. Removal of heparan sulfate by heparinase or purified heparatinase had no detectable effect on HDM binding. Treatment of GBM with neuraminidase, hyaluronidase, or chondroitinase reduced binding of HDM by a maximum of 20 to 38%. However, substitution of carboxyl anions with nonionizable glycine methyl ester residues resulted in complete elimination of HDM binding. Parallel results were obtained in studies of glomerular localization of cationized ferritin (CatF), pI 8.5. After carboxyl substitution, GBM did not bind CatF; heparinase-treated GBM bound CatF in a distribution not demonstrably different from normal. Cellulose acetate electrophoresis of glycosaminoglycan fractions prepared from treated GBM confirmed that carboxyl modification did not alter the content or charge of the heparan sulfate of GBM, but heparinase treatment removed at least 90% of heparan sulfate. The results indicate that carboxyl groups are quantitatively more important than heparan sulfate for binding of HDM in vitro. Since HDM causes proteinuria in vivo, carboxyl groups may be important for maintenance of normal permselectivity.

  14. Computer-Assisted Accent Modification: A Report on Practice Effects.

    ERIC Educational Resources Information Center

    Ferrier, Linda J.; Reid, Lawry N.; Chenausky, Karen

    1999-01-01

    This study evaluated the use of the computer-assisted accent-modification program, Speech Works, with beginning college students of English as a second language with a non-speech-language pathologist trainer. Students who had weekly one-on-one sessions with a teacher and independent practice, especially when the practice was computer monitored,…

  15. Resting-state FMRI confounds and cleanup

    PubMed Central

    Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

    2013-01-01

    The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

  16. Disease Risk Score (DRS) as a Confounder Summary Method: Systematic Review and Recommendations

    PubMed Central

    Tadrous, Mina; Gagne, Joshua J.; Stürmer, Til; Cadarette, Suzanne M.

    2013-01-01

    Purpose To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method. Methods We completed a systematic search of MEDLINE and Web of Science® to identify all English language articles that applied DRS methods. We tabulated the number of publications by year and type (empirical application, methodological contribution, or review paper) and summarized methods used in empirical applications overall and by publication year (<2000, ≥2000). Results Of 714 unique articles identified, 97 examined DRS methods and 86 were empirical applications. We observed a bimodal distribution in the number of publications over time, with a peak 1979-1980, and resurgence since 2000. The majority of applications with methodological detail derived DRS using logistic regression (47%), used DRS as a categorical variable in regression (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%) study. Few studies examined effect modification by outcome risk (23%). Conclusion Use of DRS methods has increased yet remains low. Comparative effectiveness research may benefit from more DRS applications, particularly to examine effect modification by outcome risk. Standardized terminology may facilitate identification, application, and comprehension of DRS methods. More research is needed to support the application of DRS methods, particularly in case-control studies. PMID:23172692

  17. Burner modifications for cost effective NO{sub x} control

    SciTech Connect

    Melick, T.A.; Hensley, M.E.; Gustafson, D.A.

    1998-07-01

    The development of commercial low NO{sub x} burners has provided Energy and Environmental Research Corporation (EER) with the expertise to modify existing burner equipment to provide the controlled fuel/air mixing conditions required for low NO{sub x} combustion. This approach represents a viable lower cost alternative to a full burner retrofit for many applications. EER has modified burners to lower NO{sub x} emissions at Louisville Gas and Electric's (LG and E) Cane Run Station and at Jamestown Board of Public Utilities (JBPU). This paper will discuss the method and results of these burner modifications on a 180 and 170 Mwe boiler for LG and E and four boilers at JBPU. NO{sub x} reductions of greater than 50% have been demonstrated with burner modifications only that have achieved NO{sub x} compliance on these six boilers. EER will also be modifying cell burners for Dayton Power and Light at their JM Stuart Station. Unit {number_sign}3 is a 605 Mwe B and W universal pressure opposed wall fired boiler. EER will retrofit the burners this October through November and results will be available by the first of December. With deregulation of the utility industry approaching, many utilities are looking for lower cost alternatives to satisfy NO{sub x} regulations. Justifying new low NO{sub x} burners on a boiler that is 30 to 40 years old and has limited remaining life is also difficult. Performing modifications to the existing burners provides the utility an option. Modifications are usually 2 to 4 times less expensive than new low NO{sub x} burners.

  18. Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure Modification by Infant Temperament.

    PubMed

    Chong, Shiau Yun; Chittleborough, Catherine R; Gregory, Tess; Mittinty, Murthy N; Lynch, John W; Smithers, Lisa G

    2016-01-01

    Cognitive development might be influenced by parenting practices and child temperament. We examined whether the associations between parental warmth, control and intelligence quotient (IQ) may be heightened among children in difficult temperament. Participants were from the Avon Longitudinal Study of Parents and Children (n = 7,044). Temperament at 6 months was measured using the Revised Infant Temperament Questionnaire and classified into 'easy' and 'difficult'. Parental warmth and control was measured at 24 to 47 months and both were classified into 2 groups using latent class analyses. IQ was measured at 8 years using the Wechsler Intelligence Scale for Children and dichotomized (<85 and ≥85) for analyzing effect-measure modification by temperament. Linear regression adjusted for multiple confounders and temperament showed lower parental warmth was weakly associated with lower IQ score [β = -0.52 (95% CI 1.26, 0.21)], and higher parental control was associated with lower IQ score [β = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased risk of having low IQ in temperamentally difficult children [risk ratio (RR) = 0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was also no increased risk of having low IQ in temperamentally difficult children (RR = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For both parental warmth and control, there was some evidence of negative effect-measure modification by temperament on the risk-difference scale and the risk-ratio scale. It may be more appropriate to provide parenting interventions as a universal program rather than targeting children with difficult temperament.

  19. Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure Modification by Infant Temperament

    PubMed Central

    Chong, Shiau Yun; Chittleborough, Catherine R.; Gregory, Tess; Mittinty, Murthy N.; Lynch, John W.; Smithers, Lisa G.

    2016-01-01

    Cognitive development might be influenced by parenting practices and child temperament. We examined whether the associations between parental warmth, control and intelligence quotient (IQ) may be heightened among children in difficult temperament. Participants were from the Avon Longitudinal Study of Parents and Children (n = 7,044). Temperament at 6 months was measured using the Revised Infant Temperament Questionnaire and classified into ‘easy’ and ‘difficult’. Parental warmth and control was measured at 24 to 47 months and both were classified into 2 groups using latent class analyses. IQ was measured at 8 years using the Wechsler Intelligence Scale for Children and dichotomized (<85 and ≥85) for analyzing effect-measure modification by temperament. Linear regression adjusted for multiple confounders and temperament showed lower parental warmth was weakly associated with lower IQ score [β = -0.52 (95% CI 1.26, 0.21)], and higher parental control was associated with lower IQ score [β = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased risk of having low IQ in temperamentally difficult children [risk ratio (RR) = 0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was also no increased risk of having low IQ in temperamentally difficult children (RR = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For both parental warmth and control, there was some evidence of negative effect-measure modification by temperament on the risk-difference scale and the risk-ratio scale. It may be more appropriate to provide parenting interventions as a universal program rather than targeting children with difficult temperament. PMID:27027637

  20. Structural confounding of area-level deprivation and segreation: an empirical example

    EPA Science Inventory

    The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

  1. Structural confounding of area-level deprivation and segreation: an empirical example

    EPA Science Inventory

    The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

  2. The sign of the unmeasured confounding bias under various standard populations.

    PubMed

    Chiba, Yasutaka

    2009-08-01

    Unmeasured confounders are a common problem in drawing causal inferences in observational studies. VanderWeele (Biometrics 2008, 64, 702-706) presented a theorem that allows researchers to determine the sign of the unmeasured confounding bias when monotonic relationships hold between the unmeasured confounder and the treatment, and between the unmeasured confounder and the outcome. He showed that his theorem can be applied to causal effects with the total group as the standard population, but he did not mention the causal effects with treated and untreated groups as the standard population. Here, we extend his results to these causal effects, and apply our theorems to an observational study. When researchers have a sense of what the unmeasured confounder may be, conclusions can be drawn about the sign of the bias.

  3. Burner modifications for cost effective NO{sub x} control

    SciTech Connect

    Melick, T.A.; Hensley, M.E.; Gustafson, D.A.

    1998-12-31

    The development of commercial Low NO{sub x} Burners has provided Energy and Environmental Research Corporation (EER) with the expertise to modify existing burner equipment to provide the controlled fuel/air mixing conditions required for low NO{sub x} contribution. This approach represents a viable alternative to a full burner retrofit for many applications. EER has modified burners to lower NO{sub x} emissions at Louisville Gas and Electric`s (LG and E) Cane Run Station and at Jamestown Board of Public Utilities (JBPU). This paper discusses the method and results of these burner modifications.

  4. The effectiveness and predictors of response to antipsychotic agents to treat impaired quality of life in schizophrenia: A 12-month naturalistic follow-up study with implications for confounding factors, antidepressants, anxiolytics, and mood stabilizers.

    PubMed

    Ritsner, Michael S; Gibel, Anatoly

    2006-12-30

    This study examined specific predictors of the efficacy of risperidone (RP), olanzapine (OL) and first-generation antipsychotic agents (FGAs), the role of confounding factors, and concomitant agents such as antidepressants, anxiolytics, and mood stabilizers in the treatment of health related quality of life (HRQL) impairment of schizophrenia patients. This was a community-based, open label, parallel group naturalistic study of 124 schizophrenia outpatients who received either RP, OL, FGA, or combined agents (CA). Evaluations were performed at baseline and 12 months later. They included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Distress Scale for Adverse Symptoms, and inventories for the assessment of distress severity, subjective tolerability, and self-efficacy. OL was found to be superior to RP, FGAs and CA in terms of quality of life. FGAs revealed greater therapeutic benefit than RP, which was more beneficial than combined therapy. Improvement in Q-LES-Q was revealed in patients who received antidepressants and anxiolytics, but not mood stabilizers, or anti-Parkinson drugs. This effect was independent of treatment groups and gender. Regression models revealed that changes in emotional distress and side effects were common predictors for HRQL changes across treatment groups. Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients. These findings suggest that OL is beneficial in the treatment of HRQL impairment in schizophrenia compared with RP, FGAs and CA. Special attention should be paid to specific predictors of HRQL efficacy for each antipsychotic agent, and to concomitant treatment with antidepressants and anxiolytics.

  5. [Modification of the effects of microwave irradiation on biochemical processes by using foreign protein].

    PubMed

    Podkovkin, V G; Uglova, I B

    1998-01-01

    The biochemical data on the influence of electromagnetic fields in microwave range on the hormonal-mediator regulation systems are presented. The possibility of biological effects modification under combined action of microwave radiation and foreign protein is discussed.

  6. Inhibitory effects of aromatic herbs on lipid peroxidation and protein oxidative modification by copper.

    PubMed

    Toda, Shizuo

    2003-05-01

    Aromatic herbs have been used as carminatives. Oxygen free radicals are generated in ischaemia/reperfusion injury in the stomach, and induce lipid peroxidation or protein oxidative modification. Several aromatic herbs were shown to have inhibitory effects on the generation of oxygen free radicals. It was shown that several aromatic herbs, Caryophylli Flos, Cinnamomi Cortex, Foeniculi Fructus and Zedoariae Rhizoma, have inhibitory effects on lipid peroxidation or protein oxidative modification by copper.

  7. Temperature effects in high fluence ion modification of HOPG

    NASA Astrophysics Data System (ADS)

    Andrianova, N. N.; Avilkina, V. S.; Borisov, A. M.; Mashkova, E. S.

    2012-02-01

    The ion-induced processes of HOPG (UPV-1T) modification under high-fluence (10 18-10 19 ion/cm 2) 30 keV Ar + and Ne + ion irradiation have been studied from room temperature till 400 °C. The temperature dependences of ion-induced electron emission yield have been found, in contrary to isotropic graphite MPG-8, the essentially different for HOPG between heating and following cooling measurements. For Ar + irradiation only in the 150-300 °C temperature range anomalously large depth of ion-modified surface layer with developed morphology have been found. The results are discussed in frame of the Ehrlich-Schwoebel instability.

  8. The effect of habitat modification on plant-pollinator network

    NASA Astrophysics Data System (ADS)

    Aminatun, Tien; Putra, Nugroho Susetya

    2017-08-01

    The research aimed to determine; (1) the mutualism interaction pattern of plant-pollinator on several habitat modifications; and (2) the habitat modification which showed the most stable pattern of interaction. The study was conducted in one planting season with 20 plots which each plot had 2x2 m2 width and 2 m spacing among plots, and each plot was planted with the same variety of tomato plants, i.e. "intan". Nitrogen manipulation treatment was conducted with four kinds of fertilizers, i.e. NPK (code PU), compost (code PKM), vermicompost (code PC), and manure (code PK). Each treatment had 5 plot replications. We observed the growth of tomato plants, weed and arthropod populationstwo weekly while pollinator visitation twice a week during tomato plant flowering with counting population and visitation frequence of each pollinator on each sample of tomato plants. The nectar of tomato plant flower of each treatment was tested in laboratory to see its reducing sugar and sucrose. Oganic matter and nitrogen of the soil samples of each treatment were tested in laboratory in the beginning and the end of this research. We analized the plant-pollinator network with bipartite program in R-statistics, and the abiotic and other biotic factors with descriptive analysis. The results of the research were; (1) the mutualism interaction pattern of plant-pollinator network of four treatments were varied, and (2) The pattern of plant-pollinator network of NPK fertilizer treatment showed the more stable interaction based on analysis of interaction evenness, Shannon diversity, frequency and longevity of pollinator visitation.

  9. [Effects of posttranslational modification on the activity of cytochrome P450: current progress].

    PubMed

    Li, Yu-hua; Bi, Hui-chang; Huang, Min

    2011-05-01

    Regulation of the activity of CYP450 has always been research focus of drug metabolism. The effect of compounds on the mRNA and protein expression level of CYP450 is the main purpose of most of the existing reports. In recent years, the protein modification in the posttranslation level has been found to participate in maintaining the proper function of CYP450, thus effect of posttranslational modification on the enzyme activity has been paid more and more attention. Posttranslational modifications including phosphorylation, nitration, and ubiquitination have been described to regulate the activity of CYP450. In this paper, recent developments in the effects of posttranslational modifications on the activity of CYP450 have been reviewed.

  10. A typology of four notions of confounding in epidemiology.

    PubMed

    Suzuki, Etsuji; Mitsuhashi, Toshiharu; Tsuda, Toshihide; Yamamoto, Eiji

    2017-02-01

    Confounding is a major concern in epidemiology. Despite its significance, the different notions of confounding have not been fully appreciated in the literature, leading to confusion of causal concepts in epidemiology. In this article, we aim to highlight the importance of differentiating between the subtly different notions of confounding from the perspective of counterfactual reasoning. By using a simple example, we illustrate the significance of considering the distribution of response types to distinguish causation from association, highlighting that confounding depends not only on the population chosen as the target of inference, but also on the notions of confounding in distribution and confounding in measure. This point has been relatively underappreciated, partly because some literature on the concept of confounding has only used the exposed and unexposed groups as the target populations, while it would be helpful to use the total population as the target population. Moreover, to clarify a further distinction between confounding "in expectation" and "realized" confounding, we illustrate the usefulness of examining the distribution of exposure status in the target population. To grasp the explicit distinction between confounding in expectation and realized confounding, we need to understand the mechanism that generates exposure events, not the product of that mechanism. Finally, we graphically illustrate this point, highlighting the usefulness of directed acyclic graphs in examining the presence of confounding in distribution, in the notion of confounding in expectation.

  11. A typology of four notions of confounding in epidemiology

    PubMed Central

    Suzuki, Etsuji; Mitsuhashi, Toshiharu; Tsuda, Toshihide; Yamamoto, Eiji

    2016-01-01

    Confounding is a major concern in epidemiology. Despite its significance, the different notions of confounding have not been fully appreciated in the literature, leading to confusion of causal concepts in epidemiology. In this article, we aim to highlight the importance of differentiating between the subtly different notions of confounding from the perspective of counterfactual reasoning. By using a simple example, we illustrate the significance of considering the distribution of response types to distinguish causation from association, highlighting that confounding depends not only on the population chosen as the target of inference, but also on the notions of confounding in distribution and confounding in measure. This point has been relatively underappreciated, partly because some literature on the concept of confounding has only used the exposed and unexposed groups as the target populations, while it would be helpful to use the total population as the target population. Moreover, to clarify a further distinction between confounding “in expectation” and “realized” confounding, we illustrate the usefulness of examining the distribution of exposure status in the target population. To grasp the explicit distinction between confounding in expectation and realized confounding, we need to understand the mechanism that generates exposure events, not the product of that mechanism. Finally, we graphically illustrate this point, highlighting the usefulness of directed acyclic graphs in examining the presence of confounding in distribution, in the notion of confounding in expectation. PMID:28142011

  12. Bed Sharing, SIDS Research, and the Concept of Confounding: A Review for Public Health Nurses.

    PubMed

    Keys, Elizabeth M; Rankin, James A

    2015-01-01

    Confounding is an important concept for public health nurses (PHNs) to understand when considering the results of epidemiological research. The term confounding is derived from Latin, confundere, which means to "mix-up" or "mix together". Epidemiologists attempt to derive a cause and effect relationship between two variables traditionally known as the exposure and disease (e.g., smoking and lung cancer). Confounding occurs when a third factor, known as a confounder, leads to an over- or underestimate of the magnitude of the association between the exposure and disease. An understanding of confounding will facilitate critical appraisal of epidemiological research findings. This knowledge will enable PHNs to strengthen their evidence-based practice and better prepare them for policy development and implementation. In recent years, researchers and clinicians have examined the relationship between bed sharing and sudden infant death syndrome (SIDS). The discussion regarding the risk of bed sharing and SIDS provides ample opportunity to discuss the various aspects of confounding. The purpose of this article is to use the bed sharing and SIDS literature to assist PHNs to understand confounding and to apply this knowledge when appraising epidemiological research. In addition, strategies that are used to control confounding are discussed.

  13. On the role of marginal confounder prevalence - implications for the high-dimensional propensity score algorithm.

    PubMed

    Schuster, Tibor; Pang, Menglan; Platt, Robert W

    2015-09-01

    The high-dimensional propensity score algorithm attempts to improve control of confounding in typical treatment effect studies in pharmacoepidemiology and is increasingly being used for the analysis of large administrative databases. Within this multi-step variable selection algorithm, the marginal prevalence of non-zero covariate values is considered to be an indicator for a count variable's potential confounding impact. We investigate the role of the marginal prevalence of confounder variables on potentially caused bias magnitudes when estimating risk ratios in point exposure studies with binary outcomes. We apply the law of total probability in conjunction with an established bias formula to derive and illustrate relative bias boundaries with respect to marginal confounder prevalence. We show that maximum possible bias magnitudes can occur at any marginal prevalence level of a binary confounder variable. In particular, we demonstrate that, in case of rare or very common exposures, low and high prevalent confounder variables can still have large confounding impact on estimated risk ratios. Covariate pre-selection by prevalence may lead to sub-optimal confounder sampling within the high-dimensional propensity score algorithm. While we believe that the high-dimensional propensity score has important benefits in large-scale pharmacoepidemiologic studies, we recommend omitting the prevalence-based empirical identification of candidate covariates. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.

    PubMed

    Manickam, Nandini; Joshi, Kartikeya; Bhatt, Monika J; Farabaugh, Philip J

    2016-02-29

    Cellular health and growth requires protein synthesis to be both efficient to ensure sufficient production, and accurate to avoid producing defective or unstable proteins. The background of misreading error frequency by individual tRNAs is as low as 2 × 10(-6) per codon but is codon-specific with some error frequencies above 10(-3) per codon. Here we test the effect on error frequency of blocking post-transcriptional modifications of the anticodon loops of four tRNAs in Escherichia coli. We find two types of responses to removing modification. Blocking modification of tRNA(UUC)(Glu) and tRNA(QUC)(Asp) increases errors, suggesting that the modifications act at least in part to maintain accuracy. Blocking even identical modifications of tRNA(UUU)(Lys) and tRNA(QUA)(Tyr) has the opposite effect of decreasing errors. One explanation could be that the modifications play opposite roles in modulating misreading by the two classes of tRNAs. Given available evidence that modifications help preorder the anticodon to allow it to recognize the codons, however, the simpler explanation is that unmodified 'weak' tRNAs decode too inefficiently to compete against cognate tRNAs that normally decode target codons, which would reduce the frequency of misreading. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Brain death: assessment, controversy, and confounding factors.

    PubMed

    Arbour, Richard B

    2013-12-01

    When brain injury is refractory to aggressive management and is considered nonsurvivable, with loss of consciousness and brain stem reflexes, a brain death protocol may be initiated to determine death according to neurological criteria. Clinical evaluation typically entails 2 consecutive formal neurological examinations to document total loss of consciousness and absence of brain stem reflexes and then apnea testing to evaluate carbon dioxide unresponsiveness within the brain stem. Confounding factors such as use of therapeutic hypothermia, high-dose metabolic suppression, and movements associated with complex spinal reflexes, fasciculations, or cardiogenic ventilator autotriggering may delay initiation or completion of brain death protocols. Neurodiagnostic studies such as 4-vessel cerebral angiography can rapidly document absence of blood flow to the brain and decrease intervals between onset of terminal brain stem herniation and formal declaration of death by neurological criteria. Intracranial pathophysiology leading to brain death must be considered along with clinical assessment, patterns of vital signs, and relevant diagnostic studies.

  16. 75 FR 11559 - Certain Combed Cotton Yarns: Effect of Modification of U.S.-Bahrain FTA Rules of Origin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-11

    ... COMMISSION Certain Combed Cotton Yarns: Effect of Modification of U.S.- Bahrain FTA Rules of Origin AGENCY...-103-025, Certain Combed Cotton Yarns: Effect of Modification of U.S.-Bahrain FTA Rules Of Origin... government of Bahrain on certain modifications to the rules of origin to the FTA for certain combed...

  17. Bias Analysis for Uncontrolled Confounding in the Health Sciences.

    PubMed

    Arah, Onyebuchi A

    2017-03-20

    Uncontrolled confounding due to unmeasured confounders biases causal inference in health science studies using observational and imperfect experimental designs. The adoption of methods for analysis of bias due to uncontrolled confounding has been slow, despite the increasing availability of such methods. Bias analysis for such uncontrolled confounding is most useful in big data studies and systematic reviews to gauge the extent to which extraneous preexposure variables that affect the exposure and the outcome can explain some or all of the reported exposure-outcome associations. We review methods that can be applied during or after data analysis to adjust for uncontrolled confounding for different outcomes, confounders, and study settings. We discuss relevant bias formulas and how to obtain the required information for applying them. Finally, we develop a new intuitive generalized bias analysis framework for simulating and adjusting for the amount of uncontrolled confounding due to not measuring and adjusting for one or more confounders.

  18. Effects of wing modification on an aircraft's aerodynamic parameters as determined from flight data

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1986-01-01

    A study of the effects of four wing-leading-edge modifications on a general aviation aircraft's stability and control parameters is presented. Flight data from the basic aircraft configuration and configurations with wing modifications are analyzed to determine each wing geometry's stability and control parameters. The parameter estimates and aerodynamic model forms are obtained using the stepwise regression and maximum likelihood techniques. The resulting parameter estimates and aerodynamic models are verified using vortex-lattice theory and by analysis of each model's ability to predict aircraft behavior. Comparisons of the stability and control derivative estimates from the basic wing and the four leading-edge modifications are accomplished so that the effects of each modification on aircraft stability and control derivatives can be determined.

  19. Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer’s disease

    PubMed Central

    Chow, Tiffany W; Pollock, Bruce G; Milgram, Norton W

    2007-01-01

    Objective Selective serotonin reuptake inhibitors (SSRIs) have increased cognitive performance in some clinical studies of Alzheimer’s disease (AD), but it is has been difficult to dissociate whether this is due to direct effects on cognition (neurochemical or disease-modifying) or a secondary effect of mood stabilization. We performed a systematic review for preclinical and human clinical trial evidence to support the use of SSRIs specifically for the management of cognitive decline in AD. Data sources (1) PUBMED without language restrictions from 1950s until 2004 and updated August 2006, terms: “serotonin uptake inhibitors”[MeSH] AND (“Alzheimer disease”[MeSH] OR “Cognition Disorders”[MeSH]) NOT “Parkinson disease”[MeSH] AND (Clinical Trial[ptyp] OR Letter[ptyp] OR Meta-Analysis[ptyp] OR Randomized Controlled Trial[ptyp]) AND “alzheimer disease” [MESH] OR “Alzheimer*” combined with AND to “ssri*” OR “serotonin reuptake inhibitors” [MESH] NOT Review[ptyp]. (2) Cochrane Database of Systematic Reviews, keywords “SSRI” and “Alzheimer’s”. Study selection The PubMed search yielded 57 hits. Of these, 23 were included in this review for their specificity to SSRI use in AD or indications on efficacy beyond depressive symptoms. The other 34 citations were excluded because: (1) depression or other mood or behavioral disturbance severity was the reported outcome measure, (2) effects of SSRIs on cognition were confounded by concomitant use of other drugs, (3) subjects described were young adults, and/or (4) subjects had traumatic brain injury. The Cochrane Database of Systematic Reviews, 3rd Quarter 2006, yielded six citations related to SSRIs. Data extraction Data extracted from clinical trials included name of SSRI tested, cognitive outcome measures, and adverse events reported, which could include cognitive worsening. Data synthesis Preclinical evidence for use of SSRIs to enhance cognition in AD includes an effect at the

  20. Effect of ultrasound on silver electrodeposition: Crystalline structure modification.

    PubMed

    Nevers, Aymeric; Hallez, Loïc; Touyeras, Francis; Hihn, Jean-Yves

    2017-02-27

    An attractive possibility for influencing microstructures of electrodeposited coatings, and therefore their properties such as hardness, brightness etc. resides in the use of ultrasound. This method is particularly competitive as it may result in a reduction of chemical use, or even in the complete suppression of chemicals. This paper deals with silver coatings depending strongly on current density, with two main categories identified by X-ray diffraction: one poorly structured and the other following the [110] orientation. It is interesting to note that, while changing from still to mechanically stirred conditions, the value of the current density threshold moves from 2.5mAcm(-2) to 5mAcm(-2). When ultrasound is used (575kHz or 20kHz), this coating microstructure modification threshold occurs at higher current density values when coatings are produced under sonication, while agitation is kept constant. In both cases, the shift is about 15mAcm(-2). It is noteworthy that silver electrodeposits elaborated under 20kHz ultrasound conditions appear to be less oriented than those obtained under high frequency conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The control outcome calibration approach for causal inference with unobserved confounding.

    PubMed

    Tchetgen Tchetgen, Eric

    2014-03-01

    Unobserved confounding can seldom be ruled out with certainty in nonexperimental studies. Negative controls are sometimes used in epidemiologic practice to detect the presence of unobserved confounding. An outcome is said to be a valid negative control variable to the extent that it is influenced by unobserved confounders of the exposure effects on the outcome in view, although not directly influenced by the exposure. Thus, a negative control outcome found to be empirically associated with the exposure after adjustment for observed confounders indicates that unobserved confounding may be present. In this paper, we go beyond the use of control outcomes to detect possible unobserved confounding and propose to use control outcomes in a simple but formal counterfactual-based approach to correct causal effect estimates for bias due to unobserved confounding. The proposed control outcome calibration approach is developed in the context of a continuous or binary outcome, and the control outcome and the exposure can be discrete or continuous. A sensitivity analysis technique is also developed, which can be used to assess the degree to which a violation of the main identifying assumption of the control outcome calibration approach might impact inference about the effect of the exposure on the outcome in view.

  2. Fine Particle, Ozone Exposure, and Asthma/Wheezing: Effect Modification by Glutathione S-transferase P1 Polymorphisms

    PubMed Central

    Hwang, Bing-Fang; Young, Li-Hao; Tsai, Ching-Hui; Tung, Kuan-Yen; Wang, Pei-Chuan; Su, Ming-Wei; Lee, Yungling Leo

    2013-01-01

    Background There are limited studies on the role of interaction between exposure to ambient air pollution and glutathione-S-transferase (GST) P1 on the risk of asthma/wheezing among children, which provided suggestive, but inconclusive results. Methods To assess the joint effect of air pollutants and GSTP1 on asthma/wheezing, we conducted a nationwide cross-sectional study of 3,825 children in Taiwan Children Health Study. The studied determinants were three GSTP1 Ile105Val (rs 1695) genotypes (Ile-Ile; Ile-Val and Val-Val) and expoure to ambient air pollutants. We used routine air-pollution monitoring data for ozone (O3) and particles with an aerodynamic diameter of 2.5 µm or less (PM2.5). The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM2.5 and O3. Findings In a two-stage hierarchical model adjusting for confounding, the risk of asthma was negatively associated with PM2.5 (adjusted odds ratio (OR) 0.60; 95% confidence interval (CI) 0.45, 0.82) and O3 (OR 0.74; 95% CI 0.60, 0.90) among Ile105 homozygotes, but positively associated with PM2.5 (OR 1.52; 95% CI 1.01, 2.27) and O3 (OR 1.19; 95% CI 0.91, 1.57) among those with at least one val105 allele (interaction p value = 0.001 and 0.03, respectively). A similar tendency of effect modification between PM2.5 and O3 and GSTP1 on wheezing was found. Conclusion Children who carried Ile105 variant allele and exposed to PM2.5 and O3 may be less likely to occurrence of asthma/wheezing. PMID:23357926

  3. Effects of chemical modification on the conformation and biological activity of peanut agglutinin.

    PubMed

    Nonnenmacher, D; Brossmer, R

    1981-03-27

    The effect of chemical modifications on the biological properties of peanut agglutinin was investigated. The free amino groups were modified with succinic anhydride and 1-isothiocyanato-4-benzenesulfonic acid. Though the extent of modification was 95 and 85%, respectively, these derivatives did not lose their sugar binding capacity. The agglutinating activity with neuraminidase-treated human erythrocytes and various tumor cells was reduced. The mitogenic activity tested with neuraminidase-treated human lymphocytes was also diminished The tyrosine residues were modified with tetranitromethane and further with 4-aminophenyl-alpha-D-glucopyranoside and the negatively charged 2-(4-amino-benzyl)-alpha-D-neuraminic acid. The extent of modification was 30, 28 and 6%, respectively. The agglutinating and mitogenic activities were in this case not severely changed. The influence of all these modifications on the conformation was investigated by means of CD studies in the far and near ultraviolet regions.

  4. Gaseous pollutants in particulate matter epidemiology: confounders or surrogates?

    PubMed Central

    Sarnat, J A; Schwartz, J; Catalano, P J; Suh, H H

    2001-01-01

    Air pollution epidemiologic studies use ambient pollutant concentrations as surrogates of personal exposure. Strong correlations among numerous ambient pollutant concentrations, however, have made it difficult to determine the relative contribution of each pollutant to a given health outcome and have led to criticism that health effect estimates for particulate matter may be biased due to confounding. In the current study we used data collected from a multipollutant exposure study conducted in Baltimore, Maryland, during both the summer and winter to address the potential for confounding further. Twenty-four-hour personal exposures and corresponding ambient concentrations to fine particulate matter (PM(2.5)), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide were measured for 56 subjects. Results from correlation and regression analyses showed that personal PM(2.5) and gaseous air pollutant exposures were generally not correlated, as only 9 of the 178 individual-specific pairwise correlations were significant. Similarly, ambient concentrations were not associated with their corresponding personal exposures for any of the pollutants, except for PM(2.5), which had significant associations during both seasons (p < 0.0001). Ambient gaseous concentrations were, however, strongly associated with personal PM(2.5) exposures. The strongest associations were shown between ambient O(3) and personal PM(2.5) (p < 0.0001 during both seasons). These results indicate that ambient PM(2.5) concentrations are suitable surrogates for personal PM(2.5) exposures and that ambient gaseous concentrations are surrogates, as opposed to confounders, of PM(2.5). These findings suggest that the use of multiple pollutant models in epidemiologic studies of PM(2.5) may not be suitable and that health effects attributed to the ambient gases may actually be a result of exposures to PM(2.5). PMID:11675271

  5. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    PubMed Central

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  6. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles.

    PubMed

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-06-10

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  7. Effects of Instruction on Adolescent Beginners' Acquisition of Request Modification

    ERIC Educational Resources Information Center

    Li, Qingping

    2012-01-01

    This quasiexperimental study examined the effects of different focus-on-form techniques, and the durability of such effects, on adolescent beginners' acquisition of request supportive moves. Three treatments were implemented: (1) the incidental group was exposed to input and involved in meaningful output activities; (2) the implicit group was…

  8. Effects of Instruction on Adolescent Beginners' Acquisition of Request Modification

    ERIC Educational Resources Information Center

    Li, Qingping

    2012-01-01

    This quasiexperimental study examined the effects of different focus-on-form techniques, and the durability of such effects, on adolescent beginners' acquisition of request supportive moves. Three treatments were implemented: (1) the incidental group was exposed to input and involved in meaningful output activities; (2) the implicit group was…

  9. Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability

    NASA Astrophysics Data System (ADS)

    Ngo, Thuy T. M.; Yoo, Jejoong; Dai, Qing; Zhang, Qiucen; He, Chuan; Aksimentiev, Aleksei; Ha, Taekjip

    2016-02-01

    Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility.

  10. Surface Modifications and Their Effects on Titanium Dental Implants

    PubMed Central

    Jemat, A.; Ghazali, M. J.; Razali, M.; Otsuka, Y.

    2015-01-01

    This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants. PMID:26436097

  11. Surface Modifications and Their Effects on Titanium Dental Implants.

    PubMed

    Jemat, A; Ghazali, M J; Razali, M; Otsuka, Y

    2015-01-01

    This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants.

  12. Modification of magnetohydrodynamic waves by the relativistic Hall effect

    NASA Astrophysics Data System (ADS)

    Kawazura, Yohei

    2017-07-01

    This study shows that a relativistic Hall effect significantly changes the properties of wave propagation by deriving a linear dispersion relation for relativistic Hall magnetohydrodynamics (HMHD). Whereas, in nonrelativistic HMHD, the phase and group velocities of fast magnetosonic wave become anisotropic with an increasing Hall effect, the relativistic Hall effect brings upper bounds to the anisotropies. The Alfvén wave group velocity with strong Hall effect also becomes less anisotropic than the nonrelativistic case. Moreover, the group velocity surfaces of Alfvén and fast waves coalesce into a single surface in the direction other than near perpendicular to the ambient magnetic field. It is also remarkable that a characteristic scale length of the relativistic HMHD depends on ion temperature, magnetic field strength, and density while the nonrelativistic HMHD scale length, i.e., ion skin depth, depends only on density. The modified characteristic scale length increases as the ion temperature increases and decreases as the magnetic field strength increases.

  13. Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs

    DTIC Science & Technology

    2009-05-01

    effectiveness, and (3) effects of functional polymorphisms in the UDP-glucuronosyltransferase (UGT) enzymes on breast cancer recurrence in Danish women...nested within a population-based case-control study of breast cancer recurrence among Danish women (PI: Timothy L. Lash, Chair of Mr. Ahern’s Doctoral...roster of study participants, breast cancer diagnosis and treatment data were extracted from the Danish Breast Cancer Cooperative Group (DBCG) database

  14. Effects of different substrate surface modifications on the epitaxial ZnO/Si

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Jin, Changlian; Zhan, Huahan; Chen, Xiaohang; Xu, Fuchun; Zhou, Yinghui; Wang, Huiqiong; Kang, Junyong

    2013-09-01

    To produce high quality ZnO/Si for the applications in short wavelength optoelectronic devices, the effects of different silicon surface modifications on the overgrown ZnO thin film were investigated. Samples were grown by a plasma assistant molecular beam epitaxy at room temperature, avoiding the oxidation of the Si surface and the thermal stress caused by difference of the thermal expansion coefficients between ZnO and silicon. Different modifications on the Si(100) substrate surface including nitridation, oxidation, and depositions of Mg and Zn, were employed. The effects on the overgrown ZnO layers and the interlayer SiOx were investigated by atomic force microscopy, photoluminescence, X-ray diffraction and auger depth electron spectroscopy. All the modifications were effective in different degrees at reducing the SiOx amorphous layer. However, different mechanisms resulted in distinct performance in crystal structure and optical property.

  15. Confounders of auscultatory blood pressure measurement.

    PubMed

    Baker, R H; Ende, J

    1995-04-01

    The appropriate use of any test requires the clinician to appreciate that test's limitations. By recognizing the potential confounders of the auscultatory assessment of blood pressure, the clinician minimizes the likelihood of enacting therapeutic decisions based on inaccurate data. When approaching the treatment of a hypertensive patient, several points should be kept in mind. First, the measurement of persistent and severe hypertension in a patient receiving treatment who describes symptoms of orthostatic hypotension with apparently adequate standing blood pressure or who lacks corroborating retinal, echocardiographic, or electrocardiographic signs of hypertension should raise the concern of pseudohypertension or a white-coat response. Similarly, when one finds a normal or near-normal systolic blood pressure in a patient with a clinical picture consistent with severe hypertension, one should make a directed effort to look for an unrecognized auscultatory gap. Second, marked discrepancies in measurements as obtained by different operators or in different settings should raise concern of the white-coat response or methodologic errors by one operator, such as undercuffing, excessive pressure on the head of the stethoscope, rapid deflation of the cuff, or use of different arms. In treating hypertension in even the minimally obese patient, a special point must be made that an adequate size cuff be used for all blood pressure determinations. Third, when blood pressure is determined with the patient in any but the satndardized back-and-arm-supported seated position described above, the clinician should acknowledge the possibility that the position may alter the patient's classification. Fourth, the diagnosis and management of hypertension requires multiple measurements of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Dim waters: side effects of geoengineering using ocean albedo modification

    NASA Astrophysics Data System (ADS)

    Piskozub, J.; Neumann, T.

    2012-04-01

    We use a Monte Carlo radiative transfer code to check how the recently proposed geoengineering by injection of clean or coated microbubbles into the ocean mixed layer would impact in-water light fields. We show that due to massive multiscattering inside a bubble cloud, coating the bubbles with surfactant, needed to stabilize them, would not increase their albedo change effectiveness as much as expected basing on their backscattering coefficients. However, the bubble effect on reflectance is larger than estimated previously using a discrete ordinate method of solving the radiative transfer problem. We show significant side effects of ocean albedo change needed to counter global warming expected in this century and beyond (reduction of euphotic zone depth by respectively 20% and 50% in the case of global ocean albedo change corresponding to -1.25 K and -6 K global surface temperature change and irradiance decrease at 10 m depth by respectively 40% and over 80%) even if all ocean surface was "brightened". We discuss the possible negative side effect of such in-water light dimming on marine life. We conclude that the proposed "ocean brightening" is in fact "ocean dimming" as concerns the marine environment, on a scale that in any other circumstances would be called catastrophic. Finally, we briefly discuss other possible side effect of making the surface ocean waters turbid (both optically and acoustically), of adding large amounts of surfactants to the surface ocean layers and of surface cooling of the ocean, especially within the tropics.

  17. The effects of beta-endorphin: state change modification.

    PubMed

    Veening, Jan G; Barendregt, Henk P

    2015-01-29

    Beta-endorphin (β-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how β-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of β-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.

  18. Modifications in Children's Cognitive Styles: Some Effects of Peer Modeling.

    ERIC Educational Resources Information Center

    Cohen, Stewart; Przybycien, Collette A.

    An extension of previous attempts at modifying children's cognitive styles is discussed. Specifically, the present study employed sociometric peer models in order to ascertain whether: (1) impulsivity is modifiable through observation of salient models, and (2) sociometrically selected peer models are more effective than unselected models in the…

  19. Breast milk and cognitive development—the role of confounders: a systematic review

    PubMed Central

    Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

    2013-01-01

    Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously

  20. Effect of ITO surface modification on the OLED device lifetime.

    PubMed

    Yu, Szu-Yen; Chang, Jung-Hung; Wang, Po-Sheng; Wu, Chi-I; Tao, Yu-Tai

    2014-07-01

    Pretreatment of the indium tin oxide (ITO) surface is generally adopted to improve the charge injection and device performance in the fabrication of organic light-emitting diodes (OLEDs). For the common approaches of surface treatment, such as oxygen plasma treatment, self-assembled monolayer (SAM) adsorption, and the PEDOT:PSS coating, different effects on the device lifetime were observed. A distinctly different driving voltage change with device operation time was obtained and was correlated with the device lifetime. The fast increase in driving voltage for devices based on oxygen-plasma-treated ITO is attributed to the work function change as a result of the change in the composition of the interface with device operation, whereas a rather stable work function for SAM-modified ITO is suggested due to the permanent dipoles associated with the monolayer and the protecting effect of the covalently bound monolayer on the surface composition.

  1. Inflammatory Effects of Edwardsiella ictaluri Lipopolysaccharide Modifications in Catfish Gut

    PubMed Central

    Kilbourne, Jacquelyn; Park, Jie-Yeun; Martin, Taylor; Loh, Amanda; Diaz, Ignacia; Rojas, Robert; Segovia, Cristopher; DeNardo, Dale; Curtiss, Roy

    2014-01-01

    Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to

  2. Modifications in the metabolism and myeloclastogenic effect of benzene

    SciTech Connect

    Gad-El Karim, M.M.; Harper, B.L.; Ramanujam, S.V.M.; Legator, M.S.

    1982-02-01

    Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase analysis. In a series of experiments, male and female CD-1 mice were subjected to various pretreatments: phenobarbital (PB) (0.1% in drinking water x 7 days or 80 mg/kg/day (I.P.) x 3 days before treatment), 3-methylcholanthrene (3-MCA) (30 mg/kg/day (I.P.) x 2 days), SKF-525A (80 mg/kg (I.P.) 2 hours before each treatment dose), or Aroclor-1254 (100 mg/kg) (I.P.) once, 5 days before treatment. The animals were then treated with benzene (440 or 880 mg/kg) or toluene (860 or 1720 mg/kg) or their mixture in 2 doses 24 hours apart and sacrificed 6 hours or 24 hours after the second dose. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when the mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment caused a tremendous enhancement of benzene myeloclastogenicity. The sex difference, with females constantly more resistant than males to benzene, was retained among the 3-MCA pretreated group. Toluene, in mixture with benzene, lowered the clastogenic effect in 3-MCA pretreated mice. Dose-response curves with benzene treatment alone and with 3-MCA induced groups were generated in which the former curve was lower for each dose than the latter. Urine fractions were collected at 12-hour intervals from 3-groups of 10 males gavaged with benzene, either non-induced, PB- or 3MCA induced. Catechol was the major metabolite, phenol the minor one, and hydroquinone and semiquinones were present in trace amounts.

  3. Should we adjust for a confounder if empirical and theoretical criteria yield contradictory results? A simulation study

    PubMed Central

    Lee, Paul H.

    2014-01-01

    Confounders can be identified by one of two main strategies: empirical or theoretical. Although confounder identification strategies that combine empirical and theoretical strategies have been proposed, the need for adjustment remains unclear if the empirical and theoretical criteria yield contradictory results due to random error. We simulated several scenarios to mimic either the presence or the absence of a confounding effect and tested the accuracy of the exposure-outcome association estimates with and without adjustment. Various criteria (significance criterion, Change-in-estimate(CIE) criterion with a 10% cutoff and with a simulated cutoff) were imposed, and a range of sample sizes were trialed. In the presence of a true confounding effect, unbiased estimates were obtained only by using the CIE criterion with a simulated cutoff. In the absence of a confounding effect, all criteria performed well regardless of adjustment. When the confounding factor was affected by both exposure and outcome, all criteria yielded accurate estimates without adjustment, but the adjusted estimates were biased. To conclude, theoretical confounders should be adjusted for regardless of the empirical evidence found. The adjustment for factors that do not have a confounding effect minimally effects. Potential confounders affected by both exposure and outcome should not be adjusted for. PMID:25124526

  4. Confounding in association studies: month of birth and multiple sclerosis.

    PubMed

    Fiddes, Barnaby; Wason, James; Sawcer, Stephen

    2014-10-01

    Association studies form the backbone of biomedical research, with almost every effort in the field ultimately boiling down to a comparison between groups, coupled with some form of statistical test intended to determine whether or not any observed difference is more or less than would be expected by chance. Unfortunately, although the paradigm is powerful and frequently effective, it is often forgotten that false positive association can easily arise if there is any bias or systematic difference in the way in which study subjects are selected into the considered groups. To protect against such confounding, researchers generally try to match cases and controls for extraneous variables thought to correlate with the exposures of interest. However, if seemingly homogenously distributed exposures are actually more heterogeneous than appreciated, then matching may be inadequate and false positive results can still arise. In this review, we will illustrate these fundamental issues by considering the previously proposed relationship between month of birth and multiple sclerosis. This much discussed but false positive association serves as a reminder of just how heterogeneous even easily measured environmental risk factors can be, and how easily case control studies can be confounded by seemingly minor differences in ascertainment.

  5. The Effects of Approach-Avoidance Modification on Social Anxiety Disorder: A Pilot Study

    PubMed Central

    Asnaani, Anu; Rinck, Mike; Becker, Eni; Hofmann, Stefan G.

    2014-01-01

    Cognitive bias modification has recently been discussed as a possible intervention for mental disorders. A specific form of this novel treatment approach is approach-avoidance modification. In order to examine the efficacy of approach-avoidance modification for positive stimuli associated with social anxiety, we recruited 43 individuals with social anxiety disorder and randomly assigned them to a training (implicit training to approach smiling faces) or a control (equal approach and avoidance of smiling faces) condition in three sessions over the course of a one-week period. Dependent measures included clinician ratings, self-report measures of social anxiety, and overt behavior during behavioral approach tasks. No group differences in any of the outcome measures were observed after training. In addition, while individuals in the training group showed increased approach tendency in one of the sessions, this effect was inconsistent across the three sessions and did not result in long-term changes in implicit approach tendencies between the groups over the course of the entire study. These results suggest that approach-avoidance modification might result in short-lasting effects on implicit approach tendencies towards feared positive stimuli, but this modification may not result in meaningful behavioral change or symptom reduction in individuals with social anxiety disorder. PMID:24659832

  6. The Effects of Approach-Avoidance Modification on Social Anxiety Disorder: A Pilot Study.

    PubMed

    Asnaani, Anu; Rinck, Mike; Becker, Eni; Hofmann, Stefan G

    2014-04-01

    Cognitive bias modification has recently been discussed as a possible intervention for mental disorders. A specific form of this novel treatment approach is approach-avoidance modification. In order to examine the efficacy of approach-avoidance modification for positive stimuli associated with social anxiety, we recruited 43 individuals with social anxiety disorder and randomly assigned them to a training (implicit training to approach smiling faces) or a control (equal approach and avoidance of smiling faces) condition in three sessions over the course of a one-week period. Dependent measures included clinician ratings, self-report measures of social anxiety, and overt behavior during behavioral approach tasks. No group differences in any of the outcome measures were observed after training. In addition, while individuals in the training group showed increased approach tendency in one of the sessions, this effect was inconsistent across the three sessions and did not result in long-term changes in implicit approach tendencies between the groups over the course of the entire study. These results suggest that approach-avoidance modification might result in short-lasting effects on implicit approach tendencies towards feared positive stimuli, but this modification may not result in meaningful behavioral change or symptom reduction in individuals with social anxiety disorder.

  7. Bentonite modification with hexadecylpyridinium and aluminum polyoxy cations and its effectiveness in Se(IV) removal.

    PubMed

    Orucoglu, Esra; Haciyakupoglu, Sevilay

    2015-09-01

    Usage of bentonite as a buffer material is suggested in radioactive waste repositories. Although bentonites have higher sorption ability to cations, they cannot adsorp anions due to negative surface charge. Nowadays, ongoing researches focus on increasing anion adsorption ability of the bentonites with modification. Organic-pillared bentonite (OPBent) was produced by modification of sodium bentonite with aluminum polyoxy and hexadecylpyridinium cations in this study. Variation in structure after modification was demonstrated by using different characterization techniques. Se removal efficiency of OPBent is investigated by using (75)Se, since selenium (Se) is one of the important long lived fission products found in radioactive waste and has toxic anionic species in an aqueous environment. The effect of reaction time, solid/liquid ratio, pH and concentration on the adsorption performance were examined. Se speciation and its effect onto adsorption were also investigated by measuring Eh-pH values under certain experimental conditions. Additionally, importance of the amount of Al-polyoxy cations used in modification was investigated by comparing these results with the results of other organic-pillared bentonite produced in our previous research. Experimental results confirmed that both cations were successfully placed into the bentonite interlayer and significant change in the host structure leads to increase Se adsorption. Consequently, bentonite modification improves its Se adsorption ability and further investigations are needed related to the usage of this adsorbent in other remediation studies especially in sorption of other anionic pollutants.

  8. Differential effect of three base modifications on DNA thermostability revealed by high resolution melting.

    PubMed

    López, Carlos M Rodríguez; Lloyd, Amanda J; Leonard, Kate; Wilkinson, Mike J

    2012-09-04

    High resolution melting (HRM) can detect and quantify the presence of 5-methylcytosine (5mC) in DNA samples, but the ability of HRM to diagnose other DNA modifications remains unexplored. The DNA bases N6-methyladenine and 5-hydroxymethylcytosine occur across almost all phyla. While their function remains controversial, their presence perturbs DNA structure. Such modifications could affect gene regulation, chromatin condensation and DNA packaging. Here, we reveal that DNA containing N6-methyladenine or 5-hydroxymethylcytosine exhibits reduced thermal stability compared to cytosine-methylated DNA. These thermostability changes are sufficiently divergent to allow detection and quantification by HRM analysis. Thus, we report that HRM distinguishes between sequence-identical DNA differing only in the modification type of one base. This approach is also able to distinguish between two DNA fragments carrying both N6-methyladenine and 5-methylcytosine but differing only in the distance separating the modified bases. This finding provides scope for the development of new methods to characterize DNA chemically and to allow for low cost screening of mutant populations of genes involved in base modification. More fundamentally, contrast between the thermostabilizing effects of 5mC on dsDNA compared with the destabilizing effects of N6-methyladenine (m6A) and 5-hydroxymethylcytosine (5hmC) raises the intriguing possibility of an antagonistic relationship between modification types with functional significance.

  9. Effects of cementation surface modifications on fracture resistance of zirconia.

    PubMed

    Srikanth, Ramanathan; Kosmac, Tomaz; Della Bona, Alvaro; Yin, Ling; Zhang, Yu

    2015-04-01

    To examine the effects of glass infiltration (GI) and alumina coating (AC) on the indentation flexural load and four-point bending strength of monolithic zirconia. Plate-shaped (12 mm × 12 mm × 1.0 mm or 1.5 or 2.0 mm) and bar-shaped (4 mm × 3 mm × 25 mm) monolithic zirconia specimens were fabricated. In addition to monolithic zirconia (group Z), zirconia monoliths were glass-infiltrated or alumina-coated on their tensile surfaces to form groups ZGI and ZAC, respectively. They were also glass-infiltrated on their upper surfaces, and glass-infiltrated or alumina-coated on their lower (tensile) surfaces to make groups ZGI2 and ZAC2, respectively. For comparison, porcelain-veneered zirconia (group PVZ) and monolithic lithium disilicate glass-ceramic (group LiDi) specimens were also fabricated. The plate-shaped specimens were cemented onto a restorative composite base for Hertzian indentation using a tungsten carbide spherical indenter with a radius of 3.2mm. Critical loads for indentation flexural fracture at the zirconia cementation surface were measured. Strengths of bar-shaped specimens were evaluated in four-point bending. Glass infiltration on zirconia tensile surfaces increased indentation flexural loads by 32% in Hertzian contact and flexural strength by 24% in four-point bending. Alumina coating showed no significant effect on resistance to flexural damage of zirconia. Monolithic zirconia outperformed porcelain-veneered zirconia and monolithic lithium disilicate glass-ceramics in terms of both indentation flexural load and flexural strength. While both alumina coating and glass infiltration can be used to effectively modify the cementation surface of zirconia, glass infiltration can further increase the flexural fracture resistance of zirconia. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  10. Effects of cementation surface modifications on fracture resistance of zirconia

    PubMed Central

    Srikanth, Ramanathan; Kosmac, Tomaz; Bona, Alvaro Della; Yin, Ling; Zhang, Yu

    2015-01-01

    Objectives To examine the effects of glass infiltration (GI) and alumina coating (AC) on the indentation flexural load and four-point bending strength of monolithic zirconia. Methods Plate-shaped (12 mm × 12 mm × 1.0 mm or 1.5 mm or 2.0 mm) and bar-shaped (4 mm × 3 mm × 25 mm) monolithic zirconia specimens were fabricated. In addition to monolithic zirconia (group Z), zirconia monoliths were glass-infiltrated or alumina-coated on their tensile surfaces to form groups ZGI and ZAC, respectively. They were also glass-infiltrated on their upper surfaces, and glass-infiltrated or alumina-coated on their lower (tensile) surfaces to make groups ZGI2 and ZAC2, respectively. For comparison, porcelain-veneered zirconia (group PVZ) and monolithic lithium disilicate glass-ceramic (group LiDi) specimens were also fabricated. The plate-shaped specimens were cemented onto a restorative composite base for Hertzian indentation using a tungsten carbide spherical indenter with a radius of 3.2 mm. Critical loads for indentation flexural fracture at the zirconia cementation surface were measured. Strengths of bar-shaped specimens were evaluated in four-point bending. Results Glass infiltration on zirconia tensile surfaces increased indentation flexural loads by 32% in Hertzian contact and flexural strength by 24% in four-point bending. Alumina coating showed no significant effect on resistance to flexural damage of zirconia. Monolithic zirconia outperformed porcelain-veneered zirconia and monolithic lithium disilicate glass-ceramics in terms of both indentation flexural load and flexural strength. Significance While both alumina coating and glass infiltration can be used to effectively modify the cementation surface of zirconia, glass infiltration can further increase the flexural fracture resistance of zirconia. PMID:25687628

  11. Effects of flux modifications on high strength steel weld metal

    SciTech Connect

    Franke, G.L.

    1994-12-31

    The performance of high strength steel welds is sensitive to the weld metal chemistry, and that, in turn, is dependent on the composition of the welding consumables. In the case of submerged arc welding, the flux plays an important role in determining the chemistry of the resulting weld metal. The u.S. Navy is conducting a program to gain a basic understanding of fluxes used for welding high strength steels in an effort to be able to better select the appropriate flux, or design a new flux, for a given application. The objective of the present work is to analyze the effects of a systematic chance in flux composition on weld metal chemistry and properties The dry mix of a commercial flux was modified with additions of MnO to produce a series of four experimental flux mixes with target MnO levels from 1 wt% to 4 wt%. A fifth experimental flux mix was produced with an addition of 1/2 wt% CeO{sub 2} to examine the effect of rare earth additions to the flux. Tensile and impact properties and weld metal chemistry were tested for each weldment, and correlations were made with flux composition. Weld metal Mn levels from 1.37 wt% (0.76 wt% flux MnO) to 1.75 wt% (4.26 wt% flux MnO) were achieved with the MnO-added fluxes.The small CeO{sub 2} addition appeared to improve weld metal impact performance it was concluded that a more basic knowledge of welding fluxes can be used in selecting or designing appropriate fluxes for Navy applications. Further work is required to characterize the specific effects of other flux constituents and their interactions on weld metal performance.

  12. Effect of structural modification on second harmonic generation in collagen

    NASA Astrophysics Data System (ADS)

    Stoller, Patrick C.; Reiser, Karen M.; Celliers, Peter M.; Rubenchik, Alexander M.

    2003-07-01

    The effects of structural perturbation on second harmonic generation in collagen were investigated. Type I collagen fascicles obtained from rat tails were structurally modified by increasing nonenzymatic cross-linking, by thermal denaturation, by collagenase digestion, or by dehydration. Changes in polarization dependence were observed in the dehydrated samples. Surprisingly, no changes in polarization dependence were observed in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable second harmonic signal. Prior to loss of signal, no change in polarization dependence was observed in partially heated or digested collagen.

  13. Effect of Structural Modification on Second Harmonic Generation in Collagen

    SciTech Connect

    Stoller, P C; Reiser, K M; Celliers, P M; Rubenchik, A M

    2003-04-04

    The effects of structural perturbation on second harmonic generation in collagen were investigated. Type I collagen fascicles obtained from rat tails were structurally modified by increasing nonenzymatic cross-linking, by thermal denaturation, by collagenase digestion, or by dehydration. Changes in polarization dependence were observed in the dehydrated samples. Surprisingly, no changes in polarization dependence were observed in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable second harmonic signal. Prior to loss of signal, no change in polarization dependence was observed in partially heated or digested collagen.

  14. Modifications in the metabolism and myeloclastogenic effect of benzene

    SciTech Connect

    Gad-El-Karim, M.; Harper, B.L.; Sadagopa Ramanujam, V.M.; Legator, M.S.

    1982-01-01

    Toxicity of benzene was studied in the bone marrow with the micronucleus test and metaphase analysis. Male and female CD-1 mice were subjected to pretreatments with phenobarbital, 3-methylcholanthrene (3-MCA), SKF-525A, or Aroclor-1254. The animals were then treated with benzene (440 or 880 mg/kg), or toluene (860 or 1720 mg/kg), or their mixture by gavage or I.P. in 2 doses 24 hours apart and sacrificed 6 hours or 24 hours after the second dose. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment caused a tremendous enhancement of benzene myeloclastogenicity. Dose-response curves with benzene treatment alone and with 3-MCA induced groups were generated. Urine fractions were collected from animals gavaged with benzene, either non-induced, PB- or 3MCA induced. The metabolites were quantitated by HPLC, and confirmed by GC/MS.

  15. History of the modern epidemiological concept of confounding.

    PubMed

    Morabia, Alfredo

    2011-04-01

    The epidemiological concept of confounding has had a convoluted history. It was first expressed as an issue of group non-comparability, later as an uncontrolled fallacy, then as a controllable fallacy named confounding, and, more recently, as an issue of group non-comparability in the distribution of potential outcome types. This latest development synthesised the apparent disconnect between phases of the history of confounding. Group non-comparability is the essence of confounding, and the statistical fallacy its consequence. This essay discusses how confounding was perceived in the 18th and 19th centuries, reviews how the concept evolved across the 20th century and finally describes the modern definition of confounding.

  16. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    SciTech Connect

    Wang, Daniel; Phan, Ngoc; Isely, Christopher; Bruene, Lucas; Bratlie, Kaitlin M

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  17. Scalar Modifications to Gravity from Unparticle Effects May Be Testable

    SciTech Connect

    Goldberg, Haim; Nath, Pran

    2008-01-25

    Interest has focused recently on low energy implications of a nontrivial scale invariant sector of an effective field theory with an IR fixed point, manifest in terms of 'unparticles' with peculiar properties. If unparticle stuff exists it could couple to the stress tensor and mediate a new 'fifth' force ('ungravity'). Under the assumption of strict conformal invariance in the hidden sector down to low energies, we compute the lowest order ungravity correction to the Newtonian gravitational potential and find scale invariant power law corrections of type (R{sub G}/r){sup 2d{sub U}-1}, where d{sub U} is an anomalous unparticle dimension and R{sub G} is a characteristic length scale where the ungravity interactions become significant. It is shown that a discrimination between extra dimension models and ungravity is possible in future improved submillimeter tests of gravity.

  18. Dual-effect laser handpiece for modification of tissue permeability

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen

    2011-03-01

    A new approach for improving the availability of topically applied drugs by reducing the permeability of dermis has been evaluated. The premise of this work is that photothermal vascular injury will reduce vascular uptake of drug in the dermis. The dermal distribution of two topically applied drugs, 5-fluorouracil and mitomycin C, is calculated, considering molecular diffusion and vascular uptake according to a distributed model, in the presence and absence of vascular injury. Intradermal drug exposures obtained are compared to exposures known to be effective in killing tumor cells. Combining the reduction in dermal permeability with fractional photothermal epidermal ablation to increase epidermal permeability may allow higher drug concentrations to be achieved in the skin. A newly developed laser handpiece for implementing the technique is described.

  19. [Modification of placenta blood serum proteins under low temperature effect].

    PubMed

    Fal'ko, O V; Zemlianskikh, N G; Lipina, O V; Prokopiuk, O S

    2013-01-01

    Changes in environmental physical and chemical factors upon freeze-thawing and low temperature storage of biological samples can result in impairments of protein structures. This work specifies spontaneous and diamide-induced protein aggregations of placenta blood serum stored at -20 degrees and -196 degrees C during 2 years with SDS-PAGE. It was shown that storage of placenta blood serum at low temperatures did not cause any quantitative and qualitative changes in fraction distribution of proteins denatured with SDS in comparison to the native samples which were not frozen. Application of beta-mercaptoethanol revealed that placenta blood serum proteins upon freeze-thawing did not form spontaneous aggregates linked by disulphide bridges. Oxidation of amino acid sulfhydryl groups induced by diamide and accompanied by high molecular aggregate formation proved to be a quite effective way for indirect estimation of structural changes in protein upon low temperature effects. In samples thawed after low temperature storage the protein aggregation with 4 microM diamide was significantly higher than in native serum. These discrepancies between native and frozen-thawed samples are stipulated by impairments of protein structure under low temperature and increased in accessibility of reactive SH-groups of proteins for oxidation with diamide. Structural changes in placenta blood serum proteins, which caused by low temperatures and revealed by elevated sensibility to diamide-induced aggregate formation, did not depend on temperature (-20 degrees and -196 degrees C) and storage terms (2 years and 3 weeks). They reflect protein reaction to freeze-thawing processes and could be sequence of ice crystal formation which takes place in unprotected media.

  20. Generalized Hall effect as a modification of ideal magnetohydrodynamics

    SciTech Connect

    Goodman, M.L.

    1986-01-01

    The generalized Hall effect (GHE) in the generalized Hall model (GHM) is studied as a correction to ideal magnetohydrodynamics (MHD) in the context of how it affects the linear stability of cylindrically symmetric equilibria and how it changes helically symmetric equilibria. The GHM differs from what is usually called the Hall model by including the electron pressure in the electron-momentum equations. This gives the GHM some aspects of a two-fluid model, whereas the Hall model is a one-fluid model. In both cases of cylindrical and helical symmetry, the presence of the electron pressure gradient as part of the GHE gives rise to an electric field tangent to the boundary of the plasma. This introduces an additional boundary condition in the case of a perfectly conducting plasma boundary. In the case of helical symmetry, the equilibrium equations are a generalization of the Grad-Shafranov equation to equilibria with flow and GHE. In the case of cylindrical symmetry, a class of Alfven-wave solutions that do not exist in ideal MHD is obtained and the accumulation point, with respect to large radial wavenumber, of the slow magnetoacoustic wave is shown to be changed from a finite nonzero value in ideal MHD to infinity by the GHE>

  1. Effect of plasma surface modification on the biocompatibility of UHMWPE.

    PubMed

    Kaklamani, G; Mehrban, N; Chen, J; Bowen, J; Dong, H; Grover, L; Stamboulis, A

    2010-10-01

    In this paper active screen plasma nitriding (ASPN) is used to chemically modify the surface of UHMWPE. This is an unexplored and new area of research. ASPN allows the homogeneous treatment of any shape or surface at low temperature; therefore, it was thought that ASPN would be an effective technique to modify organic polymer surfaces. ASPN experiments were carried out at 120 °C using a dc plasma nitriding unit with a 25% N(2) and 75% H(2) atmosphere at 2.5 mbar of pressure. UHMWPE samples treated for different time periods were characterized by nanoindentation, FTIR, XPS, interferometry and SEM. A 3T3 fibroblast cell line was used for in vitro cell culture experiments. Nanoindentation of UHMWPE showed that hardness and elastic modulus increased with ASPN treatment compared to the untreated material. FTIR spectra did not show significant differences between the untreated and treated samples; however, some changes were observed at 30 min of treatment in the range of 1500-1700 cm(-1) associated mainly with the presence of N-H groups. XPS studies showed that nitrogen was present on the surface and its amount increased with treatment time. Interferometry showed that no significant changes were observed on the surfaces after the treatment. Finally, cell culture experiments and SEM showed that fibroblasts attached and proliferated to a greater extent on the plasma-treated surfaces leading to the conclusion that ASPN surface treatment can potentially significantly improve the biocompatibility behaviour of polymeric materials.

  2. Effect of landfill cover layer modification on methane oxidation.

    PubMed

    Hu, Lifang; Long, Yuyang

    2016-12-01

    Levels of methane (CH4) oxidation in materials used for landfill cover attained in the laboratory are not often replicated in the field due to effects from the surrounding environment. This study investigates the three dominant factors affecting CH4 oxidation in the cover layer, namely, the thickness of cover layer, the methanotroph spraying manner, and the osmotic coefficient of the cover material. Results show that improved CH4 emission performance of the cover layer can be realized if methanotroph are introduced, meaning that a thinner cover layer is required. The highest CH4 emission reduction can be realized by spraying methanotroph into the top, middle, and bottom layers of a 30-cm thick cover layer with an osmotic coefficient of 7.76 × 10(-5) cm s(-1). Comparing results on cover layer thickness, methane monooxygenase (MMO) activity was much lower with increasing thickness meaning that the thicker cover could reduce O2 availability, thus inhibiting MMO activity. This suggests that MMO may be responsible for differences in CH4 emission reduction and/or oxidation making the osmotic coefficient an important factor for cover layer material.

  3. Cost-effective surface modification for Galinstan® lyophobicity.

    PubMed

    Kadlaskar, Shantanu Shrikant; Yoo, Jun Hyeon; Abhijeet; Lee, Jeong Bong; Choi, Wonjae

    2017-04-15

    In this paper we investigate the feasibility of using a cost-effective fabrication method based on sandblasting, chemical etching and spray coating processes, to render common surfaces to be non-wettable by Galinstan®. Although Galinstan® is a non-toxic liquid metal alternative to mercury, the viscoelastic and extremely wetting characteristics of Galinstan® have been the major bottleneck limiting the wide applicability of the gallium-based liquid metal. This paper tries to accomplish non-wettability to Galinstan® by combining surface texture and chemistry with the unique property of Galinstan®, that is, its high surface tension and yield strength that prevent the penetration of the liquid metal into surface asperities. Fabricated surfaces resemble traditional superhydrophobic (water-repellent) surfaces, and exhibit a superior non-wettability to Galinstan® as quantified by high static and dynamic contact angles, small hysteresis, as well as impact resistance. Reported fabrication method based on sandblasting, etching and spray coating is easily applicable to various surfaces ranging from metals, ceramics, to plastics and is scalable to large surfaces. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effect of modification substrate on the microstructure of hydroxyapatite coating

    NASA Astrophysics Data System (ADS)

    Realpe-Jaramillo, J.; Morales-Morales, J. A.; González-Sánchez, J. A.; Cabanzo, R.; Mejía-Ospino, E.; Rodríguez-Pereira, J.

    2017-01-01

    Bioactive hydroxyapatite (HA) coatings were fabricated by a precipitation, sol-gel and dip-coating method. The effects of the aging time and the base used to adjust pH and substrate materials on the phases and microstructures of HA coatings were studied by field emission scanning electron microscopy FESEM, energy dispersive spectroscopy EDS, X-ray photoelectron spectroscopy XPS, and the vibrations of the phosphate groups were determined by Raman spectroscopy. The results showed that all the films were composed of the phases of TiO2 and HA. With coated titanium substrate with TiO2, the crystallinity of the HA coating increases, the structure became more compact and the Ca/P ratio increased because of the loss of P in the films. The addition of sodium hydroxide (adjusting the pH level to about 10) can increase the HA content in the coating. XPS and EDS results for steel substrate and titanium showed poor calcium content as obtained with a Ca/P ratio of 1.38 and 1.58, respectively, composition is similar to that of natural apatite. However, spectroscopic results suggest the presence of a mixture of hydroxyapatite and octacalcium phosphate. The different substrate materials have a high influence on the microstructure of the separated double films. However, hydroxyapatite nanopowders coatings were obtained using a simple method, with potential biomedical applications.

  5. Magnetoresistive sensors for measurements of DNA hybridization kinetics – effect of TINA modifications

    PubMed Central

    Rizzi, G.; Dufva, M.; Hansen, M. F.

    2017-01-01

    We present the use of magnetoresistive sensors integrated in a microfluidic system for real-time studies of the hybridization kinetics of DNA labeled with magnetic nanoparticles to an array of surface-tethered probes. The nanoparticles were magnetized by the magnetic field from the sensor current. A local negative reference ensured that only the specific binding signal was measured. Analysis of the real-time hybridization using a two-compartment model yielded both the association and dissociation constants kon, and koff. The effect of probe modifications with ortho-Twisted Intercalating Nucleic Acid (TINA) was studied. Such modifications have been demonstrated to increase the melting temperature of DNA hybrids in solution and are also relevant for surface-based DNA sensing. Kinetic data for DNA probes with no TINA modification or with TINA modifications at the 5′ end (1 × TINA) or at both the 5′ and 3′ ends (2 × TINA) were compared. TINA modifications were found to provide a relative decrease of koff by a factor of 6-20 at temperatures from 57.5 °C to 60 °C. The values of kon were generally in the range between 0.5-2 × 105 M−1s−1 and showed lower values for the unmodified probe than for the TINA modified probes. The observations correlated well with measured melting temperatures of the DNA hybrids. PMID:28167835

  6. Effect of adipic dihydrazide modification on the performance of collagen/hyaluronic acid scaffold.

    PubMed

    Zhang, Ling; Xiao, Yumei; Jiang, Bo; Fan, Hongsong; Zhang, Xingdong

    2010-02-01

    Collagen and hydrazide-functionalized hyaluronic acid derivatives were hybridized by gelating and genipin crosslinking to form composite hydrogel. The study contributed to the understanding of the effects of adipic dihydrazide modification on the physicochemical and biological properties of the collagen/hyaluronic acid scaffold. The investigation included morphology observation, mechanical measurement, swelling evaluation, and collagenase degradation. The results revealed that the stability of composites was increased through adipic dihydrazide modification and genipin crosslinking. The improved biocompatibility and retention of hyaluronic acid made the composite material more favorable to chondrocytes growing, suggesting the prepared scaffold might be high potential for chondrogenesis.

  7. The effect of transverse flow on the nuclear modification factor at RHIC and LHC

    SciTech Connect

    Betz, Barbara; Gyulassy, Miklos

    2016-01-22

    We determine the nuclear modification factor at RHIC and LHC energies using a generic jet-energy loss model that is expanded by an additional flow factor accounting for the impact of transverse flow. We consider a pQCD-based ansatz with and without jet-energy loss fluctuations that is coupled to a state-of-the-art hydrodynamic prescription and includes a running coupling effect. We show that the nuclear modification factor is a rather insensitive quantity that is barely affected by the flow dynamics of the medium created in a heavy-ion collision.

  8. Meta-Analysis of the Effects of Academic Interventions and Modifications on Student Behavior Outcomes

    ERIC Educational Resources Information Center

    Warmbold-Brann, Kristy; Burns, Matthew K.; Preast, June L.; Taylor, Crystal N.; Aguilar, Lisa N.

    2017-01-01

    The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an…

  9. Effects of Lexical Modification on Incidental Vocabulary Acquisition of Iranian EFL Students

    ERIC Educational Resources Information Center

    Negari, Giti Mousapour; Rouhi, Mahdieh

    2012-01-01

    The present article reports on the results of a study designed to investigate the effects of two types of lexical modification i.e., lexical simplification and elaboration, on incidental vocabulary acquisition of Iranian EFL learners.To this end, four versions of experimental texts containing 20 target words were created: baseline and simplified…

  10. Disability acquisition and mental health: effect modification by demographic and socioeconomic characteristics using data from an Australian longitudinal study.

    PubMed

    Aitken, Zoe; Simpson, Julie Anne; Bentley, Rebecca; Kavanagh, Anne Marie

    2017-09-18

    There is evidence of a causal relationship between disability acquisition and poor mental health, but the substantial heterogeneity in the magnitude of the effect is poorly understood and may be aetiologically informative. This study aimed to identify demographic and socioeconomic factors that modify the effect of disability acquisition on mental health. The Household, Income and Labour Dynamics in Australia Survey is a nationally representative longitudinal survey of Australian households that has been conducted annually since 2001. Four waves of data were included in this analysis, from 2011 to 2014. Individuals who acquired a disability (n=387) were compared with those who remained disability-free in all four waves (n=7936). Mental health was measured using the mental health subscale of the Short Form 36 (SF-36) general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being. Linear regression models were fitted to estimate the effect of disability acquisition on mental health, testing for effect modification by key demographic and socioeconomic characteristics. To maximise causal inference, we used a propensity score approach with inverse probability of treatment weighting to control for confounding and multiple imputation using chained equations to assess the impact of missing data. On average, disability acquisition was associated with a 5-point decline in mental health score (estimated mean difference: -5.1, 95% CI -7.2 to -3.0). There was strong evidence that income and relationship status modified the effect, with more detrimental effects in the lowest (-12.5, 95% CI -18.5 to -6.5) compared with highest income quintile (-1.1, 95% CI -4.9 to 2.7) and for people not in a relationship (-8.8, 95% CI -12.9 to -4.8) compared with those who were (-3.7, 95% CI -6.1 to -1.4). Our results suggest that the detrimental effect of disability acquisition on mental health is substantially greater for socioeconomic

  11. Disability acquisition and mental health: effect modification by demographic and socioeconomic characteristics using data from an Australian longitudinal study

    PubMed Central

    Simpson, Julie Anne; Bentley, Rebecca; Kavanagh, Anne Marie

    2017-01-01

    Objectives There is evidence of a causal relationship between disability acquisition and poor mental health, but the substantial heterogeneity in the magnitude of the effect is poorly understood and may be aetiologically informative. This study aimed to identify demographic and socioeconomic factors that modify the effect of disability acquisition on mental health. Design and setting The Household, Income and Labour Dynamics in Australia Survey is a nationally representative longitudinal survey of Australian households that has been conducted annually since 2001. Four waves of data were included in this analysis, from 2011 to 2014. Participants Individuals who acquired a disability (n=387) were compared with those who remained disability-free in all four waves (n=7936). Primary outcome measure Mental health was measured using the mental health subscale of the Short Form 36 (SF-36) general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being. Methods Linear regression models were fitted to estimate the effect of disability acquisition on mental health, testing for effect modification by key demographic and socioeconomic characteristics. To maximise causal inference, we used a propensity score approach with inverse probability of treatment weighting to control for confounding and multiple imputation using chained equations to assess the impact of missing data. Results On average, disability acquisition was associated with a 5-point decline in mental health score (estimated mean difference: −5.1, 95% CI −7.2 to –3.0). There was strong evidence that income and relationship status modified the effect, with more detrimental effects in the lowest (−12.5, 95% CI −18.5 to –6.5) compared with highest income quintile (−1.1, 95% CI –4.9 to 2.7) and for people not in a relationship (−8.8, 95% CI −12.9 to –4.8) compared with those who were (−3.7, 95% CI −6.1 to –1.4). Conclusions Our results

  12. The effects of linguistic modification on ESL students' comprehension of nursing course test items.

    PubMed

    Bosher, Susan; Bowles, Melissa

    2008-01-01

    Recent research has indicated that language may be a source of construct-irrelevant variance for non-native speakers of English, or English as a second language (ESL) students, when they take exams. As a result, exams may not accurately measure knowledge of nursing content. One accommodation often used to level the playing field for ESL students is linguistic modification, a process by which the reading load of test items is reduced while the content and integrity of the item are maintained. Research on the effects of linguistic modification has been conducted on examinees in the K-12 population, but is just beginning in other areas. This study describes the collaborative process by which items from a pathophysiology exam were linguistically modified and subsequently evaluated for comprehensibility by ESL students. Findings indicate that in a majority of cases, modification improved examinees' comprehension of test items. Implications for test item writing and future research are discussed.

  13. Regularized Regression Versus the High-Dimensional Propensity Score for Confounding Adjustment in Secondary Database Analyses.

    PubMed

    Franklin, Jessica M; Eddings, Wesley; Glynn, Robert J; Schneeweiss, Sebastian

    2015-10-01

    Selection and measurement of confounders is critical for successful adjustment in nonrandomized studies. Although the principles behind confounder selection are now well established, variable selection for confounder adjustment remains a difficult problem in practice, particularly in secondary analyses of databases. We present a simulation study that compares the high-dimensional propensity score algorithm for variable selection with approaches that utilize direct adjustment for all potential confounders via regularized regression, including ridge regression and lasso regression. Simulations were based on 2 previously published pharmacoepidemiologic cohorts and used the plasmode simulation framework to create realistic simulated data sets with thousands of potential confounders. Performance of methods was evaluated with respect to bias and mean squared error of the estimated effects of a binary treatment. Simulation scenarios varied the true underlying outcome model, treatment effect, prevalence of exposure and outcome, and presence of unmeasured confounding. Across scenarios, high-dimensional propensity score approaches generally performed better than regularized regression approaches. However, including the variables selected by lasso regression in a regular propensity score model also performed well and may provide a promising alternative variable selection method.

  14. Analysis of potential genomic confounding in genetic association studies and an online genomic confounding browser (GCB).

    PubMed

    Raistrick, Christopher A; Alharbi, Khalid K; Day, Ian N M; Gaunt, Tom R

    2011-11-01

    Genome-wide association studies have transformed genetic studies of disease susceptibility, identifying many variants that may tag functional polymorphism nearby. Variants are often ascribed to a physically close gene exhibiting plausible functionality for a causal pathway. However, more physically remote genes may be at a lesser linkage or linkage disequilibrium (LD) distance from the tested SNP and could therefore contain the functional variant tagged. This analysis aims to identify instances where research may be misled by misassociation of a variant with a gene and develop tools to analyse genomic confounding. A catalogue of reported associations was systematically analysed for unreported genes which may represent the true functionality ascribed to a reported variant, calculating physical and genetic distances for all genes within 1 cM of the tagging polymorphism. Results revealed 55 SNPs where recombination was lower between the identified SNP and a physically more remote gene than initially reported, and 374 where an alternative gene was genetically and physically closer than the reported gene. Analyses show potential for genomic confounding through false inferences of variant association to a gene. An online visualization tool (http://gcb.genes.org.uk/) was developed to plot genes by physical and genetic distance relative to a variant, along with LD data. © 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

  15. Effects of cognitive bias modification training on neural alcohol cue reactivity in alcohol dependence.

    PubMed

    Wiers, Corinde E; Stelzel, Christine; Gladwin, Thomas E; Park, Soyoung Q; Pawelczack, Steffen; Gawron, Christiane K; Stuke, Heiner; Heinz, Andreas; Wiers, Reinout W; Rinck, Mike; Lindenmeyer, Johannes; Walter, Henrik; Bermpohl, Felix

    2015-04-01

    In alcohol-dependent patients, alcohol cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on cue reactivity in alcohol-dependent patients. In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol cues and 10% of soft drink cues, whereas this ratio was 50/50 in the sham training. Alcohol cue reactivity was measured with functional MRI before and after training. Before training, alcohol cue-evoked activation was observed in the amygdala bilaterally, as well as in the right nucleus accumbens, although here it fell short of significance. Activation in the amygdala correlated with craving and arousal ratings of alcohol stimuli; correlations in the nucleus accumbens again fell short of significance. After training, the bias modification group showed greater reductions in cue-evoked activation in the amygdala bilaterally and in behavioral arousal ratings of alcohol pictures, compared with the sham training group. Decreases in right amygdala activity correlated with decreases in craving in the bias modification but not the sham training group. These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.

  16. Effects of Weak Surface Modification on Co/SiO2 Catalyst for Fischer-Tropsch Reaction

    PubMed Central

    Ning, Wensheng; Shen, Hehong; Jin, Yangfu; Yang, Xiazhen

    2015-01-01

    A weak surface modification is applied to Co/SiO2 catalyst by hydrothermal treatment at 180°C for 5 h. Aluminum is introduced to Co/SiO2 catalysts during the surface modification. The effects of surface modification on Co/SiO2 catalyst are studied by changing the operating sequences of surface modification and cobalt impregnation in the catalyst preparation. Surface modification before cobalt impregnation makes Co3O4 particle small and dispersed into the deep part of enlarged pore in SiO2, while surface modification after cobalt impregnation does not obviously change the particle size of Co3O4. The improved amplitude of catalytic activity is similar for the two kinds of catalysts, but they are benefited from different factors. The content of iso-hydrocarbons in the products is increased by the surface modifications. PMID:25938725

  17. Effects of Weak Surface Modification on Co/SiO2 Catalyst for Fischer-Tropsch Reaction.

    PubMed

    Ning, Wensheng; Shen, Hehong; Jin, Yangfu; Yang, Xiazhen

    2015-01-01

    A weak surface modification is applied to Co/SiO2 catalyst by hydrothermal treatment at 180°C for 5 h. Aluminum is introduced to Co/SiO2 catalysts during the surface modification. The effects of surface modification on Co/SiO2 catalyst are studied by changing the operating sequences of surface modification and cobalt impregnation in the catalyst preparation. Surface modification before cobalt impregnation makes Co3O4 particle small and dispersed into the deep part of enlarged pore in SiO2, while surface modification after cobalt impregnation does not obviously change the particle size of Co3O4. The improved amplitude of catalytic activity is similar for the two kinds of catalysts, but they are benefited from different factors. The content of iso-hydrocarbons in the products is increased by the surface modifications.

  18. Saccade-confounded image statistics explain visual crowding.

    PubMed

    Nandy, Anirvan S; Tjan, Bosco S

    2012-01-08

    Processing of shape information in human peripheral visual fields is impeded beyond what can be expected by poor spatial resolution. Visual crowding, the inability to identify objects in clutter, has been shown to be the primary factor limiting shape perception in peripheral vision. Despite the well-documented effects of crowding, its underlying causes remain poorly understood. Given that spatial attention both facilitates learning of image statistics and directs saccadic eye movements, we propose that the acquisition of image statistics in peripheral visual fields is confounded by eye-movement artifacts. Specifically, the image statistics acquired under a peripherally deployed spotlight of attention are systematically biased by saccade-induced image displacements. These erroneously represented image statistics lead to inappropriate contextual interactions in the periphery and cause crowding.

  19. From bad to worse: collider stratification amplifies confounding bias in the "obesity paradox".

    PubMed

    Banack, Hailey R; Kaufman, Jay S

    2015-10-01

    Smoking is often identified as a confounder of the obesity-mortality relationship. Selection bias can amplify the magnitude of an existing confounding bias. The objective of the present report is to demonstrate how confounding bias due to cigarette smoking is increased in the presence of collider stratification bias using an empirical example and directed acyclic graphs. The empirical example uses data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of 15,792 men and women in the United States. Poisson regression models were used to examine the confounding effect of smoking. In the total ARIC study population, smoking produced a confounding bias of <3 percentage points. This result was obtained by comparing the incidence rate ratio (IRR) for obesity from a model adjusted for smoking was 1.07 (95 % CI 1.00, 1.15) with one that did not adjust for smoking was 1.10 (95 % CI 1.03, 1.18). However, among smokers with CVD, the obesity IRR was 0.89 (95 % CI 0.81, 0.99), while among non-smokers with CVD the obesity IRR was 1.20 (95 % CI 1.03, 1.41). The empirical and graphical explanations presented suggest that the magnitude of the confounding bias induced by smoking is greater in the presence of collider stratification bias.

  20. Negative Confounding by Essential Fatty Acids in Methylmercury Neurotoxicity Associations

    PubMed Central

    Choi, Anna L; Mogensen, Ulla B.; Bjerve, Kristian S.; Debes, Frodi; Weihe, Pal; Grandjean, Philippe; Budtz-Jørgensen, Esben

    2014-01-01

    Background Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. Methods We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. Results A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (−18.9, 95% confidence interval [CI] = −36.3, −1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (−22.0, 95% confidence interval [CI] = −39.4, −4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (−1.94, 95% CI = −3.39, −0.49). Conclusions Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure. PMID:24561639

  1. Acute effects of air pollution on pediatric asthma exacerbation: evidence of association and effect modification.

    PubMed

    Samoli, E; Nastos, P T; Paliatsos, A G; Katsouyanni, K; Priftis, K N

    2011-04-01

    We investigated the short-term effects of particulate matter with aerodynamic diameter <10 μg/m(3) (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)) and ozone (O(3)) on pediatric asthma emergency admissions in Athens, Greece over the period 2001-2004. We explored effect modification patterns by season, sex, age and by the presence of desert dust transported mainly from the Sahara area. We used daily time-series data provided by the children's hospitals and the fixed monitoring stations. The associations were investigated using Poisson regression models controlling for seasonality, weather, influenza episodes, day of the week and holiday effects. A 10 μg/m(3) increase in PM(10) was associated with a 2.54% increase (95% confidence interval (CI): 0.06%, 5.08%) in the number of pediatric asthma hospital admissions, while the same increase in SO(2) was associated with a 5.98% (95% CI: 0.88%, 11.33%) increase. O(3) was associated with a statistically significant increase in asthma admissions among older children in the summer. Our findings provide limited evidence of an association between NO(2) exposure and asthma exacerbation. Statistically significant PM(10) effects were higher during winter and during desert dust days, while SO(2) effects occurred mainly during spring. Our study confirms previously reported PM(10) effects on emergency hospital admissions for pediatric asthma and further provides evidence of stronger effects during desert dust days. We additionally report severe effects of SO(2), even at today's low concentration levels. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties

    PubMed Central

    Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

    2013-01-01

    To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement. PMID:28788404

  3. Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties.

    PubMed

    Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

    2013-11-27

    To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement.

  4. Separate and combined effects of methylphenidate and behavior modification on boys with attention deficit-hyperactivity disorder in the classroom.

    PubMed

    Pelham, W E; Carlson, C; Sams, S E; Vallano, G; Dixon, M J; Hoza, B

    1993-06-01

    This study evaluated the separate and combined effects of behavior modification and 2 doses of methylphenidate (MPH; 0.3 and 0.6 mg/kg) compared with baseline (no behavior modification and a placebo) on the classroom behavior and academic performance of 31 ADHD (attention deficit-hyperactivity disorder) boys attending a summer treatment program. Results revealed significant effects of both interventions, with the mean effect size of medication being more than twice as great as that of behavior modification. Relatively small incremental value was gained by the higher dose of medication or the addition of behavior modification, compared with the effects of the low dose of MPH. In contrast, the addition of either dose of MPH resulted in improvement beyond the effects of behavior modification alone. These group effects reflected those obtained in analyses of individual differences. Furthermore, comparisons of individual responsiveness showed that boys who responded to one treatment also responded to the other.

  5. 77 FR 59241 - Notice of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ... of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin of the Dominican... Representative. ACTION: Notice of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin...''). SUMMARY: Public Law 112-163 modified the rules of origin for certain textile and apparel goods of...

  6. Modification of the genetic effect of gamma irradiation by electric current

    SciTech Connect

    Grigor'eva, N.N.; Shakbazov, V.G.

    1985-09-01

    The authors study the effect of direct current of varying strength and polarity on the genetic damage due to gamma irradiation of Vicia faba seedlings. The modificational effect of direct current observed earlier is confirmed here. The extent and nature of this effect depends on the strength and polarity of the current as well as interval between irradiation and exposure to the electric field. Conditions having no effect on the irradiated seedlings, those protecting the cells from damage and enhancing the irradiation effect, are identified.

  7. Effects of cognitive bias modification on social anxiety: A meta-analysis.

    PubMed

    Liu, Haining; Li, Xianwen; Han, Buxin; Liu, Xiaoqian

    2017-01-01

    Cognitive bias modification (CBM), a set of techniques for modifying bias in information processing-is considered a novel intervention for social anxiety disorder (SAD), which has drawn considerable interest from researchers. However, the effects of CBM on SAD are not consistent. Some studies have demonstrated significant positive effects compared to control groups, while others have found no such effects. We conducted a meta-analysis aimed at quantitatively assessing the effects of CBM on SAD at post-test. Through a systematic literature search by two independent raters, 34 articles (36 randomized studies) including 2,550 participants were identified. A multilevel modeling approach was employed to assess the effects of CBM on SAD, and to explore the potentially crucial procedures and sample characteristics that enhance the effectiveness of benign training. In general, there were small but significant effects of CBM on the primary symptoms of SAD (g = 0.17), cognitive bias (CB) toward threat (g = 0.32), and reactivity in stressful situations (g = 0.25), but non-significant effects on secondary symptoms. However, the interpretation modification program was more effective than was attentional bias modification in reducing SAD primary symptoms and negative CB. Laboratory training procedures produced larger primary symptom reductions compared to Internet-based training, whereas the percentage of contingency and feedback about training performance boosted cognitive effects only. Finally, the following groups were more likely to benefit from CBM: younger participants (primary symptoms and cognitive effects), women (primary symptom effects), and samples with stronger CB (stressor effects). The quality of the randomized controlled trials was less than desirable, as there was some indication of publication bias in our study. Current findings broadly supported cognitive theories of SAD that consider a bidirectional or mutually reinforcing relationship between symptoms and

  8. Effects of cognitive bias modification on social anxiety: A meta-analysis

    PubMed Central

    Liu, Haining; Li, Xianwen; Han, Buxin; Liu, Xiaoqian

    2017-01-01

    Background Cognitive bias modification (CBM), a set of techniques for modifying bias in information processing—is considered a novel intervention for social anxiety disorder (SAD), which has drawn considerable interest from researchers. However, the effects of CBM on SAD are not consistent. Some studies have demonstrated significant positive effects compared to control groups, while others have found no such effects. Aims We conducted a meta-analysis aimed at quantitatively assessing the effects of CBM on SAD at post-test. Method Through a systematic literature search by two independent raters, 34 articles (36 randomized studies) including 2,550 participants were identified. A multilevel modeling approach was employed to assess the effects of CBM on SAD, and to explore the potentially crucial procedures and sample characteristics that enhance the effectiveness of benign training. Results In general, there were small but significant effects of CBM on the primary symptoms of SAD (g = 0.17), cognitive bias (CB) toward threat (g = 0.32), and reactivity in stressful situations (g = 0.25), but non-significant effects on secondary symptoms. However, the interpretation modification program was more effective than was attentional bias modification in reducing SAD primary symptoms and negative CB. Laboratory training procedures produced larger primary symptom reductions compared to Internet-based training, whereas the percentage of contingency and feedback about training performance boosted cognitive effects only. Finally, the following groups were more likely to benefit from CBM: younger participants (primary symptoms and cognitive effects), women (primary symptom effects), and samples with stronger CB (stressor effects). The quality of the randomized controlled trials was less than desirable, as there was some indication of publication bias in our study. Conclusions Current findings broadly supported cognitive theories of SAD that consider a bidirectional or mutually

  9. Alumina reinforced zirconia implants: effects of cyclic loading and abutment modification on fracture resistance.

    PubMed

    Spies, Benedikt Christopher; Sauter, Carmen; Wolkewitz, Martin; Kohal, Ralf-Joachim

    2015-03-01

    The aim of the study was to evaluate the thermomechanical behavior of alumina-toughened zirconia (ATZ) oral implants in the artificial mouth and the fracture resistance (fracture load and bending moment) in a subsequent static fracture load test. The effects of abutment modification and different cyclic loadings were evaluated. A total of 48 implants were used. 24 implants were left as machined (Group A), and 24 implants were shape modified at the abutment (Group B). Groups were divided into three subgroups composed of 8 samples each (A1/B1: no cyclic loading; A2/B2: 1.2 million cycles; A3/B3: 5 million cycles). Subsequently, all implants were statically loaded to the point of fracture. The implants showed the following survival rates after the artificial mouth: A2 and B2 100%; A3 and B3 87.5%. The following average fracture resistance values were found (fracture load [N]/bending moment [Nmm]): A1 (583/2907), B1 (516/2825), A2 (618/2737), B2 (550/3150), A3 (802/3784) and B3 (722/3809). After 5 million loading cycles a significant increase in fracture load and bending moment was found. Modification of the abutment significantly decreased the fracture load of implants without foregoing dynamic loading. However, the shape modification altered the lever arm. For that reason, a smaller load resulted in the same bending moment. Therefore, abutment modification had no significant influence on the fracture resistance of ATZ. Neither thermomechanical cycling in an aqueous environment nor modification of the abutment had a negative effect on the fracture resistance of ATZ. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  10. Effects of Selenylation Modification on Antioxidative Activities of Schisandra chinensis Polysaccharide.

    PubMed

    Yue, Chanjuan; Chen, Jin; Hou, Ranran; Liu, Jie; Li, Xiuping; Gao, Zhenzhen; Liu, Cui; Wang, Deyun; Lu, Yu; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    The selenylation modification of Schisandra chinensis polysaccharide (SCP) was conducted by the HNO3-Na2SeO3 method respectively under nine conditions according to L9(34) orthogonal design. Nine selenizing SCPs, sSCP1-sSCP9, were obtained, and their antioxidant activities were compared. In vitro test, the free radical-scavenging rates of nine sSCPs were determined for DPPH., .OH and ABTS+. sSCP1 presented the most significant effect, and could inhibit the nonenzymatic protein glycation. In vivo test, 14-day-old chickens were injected respectively with sSCP1 and SCP, the serum contents of CAT, SOD and MDA were determined. The result showed that as compared with the SCP group, the SOD and CAT activities were significantly or numerically raised and MDA content was significantly or numerically lowered in the sSCP1 group. These results indicate that selenylation modification can significantly enhance the antioxidant and antiglycative activity of SCP in vitro or in vivo. sSCP1 possesses the best efficacy and its modification conditions can be as optimal modification conditions that were 200 mg of Na2SeO3 for 500 mg of SCP, reaction temperature of 50°C and reaction time of 6 h.

  11. Effects of Selenylation Modification on Antioxidative Activities of Schisandra chinensis Polysaccharide

    PubMed Central

    Yue, Chanjuan; Chen, Jin; Hou, Ranran; Liu, Jie; Li, Xiuping; Gao, Zhenzhen; Liu, Cui; Wang, Deyun; Lu, Yu; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    The selenylation modification of Schisandra chinensis polysaccharide (SCP) was conducted by the HNO3–Na2SeO3 method respectively under nine conditions according to L9(34) orthogonal design. Nine selenizing SCPs, sSCP1–sSCP9, were obtained, and their antioxidant activities were compared. In vitro test, the free radical-scavenging rates of nine sSCPs were determined for DPPH., .OH and ABTS+. sSCP1 presented the most significant effect, and could inhibit the nonenzymatic protein glycation. In vivo test, 14-day-old chickens were injected respectively with sSCP1 and SCP, the serum contents of CAT, SOD and MDA were determined. The result showed that as compared with the SCP group, the SOD and CAT activities were significantly or numerically raised and MDA content was significantly or numerically lowered in the sSCP1 group. These results indicate that selenylation modification can significantly enhance the antioxidant and antiglycative activity of SCP in vitro or in vivo. sSCP1 possesses the best efficacy and its modification conditions can be as optimal modification conditions that were 200 mg of Na2SeO3 for 500 mg of SCP, reaction temperature of 50°C and reaction time of 6 h. PMID:26230941

  12. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  13. Adjustments for Unmeasured Confounders in Pharmacoepidemiologic Database Studies Using External Information

    PubMed Central

    Stürmer, Til; Glynn, Robert J; Rothman, Kenneth J; Avorn, Jerry; Schneeweiss, Sebastian

    2008-01-01

    Background Non-experimental studies of drug effects in large automated databases can provide timely assessment of real-life drug use, but are prone to confounding by variables that are not contained in these databases and thus cannot be controlled. Objectives To describe how information on additional confounders from validation studies can help address the problem of unmeasured confounding in the main study. Research Design Review types of validation studies that allow adjustment for unmeasured confounding and illustrate these with an example. Subjects: Main study New Jersey residents 65 years or older hospitalized between 1995 and 1997, who filled prescriptions within Medicaid or a pharmaceutical assistance program. Validation study: representative sample of Medicare beneficiaries. Measures Association between nonsteroidal anti-inflammatory drugs (NSAIDs) and mortality. Results Validation studies are categorized as internal (ie, additional information is collected on participants of the main study) or external. Availability of information on disease outcome will affect choice of analytic strategies. Using an external validation study without data on disease outcome to adjust for unmeasured confounding, propensity score calibration (PSC) leads to a plausible estimate of the association between NSAIDs and mortality in the elderly, if the biases caused by measured and unmeasured confounders go in the same direction. Conclusions Estimates of drug effects can be adjusted for confounders that are not available in the main but can be measured in a validation study. PSC uses validation data without information on disease outcome under a strong assumption. The collection and integration of validation data in pharmacoepidemiology should be encouraged. PMID:17909375

  14. Effect of bentonite modification on hardness and mechanical properties of natural rubber nanocomposites

    SciTech Connect

    Santiago, Denise Ester O.; Pajarito, Bryan B.; Mangaccat, Winna Faye F.; Tigue, Maelyn Rose M.; Tipton, Monica T.

    2016-05-18

    The effect of sodium activation, ion-exchange with tertiary amine salt, surface treatment with non-ionic surfactant, and wet grinding of bentonite on hardness and mechanical properties of natural rubber nanocomposites (NRN) was studied using full factorial design of experiment. Results of X-ray diffraction (XRD) show increase in basal spacing d of bentonite due to modification, while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirm the organic modification of bentonite. Analysis of variance (ANOVA) shows that the main effect of surface treatment increases the hardness and decreases the tensile modulus of the NRN. The surface treatment and wet grinding of bentonite decrease the tensile stresses at 100, 200 and 300% strain of NRN. Sodium activation and ion-exchange negatively affect the compressive properties, while surface treatment significantly improves the compressive properties of NRN.

  15. Effect of bentonite modification on hardness and mechanical properties of natural rubber nanocomposites

    NASA Astrophysics Data System (ADS)

    Santiago, Denise Ester O.; Pajarito, Bryan B.; Mangaccat, Winna Faye F.; Tigue, Maelyn Rose M.; Tipton, Monica T.

    2016-05-01

    The effect of sodium activation, ion-exchange with tertiary amine salt, surface treatment with non-ionic surfactant, and wet grinding of bentonite on hardness and mechanical properties of natural rubber nanocomposites (NRN) was studied using full factorial design of experiment. Results of X-ray diffraction (XRD) show increase in basal spacing d of bentonite due to modification, while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirm the organic modification of bentonite. Analysis of variance (ANOVA) shows that the main effect of surface treatment increases the hardness and decreases the tensile modulus of the NRN. The surface treatment and wet grinding of bentonite decrease the tensile stresses at 100, 200 and 300% strain of NRN. Sodium activation and ion-exchange negatively affect the compressive properties, while surface treatment significantly improves the compressive properties of NRN.

  16. Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

    USGS Publications Warehouse

    Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

    2015-01-01

    In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

  17. Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities.

    PubMed

    Boopathy, R; Balasubramanian, A S

    1985-09-02

    The effect of chemical modification on the pseudocholinesterase and aryl acylamidase activities of purified human serum pseudocholinesterase was examined in the absence and presence of butyrylcholine iodide, the substrate of pseudocholinesterase. Modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, diethylpyrocarbonate and trinitrobenzenesulfonic acid caused a parallel inactivation of both pseudocholinesterase and aryl acylamidase activities that could be prevented by butyrylcholine iodide. With phenylglyoxal and 2,4-pentanedione as modifiers there was a selective activation of pseudocholinesterase alone with no effect on aryl acylamidase. This activation could be prevented by butyrylcholine iodide. N-Ethylmaleimide and p-hydroxy-mercuribenzoate when used for modification did not have any effect on the enzyme activities. The results suggested essential tryptophan, lysine and histidine residues at a common catalytic site for pseudocholinesterase and aryl acylamidase and an arginine residue (or residues) exclusively for pseudocholinesterase. The use of N-acetylimidazole, tetranitromethane and acetic anhydride as modifiers indicated a biphasic change in both pseudocholinesterase and aryl acylamidase activities. At low concentrations of the modifiers a stimulation in activities and at high concentrations an inactivation was observed. Butyrylcholine iodide or propionylcholine chloride selectively protected the inactivation phase without affecting the activation phase. Protection by the substrates at the inactivation phase resulted in not only a reversal of the enzyme inactivation but also an activation. Spectral studies and hydroxylamine treatment showed that tyrosine residues were modified during the activation phase. The results suggested that the modified tyrosine residues responsible for the activation were not involved in the active site of pseudocholinesterase or aryl acylamidase and that they were more amenable for modification in comparison to

  18. On a preference-based instrumental variable approach in reducing unmeasured confounding-by-indication.

    PubMed

    Li, Yun; Lee, Yoonseok; Wolfe, Robert A; Morgenstern, Hal; Zhang, Jinyao; Port, Friedrich K; Robinson, Bruce M

    2015-03-30

    Treatment preferences of groups (e.g., clinical centers) have often been proposed as instruments to control for unmeasured confounding-by-indication in instrumental variable (IV) analyses. However, formal evaluations of these group-preference-based instruments are lacking. Unique challenges include the following: (i) correlations between outcomes within groups; (ii) the multi-value nature of the instruments; (iii) unmeasured confounding occurring between and within groups. We introduce the framework of between-group and within-group confounding to assess assumptions required for the group-preference-based IV analyses. Our work illustrates that, when unmeasured confounding effects exist only within groups but not between groups, preference-based IVs can satisfy assumptions required for valid instruments. We then derive a closed-form expression of asymptotic bias of the two-stage generalized ordinary least squares estimator when the IVs are valid. Simulations demonstrate that the asymptotic bias formula approximates bias in finite samples quite well, particularly when the number of groups is moderate to large. The bias formula shows that when the cluster size is finite, the IV estimator is asymptotically biased; only when both the number of groups and cluster size go to infinity, the bias disappears. However, the IV estimator remains advantageous in reducing bias from confounding-by-indication. The bias assessment provides practical guidance for preference-based IV analyses. To increase their performance, one should adjust for as many measured confounders as possible, consider groups that have the most random variation in treatment assignment and increase cluster size. To minimize the likelihood for these IVs to be invalid, one should minimize unmeasured between-group confounding.

  19. Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

    SciTech Connect

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2016-07-01

    Determining Confounding Sensitivities In Eddy Current Thin Film Measurements Ethan Gros, Lalita Udpa, Electrical Engineering, Michigan State University, East Lansing MI 48824 James A. Smith, Experiment Analysis, Idaho National Laboratory, Idaho Falls ID 83415 Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It is the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy current testing is performed using a commercially available, hand held eddy current probe (ETA3.3H spring loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe is sent to a hand held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring loaded

  20. The Effect of Substrate Temperature on Surface Modification of Polystyrene by using Nitrogen Plasma

    NASA Astrophysics Data System (ADS)

    Novi, A. F.; Santjojo, D. J. D. H.; Masruroh

    2017-05-01

    Studies on the effect of substrate temperature on the modification process of a thin layer of polystyrene samples deposited on glass by using spin coating technique have been conducted. The polystyrene thin film surface was modified by using nitrogen plasma generated in a vacuum reactor by a capacitive plasma generator with a frequency of 40 kHz. The substrate temperature was set by variation of 60, 70 and 80 °C during the modification process to determine the effect of substrate temperature on the level of roughness and hydrophobicity of the film. Observations were conducted by using optical microscopy, optical micro-profiler, and measuring the contact angle of liquid. The results showed a decrease in roughness due to modification at a temperature of 60 °C and 70 °C. On the other hand, the treatment at a temperature of 80 °C resulted in an increase of roughness. By measuring the contact angle, it was proven that hydrophobicity is not only influenced by the surface roughness of thin layers.

  1. Maternal Behavior Modifications during Pretense and Their Long-Term Effects on Toddlers’ Understanding of Pretense

    PubMed Central

    Nakamichi, Naoko

    2015-01-01

    Recent studies indicate the need to investigate the sources of toddlers’ understanding of another person's pretense. The present study is a cultural and longitudinal extension of the work of Lillard and Witherington (2004), who claimed that mothers modify their behaviors during pretense and that the some of these behavior modifications help their toddlers understand maternal pretense. Experiment 1 investigated whether mothers would change their behaviors during pretense with a sample of 31 Japanese mother–infant pairs. Experiment 2, with a subsample of 20 mother–child pairs who had participated in Experiment 1, examined whether the maternal behavior modifications at 18 months predicted their toddlers’ understanding of pretense at 24 months. The results of Experiment 1 indicated that Japanese mothers smiled more frequently, gazed at their toddlers longer, used sound effects more frequently, and engaged in more frequent snack-related actions in a “pretense condition” than in a “real condition.” In addition, some of these behaviors were significantly related to their toddlers’ apparent understanding of pretense. Experiment 2 showed that both the frequency of maternal smiles and the number of sound effects in the pretense condition at 18 months predicted toddlers’ understanding of the pretense enacted by a strange adult at 24 months. This research indicates the impact of maternal behavior modifications during pretense on the development of symbolic thought in the 2nd year of life. PMID:26430391

  2. Smoking and Hormesis as Confounding Factors in Radiation Pulmonary Carcinogenesis

    PubMed Central

    Sanders, Charles L.; Scott, Bobby R.

    2008-01-01

    Confounding factors in radiation pulmonary carcinogenesis are passive and active cigarette smoke exposures and radiation hormesis. Significantly increased lung cancer risk from ionizing radiation at lung doses < 1 Gy is not observed in never smokers exposed to ionizing radiations. Residential radon is not a cause of lung cancer in never smokers and may protect against lung cancer in smokers. The risk of lung cancer found in many epi-demiological studies was less than the expected risk (hormetic effect) for nuclear weapons and power plant workers, shipyard workers, fluoroscopy patients, and inhabitants of high-dose background radiation. The protective effect was noted for low- and mixed high- and low-linear energy transfer (LET) radiations in both genders. Many studies showed a protection factor (PROFAC) > 0.40 (40% avoided) against the occurrence of lung cancer. The ubiquitous nature of the radiation hormesis response in cellular, animal, and epidemio-logical studies negates the healthy worker effect as an explanation for radiation hormesis. Low-dose radiation may stimulate DNA repair/apoptosis and immunity to suppress and eliminate cigarette-smoke-induced transformed cells in the lung, reducing lung cancer occurrence in smokers. PMID:18648572

  3. Smoking and hormesis as confounding factors in radiation pulmonary carcinogenesis.

    PubMed

    Sanders, Charles L; Scott, Bobby R

    2006-12-06

    Confounding factors in radiation pulmonary carcinogenesis are passive and active cigarette smoke exposures and radiation hormesis. Significantly increased lung cancer risk from ionizing radiation at lung doses < 1 Gy is not observed in never smokers exposed to ionizing radiations. Residential radon is not a cause of lung cancer in never smokers and may protect against lung cancer in smokers. The risk of lung cancer found in many epidemiological studies was less than the expected risk (hormetic effect) for nuclear weapons and power plant workers, shipyard workers, fluoroscopy patients, and inhabitants of high-dose background radiation. The protective effect was noted for low- and mixed high- and low-linear energy transfer (LET) radiations in both genders. Many studies showed a protection factor (PROFAC) > 0.40 (40% avoided) against the occurrence of lung cancer. The ubiquitous nature of the radiation hormesis response in cellular, animal, and epidemio-logical studies negates the healthy worker effect as an explanation for radiation hormesis. Low-dose radiation may stimulate DNA repair/apoptosis and immunity to suppress and eliminate cigarette-smoke-induced transformed cells in the lung, reducing lung cancer occurrence in smokers.

  4. Feedback in classroom behavior modification: effects on the target and her classmates.

    PubMed

    Drabman, R S; Lahey, B B

    1974-01-01

    A behavior modification program that employed feedback with no additional contingencies was initiated and withdrawn in an ABAB design on a target child within a classroom. The disruptive behavior of the target child as well as that of her peers was monitored. Additionally, the sociometric status of the target child was recorded. Finally, the positive and negative comments made to the target by her teacher and her peers were related to initiation and withdrawal of the feedback contingency. Results indicate that (1) feedback alone may be an effective behavior modification procedure, (2) the disruptive behavior of the target's classmates changed, even though they were not directly treated, (3) sociometric status of the target was altered by behavioral contingencies, (4) positive comments by classmates to the target increased, and (5) negative comments from the teacher to the target child decreased.

  5. Effect of avidin-like proteins and biotin modification on mesenchymal stem cell adhesion

    PubMed Central

    Schmidt, Ray C.; Healy, Kevin E.

    2013-01-01

    The avidin-biotin system is a highly specific reaction that has been used in a wide range of biomedical applications, including surface modification and cell patterning. We systematically examined a number of avidin derivatives as the basis for a simple and cost effective tissue culture polystyrene substrate surface modification for human stem cell culture. Non-specific adhesion between human mesenchymal stem cells and various avidin derivatives, media conditions, and subsequent biotinylation reactions was quantified. We observed significant non-specific cell adhesion to avidin and strepthavidin, indicating that previous observations using this system may be artifactual. Seeding of cells in serum free media, blocking with bovine-serum albumin, and the use of the avidin derivative Neutravidin were all necessary for elimination of background adhesion. Neutravidin conjugated with biotinylated bsp-RGD(15) peptide provided the most robust cell adhesion, as well as the greatest increase in cell adhesion over background levels. PMID:23452388

  6. The Effect of Single-Session Interpretation Modification on Attention Bias in Socially Anxious Individuals

    PubMed Central

    Amir, Nader; Bomyea, Jessica; Beard, Courtney

    2009-01-01

    Research suggests that individuals with social anxiety interpret ambiguous social information negatively (e.g., Amir, Foa, & Coles, 1998) and that much negative interpretation bias may share a common mechanism with other information processing biases (e.g., Mathews, Mackintosh, & Fulcher, 1997). In the current study, we examined effectiveness of an interpretation modification program in changing attention biases in socially anxious individuals. Participants were randomly assigned to either an Interpretation Modification Program (IMP) that guided them to make benign interpretations of ambiguous social scenarios or an Interpretation Control Condition (ICC) that did not guide participants' interpretation in either direction. Results revealed that individuals in the IMP group demonstrated greater ability to disengage attention from threat stimuli after completing the program, while individuals in the ICC did not. These results are consistent with the hypothesis that information processing biases in anxious individuals may share a common mechanism that may contribute to the maintenance of anxiety. PMID:19926442

  7. Does attention redirection contribute to the effectiveness of attention bias modification on social anxiety?

    PubMed

    Yao, Nisha; Yu, Hongyu; Qian, Mingyi; Li, Songwei

    2015-12-01

    Attention bias modification (ABM) is designed to modify threat-related attention bias and thus alleviate anxiety. The current research examined whether consistently directing attention towards targeted goals per se contributes to ABM efficacy. We randomly assigned 68 non-clinical college students with elevated social anxiety to non-valence-specific attend-to-geometrics (AGC), attention modification (AMC), or attention control (ACC) conditions. We assessed subjective, behavioral, and physiological reactivity to a speech task and self-reported social anxiety symptoms. After training, participants in the AMC exhibited an attention avoidance from threat, and those in the AGC responded more rapidly toward targeted geometrics. There was a significant pre- to post-reduction in subjective speech distress across groups, but behavioral and physiological reactivity to speech, as well as self-report social anxiety symptoms, remained unchanged. These results lead to questions concerning effectiveness of ABM training for reducing social anxiety. Further examination of the current ABM protocol is required.

  8. Effects of tooth profile modification on dynamic responses of a high speed gear-rotor-bearing system

    NASA Astrophysics Data System (ADS)

    Hu, Zehua; Tang, Jinyuan; Zhong, Jue; Chen, Siyu; Yan, Haiyan

    2016-08-01

    A finite element node dynamic model of a high speed gear-rotor-bearing system considering the time-varying mesh stiffness, backlash, gyroscopic effect and transmission error excitation is developed. Different tooth profile modifications are introduced into the gear pair and corresponding time-varying mesh stiffness curves are obtained. Effects of the tooth profile modification on mesh stiffness are analyzed, and the natural frequencies and mode shapes of the gear-rotor-bearing transmission system are given. The dynamic responses with respect to a wide input speed region including dynamic factor, vibration amplitude near the bearing and dynamic transmission error are obtained by introducing the time-varying mesh stiffness in different tooth profile modification cases into the gear-rotor-bearing dynamic system. Effects of the tooth profile modification on the dynamic responses are studied in detail. The numerical simulation results show that both the short profile modification and the long profile modification can affect the mutation of the mesh stiffness when the number of engaging tooth pairs changes. A short profile modification with an appropriate modification amount can improve the dynamic property of the system in certain work condition.

  9. Structual Effects of Cytidine 2^' Ribose Modifications as Determined by Irmpd Action Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hamlow, Lucas; He, Chenchen; Fan, Lin; Wu, Ranran; Yang, Bo; Rodgers, M. T.; Berden, Giel; Oomens, J.

    2015-06-01

    Modified nucleosides, both naturally occurring and synthetic play an important role in understanding and manipulating RNA and DNA. Naturally occurring modified nucleosides are commonly found in functionally important regions of RNA and also affect antibiotic resistance or sensitivity. Synthetic modifications of nucleosides such as fluorinated and arabinosyl nucleosides have found uses as anti-virals and chemotherapy agents. Understanding the effect that modifications have on structure and glycosidic bond stability may lend insight into the functions of these modified nucleosides. Modifications such as the naturally occurring 2^'-O-methylation and the synthetic 2^'-fluorination are believed to help stabilize the nucleoside through the glycosidic bond stability and intramolecular hydrogen bonding. Changing the sugar from ribose to arabinose alters the stereochemistry at the 2^' position and thus shifts the 3D orientation of the 2^'-hydroxyl group, which also affects intramolecular hydrogen bonding and glycosidic bond stability. The structures of 2^'-deoxy-2^'-fluorocytidine, 2^'-O-methylcytidine and cytosine arabinoside are examined in the current work by measuring the infrared spectra in the IR fingerprint region using infrared multiple photon dissociation (IRMPD) action spectroscopy. The structures accessed in the experiments were determined via comparison of the measured IRMPD action spectra to the theoretical linear IR spectra determined by density functional theory and molecular modeling for the stable low-energy structures. Although glycosidic bond stability cannot be quantitatively determined from this data, complementary TCID studies will establish the effect of these modifications. Comparison of these modified nucleosides with their RNA and DNA analogues will help elucidate differences in their intrinsic chemistry.

  10. Surface Properties of Fluorosilicone Copolymers and Their Surface Modification Effects on PVC Film.

    PubMed

    Kim; Lee; Doh

    1998-09-15

    The fluorosilicone copolymers were synthesized using a fluorine-containing monomer and silicone-containing monomers by free-radical random copolymerization, and their surface properties and surface modification ability were investigated. The fluorine-containing monomer used was perfluoroalkyl ethyl acrylate (FA), and the silicone-containing monomers used were 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate (SiMA), vinyltrimethoxy silane (VTMS), and vinyltriethoxy silane (VTES). The surface free energies of the fluorosilicone copolymers prepared were estimated from the contact angle data measured by sessile-drop method. And, the surface free energies of poly(vinyl chloride) (PVC) films modified by the fluorosilicone copolymers were also analyzed using the contact angle data. The fluorosilicone copolymers exhibit the surface free energies of about 8-23 dyn/cm dependent on the molecular weight of the fluorosilicone copolymers. The surface free energies of the fluorosilicone copolymers decrease with increasing molecular weight in the range of 2,000-10,000 (Mw). Among the fluorosilicone copolymers prepared in this study, PFA-r-PSiMA was found to be the most effective as a surface modification agent for PVC film. The inherent surface free energy of PFA-r-PSiMA was estimated to be about 9.0 dyn/cm. The desirable molecular weight of PFA-r-PSiMA seems to be more than 4,000 (Mw). However, it is expected that the fluorosilicone copolymers having the molecular weight of much higher than 10,000 (Mw) may not be suitable as surface modification additives because their compatibility with other polymers will decrease with the molecular weight. The optimum concentration of PFA-r-PSiMA added to PVC film is about 1.0 wt.%. PFA-r-PSiMA is expectedto be an effective additive for surface modification of PVC films. Copyright 1998 Academic Press.

  11. Counselor Confounds in Evaluations of Vocational Rehabilitation Methods in Substance Dependency Treatment

    ERIC Educational Resources Information Center

    Staines, Graham L.; Cleland, Charles M.; Blankertz, Laura

    2006-01-01

    Evaluation research on vocational counseling in substance dependency treatment should distinguish between the effects of counselors and counseling methods on clients' employment outcomes. Three experimental designs permit investigation of possible confounds between these types of effects: (a) nested designs (each counselor delivers one counseling…

  12. Adjusting for Confounding Factors in Quasi-Experiments: Another Reanalysis of the Westinghouse Head Start Evaluation.

    ERIC Educational Resources Information Center

    Magidson, Jay; Sorbom, Dag

    Evaluations of social programs based upon quasi-experimental designs are typically plagued by problems of nonequivalence between the experimental and comparison group prior to the experiment. In such settings it is extremely difficult, if not impossible, to isolate the effects of the program from the confounding effects associated with the…

  13. Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

    PubMed

    Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

    2016-06-01

    Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

  14. The impact of cold spells on mortality and effect modification by cold spell characteristics

    PubMed Central

    Wang, Lijun; Liu, Tao; Hu, Mengjue; Zeng, Weilin; Zhang, Yonghui; Rutherford, Shannon; Lin, Hualiang; Xiao, Jianpeng; Yin, Peng; Liu, Jiangmei; Chu, Cordia; Tong, Shilu; Ma, Wenjun; Zhou, Maigeng

    2016-01-01

    In China, the health impact of cold weather has received little attention, which limits our understanding of the health impacts of climate change. We collected daily mortality and meteorological data in 66 communities across China from 2006 to 2011. Within each community, we estimated the effect of cold spell exposure on mortality using a Distributed Lag Nonlinear Model (DLNM). We also examined the modification effect of cold spell characteristics (intensity, duration, and timing) and individual-specific factors (causes of death, age, gender and education). Meta-analysis method was finally used to estimate the overall effects. The overall cumulative excess risk (CER) of non-accidental mortality during cold spell days was 28.2% (95% CI: 21.4%, 35.3%) compared with non-cold spell days. There was a significant increase in mortality when the cold spell duration and intensity increased or occurred earlier in the season. Cold spell effects and effect modification by cold spell characteristics were more pronounced in south China. The elderly, people with low education level and those with respiratory diseases were generally more vulnerable to cold spells. Cold spells statistically significantly increase mortality risk in China, with greater effects in southern China. This effect is modified by cold spell characteristics and individual-level factors. PMID:27922084

  15. The impact of cold spells on mortality and effect modification by cold spell characteristics

    NASA Astrophysics Data System (ADS)

    Wang, Lijun; Liu, Tao; Hu, Mengjue; Zeng, Weilin; Zhang, Yonghui; Rutherford, Shannon; Lin, Hualiang; Xiao, Jianpeng; Yin, Peng; Liu, Jiangmei; Chu, Cordia; Tong, Shilu; Ma, Wenjun; Zhou, Maigeng

    2016-12-01

    In China, the health impact of cold weather has received little attention, which limits our understanding of the health impacts of climate change. We collected daily mortality and meteorological data in 66 communities across China from 2006 to 2011. Within each community, we estimated the effect of cold spell exposure on mortality using a Distributed Lag Nonlinear Model (DLNM). We also examined the modification effect of cold spell characteristics (intensity, duration, and timing) and individual-specific factors (causes of death, age, gender and education). Meta-analysis method was finally used to estimate the overall effects. The overall cumulative excess risk (CER) of non-accidental mortality during cold spell days was 28.2% (95% CI: 21.4%, 35.3%) compared with non-cold spell days. There was a significant increase in mortality when the cold spell duration and intensity increased or occurred earlier in the season. Cold spell effects and effect modification by cold spell characteristics were more pronounced in south China. The elderly, people with low education level and those with respiratory diseases were generally more vulnerable to cold spells. Cold spells statistically significantly increase mortality risk in China, with greater effects in southern China. This effect is modified by cold spell characteristics and individual-level factors.

  16. The impact of cold spells on mortality and effect modification by cold spell characteristics.

    PubMed

    Wang, Lijun; Liu, Tao; Hu, Mengjue; Zeng, Weilin; Zhang, Yonghui; Rutherford, Shannon; Lin, Hualiang; Xiao, Jianpeng; Yin, Peng; Liu, Jiangmei; Chu, Cordia; Tong, Shilu; Ma, Wenjun; Zhou, Maigeng

    2016-12-06

    In China, the health impact of cold weather has received little attention, which limits our understanding of the health impacts of climate change. We collected daily mortality and meteorological data in 66 communities across China from 2006 to 2011. Within each community, we estimated the effect of cold spell exposure on mortality using a Distributed Lag Nonlinear Model (DLNM). We also examined the modification effect of cold spell characteristics (intensity, duration, and timing) and individual-specific factors (causes of death, age, gender and education). Meta-analysis method was finally used to estimate the overall effects. The overall cumulative excess risk (CER) of non-accidental mortality during cold spell days was 28.2% (95% CI: 21.4%, 35.3%) compared with non-cold spell days. There was a significant increase in mortality when the cold spell duration and intensity increased or occurred earlier in the season. Cold spell effects and effect modification by cold spell characteristics were more pronounced in south China. The elderly, people with low education level and those with respiratory diseases were generally more vulnerable to cold spells. Cold spells statistically significantly increase mortality risk in China, with greater effects in southern China. This effect is modified by cold spell characteristics and individual-level factors.

  17. Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics.

    PubMed

    Ananth, Cande V; Schisterman, Enrique F

    2017-08-01

    Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. "Toward a clearer definition of confounding" revisited with directed acyclic graphs.

    PubMed

    Howards, Penelope P; Schisterman, Enrique F; Poole, Charles; Kaufman, Jay S; Weinberg, Clarice R

    2012-09-15

    In a 1993 paper (Am J Epidemiol. 1993;137(1):1-8), Weinberg considered whether a variable that is associated with the outcome and is affected by exposure but is not an intermediate variable between exposure and outcome should be considered a confounder in etiologic studies. As an example, she examined the common practice of adjusting for history of spontaneous abortion when estimating the effect of an exposure on the risk of spontaneous abortion. She showed algebraically that such an adjustment could substantially bias the results even though history of spontaneous abortion would meet some definitions of a confounder. Directed acyclic graphs (DAGs) were introduced into epidemiology several years later as a tool with which to identify confounders. The authors now revisit Weinberg's paper using DAGs to represent scenarios that arise from her original assumptions. DAG theory is consistent with Weinberg's finding that adjusting for history of spontaneous abortion introduces bias in her original scenario. In the authors' examples, treating history of spontaneous abortion as a confounder introduces bias if it is a descendant of the exposure and is associated with the outcome conditional on exposure or is a child of a collider on a relevant undirected path. Thoughtful DAG analyses require clear research questions but are easily modified for examining different causal assumptions that may affect confounder assessment.

  19. Effect of meson cloud on the jet nuclear modification factor in pA collisions

    NASA Astrophysics Data System (ADS)

    Zakharov, B. G.

    2017-02-01

    We study the effect of the nucleon meson cloud on centrality dependence of the jet nuclear modification factor R pA . We find that the meson-baryon Fock components may lead to a noticeable deviation of R pA from unity. Our results for R pA show the same tendency as that observed by ATLAS in p + Pb collisions at √s = 5.02 TeV. The meson cloud suppresses the central jet events and enhances the peripheral jet events. But quantitatively the effect is somewhat smaller than in the data.

  20. [Effect of platelet CD42a modification by mPEG-SPA with different molecular masses].

    PubMed

    Zhang, Yin-ze; Xiong, Wen; Li, Zhen; Shao, Chao-peng; Li, Tian-jun; Zhao, Feng; Yang, Bao-cheng

    2007-03-01

    To observe the effect platelet antigen modification by mPEG-SPA with different molecular masses. Platelet CD42a was modified by 5 kD and 20 kD mPEG-SPA, respectively, and the fluorescence intensity of CD42a was detect by flow cytometry and the three-dimensional structure of CD42a simulated to analyze the distribution of lysine in CD42a molecule. After platelet CD42a modification by 5 kD and 20 kD mPEG-SPA, the fluorescence intensity of CD42a decreased sharply by 85.54% and 88.65%, respectively, and multiple lysine regions were identified on the surface of CD42a molecule. Both 5 kD and 20 kD mPEG-SPA allow useful modification of platelet CD42a, but 20 kD mPEG-SPA is more advantageous than 5 kD mPEG-SPA.

  1. Effect of lysine modification on the stability and cellular binding of human amyloidogenic light chains.

    PubMed

    Davern, S; Murphy, C L; O'Neill, H; Wall, J S; Weiss, D T; Solomon, A

    2011-01-01

    AL amyloidosis is characterized by the pathologic deposition as fibrils of monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs and tissues. This phenomenon has been attributed to the presence in amyloidogenic proteins of particular amino acids that cause these molecules to become unstable, as well as post-translational modifications and, in regard to the latter, we have investigated the effect of biotinylation of lysyl residues on cell binding. We utilized an experimental system designed to test if BJPs obtained from patients with AL amyloidosis or, as a control, multiple myeloma (MM), bound human fibroblasts and renal epithelial cells. As documented by fluorescence microscopy and ELISA, the amyloidogenic BJPs, as compared with MM components, bound preferentially and this reactivity increased significantly after chemical modification of their lysyl residues with sulfo-NHS-biotin. Further, based on tryptophan fluorescence and circular dichroism data, it was apparent that their conformation was altered, which we hypothesize exposed a binding site not accessible on the native protein. The results of our studies indicate that post-translational structural modifications of pathologic light chains can enhance their capacity for cellular interaction and thus may contribute to the pathogenesis of AL amyloidosis and multiple myeloma.

  2. Effect of surface modifications on the thermal and moisture behavior of wool fabric

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Zhao, Yuan; Li, Wenbin; Wang, Hao

    2015-07-01

    Thermal and moisture behavior is crucial in determining the comfort of clothing. Surface modification of fibers brings new functions and properties to fibrous materials, but the comfort of the as-made clothing changes accordingly due to different thermal and moisture behaviors. In this study, physical and chemical modifications have been conducted to wool fabric to investigate their effects on the thermal and moisture behaviors of clothing. Surface wettability, wicking properties, thermal and moisture resistance together with surface temperature and humidity of the microclimate have been tested. It has been found that the wettability of wool fabric is greatly improved and wicking properties are granted to the fabric. Higher thermal and moisture resistance have been noticed for the treated wool fabric. The treated fabric shows longer moisture liberation process and the surface temperature and humidity varies in a different way compared with untreated fabric. Understanding the thermal and moisture behaviors of fabric after surface modification would benefit the further development of surface functionalizing technology and design of next to skin clothing.

  3. The effect of hypusine modification on the intracellular localization of eIF5A

    SciTech Connect

    Lee, Seung Bum; Park, Jong Hwan; Kaevel, Joern; Sramkova, Monika; Weigert, Roberto; Park, Myung Hee

    2009-06-12

    Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential for eukaryotic cell proliferation and is the only protein containing hypusine, [N{sup {epsilon}}-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine. eIF5A also undergoes an acetylation at specific Lys residue(s). In this study, we have investigated the effect of hypusine modification and acetylation on the subcellular localization of eIF5A. Immunocytochemical analyses showed differences in the distribution of non-hypusinated eIF5A precursor and the hypusine-containing mature eIF5A. While the precursor is found in both cytoplasm and nucleus, the hypusinated eIF5A is primarily localized in cytoplasm. eIF5A mutant proteins, defective in hypusine modification (K50A, K50R) were localized in a similar manner to the eIF5A precursor, whereas hypusine-modified mutant proteins (K47A, K47R, K68A) were localized mainly in the cytoplasm. These findings provide strong evidence that the hypusine modification of eIF5A dictates its localization in the cytoplasmic compartment where it is required for protein synthesis.

  4. Effect of Lysine Modification on the Stability and Cellular Binding of Human Amyloidogenic Light Chains

    SciTech Connect

    O'Neill, Hugh Michael; Davern, Sandra M.; Murphy, Charles L.; Wall, Jonathan; Deborah, Weiss T.; Solomon, Alan

    2011-01-01

    AL amyloidosis is characterized by the pathologic deposition as fibrils of monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs and tissues. This phenomenon has been attributed to the presence in amyloidogenic proteins of particular amino acids that cause these molecules to become unstable, as well as post-translational modifications and, in regard to the latter, we have investigated the effect of biotinylation of lysyl residues on cell binding. We utilized an experimental system designed to test if BJPs obtained from patients with AL amyloidosis or, as a control, multiple myeloma (MM), bound human fibroblasts and renal epithelial cells. As documented by fluorescent microscopy and ELISA, the amyloidogenic BJPs, as compared with MM components, bound preferentially and this reactivity increased significantly after chemical modification of their lysyl residues with sulfo-NHS-biotin. Further, based on tryptophan fluorescence and circular dichorism data, it was apparent that their conformation was altered, which we hypothesize exposed a binding site not accessible on the native protein. The results of our studies indicate that post-translational structural modifications of pathologic light chains can enhance their capacity for cellular interaction and thus may contribute to the pathogenesis of AL amyloidosis and multiple myeloma.

  5. Effect of 4-Hydroxy-2-Nonenal Modification on Alpha-Synuclein Aggregation

    SciTech Connect

    Qin, Z.; Hu, D.; Han, S.; Reaney, S.H.; Monte, D.A.Di; Fink, A.L.

    2007-07-12

    Several observations have implicated oxidative stress and aggregation of the presynaptic protein alpha-synuclein in the pathogenesis of PD. alpha-Synuclein has been shown to have affinity for unsaturated fatty acids and membranes enriched in PUFAs, which are especially sensitive to oxidation under conditions of oxidative stress. One of the most important products of lipid oxidation is 4-hydroxynonenal (HNE), which has been implicated in the pathogenesis of Parkinson's disease. Consequently we investigated the effects of the interaction of HNE with alpha-synuclein. Incubation of HNE with alpha-synuclein at pH 7.4, 37oC resulted in covalent modification of the protein, with up to six HNE molecules incorporated as Michael addition products. FTIR and CD spectra indicated that HNE modification of alpha-synuclein resulted in a major conformational change involving increased beta-sheet. HNE modification of alpha-synuclein led to inhibition of fibrillation in an HNE-concentration-dependent manner. This inhibition of fibrillation was shown to be due to the formation of soluble oligomers based on SEC HPLC and AFM data. Small-angle X-ray scattering analysis indicated that the HNE-induced oligomers are compact and tightly packed. Treatment with guanidinium chloride (GuHCl) demonstrated that the HNE-induced oligomers were very stable with an extremely slow rate of dissociation. Addition of 5 uM HNE-modified oligomers to primary mesencephalic cultures caused marked neurotoxicity, since the integrity of dopaminergic and GABAergic neurons was reduced by 95% and 85%, respectively. Our observations indicate that HNE-modification of alpha-synuclein prevents fibrillation but may result in toxic oligomers which could therefore contribute to the demise of neurons subjected to oxidative damage.

  6. An education gradient in health, a health gradient in education, or a confounded gradient in both?

    PubMed

    Lynch, Jamie L; von Hippel, Paul T

    2016-04-01

    There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health.

  7. How can we enhance cognitive bias modification techniques? The effects of prospective cognition.

    PubMed

    Lee, Jong-Sun; Mathews, Andrew; Shergill, Sukhi; Chan, Daniel Ka Yiu; Majeed, Nadia; Yiend, Jenny

    2015-12-01

    Cognitive bias modification for interpretation, a computerized program which manipulates biased interpretations, has shown therapeutic promise, including evidence that negatively biased interpretations can be reduced, leading to corresponding improvements in symptoms. Cognitive bias modification for cognitive errors (CBM-errors) is a second generation CBM-I procedure which manipulates seven types of cognitive error and is especially relevant to depressive cognition. The aim of this study was to investigate whether the effects of the CBM-errors manipulation would be enhanced by adding a component facilitating prospective cognition to help embed and extend newly acquired interpretations. A sample of 80 volunteers completed a single session experiment. With a pretraining-posttraining design, we compared the effects of enhanced CBM-errors (targeting cognitive errors plus prospective cognition) with standard CBM-errors (targeting cognitive errors without prospective cognition), on interpretations of new material and mood. Significant differences between enhanced and standard CBM-errors revealed that enhanced positive training was more effective at decreasing negative interpretations compared to the standard procedure. Extending the current investigation to a sample dysphoria or depression is needed for an appropriate next step. The findings serve as 'a proof of principle' for the potential of prospective cognition to enhance the effects of CBM-errors and other similar CBM procedures. Further work to enhance the effectiveness of CBM procedures is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Effects of early cat or dog ownership on sensitisation and asthma in a high-risk cohort without disease-related modification of exposure.

    PubMed

    Almqvist, Catarina; Garden, Frances; Kemp, Andrew S; Li, Qiang; Crisafulli, Daniel; Tovey, Euan R; Xuan, Wei; Marks, Guy B

    2010-03-01

    Variation in the observed association between pet ownership and allergic disease may be attributable to selection bias and confounding. The aim of this study was to suggest a method to assess disease-related modification of exposure and second to examine how cat acquisition or dog ownership in early life affects atopy and asthma at 5 years. Information on sociodemographic factors and cat and dog ownership was collected longitudinally in an initially cat-free Australian birth cohort based on children with a family history of asthma. At age 5 years, 516 children were assessed for wheezing, and 488 for sensitisation. Data showed that by age 5 years, 82 children had acquired a cat. Early manifestations of allergic disease did not foreshadow a reduced rate of subsequent acquisition of a cat. Independent risk factors for acquiring a cat were exposure to tobacco smoke at home odds ratio (OR) 1.92 [95% confidence interval (CI) 1.13, 3.26], maternal education < or =12 years OR 1.95 [1.08, 3.51] and dog ownership OR 2.23 [1.23, 4.05]. Cat or dog exposure in the first 5 years was associated with a decreased risk of any allergen sensitisation, OR 0.50 [0.28, 0.88] but no association with wheeze OR 0.96 [0.57, 1.61]. This risk was not affected by age at which the cat was acquired or whether the pet was kept in- or outdoors. In conclusion, cat or dog ownership reduced the risk of subsequent atopy in this high-risk birth cohort. This cannot be explained by disease-related modification of exposure. Public health recommendations on the effect of cat and dog ownership should be based on birth cohort studies where possible selection bias has been taken into account.

  9. Controlling Time-Dependent Confounding by Health Status and Frailty: Restriction Versus Statistical Adjustment.

    PubMed

    McGrath, Leah J; Ellis, Alan R; Brookhart, M Alan

    2015-07-01

    Nonexperimental studies of preventive interventions are often biased because of the healthy-user effect and, in frail populations, because of confounding by functional status. Bias is evident when estimating influenza vaccine effectiveness, even after adjustment for claims-based indicators of illness. We explored bias reduction methods while estimating vaccine effectiveness in a cohort of adult hemodialysis patients. Using the United States Renal Data System and linked data from a commercial dialysis provider, we estimated vaccine effectiveness using a Cox proportional hazards marginal structural model of all-cause mortality before and during 3 influenza seasons in 2005/2006 through 2007/2008. To improve confounding control, we added frailty indicators to the model, measured time-varying confounders at different time intervals, and restricted the sample in multiple ways. Crude and baseline-adjusted marginal structural models remained strongly biased. Restricting to a healthier population removed some unmeasured confounding; however, this reduced the sample size, resulting in wide confidence intervals. We estimated an influenza vaccine effectiveness of 9% (hazard ratio = 0.91, 95% confidence interval: 0.72, 1.15) when bias was minimized through cohort restriction. In this study, the healthy-user bias could not be controlled through statistical adjustment; however, sample restriction reduced much of the bias.

  10. Side effects of the Yuzpe regimen of emergency contraception and two modifications.

    PubMed

    Shochet, Tara; Blanchard, Kelly; King, Helen; Henchcliffe, Bridget; Hunt, Janice; McCaig, Chris; Weaver, Kate; Stirling, Alex; Glasier, Anna; Webb, Anne; Ellertson, Charlotte

    2004-04-01

    We investigated side effects after the standard Yuzpe regimen or two modifications: substituting norethindrone as the progestin or eliminating the second dose. We also examined the impact of taking either dose with food. Nearly two thirds of women reported at least one side effect, the majority of which were mild or moderate. Women in our study experienced more side effects after the second dose than after the first. Taking the first dose within 1 h of a meal or snack was associated with increased nausea and vomiting; taking the second dose within 1 h of a meal or snack was associated with decreased nausea and vomiting. A targeted approach to prophylactic antiemetic use could reduce the number of women given these drugs, and the number who experience unnecessary side effects. The impact of counseling on side effects should be further evaluated.

  11. Position-dependent performance of copper phthalocyanine based field-effect transistors by gold nanoparticles modification.

    PubMed

    Luo, Xiao; Li, Yao; Lv, Wenli; Zhao, Feiyu; Sun, Lei; Peng, Yingquan; Wen, Zhanwei; Zhong, Junkang; Zhang, Jianping

    2015-01-21

    A facile fabrication and characteristics of copper phthalocyanine (CuPc)-based organic field-effect transistor (OFET) using the gold nanoparticles (Au NPs) modification is reported, thereby achieving highly improved performance. The effect of Au NPs located at three different positions, that is, at the SiO2/CuPc interface (device B), embedding in the middle of CuPc layer (device C), and on the top of CuPc layer (device D), is investigated, and the results show that device D has the best performance. Compared with the device without Au NPs (reference device A), device D displays an improvement of field-effect mobility (μ(sat)) from 1.65 × 10(-3) to 5.51 × 10(-3) cm(2) V(-1) s(-1), and threshold voltage decreases from -23.24 to -16.12 V. Therefore, a strategy for the performance improvement of the CuPc-based OFET with large field-effect mobility and saturation drain current is developed, on the basis of the concept of nanoscale Au modification. The model of an additional electron transport channel formation by FET operation at the Au NPs/CuPc interface is therefore proposed to explain the observed performance improvement. Optimum CuPc thickness is confirmed to be about 50 nm in the present study. The device-to-device uniformity and time stability are discussed for future application.

  12. Effect of arginine modification on kidney brush-border-membrane transport activity.

    PubMed

    Strevey, J; Brunette, M G; Béliveau, R

    1984-11-01

    The effect of phenylglyoxylation on brush-border-membrane functions was studied with membrane vesicles from rat kidney cortex. Na+-gradient-dependent uptake of phosphate, glucose and alanine was inhibited by 65, 88 and 70% by pre-incubation of vesicles with 50 mM-phenylglyoxal for 2 min. The inhibition showed a dependency for alkaline pH. Borate co-operativity in butanedione inactivation was used to prove that inhibition was caused by arginine modification. Intravesicular volumes, alkaline phosphatase, aminopeptidase M and Na+-H+ exchange were not affected by phenylglyoxal treatment. Inhibition of phosphate uptake was studied in more detail and showed that the chemical modification introduced by phenylglyoxal inhibited the overshoot of phosphate uptake caused by the Na+ gradient, and decreased the apparent maximal velocity of the phosphate-transport system in its interaction with Na+. Phosphate uptake measured in the absence of Na+ was not affected by phenylglyoxal. Shunting of the transmembrane electrical potential with K+ and valinomycin had no effect on phenylglyoxal inhibition, proving that the alteration of transmembrane electrical potential could not be responsible for this effect. Phenylglyoxal had no ionophoric effect on the Na+ gradients studied (1-100 mM). Na+ efflux was also unaffected by phenylglyoxal treatment. Na+, harmaline and amiloride were ineffective in protecting against phenylglyoxal inhibition, suggesting that the site modified was not an Na+-binding site. These results indicate the involvement of highly reactive arginine residues in phosphate, glucose and alanine uptake.

  13. Effect of arginine modification on kidney brush-border-membrane transport activity.

    PubMed Central

    Strevey, J; Brunette, M G; Béliveau, R

    1984-01-01

    The effect of phenylglyoxylation on brush-border-membrane functions was studied with membrane vesicles from rat kidney cortex. Na+-gradient-dependent uptake of phosphate, glucose and alanine was inhibited by 65, 88 and 70% by pre-incubation of vesicles with 50 mM-phenylglyoxal for 2 min. The inhibition showed a dependency for alkaline pH. Borate co-operativity in butanedione inactivation was used to prove that inhibition was caused by arginine modification. Intravesicular volumes, alkaline phosphatase, aminopeptidase M and Na+-H+ exchange were not affected by phenylglyoxal treatment. Inhibition of phosphate uptake was studied in more detail and showed that the chemical modification introduced by phenylglyoxal inhibited the overshoot of phosphate uptake caused by the Na+ gradient, and decreased the apparent maximal velocity of the phosphate-transport system in its interaction with Na+. Phosphate uptake measured in the absence of Na+ was not affected by phenylglyoxal. Shunting of the transmembrane electrical potential with K+ and valinomycin had no effect on phenylglyoxal inhibition, proving that the alteration of transmembrane electrical potential could not be responsible for this effect. Phenylglyoxal had no ionophoric effect on the Na+ gradients studied (1-100 mM). Na+ efflux was also unaffected by phenylglyoxal treatment. Na+, harmaline and amiloride were ineffective in protecting against phenylglyoxal inhibition, suggesting that the site modified was not an Na+-binding site. These results indicate the involvement of highly reactive arginine residues in phosphate, glucose and alanine uptake. PMID:6508741

  14. Heat Waves in the United States: Mortality Risk during Heat Waves and Effect Modification by Heat Wave Characteristics in 43 U.S. Communities

    PubMed Central

    Anderson, G. Brooke; Bell, Michelle L.

    2011-01-01

    Background Devastating health effects from recent heat waves, and projected increases in frequency, duration, and severity of heat waves from climate change, highlight the importance of understanding health consequences of heat waves. Objectives We analyzed mortality risk for heat waves in 43 U.S. cities (1987–2005) and investigated how effects relate to heat waves’ intensity, duration, or timing in season. Methods Heat waves were defined as ≥ 2 days with temperature ≥ 95th percentile for the community for 1 May through 30 September. Heat waves were characterized by their intensity, duration, and timing in season. Within each community, we estimated mortality risk during each heat wave compared with non-heat wave days, controlling for potential confounders. We combined individual heat wave effect estimates using Bayesian hierarchical modeling to generate overall effects at the community, regional, and national levels. We estimated how heat wave mortality effects were modified by heat wave characteristics (intensity, duration, timing in season). Results Nationally, mortality increased 3.74% [95% posterior interval (PI), 2.29–5.22%] during heat waves compared with non-heat wave days. Heat wave mortality risk increased 2.49% for every 1°F increase in heat wave intensity and 0.38% for every 1-day increase in heat wave duration. Mortality increased 5.04% (95% PI, 3.06–7.06%) during the first heat wave of the summer versus 2.65% (95% PI, 1.14–4.18%) during later heat waves, compared with non-heat wave days. Heat wave mortality impacts and effect modification by heat wave characteristics were more pronounced in the Northeast and Midwest compared with the South. Conclusions We found higher mortality risk from heat waves that were more intense or longer, or those occurring earlier in summer. These findings have implications for decision makers and researchers estimating health effects from climate change. PMID:21084239

  15. Soil modification by invasive plants: Effects on native and invasive species of mixed-grass prairies

    USGS Publications Warehouse

    Jordan, N.R.; Larson, D.L.; Huerd, S.C.

    2008-01-01

    Invasive plants are capable of modifying attributes of soil to facilitate further invasion by conspecifics and other invasive species. We assessed this capability in three important plant invaders of grasslands in the Great Plains region of North America: leafy spurge (Euphorbia esula), smooth brome (Bromus inermis) and crested wheatgrass (Agropyron cristatum). In a glasshouse, these three invasives or a group of native species were grown separately through three cycles of growth and soil conditioning in both steam-pasteurized and non-pasteurized soils, after which we assessed seedling growth in these soils. Two of the three invasive species, Bromus and Agropyron, exhibited significant self-facilitation via soil modification. Bromus and Agropyron also had significant facilitative effects on other invasives via soil modification, while Euphorbia had significant antagonistic effects on the other invasives. Both Agropyron and Euphorbia consistently suppressed growth of two of three native forbs, while three native grasses were generally less affected. Almost all intra- and interspecific effects of invasive soil conditioning were dependent upon presence of soil biota from field sites where these species were successful invaders. Overall, these results suggest that that invasive modification of soil microbiota can facilitate plant invasion directly or via 'cross-facilitation' of other invasive species, and moreover has potential to impede restoration of native communities after removal of an invasive species. However, certain native species that are relatively insensitive to altered soil biota (as we observed in the case of the forb Linum lewisii and the native grasses), may be valuable as 'nurse'species in restoration efforts. ?? 2007 Springer Science+Business Media B.V.

  16. Meta-analysis of the effects of lifestyle modifications on coronary and carotid atherosclerotic burden.

    PubMed

    Jhamnani, Sunny; Patel, Dhavalkumar; Heimlich, Layla; King, Fred; Walitt, Brian; Lindsay, Joseph

    2015-01-15

    Lifestyle modifications are the crux of atherosclerotic disease management. The goal of this study was to determine the effectiveness of diet and exercise in decreasing coronary and carotid atherosclerotic burden. Randomized controlled trials examining the effects of intensive lifestyle measures on atherosclerotic progression in coronary and carotid arteries as measured by baseline and follow-up quantitative coronary angiogram and ultrasonographic carotid intimal-medial thickness (CIMT), respectively, were included. Studies were excluded if the intervention additionally included a medication. MEDLINE, EMBASE, CINAHL, Cochrane Controlled Trials Registers, reports, and abstracts from major cardiology meetings were searched by 2 researchers independently and verified by the primary investigator. Standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated using random-effects model. Publication bias and heterogeneity were assessed. Fourteen trials were included. Seven used quantitative coronary angiogram, and 7 used CIMT; 1,343 lesions in 340 patients in the coronary group and 919 patients in the carotid group were analyzed. Overall, lifestyle modifications were associated with a decrease in coronary atherosclerotic burden in percent stenosis by -0.34 (95% CI -0.48 to -0.21) SMD, with no significant publication bias and heterogeneity (p = 0.21, I(2) = 28.25). Similarly, in the carotids, there was a decrease in the CIMT, in millimeter, by -0.21 (95% CI -0.36 to -0.05) SMD and by -0.13 (95% CI -0.25 to -0.02) SMD, before and after accounting for publication bias and heterogeneity (p = 0.13, I(2) = 39.91; p = 0.54, I(2) = 0), respectively. In conclusion, these results suggest that intensive lifestyle modifications are associated with a decrease in coronary and carotid atherosclerotic burden.

  17. A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

    PubMed Central

    Bramsen, Jesper B.; Pakula, Malgorzata M.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Odadzic, Dalibor; Smicius, Romualdas; Wengel, Suzy L.; Chattopadhyaya, Jyoti; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen

    2010-01-01

    Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low. PMID:20453030

  18. Estimating the effects of transcription factors binding and histone modifications on gene expression levels in human cells

    PubMed Central

    Zhang, Lu-Qiang; Li, Qian-Zhong

    2017-01-01

    Transcription factors and histone modifications are vital for the regulation of gene expression. Hence, to estimate the effects of transcription factors binding and histone modifications on gene expression, we construct a statistical model for the genome-wide 15 transcription factors binding data, 10 histone modifications profiles and DNase-I hypersensitivity data in three mammalian. Remarkably, our results show POLR2A and H3K36me3 can highly and consistently predict gene expression in three cell lines. And H3K4me3, H3K27me3 and H3K9ac are more reliable predictors than other histone modifications in human embryonic stem cells. Moreover, genome-wide statistical redundancies exist within and between transcription factors and histone modifications, and these phenomena may be caused by the regulation mechanism. In further study, we find that even though transcription factors and histone modifications offer similar effects on expression levels of genome-wide genes, the effects of transcription factors and histone modifications on predictive abilities are different for genes in independent biological processes. PMID:28454114

  19. Glycation of antibodies: Modification, methods and potential effects on biological functions.

    PubMed

    Wei, Bingchuan; Berning, Kelsey; Quan, Cynthia; Zhang, Yonghua Taylor

    2017-03-08

    Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

  20. Packet Randomized Experiments for Eliminating Classes of Confounders

    PubMed Central

    Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.

    2014-01-01

    Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088

  1. Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

    PubMed

    Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

    2016-01-01

    In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

  2. The Effects of Landscape Modifications on the Long-Term Persistence of Animal Populations

    PubMed Central

    Nabe-Nielsen, Jacob; Sibly, Richard M.; Forchhammer, Mads C.; Forbes, Valery E.; Topping, Christopher J.

    2010-01-01

    Background The effects of landscape modifications on the long-term persistence of wild animal populations is of crucial importance to wildlife managers and conservation biologists, but obtaining experimental evidence using real landscapes is usually impossible. To circumvent this problem we used individual-based models (IBMs) of interacting animals in experimental modifications of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of four species with contrasting life-history characteristics: skylark (Alauda arvensis), vole (Microtus agrestis), a ground beetle (Bembidion lampros) and a linyphiid spider (Erigone atra). This allows us to quantify the population implications of experimental modifications of landscape configuration and composition. Methodology/Principal Findings Starting with a real agricultural landscape, we progressively reduced landscape complexity by (i) homogenizing habitat patch shapes, (ii) randomizing the locations of the patches, and (iii) randomizing the size of the patches. The first two steps increased landscape fragmentation. We assessed the effects of these manipulations on the long-term persistence of animal populations by measuring equilibrium population sizes and time to recovery after disturbance. Patch rearrangement and the presence of corridors had a large effect on the population dynamics of species whose local success depends on the surrounding terrain. Landscape modifications that reduced population sizes increased recovery times in the short-dispersing species, making small populations vulnerable to increasing disturbance. The species that were most strongly affected by large disturbances fluctuated little in population sizes in years when no perturbations took place. Significance Traditional approaches to the management and conservation of populations use either classical methods of population analysis, which fail to adequately account for the spatial configurations of landscapes

  3. Combating unmeasured confounding in cross-sectional studies: evaluating instrumental-variable and Heckman selection models.

    PubMed

    DeMaris, Alfred

    2014-09-01

    Unmeasured confounding is the principal threat to unbiased estimation of treatment "effects" (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular "treatment" category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006-2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being.

  4. Adjusting for unmeasured confounding due to either of two crossed factors with a logistic regression model.

    PubMed

    Li, Li; Brumback, Babette A; Weppelmann, Thomas A; Morris, J Glenn; Ali, Afsar

    2016-08-15

    Motivated by an investigation of the effect of surface water temperature on the presence of Vibrio cholerae in water samples collected from different fixed surface water monitoring sites in Haiti in different months, we investigated methods to adjust for unmeasured confounding due to either of the two crossed factors site and month. In the process, we extended previous methods that adjust for unmeasured confounding due to one nesting factor (such as site, which nests the water samples from different months) to the case of two crossed factors. First, we developed a conditional pseudolikelihood estimator that eliminates fixed effects for the levels of each of the crossed factors from the estimating equation. Using the theory of U-Statistics for independent but non-identically distributed vectors, we show that our estimator is consistent and asymptotically normal, but that its variance depends on the nuisance parameters and thus cannot be easily estimated. Consequently, we apply our estimator in conjunction with a permutation test, and we investigate use of the pigeonhole bootstrap and the jackknife for constructing confidence intervals. We also incorporate our estimator into a diagnostic test for a logistic mixed model with crossed random effects and no unmeasured confounding. For comparison, we investigate between-within models extended to two crossed factors. These generalized linear mixed models include covariate means for each level of each factor in order to adjust for the unmeasured confounding. We conduct simulation studies, and we apply the methods to the Haitian data. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Air Pollution and Autism Spectrum Disorders: Causal or Confounded?

    PubMed

    Weisskopf, Marc G; Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L

    2015-12-01

    In the last decade, several studies have examined the association between perinatal exposure to ambient air pollution and risk of autism spectrum disorder (ASD). These studies have largely been consistent, with associations seen with different aspects of air pollution, including hazardous air toxics, ozone, particulate, and traffic-related pollution. Confounding by socioeconomic status (SES) and place of residence are of particular concern, as these can be related to ASD case ascertainment and other potential causal risk factors for ASD. While all studies take steps to address this concern, residual confounding is difficult to rule out. Two recent studies of air pollution and ASD, however, present findings that strongly argue against residual confounding, especially for factors that do not vary over relatively short time intervals. These two studies, conducted in communities around the USA, found a specific association with air pollution exposure during the 3rd, but not the 1st, trimester, when both trimesters were modeled simultaneously. In this review, we discuss confounding possibilities and then explain-with the aid of directed acyclic graphs (DAGs)-why an association that is specific to a particular time window, when multiple exposure windows are simultaneously assessed, argues against residual confounding by (even unmeasured) non-time-varying factors. In addition, we discuss why examining ambient air pollution concentration as a proxy for personal exposure helps avoid confounding by personal behavior differences, and the implications of measurement error in using ambient concentrations as a proxy for personal exposures. Given the general consistency of findings across studies and the exposure-window-specific associations recently reported, the overall evidence for a causal association between air pollution and ASD is increasingly compelling.

  6. The effect of surface modification on fretting fatigue in Ti Alloy turbine components

    NASA Astrophysics Data System (ADS)

    Chakravarty, S.; Andrews, R. G.; Painaik, P. C.; Koul, A. K.

    1995-04-01

    Severe fretting damage has been observed on the pressure surfaces of fan and compressor blade dovetails/disks in an aerospace gas turbine engine. A study has been carried out to evaluate the effect of an ion implantation technique in combination with the presently used surface treatments, such as shot peening and coating, on the fretting fatigue life of titanium alloy gas turbine engine components. The results from fretting fatigue tests, residual stress measurements, and nanoindentation tests were used to quantitatively evaluate the effect of various surface treatments on the fretting fatigue life of the fan blade and disk materials. Results from microstructural characterization and analyses of elemental and phase distributions within the implanted region are used to understand the effect of ion implantation on the surface properties of the alloys. Finally, an attempt has been made to evaluate the potential for improving the fretting fatigue life of the engine components using various surface modification techniques.

  7. Anti-Zeno-effect recovery and Lamb-shift modification in modified vacuum

    SciTech Connect

    Wang Dawei; Wang Ligang; Li Zhenghong; Zhu Shiyao

    2009-10-15

    The influence of the modification of the free vacuum on the quantum Zeno and anti-Zeno effects, as well as the Lamb (energy) shift of a multilevel atom, is studied. A unitary transformation method has been used to include the counter-rotating terms and to obtain the ground state of the whole Hamiltonian. The anti-Zeno effect is recovered if the modified density of states (DOS) has a dip near the transition frequency. The modification of DOS by a dip or a peak will change the Lamb shift compared with that in the free vacuum. Together with our unitary transformation method, there are three different methods to obtain the change in the Lamb shift. Using our method we investigate the change in the Lamb shift and obtain a formula for the change, which is the same as obtained with the method of Louisell [Quantum Statistical Properties of Radiation (Wiley, New York, 1973)] but different from the method of Cohen-Tannoudji et al. [Atom-Photon Interactions: Basic Processes and Applications (Wiley, New York, 1992), pp. 317 and 417]. The correctness of the Lamb shift formulas obtained by the three methods can be easily testified experimentally.

  8. Effect Modification by Environmental Quality on the Association between Heatwaves and Mortality in Alabama, United States.

    PubMed

    Jian, Yun; Wu, Connor Y H; Gohlke, Julia M

    2017-09-28

    Background: Previous studies have shown that heatwaves are associated with increased mortality. However, it remains unclear whether the associations between heatwaves and mortality are modified by the environmental quality. Methods: We used the United States (US) Environmental Protection Agency's Environmental Quality Index (EQI) and its five domain indices (air, water, land, built, and sociodemographic) to represent the cumulative environmental quality. We applied a time-stratified case-crossover design to analyze the disparities in the association between heatwaves and non-accidental deaths (NAD) among counties with different environmental qualities, in metropolitan areas in Alabama (AL), United States. Results: We found significant associations between heatwaves and NAD and a significant effect modification of this relationship by EQI. There were higher odds ratios in counties with the worst cumulative environmental qualities compared to counties with the best cumulative environmental qualities. For example, the percent change in odds ratio (mean and (95% CI)) between heatwave days and non-heatwave days was -10.3% (-26.6, 9.6) in counties with an overall EQI of 1 (the best overall environment) and 13.2% (4.9, 22.2) in counties with an overall EQI of 3 (the worst overall environment). Among the five domains, air quality had the strongest effect modification on the association. Conclusion: Our findings provide evidence that the associations between heatwaves and NAD vary among areas with different environmental qualities. These findings suggest that integration of air quality and heatwave warning systems may provide greater protection to public health.

  9. Effect of surface modification on carbon fiber and its reinforced phenolic matrix composite

    NASA Astrophysics Data System (ADS)

    Yuan, Hua; Wang, Chengguo; Zhang, Shan; Lin, Xue

    2012-10-01

    In this work, polyacrylonitrile (PAN)-based carbon fiber were chemically modified with H2SO4, KClO3 and silane coupling agent (γ-aminopropyltriethoxysilane, APS), and carbon fiber reinforced phenolic matrix composites were prepared. The structural and surface characteristics of the carbon fiber were investigated by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), laser Raman scattering (LRS) and Fourier transform infrared spectroscopy (FTIR). Single fiber mechanical properties, specific surface area, composite impact properties and interfacial shear strength (ILSS) were researched to indicate the effects of surface modification on fibers and the interaction between modified fiber surface and phenolic matrix. The results showed that carbon fiber surface modification by oxidation and APS can strengthen fiber surface chemical activity and enlarge the fiber surface area as well as its roughness. When carbon fiber (CF) is oxidized treatment, the oxygen content as well as the O/C ratio will be obviously increased. Oxygen functional groups increase with oxidation time increasing. Carbon fiber treated with APS will make Csbnd Osbnd R content increase and Osbnd Cdbnd O content decrease due to surface reaction. Proper treatment of carbon fiber with acid and silane coupling agent prove an effective way to increase the interfacial adhesion and improve the mechanical and outdoor performance of the resulting fiber/resin composites.

  10. Bipolar transport in organic field-effect transistors: organic semiconductor blends versus contact modification

    NASA Astrophysics Data System (ADS)

    Opitz, Andreas; Kraus, Michael; Bronner, Markus; Wagner, Julia; Brütting, Wolfgang

    2008-07-01

    The achievement of bipolar transport is an important feature of organic semiconductors, both for a fundamental understanding of transport properties and for applications such as complementary electronic devices. We have investigated two routes towards organic field-effect transistors exhibiting bipolar transport characteristics. As a first step, ambipolar field-effect transistors are realized by mixtures of p-conducting copper-phthalocyanine (CuPc) and n-conducting buckminsterfullerene (C60). As a second step, bipolar transport in copper-phthalocyanine is achieved by a modification of the gate dielectric in combination with a controlled variation of the electrode materials used for carrier injection. The analysis involves the determination of charge-carrier mobilities and contact resistances by a single curve analysis and by the transfer length method. Comparison of both types of samples indicates that percolation is a crucial feature in mixtures of both materials to achieve ambipolar carrier flow, whereas in neat films of one single material suitable contact modification allows for bipolar charge-carrier transport. In the latter case, the obtained electron and hole mobilities differ by less than one order of magnitude.

  11. Longevity of attentional bias modification effects for food cues in overweight and obese individuals.

    PubMed

    Kemps, Eva; Tiggemann, Marika; Hollitt, Sarah

    2016-01-01

    Accumulating evidence shows that overweight individuals exhibit an attentional bias for food and that this bias can be modified. This study investigated the longevity of such modification effects. Using a dot probe paradigm, a community sample of overweight and obese women (N = 104) was trained to direct attention towards ('attend') or away from ('avoid') food pictures. Participants completed five weekly training sessions. Attentional bias was measured before and after training, at 24 h and one-week follow-up. To increase generalisability, at each of the post-training and follow-up assessments, participants were shown a mix of old and new food pictures. They also completed another implicit bias measure, i.e. a word stem task. Attentional bias for food increased in the 'attend' group and decreased in the 'avoid' group. These retraining effects were maintained at 24 h and one-week follow-up, and extended to new food pictures. Participants in the 'avoid' group also produced relatively fewer food words on the word stem task than those in the 'attend' group. Results are consistent with predictions of cognitive-motivational models that attentional biases are malleable. They further suggest that attentional bias modification, which targets the implicit processes that underlie the heightened food responsivity in overweight individuals, could help combat pathological (over)eating.

  12. Effects of oxidative modification on gel properties of isolated porcine myofibrillar protein by peroxyl radicals.

    PubMed

    Zhou, Feibai; Zhao, Mouming; Zhao, Haifeng; Sun, Weizheng; Cui, Chun

    2014-04-01

    AAPH-derived (2,2'-azobis (2-amidinopropane) dihydrochloride) peroxyl radicals were selected as representative free radicals of lipid peroxidation to investigate the effects of oxidative modifications on isolated porcine myofibrillar protein structures as well as their rheological and gelling properties. Incubation of myofibrillar protein with increasing concentrations of AAPH resulted in a gradual increase (p<0.05) in carbonyl content and SH→S-S conversion. Results from SDS-PAGE indicated that medium (~1 mM) and relatively high (>3 mM) concentrations of AAPH induced aggregation of myosin and denaturation of myosin, troponin and tropomyosin, respectively. These structural changes resulted in changes on gelation of myofibrillar protein. Low level protein oxidation (AAPH≤0.5 mM) had no remarkable effect (p>0.05) on the viscoelastic pattern of myofibrillar protein gelation. Moderate oxidative modification (AAPH~1mM) enhanced the water-holding capacity (WHC) and texture properties of gels, while further oxidation (AAPH>3mM) significantly reduced the gel quality.

  13. Contribution of covalent protein modification to the antiinflammatory effects of cyclopentenone prostaglandins.

    PubMed

    Pérez-Sala, Dolores; Cernuda-Morollón, Eva; Pineda-Molina, Estela; Cañada, F Javier

    2002-11-01

    Cyclopentenone prostaglandins, which are produced during inflammatory processes, may exert a negative feedback on inflammation. These reactive compounds may form covalent adducts with thiol groups in glutathione or in proteins. The transcription factor NF-kappaB is key for the expression of numerous proinflammatory genes. We have observed that treatment of mesangial cells with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) inhibits the cytokine-elicited DNA binding activity of NF-kappaB, both in intact cells and in isolated nuclear extracts, thus suggesting a direct effect on DNA binding. By using a biotinylated 15d-PGJ(2) derivative, we have observed that 15d-PGJ(2) forms an adduct with the p50 subunit of NF-kappaB, as shown by Western blot and detection with horseradish peroxidase-conjugated streptavidin. In contrast, a p50 construct that bears a mutation in the cysteine residue involved in DNA binding (Cys62Ser) and is not susceptible to inhibition by 15d-PGJ(2) does not incorporate biotinylated 15d-PGJ(2). The labeling of several polypeptides after incubation of cells with biotinylated 15d-PGJ(2) suggests that there may be multiple targets for modification by 15d-PGJ(2). We propose that the covalent modification of NF-kappaB (and potentially other proteins) by 15d-PGJ(2) may contribute to the antiinflammatory effects of this prostaglandin.

  14. Effects of modifications to the space shuttle entry guidance and control systems

    NASA Technical Reports Server (NTRS)

    Powell, R. W.; Stone, H. W.; Rowell, L. F.

    1976-01-01

    A nonlinear six degree of freedom entry simulation study was conducted to identify space shuttle guidance and control system software modifications which reduce the control system sensitivity to the guidance system sampling frequency. Several modifications which eliminated the control system sensitivity and associated control limit cycling were examined. The result of the modifications was a reduction in required reaction control system fuel.

  15. [Effect of chemical modification of lipase on the regulation of its lipolytic activity in reversed micelles].

    PubMed

    Pavlenko, I M; Kliachko, N L; Levashov, A V

    2005-01-01

    Hydrophilized and hydrophobized forms of the lipase from Mucor miehei were obtained by its chemical modification with cellobiose and N-hydroxysuccinimidyl palmitate with a modification degree of 4 in both cases. A comparative analysis of the regulation of the catalytic activities of the native and modified lipases was carried out in the system of reversed micelles of OT aerosol (AOT) in isooctane. The level of catalytic activity of all the lipase preparations in the micellar medium was found to be higher than that in aqueous solution. The chemical modification of lipase did not result in a change in the regulation of the oligomeric composition of the enzyme controlled by the degree of micelle hydration omega0 (micelle size). The kcat dependences on omega0 for each lipase preparation exhibit two maxima, corresponding to the functioning of lipase monomers and tetramers. The changes in the hydrophilic-lipophilic balance of the lipase surface significantly affect the character of the regulation of enzyme activity due to changes in the surfactant concentration (the number of micelles). The lipase hydrophobization results in a decrease in the enzyme activation effect with an increase in the AOT concentration in comparison with the native lipase. The lipase hydrophilization dramatically decreases the activity of lipase tetramer when the AOT concentration is increased. The catalytic activity of the monomer of hydrophilized lipase is practically independent of the AOT concentration. Kinetic data indicate a mixed type of activation of both oligomeric forms of the native and the hydrophobized lipase by AOT molecules and the noncompetitive type of the activation and AOT inhibition of the monomer and the tetramer of the hydrophilized lipase, respectively. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.

  16. Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

    PubMed Central

    DeMaris, Alfred

    2014-01-01

    Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

  17. On negative outcome control of unobserved confounding as a generalization of difference-in-differences

    PubMed Central

    Sofer, Tamar; Richardson, David B.; Colicino, Elena; Schwartz, Joel; Tchetgen Tchetgen, Eric J.

    2016-01-01

    The difference-in-differences (DID) approach is a well known strategy for estimating the effect of an exposure in the presence of unobserved confounding. The approach is most commonly used when pre-and post-exposure outcome measurements are available, and one can assume that the association of the unobserved confounder with the outcome is equal in the two exposure groups, and constant over time. Then, one recovers the treatment effect by regressing the change in outcome over time on the exposure. In this paper, we interpret the difference-in-differences as a negative outcome control (NOC) approach. We show that the pre-exposure outcome is a negative control outcome, as it cannot be influenced by the subsequent exposure, and it is affected by both observed and unobserved confounders of the exposure-outcome association of interest. The relation between DID and NOC provides simple conditions under which negative control outcomes can be used to detect and correct for confounding bias. However, for general negative control outcomes, the DID-like assumption may be overly restrictive and rarely credible, because it requires that both the outcome of interest and the control outcome are measured on the same scale. Thus, we present a scale-invariant generalization of the DID that may be used in broader NOC contexts. The proposed approach is demonstrated in simulations and on a Normative Aging Study data set, in which Body Mass Index is used for NOC of the relationship between air pollution and inflammatory outcomes. PMID:28239233

  18. The Influence of Age on the Effects of Lifestyle Modification and Metformin in Prevention of Diabetes

    PubMed Central

    Crandall, Jill; Schade, David; Ma, Yong; Fujimoto, Wilfred Y.; Barrett-Connor, Elizabeth; Fowler, Sarah; Dagogo-Jack, Sam; Andres, Reubin

    2007-01-01

    Background The incidence of type 2 diabetes increases with age. It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults. Methods The Diabetes Prevention Program (DPP) demonstrated that an intensive lifestyle intervention (ILS) or metformin could prevent or delay diabetes. A predefined secondary outcome of DPP was to determine if treatment effects varied by age. Results At baseline, participants aged 60–85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups. Diabetes incidence rates did not differ by age in the placebo group, but ILS was more effective with increasing age (6.3, 4.9, and 3.3 cases per 100 person-years, in the 25–44, 45–59, and 60–85 year age groups, respectively; ptrend = .007). Participants aged 60–85 years had the most weight loss and metabolic equivalent (MET)-hours of physical activity. The metformin group showed a trend toward higher diabetes incidence among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in the 25–44, 45–59, and 60–85 year age groups, respectively; ptrend = .07); and diabetes risk increased with age (hazard ratio [age 60–85 vs 25–44] 1.63, p .02), after adjusting for the greater weight loss in the 60–85 year age group. Conclusions Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity. The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion. A lifestyle modification program can be recommended for older individuals at high risk for type 2 diabetes. PMID:17077202

  19. A meta-analysis of the effect of cognitive bias modification on anxiety and depression.

    PubMed

    Hallion, Lauren S; Ruscio, Ayelet Meron

    2011-11-01

    Cognitive biases have been theorized to play a critical role in the onset and maintenance of anxiety and depression. Cognitive bias modification (CBM), an experimental paradigm that uses training to induce maladaptive or adaptive cognitive biases, was developed to test these causal models. Although CBM has generated considerable interest in the past decade, both as an experimental paradigm and as a form of treatment, there have been no quantitative reviews of the effect of CBM on anxiety and depression. This meta-analysis of 45 studies (2,591 participants) assessed the effect of CBM on cognitive biases and on anxiety and depression. CBM had a medium effect on biases (g = 0.49) that was stronger for interpretation (g = 0.81) than for attention (g = 0.29) biases. CBM further had a small effect on anxiety and depression (g = 0.13), although this effect was reliable only when symptoms were assessed after participants experienced a stressor (g = 0.23). When anxiety and depression were examined separately, CBM significantly modified anxiety but not depression. There was a nonsignificant trend toward a larger effect for studies including multiple training sessions. These findings are broadly consistent with cognitive theories of anxiety and depression that propose an interactive effect of cognitive biases and stressors on these symptoms. However, the small effect sizes observed here suggest that this effect may be more modest than previously believed.

  20. The impact of ambient fine particles on influenza transmission and the modification effects of temperature in China: A multi-city study.

    PubMed

    Chen, Gongbo; Zhang, Wenyi; Li, Shanshan; Zhang, Yongming; Williams, Gail; Huxley, Rachel; Ren, Hongyan; Cao, Wei; Guo, Yuming

    2017-01-01

    There is good evidence that air pollution is a risk factor for adverse respiratory and vascular health outcomes. However, data are limited as to whether ambient fine particles contribute to the transmission of influenza and if so, how the association is modified by weather conditions. We examined the relationship between ambient PM2.5 and influenza incidence at the national level in China and explored the associations at different temperatures. Daily data on concentrations of particulate matter with aerodynamic diameter<2.5μm (PM2.5) and influenza incidence counts were collected in 47 Chinese cities. A Poisson regression model was used to estimate the city-specific PM2.5-influenza association, after controlling for potential confounders. Then, a random-effect meta-analysis was used to pool the effects at national level. In addition, stratified analyses were performed to examine modification effects of ambient temperature. For single lag models, the highest effect of ambient PM2.5 on influenza incidence appeared at lag day 2, with relative risk (RR) of 1.015 (95% confidence interval (CI): 1.004, 1.025) associated with a 10μg/m(3) increase in PM2.5. For moving average lag models, the significant association was found at lag 2-3days, with RR of 1.020 (95% CI: 1.006, 1.034). The RR of influenza transmission associated with PM2.5 was higher for cold compared with hot days. Overall, 10.7% of incident influenza cases may result from exposure to ambient PM2.5. Ambient PM2.5 may increase the risk of exposure to influenza in China especially on cooler days. Control measures to reduce PM2.5 concentrations could potentially also be of benefit in lowering the risk of exposure and subsequent transmission of influenza in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Threshold of Embedded M Collider Bias and Confounding Bias

    ERIC Educational Resources Information Center

    Kelcey, Benjamin; Carlisle, Joanne

    2011-01-01

    Of particular import to this study, is collider bias originating from stratification on retreatment variables forming an embedded M or bowtie structural design. That is, rather than assume an M structural design which suggests that "X" is a collider but not a confounder, the authors adopt what they consider to be a more reasonable…

  2. HIV-1: the confounding variables of virus neutralization.

    PubMed

    Nara, Peter L; Lin, George

    2005-06-01

    The development of an effective vaccine against HIV-1 would be greatly facilitated by the ability to elicit potent, high affinity antibodies that are capable of broad neutralization, viral inactivation and protection against infection and/or disease. New insights into the structure and function of the HIV-1 envelope glycoprotein (Env) that mediates viral fusion and entry may ultimately lead to strategies successful in eliciting these protective antibody responses. Insights have been gained regarding HIV-1 Env attachment and receptor engagement, the fusion process and kinetics, and the structural/functional attributes of Env that allow humoral immune evasion. In addition, studies of a limited number of broadly neutralizing human monoclonal antibodies have shed some light as to how antibodies may penetrate the immune evading armor that HIV-1 has evolved. As the elusive goal of generating these types of antibodies emerge and are developed in the context of generating new candidate HIV-1 vaccines, a relevant in vitro measurement of neutralization by these types of antibodies becomes a complex task. This is in part due to a list of confounding variables which include: the physical and genomic nature (amino acid variation) of the infecting virion, the type of target cells, the concentration and clonality of the reactants, assay format and design, the affinity and kinetics of the reaction, receptors/coreceptors and attachment factors, and soluble host factors. This review will focus on the past, current, and future knowledge required to advance the field of HIV-1 humoral immunity as it impacts future HIV-1 vaccine development.

  3. Estimation of mutagenic effect and modifications of mitosis by silver nanoparticles.

    PubMed

    Prokhorova, I M; Kibrik, B S; Pavlov, A V; Pesnya, D S

    2013-12-01

    We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles (Allium test). Chromosome aberrations and laggings and micronuclei were simultaneously registered in the same sample. Mitotic and phase indexes were calculated. No mutagenic effects were detected after treatment with silver nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in a concentration of 50 mg/liter significantly increased the mitotic index. Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in mitotic index, but did not affect the ratio of phase indexes. Exposure to silver nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by modification of mitosis.

  4. Brownian dynamics simulation of the effect of histone modification on nucleosome structure

    NASA Astrophysics Data System (ADS)

    Li, Wei; Dou, Shuo-Xing; Xie, Ping; Wang, Peng-Ye

    2007-05-01

    Using Brownian dynamics we simulate the effect of histone modification, such as phosphorylation, acetylation, and methylation, on nucleosome structure by varying the interaction force between DNA and the histone octamer. The simulation shows that the structural stability of nucleosome is very sensitive to the interaction force, and the DNA unwrapping from the modified histone octamer usually occurs turn by turn. Furthermore, the effects of temperature and DNA break as well as the competition between modified and normal histone octamers are investigated, with the simulation results being in agreement with the experimental observation that phosphorylated nucleosomes near DNA breaks are more easily depleted. Though the simulation study may only give a coarse grained view of the DNA unwrapping process for the modified histone octamer, it may provide insight into the mechanism of DNA repair.

  5. Resistive memory for harsh electronics: immunity to surface effect and high corrosion resistance via surface modification.

    PubMed

    Huang, Teng-Han; Yang, Po-Kang; Lien, Der-Hsien; Kang, Chen-Fang; Tsai, Meng-Lin; Chueh, Yu-Lun; He, Jr-Hau

    2014-03-18

    The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics.

  6. Resistive Memory for Harsh Electronics: Immunity to Surface Effect and High Corrosion Resistance via Surface Modification

    NASA Astrophysics Data System (ADS)

    Huang, Teng-Han; Yang, Po-Kang; Lien, Der-Hsien; Kang, Chen-Fang; Tsai, Meng-Lin; Chueh, Yu-Lun; He-Hau, Jr.

    2014-03-01

    The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics.

  7. Resistive Memory for Harsh Electronics: Immunity to Surface Effect and High Corrosion Resistance via Surface Modification

    PubMed Central

    Huang, Teng-Han; Yang, Po-Kang; Lien, Der-Hsien; Kang, Chen-Fang; Tsai, Meng-Lin; Chueh, Yu-Lun; He, Jr-Hau

    2014-01-01

    The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics. PMID:24638086

  8. Temperature, temperature extremes, and mortality: a study of acclimatisation and effect modification in 50 US cities.

    PubMed

    Medina-Ramón, M; Schwartz, J

    2007-12-01

    The authors examined the increase in mortality associated with hot and cold temperature in different locations, the determinants of the variability in effect estimates, and its implications for adaptation. The authors conducted a case-crossover study in 50 US cities. They used daily mortality and weather data for 6 513 330 deaths occurring during 1989-2000. Exposure was assessed using two approaches. First, the authors determined exposure to extreme temperatures using city-specific indicator variables based on the local temperature distribution. Secondly, they used piecewise linear variables to assess exposure to temperature on a continuous scale above/below a threshold. Effects of hot and cold temperature were examined in season-specific models. In a meta-analysis of the city-specific results, the authors examined several city characteristics as effect modifiers. Mortality increases associated with both extreme cold (2-day cumulative increase 1.59% (95% CI 0.56 to 2.63)) and extreme heat (5.74% (95% CI 3.38 to 8.15)) were found, the former being especially marked for myocardial infarction and cardiac arrest deaths. The increase in mortality was less marked at less extreme temperatures. The effect of extreme cold (defined as a percentile) was homogeneous across cities with different climates, suggesting that only the unusualness of the cold temperature (and not its absolute value) had a substantial impact on mortality (that is, acclimatisation to cold). Conversely, heat effects were quite heterogeneous, with the largest effects observed in cities with milder summers, less air conditioning and higher population density. Adjustment for ozone led to similar results, but some residual confounding could be present due to other uncontrolled pollutants. The authors confirmed in a large sample of cities that both cold and hot temperatures increase mortality risk. These findings suggest that increases in heat-related mortality due to global warming are unlikely to be

  9. Temperature, temperature extremes, and mortality: a study of acclimatisation and effect modification in 50 US cities

    PubMed Central

    Medina-Ramón, M; Schwartz, J

    2007-01-01

    Objectives The authors examined the increase in mortality associated with hot and cold temperature in different locations, the determinants of the variability in effect estimates, and its implications for adaptation. Methods The authors conducted a case-crossover study in 50 US cities. They used daily mortality and weather data for 6 513 330 deaths occurring during 1989–2000. Exposure was assessed using two approaches. First, the authors determined exposure to extreme temperatures using city-specific indicator variables based on the local temperature distribution. Secondly, they used piecewise linear variables to assess exposure to temperature on a continuous scale above/below a threshold. Effects of hot and cold temperature were examined in season-specific models. In a meta-analysis of the city-specific results, the authors examined several city characteristics as effect modifiers. Results Mortality increases associated with both extreme cold (2-day cumulative increase 1.59% (95% CI 0.56 to 2.63)) and extreme heat (5.74% (95% CI 3.38 to 8.15)) were found, the former being especially marked for myocardial infarction and cardiac arrest deaths. The increase in mortality was less marked at less extreme temperatures. The effect of extreme cold (defined as a percentile) was homogeneous across cities with different climates, suggesting that only the unusualness of the cold temperature (and not its absolute value) had a substantial impact on mortality (that is, acclimatisation to cold). Conversely, heat effects were quite heterogeneous, with the largest effects observed in cities with milder summers, less air conditioning and higher population density. Adjustment for ozone led to similar results, but some residual confounding could be present due to other uncontrolled pollutants. Conclusions The authors confirmed in a large sample of cities that both cold and hot temperatures increase mortality risk. These findings suggest that increases in heat-related mortality

  10. Effect of silica gel modification with cyclofructans on properties of hydrophilic interaction liquid chromatography stationary phases.

    PubMed

    Kozlík, Petr; Símová, Veronika; Kalíková, Květa; Bosáková, Zuzana; Armstrong, Daniel W; Tesařová, Eva

    2012-09-28

    Hydrophilic interaction liquid chromatography (HILIC) offers very good possibilities for separation of polar compounds as an alternative to reversed phase HPLC where polar compounds are not sufficiently retained. HILIC is becoming more popular for the analysis of biologically interesting (active) analytes. Various stationary phases are commercially available however, development of new materials (sorbents) suitable for HILIC systems still continues. Silica gel columns can be used directly but their modification can improve separation ability of the stationary phases. Cyclofructan-based stationary phases are demonstrated as possible HILIC columns in this work. The effect of silica gel modification by cyclofructan and a derivatized cyclofructan was studied in detail. HILIC separation systems with silica gel, cyclofructan and isopropyl cyclofructan modified silica stationary phases were compared. The detailed study of chromatographic behavior of peptides revealed that multimodal retention mechanism is present in systems with these stationary phases. Mobile phase composition changes the types of interactions and their strengths. It appears that ability to donate protons and dispersion forces are the main interactions that affect retention in HILIC with cyclofructan-based columns while they are less important in separation systems with bare silica stationary phase. Suitability of cyclofructan-based stationary phases in HILIC for separation of pentapeptides and nonapeptides was demonstrated.

  11. Effect of carbon surface modification with dimethylamine on reactive adsorption of NO(x).

    PubMed

    Deliyanni, Eleni; Bandosz, Teresa J

    2011-03-01

    The wood-based activated carbon, either as received or oxidized with nitric acid, was exposed to dimethylamine vapors. This modification was expected to introduce nitrogen groups. Then, the modified samples were used as adsorbents of NO(2) under dynamic conditions. Both NO(2) breakthrough curves and the NO concentration curves were recorded. The samples before and after exposure to NO(2) were characterized using adsorption of nitrogen, elemental analysis, potentiometric titration, FTIR, and thermal analysis. Modifications with amines resulted in an increase in NO(2) adsorption and in a decrease in NO emission. The effects were more visible when oxidation was used as a pretreatment of the carbon surface. This process increased the incorporation of nitrogen to the carbon matrix via acid-based reactions resulting in the formation of amides and amine carboxylic salts. Besides this, dimethylamine was strongly adsorbed on the carbon surface via hydrogen bonding with oxygen-containing groups. When the samples were exposed to nitrogen dioxide, there was an indication that nitramine and nitrosoamine were formed in the reactions of NO(2) with either amides or amines. In the reactions of amines with NO, nitrosoamines are the likely products. As a next step, the surface of the carbon matrix is reoxidized by NO(2), which is accompanied by the release of NO.

  12. Effect of mycotoxin-containing diets on epigenetic modifications of mouse oocytes by fluorescence microscopy analysis.

    PubMed

    Zhu, Cheng-Cheng; Hou, Yan-Jun; Han, Jun; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    Mycotoxins, such as aflatoxin (AF), fumonisin B1, zearalenone (ZEA), and deoxynivalenol (DON), are commonly found in many food commodities. Mycotoxins have been shown to increase DNA methylation levels in a human intestinal cell line. We previously showed that the developmental competence of oocytes was affected in mice that had been fed a mycotoxin-containing diet. In this study, we explored possible mechanisms of low mouse oocyte developmental competence after mycotoxin treatment in an epigenetic modification perspective. Mycotoxin-contaminated maize (DON at 3,875 μg/kg, ZEA at 1,897 μg/kg, and AF at 806 μg/kg) was included in diets at three different doses (mass percentage: 0, 15, and 30%) and fed to mice for 4 weeks. The fluorescence intensity analysis showed that the general DNA methylation levels increased in oocytes from high dose mycotoxin-fed mice. Mouse oocyte histone methylation was also altered. H3K9me3 and H4K20me3 level increased in oocytes from mycotoxin-fed mice, whereas H3K27me3 and H4K20me2 level decreased in oocytes from mycotoxin-fed mice. Thus, our results indicate that naturally occurring mycotoxins have effects on epigenetic modifications in mouse oocytes, which may be one of the reasons for reduced oocyte developmental competence.

  13. Effect of different modifications of BEA-zeolites on operational characteristics of conductometric biosensor.

    PubMed

    Kucherenko, I S; Soldatkin, Capital O Cyrillic О; Soy, E; Kirdeciler, K; Öztürk, S; Akata, B; Jaffrezic-Renault, N; Soldatkin, A P; Dzyadevych, S V

    2012-08-01

    Effect of different modifications of zeolite Na(+)-BEA on working characteristics of urease-based conductometric biosensor was studied. As the biosensor sensitive elements were used bioselective membranes based on urease and various zeolites immobilised with bovine serum albumin on the surface of conductometric transducers. Influence of zeolites on sensitivity of urea biosensor was investigated as well as reproducibility of biosensor signal and reproducibility of activity of the bioselective element after different variants of urease immobilisation on the surface of conductometric transducer. The biosensors based on zeolites (NH4(+)-BEA 30 and H(+)-BEA 30) were shown to be the most sensitive. Concentration of these zeolites in the bioselective membrane was optimized. Use of zeolites modified with methyl viologen and silver was ascertained to be of no prospect for urea conductometric biosensors. It was demonstrated that characteristics of urea biosensors can be regulated, varying zeolites modifications and their concentrations in bioselective membranes. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Effect of Light on Chemical Modification of Chloroplast Ferredoxin-NADP Reductase 1

    PubMed Central

    Carrillo, Nestor; Lucero, Héctor A.; Vallejos, Rubén H.

    1980-01-01

    Chemical modification of spinach chloroplasts by phenylglyoxal and dansyl chloride resulted in inhibition of NADP photoreduction. The rate of inactivation was higher with both reagents when modification was carried out in the light with methylviologen or phenazine methosulfate present. Uncouplers prevent the effect of light. Electron transport from water to methylviologen was not affected by the modifiers. The presence of 10 millimolar NADP completely protected the membrane-bound reductase against inactivation by phenylglyoxal. With lower concentrations, protection was higher in the light than in the dark. The apparent dissociation constants of the enzyme-substrate complex for NADP were 0.9 and 0.1 millimolar for the dark and light inactivation, respectively. Inactivation of NADP photoreduction by dansyl chloride was completely prevented by ferredoxin, but only partially by nucleotides. The diaphorase activity was inhibited in chloroplasts modified by phenylglyoxal, but not when modified by dansyl chloride. The results suggest that energizing thylakoid membranes by light induces a conformational change in membrane-bound ferredoxin-NADP reductase, and that the reductase is an allotopic enzyme. PMID:16661221

  15. The catalytic activity of horse spleen apoferritin. Preliminary kinetic studies and the effect of chemical modification

    PubMed Central

    Bryce, Charles F. A.; Crichton, Robert R.

    1973-01-01

    1. Horse spleen apoferritin catalyses the oxidation of Fe2+ to Fe3+ with molecular O2 as electron acceptor under conditions where a number of other proteins have no such effect. The product is similar to ferritin by a number of criteria. 2. The progress curve is hyperbolic and the increase in initial velocity is linear with increasing apoferritin concentration. With respect to Fe2+ the reaction follows Michaelis–Menten kinetics. The pH-dependence of the reaction was determined between pH4.3 and 6.0. 3. Modification of both tryptophan residues/apoferritin subunit with 2-nitrophenylsulphenyl chloride does not affect either kcat. or Km for the oxidation. Neither does the guanidination of seven out of nine lysine residues/subunit, the modification of nine out of ten arginine residues/subunit with cyclohexanedione, or the nitration of one out of five tyrosine residues/subunit with tetranitromethane. 4. The carboxymethylation of two out of three cysteine residues/subunit and of one out of six histidine residues/subunit can be achieved with iodoacetic acid. This carboxymethylated apoferritin is completely inactive in Fe2+ oxidation. 5. Apoferritin does not take up Fe3+. It appears from these results that Fe2+ is the form in which iron is taken up by ferritin in a reaction where the protein acts as an enzyme which traps the product in the interior of the protein shell. ImagesPLATE 1PLATE 2 PMID:4737426

  16. Effect of plasma processing and organosilane modifications of polyethylene on Aeromonas hydrophila biofilm formation.

    PubMed

    Kregiel, Dorota; Niedzielska, Kamila

    2014-01-01

    The aim of our research was to study how the modifications of polyethylene--a material commonly used in medicine and water industry--influence bacterial cell attachment and biofilm formation. The native surface was activated and modified using two-step process consisting in the activation of native surface with a H2O vapor plasma followed by its treatment with various organosilanes, namely, [3(tertbutylamine-2hydroxy) propyloxypropyl] diethoxymethylsilane, 1H,1H,2H,2H-perfluorooctylmethyldimethoxysilane, dimethoxydimethylsilane, and isobutylmethyldimethoxysilane. The effect of polyethylene modification after chemical treatment was analyzed using surface tension measurement. The adhesive properties of Aeromonas hydrophila LOCK0968 were studied in water with a low concentration of organic compounds, using luminometric and microscopic methods, and the viability of the adhered bacterial cells was evaluated using the colony forming units method. After two-week incubation the chemically modified materials exhibited better antiadhesive and antibacterial characteristics in comparison to the native surface. Among the examined modifying agents, dimethoxydimethylsilane showed the best desired properties.

  17. Effect of surface chemical modification of bioceramic on phenotype of human bone-derived cells.

    PubMed

    Zreiqat, H; Evans, P; Howlett, C R

    1999-03-15

    In the search for methods to improve the biocompatibility of prosthetic materials, attention has recently been directed toward the potential use of surface chemical modification and its influence on cellular behavior. This in vitro study investigates the effect of surface chemistry modification of bioceramics on human bone-derived cells (HBDCs) grown on biomaterial surfaces for 2 weeks. Cells were cultured on either alumina (Al2O3), alumina doped with magnesium ions ([Mg]-Al2O3), or hydroxyapatite (HAP), as well as tissue culture polystyrene (TCPS). Expression of alkaline phosphatase (ALP), thrombospondin (Tsp), osteopontin (OP), osteocalcin (OC), osteonectin (ON/SPARC), type I collagen (Col I), and bone sialoprotein (BSP) were determined in terms of mRNAs and proteins. Protein levels for ALP, OP, OC, and BSP were significantly (p < 0. 05) greater at day 5 in HBDCs cultured on [Mg]-Al2O3 compared to those cells grown on Al2O3. At day 14 the levels of ALP, Tsp, Col I, OP, ON/SPARC, and BSP rose significantly (p < 0.05) above those occurring in HBDCs grown on Al2O3, HAP, and TCPS. This suggests that HBDCs from the same patient respond to differences in the surface chemical groups. This study confirms that the chemistry of a substratum, which facilitates cellular adhesion, will enhance cellular differentiation. Copyright 1999 John Wiley & Sons, Inc.

  18. Transient Response Dynamic Module Modifications to Include Static and Kinetic Friction Effects

    NASA Technical Reports Server (NTRS)

    Misel, J. E.; Nenno, S. B.; Takahashi, D.

    1984-01-01

    A methodology that supports forced transient response dynamic solutions when both static and kinetic friction effects are included in a structural system model is described. Modifications that support this type of nonlinear transient response solution are summarized for the transient response dynamics (TRD) NASTRAN module. An overview of specific modifications for the NASTRAN processing subroutines, INITL, TRD1C, and TRD1D, are described with further details regarding inspection of nonlinear input definitions to define the type of nonlinear solution required, along with additional initialization requirements and specific calculation subroutines to successfully solve the transient response problem. The extension of the basic NASTRAN nonlinear methodology is presented through several stages of development to the point where constraint equations and residual flexibility effects are introduced into the finite difference Newmark-Beta recurrsion formulas. Particular emphasis is placed on cost effective solutions for large finite element models such as the Space Shuttle with friction degrees of freedom between the orbiter and payloads mounted in the cargo bay. An alteration to the dynamic finite difference equations of motion is discussed, which allows one to include friction effects at reasonable cost for large structural systems such as the Space Shuttle. Data are presented to indicate the possible impact of transient friction loads to the payload designer for the Space Shuttle. Transient response solution data are also included, which compare solutions without friction forces and those with friction forces for payloads mounted in the Space Shuttle cargo bay. These data indicate that payload components can be sensitive to friction induced loads.

  19. Magnetic zenith effect in the ionospheric modification by an X-mode HF heater wave

    NASA Astrophysics Data System (ADS)

    Blagoveshchenskaya, N. F.; Borisova, T. D.; Haggstrom, I.; Rietveld, M. T.; Yeoman, T. K.

    2013-12-01

    We report experimental results aimed at an investigation of the magnetic zenith effect in the high latitude ionosphere F region from ionospheric modification by powerful HF heater wave with X-polarization. The ionospheric modification was produced by the HF heating facility at Tromsø (Norway) using the phased array with a narrow beam with of 6 degrees. Effective radiated power was varied between 450 and 1000 MW. The HF pump wave radiated in different directions relative to the magnetic field from 90 degrees (vertical) to 78 degrees (magnetic zenith) at frequencies near or above the ordinary-mode critical frequency. The response of the ionosphere plasma to the HF pump wave impact was checked by the UHF incoherent scatter radar located in the immediate vicinity of the HF heater. UHF radar was probing the plasma parameters, such as electron density and temperature (Ne and Te), HF-induced plasma and ion lines in the altitude range from 90 to 600 km. It was running in a scanning mode when UHF radar look angles were changed from 74 to 90 degrees by 1 or 2 degree step. It was clearly demonstrated that the strongest heater-induced effects took place in the magnetic field-aligned direction when HF pointing was also to the magnetic zenith. It was found that strong Ne enhancement of up to 80 % along magnetic field (artificial density ducts) were excited only under HF pumping towards magnetic zenith. The width of the artificial ducts comes to only 2 degrees. The Ne increases were accompanied by the Te enhancements of up to about 50 %. Less pronounced Te increases were also observed in the directions of 84 and 90 degrees. Strong Ne enhancements can be accompanied by excitation of strong HF-induced plasma and ion lines. Thus experimental results obtained points to the strong magnetic zenith effect due to self-focusing powerful HF radio wave with X-mode polarization.

  20. Efforts to adjust for confounding by neighborhood using complex survey data.

    PubMed

    Brumback, Babette A; Dailey, Amy B; He, Zhulin; Brumback, Lyndia C; Livingston, Melvin D

    2010-08-15

    In social epidemiology, one often considers neighborhood or contextual effects on health outcomes, in addition to effects of individual exposures. This paper is concerned with the estimation of an individual exposure effect in the presence of confounding by neighborhood effects, motivated by an analysis of National Health Interview Survey (NHIS) data. In the analysis, we operationalize neighborhood as the secondary sampling unit of the survey, which consists of small groups of neighboring census blocks. Thus the neighborhoods are sampled with unequal probabilities, as are individuals within neighborhoods. We develop and compare several approaches for the analysis of the effect of dichotomized individual-level education on the receipt of adequate mammography screening. In the analysis, neighborhood effects are likely to confound the individual effects, due to such factors as differential availability of health services and differential neighborhood culture. The approaches can be grouped into three broad classes: ordinary logistic regression for survey data, with either no effect or a fixed effect for each cluster; conditional logistic regression extended for survey data; and generalized linear mixed model (GLMM) regression for survey data. Standard use of GLMMs with small clusters fails to adjust for confounding by cluster (e.g. neighborhood); this motivated us to develop an adaptation. We use theory, simulation, and analyses of the NHIS data to compare and contrast all of these methods. One conclusion is that all of the methods perform poorly when the sampling bias is strong; more research and new methods are clearly needed.

  1. Adjusting for unmeasured confounding in nonrandomized longitudinal studies: a methodological review.

    PubMed

    Streeter, Adam J; Lin, Nan Xuan; Crathorne, Louise; Haasova, Marcela; Hyde, Christopher; Melzer, David; Henley, William E

    2017-07-01

    Motivated by recent calls to use electronic health records for research, we reviewed the application and development of methods for addressing the bias from unmeasured confounding in longitudinal data. Methodological review of existing literature. We searched MEDLINE and EMBASE for articles addressing the threat to causal inference from unmeasured confounding in nonrandomized longitudinal health data through quasi-experimental analysis. Among the 121 studies included for review, 84 used instrumental variable analysis (IVA), of which 36 used lagged or historical instruments. Difference-in-differences (DiD) and fixed effects (FE) models were found in 29 studies. Five of these combined IVA with DiD or FE to try to mitigate for time-dependent confounding. Other less frequently used methods included prior event rate ratio adjustment, regression discontinuity nested within pre-post studies, propensity score calibration, perturbation analysis, and negative control outcomes. Well-established econometric methods such as DiD and IVA are commonly used to address unmeasured confounding in nonrandomized longitudinal studies, but researchers often fail to take full advantage of available longitudinal information. A range of promising new methods have been developed, but further studies are needed to understand their relative performance in different contexts before they can be recommended for widespread use. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Comparison of antioxidative and chelating effects of daidzein and daidzin on protein oxidative modification by copper in vitro.

    PubMed

    Toda, S; Shirataki, Y

    2001-01-01

    Daidzein and its glycoside daidzin are isoflavones. Their antioxidative effects were compared in vitro. Although both compounds inhibited protein oxidative modification by copper, the inhibitory effect of daidzein was stronger than that of daidzin. Because daidzein showed a greater affinity for Cu2+, the antioxidant effect of these isoflavones may be dependent on their respective copper-chelating abilities.

  3. Effects of energetic particle phase space modifications by instabilities on integrated modeling

    NASA Astrophysics Data System (ADS)

    Podestà, M.; Gorelenkova, M.; Fredrickson, E. D.; Gorelenkov, N. N.; White, R. B.

    2016-11-01

    Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effective tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.

  4. Effects of energetic particle phase space modifications by instabilities on integrated modeling

    SciTech Connect

    Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.; Gorelenkov, N. N.; White, R. B.

    2016-07-22

    Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effective tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Furthermore, those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.

  5. Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor.

    PubMed

    Oesterlin, Lena K; Goody, Roger S; Itzen, Aymelt

    2012-04-10

    Intracellular vesicular trafficking is regulated by approximately 60 members of the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle between inactive and active states as well as between cytosolic and membrane bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is mediated by interaction with the protein GDP dissociation inhibitor (GDI) that binds to prenylated inactive (GDP-bound) Rab proteins. Because the Rab:GDP:GDI complex is of high affinity, the question arises of how GDI can be displaced efficiently from Rab protein in order to allow the necessary recruitment of the Rab to its specific target membrane. While there is strong evidence that DrrA, as a bacterially encoded GDP/GTP exchange factor, contributes to this event, we show here that posttranslational modifications of Rabs can also modulate the affinity for GDI and thus cause effective displacement of GDI from Rab:GDI complexes. These activities have been found associated with the phosphocholination and adenylylation activities of the enzymes AnkX and DrrA/SidM, respectively, from the pathogenic bacterium Legionella pneumophila. Both modifications occur after spontaneous dissociation of Rab:GDI complexes within their natural equilibrium. Therefore, the effective GDI displacement that is observed is caused by inhibition of reformation of Rab:GDI complexes. Interestingly, in contrast to adenylylation by DrrA, AnkX can covalently modify inactive Rabs with high catalytic efficiency even when GDP is bound to the GTPase and hence can inhibit binding of GDI to Rab:GDP complexes. We therefore speculate that human cells could employ similar mechanisms in the absence of infection to effectively displace Rabs from GDI.

  6. Effects of energetic particle phase space modifications by instabilities on integrated modeling

    SciTech Connect

    Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.; Gorelenkov, N. N.; White, R. B.

    2016-07-22

    Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effective tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Furthermore, those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.

  7. Modification of the anxiolytic effects of 5-HT1A agonists by shock intensity.

    PubMed

    Meneses, A; Hong, E

    1993-11-01

    Contradictory evidence exists concerning the anxiolytic effects of 5-HT1A agonists in the conflict test. In the present work, a modification of the Vogel conflict model was used to assess different doses of diazepam (0.1-5.6 mg/kg), ipsapirone (1.0-17.8 mg/kg), buspirone (1.7-17.8 mg/kg), and indorenate (0.56-17.8 mg/kg) in rats receiving two different electric shock intensities (0.16 and 0.32 mA). The results show that the three 5-HT1A agonists had a smaller anticonflict effect than diazepam. The anticonflict effect with each compound was of a greater magnitude at 0.16 mA intensity than at 0.32 mA. This study shows that, using different electric shock intensities, compounds produce a differential effect: the anticonflict effects were more pronounced with the lower electric shock intensity than with the higher intensity. The present results suggest that the use of different shock intensities can play distinct roles over the drug's effect in the conflict test.

  8. Clinical effectiveness of attentional bias modification training in abstinent alcoholic patients.

    PubMed

    Schoenmakers, Tim M; de Bruin, Marijn; Lux, Irja F M; Goertz, Alexa G; Van Kerkhof, Dorieke H A T; Wiers, Reinout W

    2010-06-01

    A new training to decrease attentional bias (attentional bias modification training, ABM) was tested in a randomized controlled experimental study with alcohol-dependent patients as an addition to cognitive behavioral therapy. In alcohol dependence, attentional bias has been associated with severity of alcoholism, craving, treatment outcome, and relapse. Forty-three patients with DSM-IV diagnosis of alcohol dependence were randomly assigned to an ABM intervention or control training. The procedure consisted of five sessions in which patients were trained to disengage attention from alcohol-related stimuli (ABM condition) or in which they were trained on an irrelevant reaction-time test (control condition). We measured the effects of ABM on the visual-probe task, with stimuli that were presented in the ABM and with new stimuli. Craving was measured with the Desires for Alcohol Questionnaire. Follow-up data were gathered for overall treatment success, and relapse up to 3 months after the intervention. ABM was effective in increasing the ability to disengage from alcohol-related cues. This effect generalized to untrained, new stimuli. There were no significant effects on subjective craving. For other outcome measures there were indications of clinically relevant effects. Results indicate that ABM among alcohol-dependent patients was effective and that it may affect treatment progression. Large-scale trials are warranted to further investigate this new field. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Which Propensity Score Method Best Reduces Confounder Imbalance? An Example From a Retrospective Evaluation of a Childhood Obesity Intervention.

    PubMed

    Schroeder, Krista; Jia, Haomiao; Smaldone, Arlene

    Propensity score (PS) methods are increasingly being employed by researchers to reduce bias arising from confounder imbalance when using observational data to examine intervention effects. The purpose of this study was to examine PS theory and methodology and compare application of three PS methods (matching, stratification, weighting) to determine which best improves confounder balance. Baseline characteristics of a sample of 20,518 school-aged children with severe obesity (of whom 1,054 received an obesity intervention) were assessed prior to PS application. Three PS methods were then applied to the data to determine which showed the greatest improvement in confounder balance between the intervention and control group. The effect of each PS method on the outcome variable-body mass index percentile change at one year-was also examined. SAS 9.4 and Comprehensive Meta-analysis statistical software were used for analyses. Prior to PS adjustment, the intervention and control groups differed significantly on seven of 11 potential confounders. PS matching removed all differences. PS stratification and weighting both removed one difference but created two new differences. Sensitivity analyses did not change these results. Body mass index percentile at 1 year decreased in both groups. The size of the decrease was smaller in the intervention group, and the estimate of the decrease varied by PS method. Selection of a PS method should be guided by insight from statistical theory and simulation experiments, in addition to observed improvement in confounder balance. For this data set, PS matching worked best to correct confounder imbalance. Because each method varied in correcting confounder imbalance, we recommend that multiple PS methods be compared for ability to improve confounder balance before implementation in evaluating treatment effects in observational data.

  10. Determining confounding sensitivities in eddy current thin film measurements

    NASA Astrophysics Data System (ADS)

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2017-02-01

    Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done by using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It was the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy-current testing was performed using a commercially available, hand-held eddy-current probe (ETA3.3H spring-loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe was sent to a hand-held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring-loaded eddy probe was at measuring film thickness under varying experimental conditions. This research studied the effects of a number of factors such as i) conductivity, ii) edge effect, iii) surface finish of base material and iv) cable condition.

  11. Handling stress may confound murine gut microbiota studies.

    PubMed

    Allen-Blevins, Cary R; You, Xiaomeng; Hinde, Katie; Sela, David A

    2017-01-01

    Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes. Our results demonstrate

  12. Handling stress may confound murine gut microbiota studies

    PubMed Central

    Allen-Blevins, Cary R.; You, Xiaomeng; Hinde, Katie

    2017-01-01

    Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes

  13. Effects of modifying agents on surface modifications of magnesium oxide whiskers

    NASA Astrophysics Data System (ADS)

    Zhao, Yun; Liu, Bei; Yang, Jinjun; Jia, Junping; You, Chen; Chen, Minfang

    2016-12-01

    In this work, the MgO whiskers have been treated by several modifying agents including the mixture of DL-malic acid oligo-L-lactide (g), aluminate coupling agent (Al) and stearic acid (Sa). The morphologies, covering quantity, compositions and components of the whiskers before and after the modifications were investigated by SEM, TG, XRD and FT-IR, respectively. Comparisons have been made on the morphologies of modified whiskers by different modifiers tailoring. The results show that the MgO whiskers treated by stearic acid have superior performance to the others, especially in terms of uniform dispersion. In contrast, both the mixture of DL-malic acid oligo-L-lactide and aluminate coupling agent have the negative effects on whiskers' dispersibility. FT-IR reveals that the chemical bonds were formed between the whiskers and each modifying agent and the XRD testing demonstrate that the crystal structures of the modified whiskers were well maintained without significant change.

  14. Chemical modifications of algal mannans and xylomannans: effects on antiviral activity.

    PubMed

    Pérez Recalde, Mercedes; Carlucci, María J; Noseda, Miguel D; Matulewicz, María C

    2012-01-01

    The structures of two sulfated xylomannans extracted from the red alga Nemalion helminthoides were determined. These two fractions plus a sulfated mannan, isolated from the same alga and whose structure was previously reported, were subjected to chemical modification. The mannan was oversulfated with SO(3)-pyridine in dimethyl sulfoxide at 60 °C during two and three hours and the xylomannans were subjected to Smith degradation in order to eliminate xylose side-chains. Structural analysis of all derivatives was carried out by methylation analysis and (13)C NMR spectroscopy. Antiviral activity against herpes simplex virus type 1 and 2, and dengue virus type 2 of native and modified mannans and xylomannans was estimated. Anticoagulant effect of the active fractions was also determined.

  15. Cognitive Bias Modification for Interpretation in Major Depression: Effects on Memory and Stress Reactivity

    PubMed Central

    Joormann, Jutta; Waugh, Christian E.; Gotlib, Ian H.

    2014-01-01

    Interpreting ambiguous stimuli in a negative manner is a core bias associated with depression. Investigators have used cognitive bias modification for interpretation (CBM-I) to demonstrate that it is possible to experimentally induce and modify these biases. This study extends previous research by examining whether CBM-I affects not only interpretation, but also memory and physiological stress response in individuals diagnosed with Major Depressive Disorder (MDD). We found that CBM-I was effective in inducing an interpretive bias. Participants also exhibited memory biases that corresponded to their training condition and demonstrated differential physiological responding in a stress task. These results suggest that interpretation biases in depression can be modified, and that this training can lead to corresponding changes in memory and to decreases in stress reactivity. Findings from this study highlight the importance of examining the relations among different cognitive biases in MDD and the possibility of modifying cognitive biases. PMID:25593790

  16. Modification of β-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation

    PubMed Central

    2016-01-01

    β-Sheet forming peptides have attracted significant interest for the design of hydrogels for biomedical applications. One of the main challenges is the control and understanding of the correlations between peptide molecular structure, the morphology, and topology of the fiber and network formed as well as the macroscopic properties of the hydrogel obtained. In this work, we have investigated the effect that functionalizing these peptides through their hydrophobic face has on their self-assembly and gelation. Our results show that the modification of the hydrophobic face results in a partial loss of the extended β-sheet conformation of the peptide and a significant change in fiber morphology from straight to kinked. As a consequence, the ability of these fibers to associate along their length and form large bundles is reduced. These structural changes (fiber structure and network topology) significantly affect the mechanical properties of the hydrogels (shear modulus and elasticity). PMID:27089379

  17. [VLP vaccines and effects of HIV-1 Env protein modifications on their antigenic properties].

    PubMed

    Vzorov, A N; Compans, R W

    2016-01-01

    An ideal protective HIV-1 vaccine can elicit broadly neutralizing antibodies, capable of preventing HIV transmission. The strategies of designing vaccines include generation of soluble recombinant proteins which mimic the native Env complex and are able to enhance the immunogenicity of gp120. Recent data indicate that the cytoplasmic tail (CT) of the Env protein has multiple functions, which can affect the early steps of infection, as well as viral assembly and antigenic properties. Modifications in the CT can be used to induce conformational changes in functional regions of gp120 and to stabilize the trimeric structure, avoiding immune misdirection and induction of non-neutralizing antibody responses. Env-trimers with modified CTs in virus-like particles (VLPs) are able to induce antibodies with broad spectrum neutralizing activity and high avidity and have the potential for developing an effective vaccine against HIV.

  18. The Effect of Structural Modifications on Ionic Conductivity in Newly-Designed Polyester Electrolytes

    NASA Astrophysics Data System (ADS)

    Pesko, Danielle; Jung, Yuki; Coates, Geoff; Balsara, Nitash

    2015-03-01

    Gaining a fundamental understanding of the relationship between molecular structure and ionic conductivity of polymer electrolytes is an essential step toward designing next generation materials for battery applications. In this study, we use a systematic set of newly-designed polyesters with varying side-chain lengths and oxygen functional groups to elucidate the effects of structural modifications on the conductive properties of the corresponding electrolytes. Mixtures of polyesters and lithium bis(trifluromethanesulfonyl)imide (LiTFSI) were characterized using ac impedance spectroscopy to measure the ionic conductivity at various temperatures and salt concentrations. The relative conductivities of these electrolytes in the dilute limit are directly comparable to results of molecular dynamics simulations performed using the same polymers. The simulations correspond well with the experimental results, and provide molecular level insight about the solvation environment of the lithium ions and how the ions transport through these polyesters.

  19. Cognitive Bias Modification for Interpretation in Major Depression: Effects on Memory and Stress Reactivity.

    PubMed

    Joormann, Jutta; Waugh, Christian E; Gotlib, Ian H

    2015-01-01

    Interpreting ambiguous stimuli in a negative manner is a core bias associated with depression. Investigators have used cognitive bias modification for interpretation (CBM-I) to demonstrate that it is possible to experimentally induce and modify these biases. This study extends previous research by examining whether CBM-I affects not only interpretation, but also memory and physiological stress response in individuals diagnosed with Major Depressive Disorder (MDD). We found that CBM-I was effective in inducing an interpretive bias. Participants also exhibited memory biases that corresponded to their training condition and demonstrated differential physiological responding in a stress task. These results suggest that interpretation biases in depression can be modified, and that this training can lead to corresponding changes in memory and to decreases in stress reactivity. Findings from this study highlight the importance of examining the relations among different cognitive biases in MDD and the possibility of modifying cognitive biases.

  20. Effectiveness of a volunteer-delivered lifestyle modification program for reducing cardiovascular disease risk factors.

    PubMed

    Rankin, Paul; Morton, Darren P; Diehl, Hans; Gobble, John; Morey, Peter; Chang, Esther

    2012-01-01

    Lifestyle modification has been demonstrated to effectively reduce the risk factors associated with cardiovascular disease, but there is a perception that it is costly to administer and resource. The present study examined the results achieved by a 30-day lifestyle modification program (Coronary Health Improvement Project) delivered by volunteers in a community setting. Changes in selected biometric measures of 5,070 participants in the Coronary Health Improvement Project programs delivered throughout North America (January 2006 to October 2009), were assessed. Overall, significant reductions (p < 0.001) were recorded in body mass (-3.2%), systolic and diastolic blood pressure (-4.9% and -5.3%, respectively), total cholesterol (-11.0%), low-density lipoprotein cholesterol (-13.0%), triglycerides (-7.7%), and fasting plasma glucose (-6.1%). Stratification of the data revealed more dramatic responses in those presenting with the greatest risk factor levels. Those presenting with cholesterol levels >280 mg/dl recorded an average reduction of 19.8%. A mean decrease of 16.1% in low-density lipoprotein levels was observed among those who entered the program with a low-density lipoprotein level >190 mg/dl. Individuals who presented with triglycerides >500 mg/dl recorded a mean reduction of 44.1%. The Framingham assessment forecast that approximately 70 cardiac events would be averted during the subsequent decade in the cohort because of the program. In conclusion, significant reductions in cardiovascular disease risk factors can be achieved in a 30-day lifestyle intervention delivered by volunteers, providing a cost-effective mode of administering lifestyle medicine. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effect of mediterranean diet in diabetes control and cardiovascular risk modification: a systematic review.

    PubMed

    Sleiman, Dana; Al-Badri, Marwa R; Azar, Sami T

    2015-01-01

    Over the past few years, there has been a worldwide significant increase in the incidence of type II diabetes mellitus with both increase in morbidity and mortality. Controlling diabetes through life style modifications, including diet and exercise has always been the cornerstone in diabetes management. Increasing evidence suggests that the Mediterranean diet could be of benefit in diseases associated with chronic inflammation, including metabolic syndrome, diabetes, obesity as well as atherosclerosis, cancer, pulmonary diseases, and cognition disorders As a matter of fact, a number of studies addressed the relationship between Mediterranean diet and diabetes control. The result of these studies was conflicting. Some were able to elicit a protective role, while others showed no added benefit. As a result; we decided to conduct a systematic review to have a better understanding of the relationship between adherence to Mediterranean diet and diabetes control. A systematic review was conducted on the effect of Mediterranean diet in diabetes control and cardiovascular risk modification as well as the possible mechanism through which this diet might exhibit its beneficial role. We did a comprehensive search of multiple electronic databases such as Medline, Google Scholars, PubMed, and the Cochrane central register data until May 2014. We included cross-sectional, prospective, and controlled clinical trials that looked at the associations between Mediterranean diet and indices of diabetes control such HbA1c, fasting glucose, and homeostasis model assessment, in addition to cardiovascular and peripheral vascular outcomes. Most of the studies showed favorable effects of Mediterranean diet on glycemic control and CVD, although a certain degree of controversy remains regarding some issues, such as obesity. Important methodological differences and limitations in the studies make it difficult to compare results, thus further longer term studies are needed to evaluate the long

  2. Tribocorrosion studies of metallic biomaterials: The effect of plasma nitriding and DLC surface modifications.

    PubMed

    Zhao, Guo-Hua; Aune, Ragnhild E; Espallargas, Nuria

    2016-10-01

    The medical grade pure titanium, stainless steel and CoCrMo alloy have been utilized as biomaterials for load-bearing orthopedic prosthesis. The conventional surgery metals suffer from a combined effect of wear and corrosion once they are implanted, which may significantly accelerate the material degradation process. In this work, the tribocorrosion performance of the metallic biomaterials with different surface modifications was studied in the simulated body fluid for the purpose of investigating the effect of the surface treatments on the tribocorrosion performance and eventually finding the most suitable implantation materials. The metals were subjected to surface modifications by plasma nitriding in different treatment temperatures or physical vapor deposition (PVD) to produce diamond-like carbon (DLC) coating, respectively. The dry wear and tribocorrosion properties of the samples were evaluated by using a reciprocating ball-on-disc tribometer equipped with an electrochemical cell. Prior to the tribocorrosion tests, their electrochemical behavior was measured by the potentiodynamic polarization in phosphate buffer saline (PBS) solution at room temperature. Both stainless steel and CoCrMo after low temperature nitriding kept their passive nature by forming an expanded austenite phase. The DLC coated samples presented the low anodic corrosion current due to the chemical inertness of the carbon layer. During the tribocorrosion tests at open circuit potential, the untreated and low temperature nitrided samples exhibited significant potential drop towards the cathodic direction, which was a result of the worn out of the passive film. Galvanic coupling was established between the depassivated (worn) area and the still passive (unworn) area, making the materials suffered from wear-accelerated corrosion. The DLC coating performed as a solid lubricant in both dry wear and tribocorrosion tests, and the resulting wear after the tests was almost negligible. Copyright

  3. Effects of energetic particle phase space modifications by instabilities on integrated modeling

    DOE PAGES

    Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.; ...

    2016-07-22

    Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effectivemore » tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Furthermore, those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.« less

  4. Effects of initial saturation on properties modification and displacement of tetrachloroethene with aqueous isobutanol

    NASA Astrophysics Data System (ADS)

    Boyd, Glen R.; Ocampo-Gómez, Ana M.; Li, Minghua; Husserl, Johana

    2006-11-01

    Packed column experiments were conducted to study effects of initial saturation of tetrachloroethene (PCE) in the range of 1.0-14% pore volume (PV) on mobilization and downward migration of the non-aqueous phase liquid (NAPL) product upon contact with aqueous isobutanol (˜ 10 vol.%). This study focused on the consequences of swelling beyond residual saturation. Columns were packed with mixtures of neat PCE, water and glass beads and waterflooded to establish a desired homogeneous residual saturation, and then flooded with aqueous isobutanol under controlled hydraulic conditions. Results showed a critical saturation of approximately 8% PV for these packed column experimental conditions. At low initial PCE saturations (< 8% PV), experimental results showed reduced risk of NAPL-product migration upon contact with aqueous isobutanol. At higher initial PCE saturations (> 8% PV), results showed NAPL-product mobilization and downward migration which was attributed to interfacial tension (IFT) reduction, swelling of the NAPL-product, and reduced density modification. Packed column results were compared with good agreement to theoretical predictions of NAPL-product mobilization using the total trapping number, NT. In addition to the packed column study, preliminary batch experiments were conducted to study the effects of PCE volumetric fraction in the range of 0.5-20% on density, viscosity, and IFT modification as a function of time following contact with aqueous isobutanol (˜ 10 vol.%). Modified NAPL-product fluid properties approached equilibrium within approximately 2 h of contact for density and viscosity. IFT reduction occurred immediately as expected. Measured fluid properties were compared with good agreement to theoretical equilibrium predictions based on UNIQUAC. Overall, this study demonstrates the importance of initial DNAPL saturation, and the associated risk of downward NAPL-product migration, in applying alcohol flooding for remediation of DNAPL contaminated

  5. Effects of initial saturation on properties modification and displacement of tetrachloroethene with aqueous isobutanol.

    PubMed

    Boyd, Glen R; Ocampo-Gómez, Ana M; Li, Minghua; Husserl, Johana

    2006-11-20

    Packed column experiments were conducted to study effects of initial saturation of tetrachloroethene (PCE) in the range of 1.0-14% pore volume (PV) on mobilization and downward migration of the non-aqueous phase liquid (NAPL) product upon contact with aqueous isobutanol ( approximately 10 vol.%). This study focused on the consequences of swelling beyond residual saturation. Columns were packed with mixtures of neat PCE, water and glass beads and waterflooded to establish a desired homogeneous residual saturation, and then flooded with aqueous isobutanol under controlled hydraulic conditions. Results showed a critical saturation of approximately 8% PV for these packed column experimental conditions. At low initial PCE saturations (<8% PV), experimental results showed reduced risk of NAPL-product migration upon contact with aqueous isobutanol. At higher initial PCE saturations (>8% PV), results showed NAPL-product mobilization and downward migration which was attributed to interfacial tension (IFT) reduction, swelling of the NAPL-product, and reduced density modification. Packed column results were compared with good agreement to theoretical predictions of NAPL-product mobilization using the total trapping number, N(T). In addition to the packed column study, preliminary batch experiments were conducted to study the effects of PCE volumetric fraction in the range of 0.5-20% on density, viscosity, and IFT modification as a function of time following contact with aqueous isobutanol ( approximately 10 vol.%). Modified NAPL-product fluid properties approached equilibrium within approximately 2 h of contact for density and viscosity. IFT reduction occurred immediately as expected. Measured fluid properties were compared with good agreement to theoretical equilibrium predictions based on UNIQUAC. Overall, this study demonstrates the importance of initial DNAPL saturation, and the associated risk of downward NAPL-product migration, in applying alcohol flooding for

  6. Asthma morbidity and ambient air pollution: effect modification by residential traffic-related air pollution.

    PubMed

    Delfino, Ralph J; Wu, Jun; Tjoa, Thomas; Gullesserian, Sevan K; Nickerson, Bruce; Gillen, Daniel L

    2014-01-01

    Ambient air pollution has been associated with asthma-related hospital admissions and emergency department visits (hospital encounters). We hypothesized that higher individual exposure to residential traffic-related air pollutants would enhance these associations. We studied 11,390 asthma-related hospital encounters among 7492 subjects 0-18 years of age living in Orange County, California. Ambient exposures were measured at regional air monitoring stations. Seasonal average traffic-related exposures (PM2.5, ultrafine particles, NOx, and CO) were estimated near subjects' geocoded residences for 6-month warm and cool seasonal periods, using dispersion models based on local traffic within 500 m radii. Associations were tested in case-crossover conditional logistic regression models adjusted for temperature and humidity. We assessed effect modification by seasonal residential traffic-related air pollution exposures above and below median dispersion-modeled exposures. Secondary analyses considered effect modification by traffic exposures within race/ethnicity and insurance group strata. Asthma morbidity was positively associated with daily ambient O3 and PM2.5 in warm seasons and with CO, NOx, and PM2.5 in cool seasons. Associations with CO, NOx, and PM2.5 were stronger among subjects living at residences with above-median traffic-related exposures, especially in cool seasons. Secondary analyses showed no consistent differences in association, and 95% confidence intervals were wide, indicating a lack of precision for estimating these highly stratified associations. Associations of asthma with ambient air pollution were enhanced among subjects living in homes with high traffic-related air pollution. This may be because of increased susceptibility (greater asthma severity) or increased vulnerability (meteorologic amplification of local vs. correlated ambient exposures).

  7. The effect of surface modification and aprotinin on cellular injury during simulated cardiopulmonary bypass.

    PubMed

    Greenfield, Benjamin L; Brinkman, Kelly R; Koziol, Kelly L; McCann, Martin W; Merrigan, Kellie A; Steffen, Lee P; Woods, Kylie A; Stammers, Alfred H; Hock, Lynette M

    2002-12-01

    Cardiopulmonary bypass (CPB) elicits derangements to the formed elements of blood because of the physical stresses of extracorporeal flow. Methods of reducing the impact of CPB include circuit surface modification and pharmacological supplementation. The purpose of this study was to examine the effects of aprotinin in combination with surface modification during simulated CPB. Fresh whole bovine blood was used to prime standard CPB circuits divided into four groups (N = 3): control (CTR), aprotinin 300 KIU/mL (APR), Poly (2-methoxyethylacrylate) coating (PMEA), and APR with PMEA (APR-PMEA). Physical stresses included venous reservoir negative pressure (-85 mmHg), arterial line pressure of 150 mmHg at 5 LPM, and air-blood interface, applied over a 90-minute period. Samples were drawn at the following times: 0, 10, 45, and 90 minutes. Endpoints included platelet count (PLT), plasma-free hemoglobin (PFHb), and thromboelastography (TEG). PLT did not change (138.9 +/- 15.0 vs. 102.9 +/- 21.0, p = ns) throughout the 90-minute experimental periods in any group. PFHb increased significantly (mean of 19- fold) throughout the experiment, but was not affected by any treatment. The TEG index declined in the CTR (3.6 +/- 0.4 vs. -16.2 +/- 2.9, p < .0003), PMEA (5.9 +/- 0.8 vs. -2.7 +/- 3.8, p < .02), and APR-PMEA (4.6 +/- 1.0 vs. -2.8 +/- 0.3 p < .0003) groups, but not in the APR group (3.6 +/- 2.2 vs. -1.3 +/- 3.3 p = .10). In conclusion, neither APR nor PMEA had an effect on either red cell hemolysis or PLT, but APR treatment alone significantly attenuated the derangements in coagulation induced in this extracorporeal model.

  8. Effect of surface modification and UVA photoactivation on antibacterial bioactivity of zinc oxide powder

    NASA Astrophysics Data System (ADS)

    Ann, Ling Chuo; Mahmud, Shahrom; Bakhori, Siti Khadijah Mohd; Sirelkhatim, Amna; Mohamad, Dasmawati; Hasan, Habsah; Seeni, Azman; Rahman, Rosliza Abdul

    2014-02-01

    The effects of surface modification of zinc oxide (ZnO) powder and UVA illumination on the powder towards Escherichia coli and Staphylococcus aureus were investigated. FESEM-EDS results showed that oxygen annealing increased the O:Zn ratio on the surface of ZnO-rod and ZnO-plate samples. Surface conductances of ZnO-rod and ZnO-plate pellets were reduced from 1.05 nS to 0.15 nS and 1.34 nS to 0.23 nS, respectively. Meanwhile, UVA illumination on the surface of the ZnO-rod and ZnO-plate samples was found to improve surface conductance to 7.08 nS and 6.51 nS, respectively, due to the release of charge carrier. Photoluminescence results revealed that oxygen annealing halved the UV emission intensity and green emission intensity, presumably caused by oxygen absorption in the ZnO lattice. The antibacterial results showed that oxygen-treated ZnO exhibited slightly higher growth inhibition on E. coli and S. aureus compared with unannealed ZnO. UVA illumination on ZnO causes the greatest inhibition toward E. coli and S. aureus. Under the UVA excitation, the inhibition of E. coli increased by 18% (ZnO-rod) and 13% (ZnO-plate) while the inhibition of S. aureus increased by 22% (ZnO-rod) and 21% (ZnO-plate). Release of reactive oxygen species were proposed in antibacterial mechanisms, which were aided by surface modification and UVA photoactivation. The reactive oxygen species disrupted the DNA and protein synthesis of the bacterial cell, causing bacteriostatic effects toward E. coli and S. aureus.

  9. The "Dry-Run" Analysis: A Method for Evaluating Risk Scores for Confounding Control.

    PubMed

    Wyss, Richard; Hansen, Ben B; Ellis, Alan R; Gagne, Joshua J; Desai, Rishi J; Glynn, Robert J; Stürmer, Til

    2017-05-01

    A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the "dry-run" analysis, which divides the unexposed population into "pseudo-exposed" and "pseudo-unexposed" groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Oxidative Modification in Human Hair: The Effect of the Levels of Cu (II) Ions, UV Exposure and Hair Pigmentation.

    PubMed

    Grosvenor, Anita J; Marsh, Jennifer; Thomas, Ancy; Vernon, James A; Harland, Duane P; Clerens, Stefan; Dyer, Jolon M

    2016-01-01

    Protein oxidative degradation is implicated in a wide range of deleterious effects. For human hair, this oxidative damage can lead to significant observable changes in fiber physical and visual properties. A redox proteomic approach was applied to map molecular modification in human hair proteins and correlate this modification with the abundance of copper (II) ions, the levels of UV exposure and the general level of hair pigmentation. An increase in oxidative modification was observed with increasing copper (II) ion levels, regardless of the pigmentation level. Significantly, increased protein oxidative modification was also observed to occur in both lightly and darkly pigmented hair tresses even in the absence of irradiation, albeit at lower relative levels. Modification levels increased with increased copper (II) ion concentration. This new finding indicates that the level of copper (II) ions in human hair plays a key role in mediating protein oxidation, with or without exposure to UV light. Overall, these results strongly suggest that minimization of the level of copper (II) ions in human hair will mitigate and/or slow protein oxidative modification and therefore lower overall hair damage. © 2015 The American Society of Photobiology.

  11. The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

    2015-05-01

    Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

  12. Impacts of temperature change on ambulance dispatches and seasonal effect modification.

    PubMed

    Cheng, Jian; Xu, Zhiwei; Zhao, Desheng; Xie, Mingyu; Yang, Huihui; Wen, Liying; Li, Kesheng; Su, Hong

    2016-12-01

    Ambulance dispatch is a proxy of acute health outcomes, and growing epidemiological evidence documented its relation to extreme temperature events. Research, however, on short-term temperature change and ambulance dispatches is scarce. We aimed to investigate the effect of short-term temperature change on ambulance dispatches and potential modification by season. Daily data on ambulance dispatch and weather factors were collected in Huainan, a Chinese inland city from December 2011 through December 2013. A Poison generalized linear regression model combined with distributed lag nonlinear model was constructed to examine the association of temperature change between neighboring days (TCN) with ambulance dispatches. The effect modification by season was also examined. There were 48,700 ambulance attendances during the study period. A statistically significant association of TCN with ambulance dispatches was observed. Temperature rise between neighboring days (TCN > 0) was associated with elevated adverse risk of ambulance dispatches, and the effects appeared to be acute (lag0, on the current day) and could last for at least a week, while temperature drop between neighboring days (TCN < 0) had a protective effect. For a 1 °C increase of TCN at lag0 and lag06 (on the 7-day moving average), the risk of ambulance dispatches increased by 2 % (95 % CI 1-3 %) and 7 (95 % CI 1-13 %), respectively. Extreme TCN increase (95th percentile, 3.3 °C vs. 0 °C) at lag0 and lag05 was accompanied by 6 (95 % CI 3-8 %) and 27 % (95 % CI 12-44 %) increase in ambulance dispatches. Ambulance dispatches were more vulnerable to extremely great temperature rise in summer and autumn. TCN was adopted for the first time to quantify the impact of short-term temperature change on ambulance dispatches. Temperature drop between neighboring days (TCN < 0) had a protective effect on ambulance dispatches, while temperature rise between neighboring days (TCN > 0) could acutely

  13. Impacts of temperature change on ambulance dispatches and seasonal effect modification

    NASA Astrophysics Data System (ADS)

    Cheng, Jian; Xu, Zhiwei; Zhao, Desheng; Xie, Mingyu; Yang, Huihui; Wen, Liying; Li, Kesheng; Su, Hong

    2016-12-01

    Ambulance dispatch is a proxy of acute health outcomes, and growing epidemiological evidence documented its relation to extreme temperature events. Research, however, on short-term temperature change and ambulance dispatches is scarce. We aimed to investigate the effect of short-term temperature change on ambulance dispatches and potential modification by season. Daily data on ambulance dispatch and weather factors were collected in Huainan, a Chinese inland city from December 2011 through December 2013. A Poison generalized linear regression model combined with distributed lag nonlinear model was constructed to examine the association of temperature change between neighboring days (TCN) with ambulance dispatches. The effect modification by season was also examined. There were 48,700 ambulance attendances during the study period. A statistically significant association of TCN with ambulance dispatches was observed. Temperature rise between neighboring days (TCN > 0) was associated with elevated adverse risk of ambulance dispatches, and the effects appeared to be acute (lag0, on the current day) and could last for at least a week, while temperature drop between neighboring days (TCN < 0) had a protective effect. For a 1 °C increase of TCN at lag0 and lag06 (on the 7-day moving average), the risk of ambulance dispatches increased by 2 % (95 % CI 1-3 %) and 7 (95 % CI 1-13 %), respectively. Extreme TCN increase (95th percentile, 3.3 °C vs. 0 °C) at lag0 and lag05 was accompanied by 6 (95 % CI 3-8 %) and 27 % (95 % CI 12-44 %) increase in ambulance dispatches. Ambulance dispatches were more vulnerable to extremely great temperature rise in summer and autumn. TCN was adopted for the first time to quantify the impact of short-term temperature change on ambulance dispatches. Temperature drop between neighboring days (TCN < 0) had a protective effect on ambulance dispatches, while temperature rise between neighboring days (TCN > 0) could acutely trigger the increase in

  14. Simultaneous dimension reduction and adjustment for confounding variation.

    PubMed

    Lin, Zhixiang; Yang, Can; Zhu, Ying; Duchi, John; Fu, Yao; Wang, Yong; Jiang, Bai; Zamanighomi, Mahdi; Xu, Xuming; Li, Mingfeng; Sestan, Nenad; Zhao, Hongyu; Wong, Wing Hung

    2016-12-20

    Dimension reduction methods are commonly applied to high-throughput biological datasets. However, the results can be hindered by confounding factors, either biological or technical in origin. In this study, we extend principal component analysis (PCA) to propose AC-PCA for simultaneous dimension reduction and adjustment for confounding (AC) variation. We show that AC-PCA can adjust for (i) variations across individual donors present in a human brain exon array dataset and (ii) variations of different species in a model organism ENCODE RNA sequencing dataset. Our approach is able to recover the anatomical structure of neocortical regions and to capture the shared variation among species during embryonic development. For gene selection purposes, we extend AC-PCA with sparsity constraints and propose and implement an efficient algorithm. The methods developed in this paper can also be applied to more general settings. The R package and MATLAB source code are available at https://github.com/linzx06/AC-PCA.

  15. Confounding factors affect the pathophysiology of eosinophilic esophagitis.

    PubMed

    Elitsur, Yoram

    2012-09-07

    Eosinophilic esophagitis is a newly diagnosed esophageal disease in adult and children. The clinical and pathological characteristics of this disease have been established and were recently summarized in the expert clinical guideline published in 2011. In spite of the wide knowledge accumulated on this disease, there are many areas where scientific data are missing, especially in regard to the disease's pathophysiology. Recent publications have suggested that other confounding factors modify the disease and may affect its clinical-phenotypic presentation. Those factors may include place of living, air pollution, race, genetic factors and other. In the present report we discussed and review those confounding factors, the new developments, and what direction we should go to further advance our knowledge of this disease.

  16. Isotopic enrichment of amino acids in urine following oral infusions of L-[1-(13)C]phenylalanine and L-[1-(13)C]lysine in humans: confounding effect of D-[13C]amino acids.

    PubMed

    Darling, P B; Bross, R; Wykes, L J; Ball, R O; Pencharz, P B

    1999-06-01

    Urine sampling of the free amino acid pool serves to reflect plasma enrichment and is used as a noninvasive means to determine isotope enrichment in studies of amino acid metabolism. We determined the effect of D-[13C]phenylalanine and D-[13C]lysine content of tracers on urinary amino acid enrichment following oral infusion of L-[13C]phenylalanine in 18 preterm infants and L-[1-(13)C]lysine in seven healthy adult females. Urinary [13C]phenylalanine enrichment was higher (P < .0001) for L-[13C]phenylalanine containing 0.4% D-[13C]phenylalanine (28.6 +/- 7.1) versus L-[1-(13)C]phenylalanine that contained undetectable D-[13C]phenylalanine (10.2 +/- 1.5). D-[13C]phenylalanine, measured by chiral column gas chromatography-mass spectrometry (GC-MS), accounted for 10% to 30% (20.5% +/- 7%) of total phenylalanine in the urine of infants who received 0.4% D-[13C]phenylalanine, and was absent from the urine of infants receiving tracer with undetectable [13C]phenylalanine. Urinary L-[13C]phenylalanine enrichment did not differ between tracer groups (9.8 +/- 1.5 and 9.8 +/- 2.5). In adult females, the use of L-[1-(13)C]lysine (1.6% D-lysine) resulted in a higher (P < .02) urine total L,D-[13C]lysine enrichment compared with plasma enrichment (40.8 +/- 4.1 v 11.1 +/- 0.7). This study demonstrates the significant presence of D-[13C]amino acids in urine that originate as contaminants from commercially manufactured tracers, as a result of renal tubular discrimination of D-amino acids. A tracer containing detectable amounts of D-[13C]isomer cannot be recommended for any study in which urine will be used to reflect enrichment in the arterial plasma pool.

  17. Investigation of modification X-ray induced bystander effect in vitro.

    PubMed

    Shemetun, O V; Talan, O O

    2014-09-01

    Objective - to investigate the modification of bystander effect induced by X-irradiation of human peripheral blood in vitro by application of antioxidant vitamin medication. Material and methods. Modeling of radiation-induced bystander effect in vitro in mixed lymphocyte cultures exposed to dose of 1 Gy and non-irradiated blood lymphocytes of persons of different sexes, GTG-staining of metaphase chromosomes and their cytogenetic analysis; application of antioxidant preparation (soluble forms of vitamins E, C and A) in concentration 40 μg/ml. Results. Under the introduction of antioxidant preparation into mixed culture before lymphocytes cultivation frequency of chromosomal aberrations in bystander cells did not significantly different from the control (p > 0.05). application of antioxidant preparation modifies the radiation-induced bystander effect in unirradiated human peripheral blood lymphocytes under their joint cultivation with lymphocytes irradiated in dose of 1 Gy. Antioxidant prevents the development of secondary oxidative stress in unirradiated cells, eliminates the development in them of radiation-induced bystander effect and ensures the preservation of stability of their chromosome apparatus. O. V. Shemetun, O. O. Talan.

  18. Effects of methylphenidate alone and in combination with behavior modification procedures on the behavior and academic performance of hyperactive children.

    PubMed

    Wolraich, M; Drummond, T; Salomon, M K; O'Brien, M L; Sivage, C

    1978-03-01

    Twenty hyperactive 6- to 9-year-old children of normal intelligence were studied in a half-day laboratory classroom in a 2-week period baseline-treatment-reversal design for behavior modification. Under double-blind conditions half the children were placed on .3 mg/kg of Ritalin and half on placebo for the entire program. The classroom program consisted of a group period with immediate reinforcement possible, and an individual time period without immediate reinforcement possible. Behavior modification caused a significant decrease in nonattending, out-of-seat, inappropriate vocalizing and inappropriate peer interaction behavior in the group period. Fidgeting, a nontargeted behavior, was not significantly decreased during this period but did significantly decrease as a result of medication. No other drug effects occurred during this period. During the individual period, the results were essentially reversed. There were no significant behavior modification effects observed. Significant reductions resulted from medication in all behaviors except out-of-seat and fidgeting. Behavior modification alone significantly affected the two academic measures. No signigicant effects were seen on the Conners Abbreviated Teacher Rating Scale. No significant interactions were noted between medication and behavior modification.

  19. Antiprotozoal Effect of Saponins in the Rumen Can Be Enhanced by Chemical Modifications in Their Structure

    PubMed Central

    Ramos-Morales, Eva; de la Fuente, Gabriel; Duval, Stephane; Wehrli, Christof; Bouillon, Marc; Lahmann, Martina; Preskett, David; Braganca, Radek; Newbold, Charles J.

    2017-01-01

    The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented. PMID:28382023

  20. Post-translational modification of osteopontin: Effects on in vitro hydroxyapatite formation and growth

    SciTech Connect

    Boskey, Adele L.; Christensen, Brian; Taleb, Hayat; Sorensen, Esben S.

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Thrombin-cleaved fragments of milk-osteopontin effect hydroxyapatite formation differently. Black-Right-Pointing-Pointer N- and C-terminal fragments promoted hydroxyapatite formation and growth. Black-Right-Pointing-Pointer A central fragment inhibited hydroxyapatite formation and growth. Black-Right-Pointing-Pointer Binding to collagen or hydroxyapatite seed crystals modified these effects. -- Abstract: The manuscript tests the hypothesis that posttranslational modification of the SIBLING family of proteins in general and osteopontin in particular modify the abilities of these proteins to regulate in vitro hydroxyapatite (HA) formation. Osteopontin has diverse effects on hydroxyapatite (HA) mineral crystallite formation and growth depending on the extent of phosphorylation. We hypothesized that different regions of full-length OPN would also have distinct effects on the mineralization process. Thrombin fragmentation of milk OPN (mOPN) was used to test this hypothesis. Three fragments were tested in a de novo HA formation assay; an N-terminal fragment (aa 1-147), a central fragment (aa 148-204) denoted SKK-fragment and a C-terminal fragment (aa 205-262). Compared to intact mOPN the C- and N-terminal fragments behaved comparably, promoting HA formation and growth, but the central SKK-fragment acted as a mineralization inhibitor. In a seeded growth experiment all fragments inhibited mineral proliferation, but the SKK-fragment was the most effective inhibitor. These effects, seen in HA-formation and seeded growth assays in a gelatin gel system and in a pH-stat experiment were lost when the protein or fragments were dephosphorylated. Effects of the fully phosphorylated protein and fragments were also altered in the presence of fibrillar collagen. The diverse effects can be explained in terms of the intrinsically disordered nature of OPN and its fragments which enable them to interact with their multiple partners.

  1. The effect of hydrophilic titanium surface modification on macrophage inflammatory cytokine gene expression.

    PubMed

    Hamlet, Stephen; Alfarsi, Mohammed; George, Roy; Ivanovski, Saso

    2012-05-01

    Chemical modification of microrough titanium dental implants to produce a hydrophilic surface with increased wettability and improved surface energy has been demonstrated clinically to achieve superior bone wound healing and osseointegration compared to that achieved with a microrough titanium surface alone. As the recruitment of the necessary osseoinductive precursors involved in bone wound healing and osseointegration to the wound site is facilitated by the action of cytokines, this study sought to determine the in vitro effect of hydrophilic surface modification on the expression of pro-inflammatory cytokines from adherent macrophages. The surface topography and composition of the titanium surfaces was characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. Macrophage attachment and proliferation was assessed using an MTT assay. The expression of 84 pro-inflammatory cytokines and chemokines by adherent RAW 264.7 cells, a murine leukaemic monocyte cell line, was assessed by PCR array after 24 h culture on either smooth polished, sand-blasted acid-etched (SLA) or hydrophilic-modified SLA (SLActive) titanium surfaces. Following 24 h culture on titanium, surface microroughness activated pro-inflammatory cytokine gene transcription in RAW 264.7 cells. Although there was no significant difference in the degree of cellular attachment or proliferation of RAW 264.7 cells to the different titanium surfaces, by 24 h the hydrophilic surface elicited a gene expression profile with significant down-regulation of the key pro-inflammatory cytokines Tnfα, IL-1α, IL-1β and the chemokine Ccl-2. Down-regulation of the expression of pro-inflammatory cytokine genes may thus modulate the inflammatory response and may facilitate the enhanced bone wound healing and osseointegration observed clinically using implants with a microrough hydrophilic surface. © 2011 John Wiley & Sons A/S.

  2. Surface modification and laser pulse length effects on internal energy transfer in DIOS.

    PubMed

    Luo, Guanghong; Chen, Yong; Siuzdak, Gary; Vertes, Akos

    2005-12-29

    Benzyl-substituted benzylpyridinium (BP) chloride salts were used as a source of thermometer ions to probe the internal energy (IE) transfer in desorption/ionization on porous silicon (DIOS). To modify their wetting properties and the interaction energies with the thermometer ions, the DIOS surfaces were silylated to produce trimethylsilyl- (TMS), amine- (NH2), perfluoroalkyl- (PFA), and perfluorophenyl-derivatized (PFP) surfaces. Two laser sources--a nitrogen laser with pulse length of 4 ns and a mode locked 3 x omega Nd:YAG laser with a pulse length of 22 ps--were utilized to induce desorption/ionization and fragmentation at various laser fluence levels. The corresponding survival yields were determined as indicators of the IE transfer and the IE distributions were extracted. In most cases, with increasing the laser fluence in a broad range (approximately 20 mJ/cm2), no change in IE transfer was observed. For ns excitation, this was in remarkable contrast with MALDI, where increasing the laser fluence resulted in sharply (within approximately 5 mJ/cm2) declining survival yields. Derivatization of the porous silicon surface did not affect the survival yields significantly but had a discernible effect on the threshold fluence for ion production. The IE distributions determined for DIOS and MALDI from alpha-cyano-4-hydroxycinnamic acid reveal that the mean IE value is always lower for the latter. Using the ps laser, the IE distribution is always narrower for DIOS, whereas for ns laser excitation the width depends on surface modification. Most of the differences between MALDI and DIOS described here are compatible with the different dimensionality of the plume expansion and the differences in the activation energy of desorption due to surface modifications.

  3. Effects of Modification of Pain Protocol on Incidence of Post Operative Nausea and Vomiting.

    PubMed

    Schwarzkopf, Ran; Snir, Nimrod; Sharfman, Zachary T; Rinehart, Joseph B; Calderon, Michael-David; Bahn, Esther; Harrington, Brian; Ahn, Kyle

    2016-01-01

    A Perioperative Surgical Home (PSH) care model applies a standardized multidisciplinary approach to patient care using evidence-based medicine to modify and improve protocols. Analysis of patient outcome measures, such as postoperative nausea and vomiting (PONV), allows for refinement of existing protocols to improve patient care. We aim to compare the incidence of PONV in patients who underwent primary total joint arthroplasty before and after modification of our PSH pain protocol. All total joint replacement PSH (TJR-PSH) patients who underwent primary THA (n=149) or TKA (n=212) in the study period were included. The modified protocol added a single dose of intravenous (IV) ketorolac given in the operating room and oxycodone immediate release orally instead of IV Hydromorphone in the Post Anesthesia Care Unit (PACU). The outcomes were (1) incidence of PONV and (2) average pain score in the PACU. We also examined the effect of primary anesthetic (spinal vs. GA) on these outcomes. The groups were compared using chi-square tests of proportions. The incidence of post-operative nausea in the PACU decreased significantly with the modified protocol (27.4% vs. 38.1%, p=0.0442). There was no difference in PONV based on choice of anesthetic or procedure. Average PACU pain scores did not differ significantly between the two protocols. Simple modifications to TJR-PSH multimodal pain management protocol, with decrease in IV narcotic use, resulted in a lower incidence of postoperative nausea, without compromising average PACU pain scores. This report demonstrates the need for continuous monitoring of PSH pathways and implementation of revisions as needed.

  4. Nanostructured lipid carriers used for oral delivery of oridonin: an effect of ligand modification on absorption.

    PubMed

    Zhou, Xiaotong; Zhang, Xingwang; Ye, Yanghuan; Zhang, Tianpeng; Wang, Huan; Ma, Zhiguo; Wu, Baojian

    2015-02-20

    Oridonin (Ori) is a natural compound with notable anti-inflammation and anti-cancer activities. However, therapeutic use of this compound is limited by its poor solubility and low bioavailability. Here a novel biotin-modified nanostructured lipid carrier (NLC) was developed to enhance the bioavailability of Ori. The effect of ligand (biotin) modification on oral absorption of Ori encapsulated in NLCs was also explored. Ori-loaded NLCs (Ori-NLCs) were prepared by the melt dispersion-high pressure homogenization method. Biotin modification of Ori-NLCs was achieved by EDC and NHS in aqueous phase. The obtained biotin-decorated Ori-NLCs (Bio-Ori-NLCs) were 144.9nm in size with an entrapment efficiency of 49.54% and a drug load of 4.81%. Oral bioavailability was enhanced by use of Bio-Ori-NLCs with a relative bioavailability of 171.01%, while the value of non-modified Ori-NLCs was improved to 143.48%. Intestinal perfusion showed that Ori solution unexpectedly exhibited a moderate permeability, indicating that permeability was not a limiting factor of Ori absorption. Ori could be rapidly metabolized that was the main cause of low bioavailability. However, there was a difference in the enhancement of bioavailability between Bio-Ori-NLCs and conventional NLCs. Although severe lipolyses happened both on Bio-Ori-NLCs and non-modified NLCs, the performance of Bio-Ori-NLCs in the bioavailability improvement was more significant. Overall, Bio-Ori-NLCs can further promote the oral absorption of Ori by a ligand-mediated active transport. It may be a promising carrier for the oral delivery of Ori. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Correction of confounding bias in non-randomized studies by appropriate weighting.

    PubMed

    Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

    2011-03-01

    In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effect of Timbre and Register Modifications of Musical Stimuli on Young Children's Identification of Chord Changes.

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia

    1994-01-01

    Reviews research related to children's musical development. Reports on a study of 125 kindergarten and first-grade students on the impact of modification of timbre and register of musical stimuli. Finds that timbre modification helped children recognize chord changes with first graders identifying more changes than did kindergartners. (CFR)

  7. Study of the modifications needed for effective operation NASTRAN on IBM virtual storage computers

    NASA Technical Reports Server (NTRS)

    Mccormick, C. W.; Render, K. H.

    1975-01-01

    The necessary modifications were determined to make NASTRAN operational under virtual storage operating systems (VS1 and VS2). Suggested changes are presented which will make NASTRAN operate more efficiently under these systems. Estimates of the cost and time involved in design, coding, and implementation of all suggested modifications are included.

  8. Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

    PubMed

    Tuk, Bert

    2016-01-01

    Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

  9. [Mechanisms of 232Th effects on Chlorella vulgaris Beljer and modifications of it's toxic effect with caffeine and buthionine sulfoximine].

    PubMed

    Evseeva, T I; Maĭstrenko, T A; Geras'kin, S A; Belykh, E S

    2006-01-01

    232Th effects and its modifications with caffeine and D, L-buthionine-(S, R)-sulphoximine in Chlorella vulgaris Beijer cells was studied with use an optical density measure after 24 hours growth. Was shown relationship between concentration and toxic effect that is nonlinear and characterized with three parts different in induced damages level. In the first concentration range (0.001-1.551 micromol/l) chlorella growth parameters don't significantly differ from control ones. In the second one (1.724-3.017 micromol/1) statistically significant increase of optical density is but the effect does not dependent on 232Th concentration. The 232Th concentration (>3.448 micromol/l) increase the monotonous decrease in optical density was observed. The main role in 232Th toxic effect decrease make processes of DNA reparation, but not free radical scavenging with glutathione.

  10. A two-stage strategy to accommodate general patterns of confounding in the design of observational studies

    PubMed Central

    Haneuse, Sebastien; Schildcrout, Jonathan; Gillen, Daniel

    2012-01-01

    Accommodating general patterns of confounding in sample size/power calculations for observational studies is extremely challenging, both technically and scientifically. While employing previously implemented sample size/power tools is appealing, they typically ignore important aspects of the design/data structure. In this paper, we show that sample size/power calculations that ignore confounding can be much more unreliable than is conventionally thought; using real data from the US state of North Carolina, naive calculations yield sample size estimates that are half those obtained when confounding is appropriately acknowledged. Unfortunately, eliciting realistic design parameters for confounding mechanisms is difficult. To overcome this, we propose a novel two-stage strategy for observational study design that can accommodate arbitrary patterns of confounding. At the first stage, researchers establish bounds for power that facilitate the decision of whether or not to initiate the study. At the second stage, internal pilot data are used to estimate key scientific inputs that can be used to obtain realistic sample size/power. Our results indicate that the strategy is effective at replicating gold standard calculations based on knowing the true confounding mechanism. Finally, we show that consideration of the nature of confounding is a crucial aspect of the elicitation process; depending on whether the confounder is positively or negatively associated with the exposure of interest and outcome, naive power calculations can either under or overestimate the required sample size. Throughout, simulation is advocated as the only general means to obtain realistic estimates of statistical power; we describe, and provide in an R package, a simple algorithm for estimating power for a case–control study. PMID:22130627

  11. A two-stage strategy to accommodate general patterns of confounding in the design of observational studies.

    PubMed

    Haneuse, Sebastien; Schildcrout, Jonathan; Gillen, Daniel

    2012-04-01

    Accommodating general patterns of confounding in sample size/power calculations for observational studies is extremely challenging, both technically and scientifically. While employing previously implemented sample size/power tools is appealing, they typically ignore important aspects of the design/data structure. In this paper, we show that sample size/power calculations that ignore confounding can be much more unreliable than is conventionally thought; using real data from the US state of North Carolina, naive calculations yield sample size estimates that are half those obtained when confounding is appropriately acknowledged. Unfortunately, eliciting realistic design parameters for confounding mechanisms is difficult. To overcome this, we propose a novel two-stage strategy for observational study design that can accommodate arbitrary patterns of confounding. At the first stage, researchers establish bounds for power that facilitate the decision of whether or not to initiate the study. At the second stage, internal pilot data are used to estimate key scientific inputs that can be used to obtain realistic sample size/power. Our results indicate that the strategy is effective at replicating gold standard calculations based on knowing the true confounding mechanism. Finally, we show that consideration of the nature of confounding is a crucial aspect of the elicitation process; depending on whether the confounder is positively or negatively associated with the exposure of interest and outcome, naive power calculations can either under or overestimate the required sample size. Throughout, simulation is advocated as the only general means to obtain realistic estimates of statistical power; we describe, and provide in an R package, a simple algorithm for estimating power for a case-control study.

  12. The importance of scale for spatial-confounding bias and precision of spatial regression estimators

    PubMed Central

    Paciorek, Christopher J

    2010-01-01

    Residuals in regression models are often spatially correlated. Prominent examples include studies in environmental epidemiology to understand the chronic health effects of pollutants. I consider the effects of residual spatial structure on the bias and precision of regression coefficients, developing a simple framework in which to understand the key issues and derive informative analytic results. When unmeasured confounding introduces spatial structure into the residuals, regression models with spatial random effects and closely-related models such as kriging and penalized splines are biased, even when the residual variance components are known. Analytic and simulation results show how the bias depends on the spatial scales of the covariate and the residual: one can reduce bias by fitting a spatial model only when there is variation in the covariate at a scale smaller than the scale of the unmeasured confounding. I also discuss how the scales of the residual and the covariate affect efficiency and uncertainty estimation when the residuals are independent of the covariate. In an application on the association between black carbon particulate matter air pollution and birth weight, controlling for large-scale spatial variation appears to reduce bias from unmeasured confounders, while increasing uncertainty in the estimated pollution effect. PMID:21528104

  13. Density-dependent biodiversity effects on physical habitat modification by freshwater bivalves.

    PubMed

    Allen, Daniel C; Vaughn, Caryn C

    2011-05-01

    Several decades of research have shown that biodiversity affects ecosystem processes associated with resource capture and the production of biomass within trophic levels. Although there are good reasons to expect that biodiversity influences non-trophic ecosystem processes, such as the physical creation or modification of habitat, studies investigating the role of biodiversity on physical processes are scarce. Here we report the results of a study using artificial streams to test the influence of freshwater mussel biodiversity on gravel erosion during high flows while manipulating mussel abundance. Mussel species vary in traits that should influence their effects on erosion, such as size, shell morphology, and burrowing behavior. We found that mussel species richness was associated with an increase in erosion at both low and high densities. Planned contrasts showed that the erosion observed in species mixtures was purely additive at low density, indicating that erosion in a species polyculture could routinely be predicted by the performance of monocultures. However, at high density certain combinations of species showed nonadditive effects on erosion, suggesting that organism abundance can fundamentally alter biodiversity effects. Although this may have been a result of altered species interactions at high density, our study design cannot confirm this.

  14. Saturation and hysteresis effects in ionospheric modification experiments observed by the CUTLASS and EISCAT radars

    NASA Astrophysics Data System (ADS)

    Wright, D. M.; Davies, J. A.; Yeoman, T. K.; Robinson, T. R.; Shergill, H.

    2006-03-01

    The results of high latitude ionospheric modification experiments utilising the EISCAT heating facility at Tromsø are presented. As a result of the interaction between the high power pump waves and upper hybrid waves in the ionosphere, field-aligned electron density irregularities are artificially excited. Observations of these structures with the CUTLASS coherent HF radars and the EISCAT incoherent UHF radar exhibit hysteresis effects as the heater output power is varied. These are explained in terms of the two-stage mechanism which leads to the growth of the irregularities. Experiments which involve preconditioning of the ionosphere also indicate that hysteresis could be exploited to maximise the intensity of the field-aligned irregularities, especially where the available heater power is limited.

    In addition, the saturation of the irregularity amplitude is considered. Although, the rate of irregularity growth becomes less rapid at high heater powers it does not seem to fully saturate, indicating that the amplification would continue beyond the capabilities of the Tromsø heater - currently the most powerful of its kind. It is shown that the CUTLASS radars are sensitive to irregularities produced by very low heater powers (effective radiated powers <4 MW). This fact is discussed from the perspective of a new heating facility, SPEAR, located on Spitzbergen and capable of transmitting high frequency radio waves with an effective radiated power ~10% of that of the Tromsø heater (28MW).

  15. Effects of centrifugal modification of magnetohydrodynamic equilibrium on resistive wall mode stability

    NASA Astrophysics Data System (ADS)

    Shiraishi, J.; Aiba, N.; Miyato, N.; Yagi, M.

    2014-08-01

    Toroidal rotation effects are self-consistently taken into account not only in the linear magnetohydrodynamic (MHD) stability analysis but also in the equilibrium calculation. The MHD equilibrium computation is affected by centrifugal force due to the toroidal rotation. To study the toroidal rotation effects on resistive wall modes (RWMs), a new code has been developed. The RWMaC modules, which solve the electromagnetic dynamics in vacuum and the resistive wall, have been implemented in the MINERVA code, which solves the Frieman-Rotenberg equation that describes the linear ideal MHD dynamics in a rotating plasma. It is shown that modification of MHD equilibrium by the centrifugal force significantly reduces growth rates of RWMs with fast rotation in the order of M2 = 0.1 where M is the Mach number. Moreover, it can open a stable window which does not exist under the assumption that the rotation affects only the linear dynamics. The rotation modifies the equilibrium pressure gradient and current density profiles, which results in the change of potential energy including rotational effects.

  16. Effect of sulfhydryl modification on rat kidney basolateral plasma membrane transport function.

    PubMed

    Ansari, Rais A; Rizvi, Syed A A; Husain, Kazim; Lymperopoulos, Anastasios; Berndt, William O

    2012-10-01

    Transport processes are the hallmark of functioning kidney. Various nephrotoxicants disrupt the transport processes to manifest nephrotoxicity. Of several nephrotoxicants, mercuric chloride (HgCl(2)) depletes the reduced glutathione (GSH) in kidney and has been observed to affect the in vitro p-aminohippurate (PAH) transport by basolateral (BL) membrane vesicles. The role of renal nonprotein sulfhydryls such as, reduced GSH has been demonstrated to affect the PAH transport by BL membrane vesicles. The role of protein sulfhydryls in transport process of PAH by BL membrane is not known. Due to mercury mediated effects on sulfhydryls, the effects of protein-sulfhydryls (-SH) modifying reagents in the current study were investigated on PAH transport by BL membrane. It was observed that modification of -SH by p-chloromercuribenzoate sulphate (pCMBS), and mercuric chloride (HgCl(2)) decreased while recovering the protein -SH with dithiothreitol treatment provided protection against the effects of pCMBS, and HgCl(2) on PAH transport by BL membrane vesicles.

  17. Effects of laser fluence on silicon modification by four-beam laser interference

    SciTech Connect

    Zhao, Le; Li, Dayou; Wang, Zuobin Yue, Yong; Zhang, Jinjin; Yu, Miao; Li, Siwei

    2015-12-21

    This paper discusses the effects of laser fluence on silicon modification by four-beam laser interference. In this work, four-beam laser interference was used to pattern single crystal silicon wafers for the fabrication of surface structures, and the number of laser pulses was applied to the process in air. By controlling the parameters of laser irradiation, different shapes of silicon structures were fabricated. The results were obtained with the single laser fluence of 354 mJ/cm{sup 2}, 495 mJ/cm{sup 2}, and 637 mJ/cm{sup 2}, the pulse repetition rate of 10 Hz, the laser exposure pulses of 30, 100, and 300, the laser wavelength of 1064 nm, and the pulse duration of 7–9 ns. The effects of the heat transfer and the radiation of laser interference plasma on silicon wafer surfaces were investigated. The equations of heat flow and radiation effects of laser plasma of interfering patterns in a four-beam laser interference distribution were proposed to describe their impacts on silicon wafer surfaces. The experimental results have shown that the laser fluence has to be properly selected for the fabrication of well-defined surface structures in a four-beam laser interference process. Laser interference patterns can directly fabricate different shape structures for their corresponding applications.

  18. Effects of behavior modification on body image, depression and body fat in obese Korean elementary school children.

    PubMed

    Moon, Young Im; Park, Ho Ran; Koo, Hyun Young; Kim, Hyo Shin

    2004-02-29

    This study was performed to investigate the effects of behavior modification on body image, depression and body fat in obese elementary school children. Sixty-two elementary students of the 4th to 6th grade were selected from two different Seoul schools. Thirty-four children in one school were designated as the experimental group, and 28 children from the other school as the control group. The experimental group received 60 - 70 minutes of behavior modification, once a week, for 8 weeks. The control group received neither management nor treatment. The results indicated a significant improvement of body image and a reduction in the increase rate of body fat for the experimental group. This finding strongly supports the theory that behavior modification can be used as an effective strategy in the treatment of obese children.

  19. The effect of chemical modification with pyromellitic anhydride on structure, function, and thermal stability of horseradish peroxidase.

    PubMed

    Hassani, Leila

    2012-06-01

    The stability of enzymes remains a critical issue in biotechnology. Compared with the strategies for obtaining stable enzymes, chemical modification is a simple and effective technique. In the present study, chemical modification of horseradish peroxidase (HRP) was carried out with pyromellitic anhydride. HRP has achieved a prominent position in the pharmaceutical, chemical, and biotechnological industries. In this study, the effect of chemical modification on thermal stability, structure, and function of the enzyme was studied by fluorescence, circular dichroism, and absorbance measurements. The results indicated a decrease in compactness of the structure and a considerable enhancement in thermal stability of HRP below 60 °C. It seems the charge replacement and introduction of the bulky group bring about the observed structural and the functional changes.

  20. Confounding effects of spatial variation on shifts in phenology.

    PubMed

    de Keyzer, Charlotte W; Rafferty, Nicole E; Inouye, David W; Thomson, James D

    2017-05-01

    Shifts in the timing of life history events have become an important source of information about how organisms are responding to climate change. Phenological data have generally been treated as purely temporal, with scant attention to the inherent spatial aspects of such data. However, phenological data are tied to a specific location, and considerations of sampling design, both over space and through time, can critically affect the patterns that emerge. Focusing on flowering phenology, we describe how purely spatial shifts, such as adding new study plots, or the colonization of a study plot by a new species, can masquerade as temporal shifts. Such shifts can look like responses to climate change but are not. Furthermore, the same aggregate phenological curves can be composed of individuals with either very different or very similar phenologies. We conclude with a set of recommendations to avoid ambiguities arising from the spatiotemporal duality of phenological data.

  1. Effect of Cast Modification on Denture Base Adaptation Following Maxillary Complete Denture Processing.

    PubMed

    Sayed, Mohammed E; Porwal, Amit; Ehrenberg, David; Weiner, Saul

    2017-01-19

    To investigate the effect of cast modifications on denture base adaptation in coronal and sagittal projections following maxillary complete denture processing. A total of 60 edentulous maxillary casts (n = 10) were distributed among six groups. Group 1 was the control group with no modification, groups 2 through 6 included a butterfly postdam preparation, groups 3 and 4 also included a 10-mm wide/4-mm deep box with addition of four round holes in group 4, and groups 5 and 6 also included a 20-mm wide/4-mm deep box with addition of four round holes in group 6. The boxes were prepared at the mid-heel area of the casts. Two layers of baseplate wax (1 mm each) were used to standardize denture base thickness across the groups. A standard technique was used to replicate the denture tooth set-up, and standardized processing was done for all the groups. Following deflasking, casts with the dentures were sectioned in the coronal and sagittal directions. Microscopic pictures were taken at preselected points. Data were organized in tables, and statistical analyses were performed using repeated measure ANOVA, Tukey post hoc tests, and post hoc comparison tests set at 5% level of significance. Maximum gaps were measured at the mid-palatal area followed by nearby areas and the areas near ridge crests in both coronal and sagittal projections. The analyses revealed significant differences between the groups in coronal projection (1/2, 3/4, 5/6) and sagittal projection (1, 2, 3/4, 5/6) without significant differences within the pairs. The groups were ranked from the highest group 1 to the lowest group 6 relative to the gap means. Post hoc comparisons showed that points 1C and 2A had the highest gap means across the study groups. Within the limitations of this study, it can be extrapolated that the denture base adaptation can be effectively increased with the box preparation at the mid-heel aspect of the casts. Significant reduction of gaps was seen when the box size increased from

  2. Evaluating the cost-effectiveness of lifestyle modification versus metformin therapy for the prevention of diabetes in Singapore.

    PubMed

    Png, May Ee; Yoong, Joanne Su-Yin

    2014-01-01

    In Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective. Cost effectiveness was analysed from 2010-2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars. The total economic cost for non-diabetic subjects from the societal perspective was US$25,867, US$28,108 and US$26,177 for placebo, lifestyle modification and metformin intervention respectively. For diabetic patients, the total economic cost from the societal perspective was US$32,921, US$35,163 and US$33,232 for placebo, lifestyle modification and metformin intervention respectively. Lifestyle modification relative to placebo is likely to be associated with an incremental cost per QALY gained at US$36,663 while that of metformin intervention is likely to be US$6,367 from a societal perspective. Based on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However, the cost of lifestyle modification from the societal

  3. Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

    PubMed

    Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2016-11-01

    It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up.

  4. Mediation Analysis With Intermediate Confounding: Structural Equation Modeling Viewed Through the Causal Inference Lens

    PubMed Central

    De Stavola, Bianca L.; Daniel, Rhian M.; Ploubidis, George B.; Micali, Nadia

    2015-01-01

    The study of mediation has a long tradition in the social sciences and a relatively more recent one in epidemiology. The first school is linked to path analysis and structural equation models (SEMs), while the second is related mostly to methods developed within the potential outcomes approach to causal inference. By giving model-free definitions of direct and indirect effects and clear assumptions for their identification, the latter school has formalized notions intuitively developed in the former and has greatly increased the flexibility of the models involved. However, through its predominant focus on nonparametric identification, the causal inference approach to effect decomposition via natural effects is limited to settings that exclude intermediate confounders. Such confounders are naturally dealt with (albeit with the caveats of informality and modeling inflexibility) in the SEM framework. Therefore, it seems pertinent to revisit SEMs with intermediate confounders, armed with the formal definitions and (parametric) identification assumptions from causal inference. Here we investigate: 1) how identification assumptions affect the specification of SEMs, 2) whether the more restrictive SEM assumptions can be relaxed, and 3) whether existing sensitivity analyses can be extended to this setting. Data from the Avon Longitudinal Study of Parents and Children (1990–2005) are used for illustration. PMID:25504026

  5. Mediation analysis with intermediate confounding: structural equation modeling viewed through the causal inference lens.

    PubMed

    De Stavola, Bianca L; Daniel, Rhian M; Ploubidis, George B; Micali, Nadia

    2015-01-01

    The study of mediation has a long tradition in the social sciences and a relatively more recent one in epidemiology. The first school is linked to path analysis and structural equation models (SEMs), while the second is related mostly to methods developed within the potential outcomes approach to causal inference. By giving model-free definitions of direct and indirect effects and clear assumptions for their identification, the latter school has formalized notions intuitively developed in the former and has greatly increased the flexibility of the models involved. However, through its predominant focus on nonparametric identification, the causal inference approach to effect decomposition via natural effects is limited to settings that exclude intermediate confounders. Such confounders are naturally dealt with (albeit with the caveats of informality and modeling inflexibility) in the SEM framework. Therefore, it seems pertinent to revisit SEMs with intermediate confounders, armed with the formal definitions and (parametric) identification assumptions from causal inference. Here we investigate: 1) how identification assumptions affect the specification of SEMs, 2) whether the more restrictive SEM assumptions can be relaxed, and 3) whether existing sensitivity analyses can be extended to this setting. Data from the Avon Longitudinal Study of Parents and Children (1990-2005) are used for illustration.

  6. Multiple imputation for handling systematically missing confounders in meta-analysis of individual participant data.

    PubMed

    Resche-Rigon, Matthieu; White, Ian R; Bartlett, Jonathan W; Peters, Sanne A E; Thompson, Simon G

    2013-12-10

    A variable is 'systematically missing' if it is missing for all individuals within particular studies in an individual participant data meta-analysis. When a systematically missing variable is a potential confounder in observational epidemiology, standard methods either fail to adjust the exposure-disease association for the potential confounder or exclude studies where it is missing. We propose a new approach to adjust for systematically missing confounders based on multiple imputation by chained equations. Systematically missing data are imputed via multilevel regression models that allow for heterogeneity between studies. A simulation study compares various choices of imputation model. An illustration is given using data from eight studies estimating the association between carotid intima media thickness and subsequent risk of cardiovascular events. Results are compared with standard methods and also with an extension of a published method that exploits the relationship between fully adjusted and partially adjusted estimated effects through a multivariate random effects meta-analysis model. We conclude that multiple imputation provides a practicable approach that can handle arbitrary patterns of systematic missingness. Bias is reduced by including sufficient between-study random effects in the imputation model.

  7. [Effect of modification of the N-terminal region of molecule on the expression of neotropic effect of semax analogues].

    PubMed

    Glazova, N Iu; Sebentsova, E A; Levitskaia, N G; Andreeva, L A; Alfeeva, L Iu; Kamenskiĭ, A A; Miasoedov, N F

    2005-01-01

    A comparative study of neotropic activity of semax (MEHFPGP), an analogue of the ACTH(4-10), and some of its derivatives in which the N-terminal methionine was modified or substituted with other amino acid residues was performed. The effect of these peptides on learning of albino rats in tests with positive (alimentary) and negative (pain) reinforcement was studied. In the case of modification of methionine by attachment of the gluconic-acid residue or substitution of methionine with lysine, the neotropic effect of the peptide was retained. The substitution of methionine with tryptophan or serine resulted in a decrease in the neotropic activity. The substitution of methionine with glycine, threonine, or alanine caused a complete loss of the neotropic activity of the peptide. Therefore, the amino acid residue located at position 1 of the heptapeptide analogue semax, plays a key role in retaining the neotropic effects of the peptide and determines the degree of their expression.

  8. Effects of channel modifications on the hydrology of Chicod Creek basin, North Carolina, 1975-87

    USGS Publications Warehouse

    Mason, R.R.; Simmons, C.E.; Watkins, S.A.

    1990-01-01

    Drainage modifications in this Coastal Plain basin from 1978 to 1981 consisted of channel excavation and clearing of blockages. A study was begun in 1975 to define hydrologic conditions of the basin before, during, and after modifications and to determine what changes were attributed to modifications. Surface-water conditions were altered during and following modifications. Minimum flow at Juniper Branch was increased from less than 0.1 cu ft/sec to 0.4 cu ft/second;streamflow variability was reduced from an index of 0.87 to 0.49. In-channel velocity at Chicod Creek was increased from a mean of 0.4 ft/sec to 1.5 ft/sec. Substantial groundwater level declines were observed in wells 180 and 250 ft from Juniper Branch during the modifications phase;these were 0.4 and 0.2 ft, respectively. However, most surface-water and groundwater conditions returned nearly to premodification levels by 1987. Water-quality characteristics monitored during the investigation included physical, chemical, and bacteriological characteristics. Physical characteristics monitored were suspended sediment, temperature, dissolved oxygen, and pH. Of these physical characteristics, only sediment concentrations increased substantially during channel modifications. Chemical characteristics studied were major dissolved constituents, nutrients, trace metals, and pesticides. Substantial changes ranged from a decline in total iron concentrations of 77% to an increase in total nitrite concentrations of 130%. Changes in many chemical characteristics persisted following channel modifications. Bacterial counts did not change substantially.

  9. Flaperon Modification Effect on Jet-Flap Interaction Noise Reduction for Chevron Nozzles

    NASA Technical Reports Server (NTRS)

    Thomas, Russell H.; Mengle, Vinod G.; Stoker, Robert W.; Brusniak, Leon; Elkoby, Ronen

    2007-01-01

    Jet-flap interaction (JFI) noise can become an important component of far field noise when a flap is immersed in the engine propulsive stream or is in its entrained region, as in approach conditions for under-the-wing engine configurations. We experimentally study the effect of modifying the flaperon, which is a high speed aileron between the inboard and outboard flaps, at both approach and take-off conditions using scaled models in a free jet. The flaperon modifications were of two types: sawtooth trailing edge and mini vortex generators (vg s). Parametric variations of these two concepts were tested with a round coaxial nozzle and an advanced chevron nozzle, with azimuthally varying fan chevrons, using both far field microphone arrays and phased microphone arrays for source diagnostics purposes. In general, the phased array results corroborated the far field results in the upstream quadrant pointing to JFI near the flaperon trailing edge as the origin of the far field noise changes. Specific sawtooth trailing edges in conjunction with the round nozzle gave marginal reduction in JFI noise at approach, and parallel co-rotating mini-vg s were somewhat more beneficial over a wider range of angles, but both concepts were noisier at take-off conditions. These two concepts had generally an adverse JFI effect when used in conjunction with the advanced chevron nozzle at both approach and take-off conditions.

  10. Effect of climatic warming on the Pacific walrus, and potential modification of its helminth fauna.

    PubMed

    Rausch, Robert L; George, John C; Brower, Harry K

    2007-10-01

    The decreasing extent of sea-ice in the arctic basin as a consequence of climatic warming is modifying the behavior and diets of pagophilic pinnipeds, including the Pacific walrus, Odobenus rosmarus divergens Illiger, the species emphasized here. Mammals such as the walrus and bearded seal, Erignathus barbatus (Erxleben), cannot remain associated with the sea-ice, and continue to feed on their usual diet of benthic invertebrates inhabiting coastal waters to a depth of approximately 100 m, when the northwestward retreating ice reaches deep waters beyond the margins of the continental shelf. With reduction of their customary substrate (ice), the walrus has become more pelagic and preys more often on ringed seals, Phoca hispida Schreber. Dietary changes, with modifications of helminth faunas, may be induced by various factors. Increased consumption of mammals or their remains by walruses may lead to a higher prevalence of trichinellosis in them and to more frequent occurrence in indigenous peoples inhabiting the arctic coasts. To assess predicted effects on the composition of helminth fauna of the walrus, we recommend systematic surveys of their helminths as part of research on effects of climatic warming.

  11. Synergetic effects of DNA methylation and histone modification during mouse induced pluripotent stem cell generation

    PubMed Central

    Wang, Guiying; Weng, Rong; Lan, Yuanyuan; Guo, Xudong; Liu, Qidong; Liu, Xiaoqin; Lu, Chenqi; Kang, Jiuhong

    2017-01-01

    DNA methylation and histone methylation (H3K27me3) have been reported as major barriers to induced pluripotent stem cell (iPSC) generation using four core transcription factors (Oct4, Sox2, Klf4, and c-Myc, termed OSKM). Here, to illustrate the possibility of deriving iPSCs via demethylation, as well as the exact effects of DNA methylation and histone modification on gene expression regulation, we performed RNA sequencing to characterize the transcriptomes of ES cells and iPSCs derived by demethylation with miR-29b or shDnmt3a, and carried out integrated analyses. Results showed that OSKM + miR-29b-iPSC was more close to ES cells than the others, and up-regulated genes typically presented with methylated CpG-dense promoters and H3K27me3-enriched regions. The differentially expressed genes caused by introduction of DNA demethylation during somatic cell reprogramming mainly focus on stem cell associated GO terms and KEGG signaling pathways, which may decrease the tumorigenesis risk of iPSCs. These findings indicated that DNA methylation and histone methylation have synergetic effects on regulating gene expression during iPSC generation, and demethylation by miR-29b is better than shDnmt3a for iPSC quality. Furthermore, integrated analyses are superior for exploration of slight differences as missed by individual analysis. PMID:28155862

  12. Temperature, myocardial infarction, and mortality: effect modification by individual- and area-level characteristics.

    PubMed

    Madrigano, Jaime; Mittleman, Murray A; Baccarelli, Andrea; Goldberg, Robert; Melly, Steven; von Klot, Stephanie; Schwartz, Joel

    2013-05-01

    Although several studies have examined associations between temperature and cardiovascular-disease-related mortality, fewer have investigated the association between temperature and the development of acute myocardial infarction (MI). Moreover, little is known about who is most susceptible to the effects of temperature. We analyzed data from the Worcester Heart Attack Study, a community-wide investigation of acute MI in residents of the Worcester (MA) metropolitan area. We used a case-crossover approach to examine the association of apparent temperature with acute MI occurrence and with all-cause in-hospital and postdischarge mortality. We examined effect modification by sociodemographic characteristics, medical history, clinical complications, and physical environment. A decrease in an interquartile range in apparent temperature was associated with an increased risk of acute MI on the same day (hazard ratio = 1.15 [95% confidence interval = 1.01-1.31]). Extreme cold during the 2 days prior was associated with an increased risk of acute MI (1.36 [1.07-1.74]). Extreme heat during the 2 days prior was also associated with an increased risk of mortality (1.44 [1.06-1.96]). Persons living in areas with greater poverty were more susceptible to heat. Exposure to cold increased the risk of acute MI, and exposure to heat increased the risk of dying after an acute MI. Local area vulnerability should be accounted for as cities prepare to adapt to weather fluctuations as a result of climate change.

  13. Dependence of Ion Energy on PTFE Surface Modification Effect by Nitrogen Ion Irradiation

    NASA Astrophysics Data System (ADS)

    Nakayama, Akihiko; Iwao, Toru; Yumoto, Motoshige

    PTFE (Poly-tetra-fluoro-ethylene) has superior characteristic. But, it has low adhesion force. In order to improve adhesion force, we have studied on surface modification of PTFE by using discharge under high E/n (E:electric field, n:particle density) condition in nitrogen. From the results, it was deduced that ion energy around 40 eV is effective for polar groups introduction. In addition, treated surface unevenness did not increase compared with the untreated one. Then, we performed nitrogen ion irradiation by changing ion energy. From the results, it is shown that low ion energy is effective for polar groups introduction. It is also shown that high energy ion suppresses surface roughness. Thus, we measured surface energy and composition of samples irradiated by high and low energy ions. When ion with 30 eV was irradiated for 5 minute and following it ion with 1060 eV was irradiated for 10 second, many polar groups were introduced and surface unevenness was kept at the untreatment level. From the results by XPS (X-ray Photoelectron Spectroscopy) analysis and FT-IR (Fourier transform Infrared Spectroscopy) analysis by using the ATR (Attenuated Total Reflection) method, it was confirmed that polar groups of oxygen component and cross-linked structure via nitrogen or carbon was introduced at the surface.

  14. Modification of foaming properties of soy protein isolate by high ultrasound intensity: Particle size effect.

    PubMed

    Morales, Rocío; Martínez, Karina D; Pizones Ruiz-Henestrosa, Víctor M; Pilosof, Ana M R

    2015-09-01

    The effect of high intensity ultrasound (HIUS) may produce structural modifications on proteins through a friendly environmental process. Thus, it can be possible to obtain aggregates with a determined particle size, and altering a defined functional property at the same time. The objective of this work was to explore the impact of HIUS on the functionality of a denatured soy protein isolate (SPI) on foaming and interfacial properties. SPI solutions at pH 6.9 were treated with HIUS for 20 min, in an ultrasonic processor at room temperature, at 75, 80 and 85°C. The operating conditions were: 20 kHz, 4.27 ± 0.71 W and 20% of amplitude. It was determined the size of the protein particles, before and after the HIUS treatment, by dynamic light scattering. It was also analyzed the interfacial behavior of the different systems as well as their foaming properties, by applying the whipping method. The HIUS treatment and HIUS with temperature improved the foaming capacity by alteration of particle size whereas stability was not modified significantly. The temperature of HIUS treatment (80 and 85°C) showed a synergistic effect on foaming capacity. It was found that the reduction of particle size was related to the increase of foaming capacity of SPI. On the other hand, the invariable elasticity of the interfacial films could explain the stability of foams over time.

  15. Effects of genetic modification on herbivore-induced volatiles from maize.

    PubMed

    Dean, Jennifer M; De Moraes, Consuelo M

    2006-04-01

    Large-scale implementation of transgenic crop varieties raises concerns about possible nontarget effects on other organisms. This study examines the effects of genetic modification on plant volatile production and its potential impact on arthropod population dynamics. We compared herbivore-induced volatile emissions from Bacillus thuringiensis Berliner (Bt) maize plants to those from a nontransformed isoline following exposure to various types of leaf damage. When equal numbers of Helicoverpa zea Boddie (Lepidoptera: Noctuidae) larvae fed on Bt and non-Bt maize, volatile emissions were significantly lower in the transgenic plants, which also exhibited less leaf damage. When damage levels were controlled by adding more larvae to Bt plants, the plants' volatile emissions increased but displayed significant differences from those of nontransgenic plants. Significantly higher amounts of linalool, beta-myrcene, and geranyl acetate were released from transgenic maize than from non-Bt plants. Manipulating the duration of feeding by individual larvae to produce similar damage patterns resulted in similar volatile profiles for Bt and non-Bt plants. Controlling damage levels more precisely by mechanically wounding leaves and applying larval regurgitant likewise resulted in similar emission patterns for Bt and non-Bt maize. Overall, changes in the herbivore-induced volatile profiles of Bt maize appeared to be a consequence of altered larval feeding behavior rather than of changes in biochemical plant defense pathways. The implications of these findings for understanding the impacts of plant-mediated cues on pest and natural enemy behavior in transgenic crop systems are discussed.

  16. Effects of surface modification of talc on mechanical properties of polypropylene/talc composites

    NASA Astrophysics Data System (ADS)

    Liu, Keyan; Stadlbauer, Wolfgang; Zitzenbacher, Gernot; Paulik, Christian; Burgstaller, Christoph

    2016-03-01

    Low compatibility of polymer matrix and dispersed filler negatively affects the performance of polymeric composites. In order to improve the adhesion between the components in a compound the polymer matrix or/and the filler particles should be modified with a compatibilizer or/and a coupling agent. An overview of our current research on the effect of the addition of silane treated and untreated talc powders on the mechanical properties of polypropylene/talc composites is presented in this paper. Different silane coupling agents (3-aminopropyltriethoxysilane, 3-glycidoxypropyltrimethoxysilane and 3-methacryloxypropyltrimethoxysilane) were used to improve the adhesion at the surface of talc powders. Maleic anhydride grafted polypropylene was utilized to increase the adhesion between the polypropylene matrix and talc powders. The content of maleic anhydride grafted polypropylene (MA-g-PP) was varied between 1 and 5 wt% in polypropylene/talc composites. The surface modification of talc powders has a significant effect on the interfacial structure and the mechanical properties such as tensile strength and impact strength of polypropylene/talc composites. The experiments show that polypropylene grafted with maleic anhydride together with silane surface treatment exhibits the highest potential for improvements in this field.

  17. Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

    SciTech Connect

    Singh, Nrashant; Kumar, D.; Lal, Kewal; Raisuddin, S.; Sahu, Anand P.

    2010-02-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

  18. Effect of lycopene and {beta}-carotene on peroxynitrite-mediated cellular modifications

    SciTech Connect

    Muzandu, Kaampwe; Ishizuka, Mayumi; Sakamoto, Kentaro Q.; Shaban, Zein; El Bohi, Khlood; Kazusaka, Akio; Fujita, Shoichi . E-mail: fujita@vetmed.hokudai.ac.jp

    2006-09-15

    Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and {beta}-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 {mu}M) of lycopene and {beta}-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 {mu}M). The protective effects of lycopene and {beta}-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.

  19. A Randomized Controlled Study to Examine the Effect of a Lifestyle Modification Program in OSA.

    PubMed

    Ng, Susanna S S; Chan, Ruth S M; Woo, Jean; Chan, Tat-On; Cheung, Bernice H K; Sea, Mandy M M; To, Kin-Wang; Chan, Ken K P; Ngai, Jenny; Yip, Wing-Ho; Ko, Fanny W S; Hui, David S C

    2015-11-01

    Obesity is an important risk factor for OSA. This study aimed to assess the effect of weight reduction through a lifestyle modification program (LMP) on patients with moderate to severe OSA. This was a parallel group, randomized controlled trial. Altogether, 104 patients with moderate to severe OSA diagnosed on portable home sleep monitoring were randomized to receive a dietician-led LMP or usual care for 12 months. The primary outcome was reduction of apnea-hypopnea index (AHI) at 12 months as assessed by portable home sleep monitoring. In the intention-to-treat analysis (ITT), LMP (n = 61) was more effective in reducing AHI from baseline (16.9% fewer events in the LMP group vs 0.6% more events in the control group, P = .011). LMP was more effective in reducing BMI (-1.8 kg/m2, 6.0% of the initial BMI; -0.6 kg/m2, 2.0% of the initial BMI in control group; P < .001). The reduction in daytime sleepiness as assessed by Epworth Sleepiness Scale was not significant in ITT but was more in the LMP group (-3.5 in the LMP group vs -1.1 in the control group, P = .004) by treatment per protocol analysis. There was modest improvement in mental health in the Short Form Health Survey. Eating behavior was improved with increased intake of protein and fiber. These changes were observed 4 months after the initial intensive diet counseling and persisted at 12 months. LMP was effective in reducing the severity of OSA and daytime sleepiness. The beneficial effect was sustained in 12 months. ClinicalTrials.gov; No.: NCT01384760; URL: www.clinicaltrials.gov.

  20. Method of predictive studies of the effectiveness of spacecraft modifications with integrated subsystem replacement

    NASA Astrophysics Data System (ADS)

    Matveev, Yu. A.; Lamzin, V. A.; Lamzin, V. V.

    2016-12-01

    The article reviews application features of the method of bilevel coordinated optimization of spacecraft modification parameters during integrated replacement of subsystems. The algorithm for problem solution is presented in the article. It is shown that in the case of implementation of a balanced bilevel schematic of optimization search, the agreement of project solutions for spacecraft modification is provided by integrated replacement of subsystems. Project models are shown for the problem solution of optimization parameters for spacecraft modification with the integrated replacement of subsystems of the payload equipment module and a unified space platform.

  1. Radiation-induced alterations in histone modification patterns and their potential impact on short-term radiation effects

    PubMed Central

    Friedl, Anna A.; Mazurek, Belinda; Seiler, Doris M.

    2012-01-01

    Detection and repair of radiation-induced DNA damage occur in the context of chromatin. An intricate network of mechanisms defines chromatin structure, including DNA methylation, incorporation of histone variants, histone modifications, and chromatin remodeling. In the last years it became clear that the cellular response to radiation-induced DNA damage involves all of these mechanisms. Here we focus on the current knowledge on radiation-induced alterations in post-translational histone modification patterns and their effect on the chromatin accessibility, transcriptional regulation and chromosomal stability. PMID:23050241

  2. Threats to internal validity in exercise science: a review of overlooked confounding variables.

    PubMed

    Halperin, Israel; Pyne, David B; Martin, David T

    2015-10-01

    Internal validity refers to the degree of control exerted over potential confounding variables to reduce alternative explanations for the effects of various treatments. In exercise and sports-science research and routine testing, internal validity is commonly achieved by controlling variables such as exercise and warm-up protocols, prior training, nutritional intake before testing, ambient temperature, time of testing, hours of sleep, age, and gender. However, a number of other potential confounding variables often do not receive adequate attention in sports physiology and performance research. These confounding variables include instructions on how to perform the test, volume and frequency of verbal encouragement, knowledge of exercise endpoint, number and gender of observers in the room, influence of music played before and during testing, and the effects of mental fatigue on performance. In this review the authors discuss these variables in relation to common testing environments in exercise and sports science and present some recommendations with the goal of reducing possible threats to internal validity.

  3. The impact of latent confounders in directed network analysis in neuroscience.

    PubMed

    Ramb, Rebecca; Eichler, Michael; Ing, Alex; Thiel, Marco; Weiller, Cornelius; Grebogi, Celso; Schwarzbauer, Christian; Timmer, Jens; Schelter, Björn

    2013-08-28

    In the analysis of neuroscience data, the identification of task-related causal relationships between various areas of the brain gives insights about the network of physiological pathways that are active during the task. One increasingly used approach to identify causal connectivity uses the concept of Granger causality that exploits predictability of activity in one region by past activity in other regions of the brain. Owing to the complexity of the data, selecting components for the analysis of causality as a preprocessing step has to be performed. This includes predetermined-and often arbitrary-exclusion of information. Therefore, the system is confounded by latent sources. In this paper, the effect of latent confounders is demonstrated, and paths of influence among three components are studied. While methods for analysing Granger causality are commonly based on linear vector autoregressive models, the effects of latent confounders are expected to be present also in nonlinear systems. Therefore, all analyses are also performed for a simulated nonlinear system and discussed with regard to applications in neuroscience.

  4. Structural and physico-chemical properties of insoluble rice bran fiber: effect of acid–base induced modifications

    USDA-ARS?s Scientific Manuscript database

    The structural modifications of insoluble rice bran fiber (IRBF) by sequential regimes of sulphuric acid (H2SO4) and their effects on the physicochemical attributes were studied. The increment of H2SO4 concentration resulted in decreased water holding capacity that ultimately enhanced the oil bindin...

  5. Effect of Web-based lifestyle modification on weight control: a meta-analysis.

    PubMed

    Kodama, S; Saito, K; Tanaka, S; Horikawa, C; Fujiwara, K; Hirasawa, R; Yachi, Y; Iida, K T; Shimano, H; Ohashi, Y; Yamada, N; Sone, H

    2012-05-01

    Web-based treatment programs are attractive in primary care because of their ability to reach numerous individuals at low cost. Our aim of this meta-analysis is to systematically review the weight loss or maintenance effect of the Internet component in obesity treatment programs. MEDLINE and EMBASE literature searches were conducted to identify studies investigating the effect of Web-based individualized advice on lifestyle modification on weight loss. Randomized controlled trials that consisted of a Web-user experimental and non-Web user control group were included. Weight changes in the experimental group in comparison with the control group were pooled with a random-effects model. A total of 23 studies comprising 8697 participants were included. Overall, using the Internet had a modest but significant additional weight-loss effect compared with non-Web user control groups (-0.68 kg, P=0.03). In comparison with the control group, stratified analysis indicated that using the Internet as an adjunct to obesity care was effective (-1.00 kg, P<0.001), but that using it as a substitute for face-to-face support was unfavorable (+1.27 kg, P=0.01). An additional effect on weight control was observed when the aim of using the Internet was initial weight loss (-1.01 kg; P=0.03), but was not observed when the aim was weight maintenance (+0.68 kg; P=0.26). The relative effect was diminished with longer educational periods (P-trend=0.04) and was insignificant (-0.20 kg; P=0.75) in studies with educational periods of 12 months or more. The current meta-analysis indicates that the Internet component in obesity treatment programs has a modest effect on weight control. However, the effect was inconsistent, largely depending on the type of usage of the Internet or the period of its use.

  6. Effect of surface modifications on ZnO nanorod arrays electrode for dye-sensitized solar cells.

    PubMed

    Qin, Zi; Huang, Yunhua; Liao, Qingliang; Zhang, Zheng; Zhang, Yue

    2012-01-01

    High quality, large area and well-oriented ZnO nanorod arrays electrodes were successfully synthesized on conductive transparent oxide substrates by low-temperature hydrothermal methods for dye-sensitized solar cells. Aiming at getting further enhancement and study the effect of the surface modification on cell performance, ZnO thin film and ZnO nanoparticles are carried out to modify the as-grown ZnO nanorod arrays. The morphology, structure and photoluminescence property of the modified ZnO electrodes are characterized in detail. Furthermore, the I-V characterization result shows that these modification methods have distinct influences on the performance of the cell based on ZnO nanorod arrays electrode. The overall conversion efficiency can be optimized by choosing the suitable modification route.

  7. Diagnostics for Confounding of Time-varying and Other Joint Exposures.

    PubMed

    Jackson, John W

    2016-11-01

    The effects of joint exposures (or exposure regimes) include those of adhering to assigned treatment versus placebo in a randomized controlled trial, duration of exposure in a cohort study, interactions between exposures, and direct effects of exposure, among others. Unlike the setting of a single point exposure (e.g., propensity score matching), there are few tools to describe confounding for joint exposures or how well a method resolves it. Investigators need tools that describe confounding in ways that are conceptually grounded and intuitive for those who read, review, and use applied research to guide policy. We revisit the implications of exchangeability conditions that hold in sequentially randomized trials, and the bias structure that motivates the use of g-methods, such as marginal structural models. From these, we develop covariate balance diagnostics for joint exposures that can (1) describe time-varying confounding, (2) assess whether covariates are predicted by prior exposures given their past, the indication for g-methods, and (3) describe residual confounding after inverse probability weighting. For each diagnostic, we present time-specific metrics that encompass a wide class of joint exposures, including regimes of multivariate time-varying exposures in censored data, with multivariate point exposures as a special case. We outline how to estimate these directly or with regression and how to average them over person-time. Using a simulated example, we show how these metrics can be presented graphically. This conceptually grounded framework can potentially aid the transparent design, analysis, and reporting of studies that examine joint exposures. We provide easy-to-use tools to implement it.

  8. Milk whey protein modification by coffee-specific phenolics: effect on structural and functional properties.

    PubMed

    Ali, Mostafa; Homann, Thomas; Khalil, Mahmoud; Kruse, Hans-Peter; Rawel, Harshadrai

    2013-07-17

    A suitable vehicle for integration of bioactive plant constituents is proposed. It involves modification of proteins using phenolics and applying these for protection of labile constituents. It dissects the noncovalent and covalent interactions of β-lactoglobulin with coffee-specific phenolics. Alkaline and polyphenol oxidase modulated covalent reactions were compared. Tryptic digestion combined with MALDI-TOF-MS provided tentative allocation of the modification type and site in the protein, and an in silico modeling of modified β-lactoglobulin is proposed. The modification delivers proteins with enhanced antioxidative properties. Changed structural properties and differences in solubility, surface hydrophobicity, and emulsification were observed. The polyphenol oxidase modulated reaction provides a modified β-lactoglobulin with a high antioxidative power, is thermally more stable, requires less energy to unfold, and, when emulsified with lutein esters, exhibits their higher stability against UV light. Thus, adaptation of this modification provides an innovative approach for functionalizing proteins and their uses in the food industry.

  9. Effect of mechanochemical modification on the surfactant and structural properties of humic and himatomelanic acids

    NASA Astrophysics Data System (ADS)

    Mal'tseva, E. V.; Shekhovtsova, N. S.; Shilyaeva, L. P.; Yudina, N. V.

    2017-07-01

    The structural properties of humic and himatomelanic acids are studied by means of 1H NMR spectroscopy and differential thermal analysis after mechanochemical modification of peat. The relationship between the structural modification of humic and himatomelanic acids and their surfactant properties in aqueous solutions is established. It is shown that the critical micelle concentration of transformed himatomelanic acids is halved in comparison to the initial sample, while the adsorption equilibrium constant grows by 9 times.

  10. Effects of wave function modifications on calculated H bond C and C tbond C stretching frequencies

    NASA Astrophysics Data System (ADS)

    Lopes, Kelson C.; Fragoso, Wallace D.; Ramos, Mozart N.; Pereira, Arquimedes M.; Araújo, Regiane C. M. U.

    Two-level factorial design (FD) and principal component (PC) models are used to determine the effects of wave function modifications on calculated H bond C and C tbond C harmonic stretching frequencies for the H bond C tbond CH, H bond C tbond CF, H bond C tbond CCl, H bond C tbond CCCH, H bond C tbond CCN and H bond C tbond CCH3 molecules. Our results have shown that valence (val), diffuse (dif), polarization (pol), and electron correlation (corr) main effects as well as some second-order interaction effects are significant to build factorial models for these vibrational frequencies. For instance, when valence and diffuse functions are introduced in the basis set, the calculated H bond C and C tbond C stretching frequencies decrease. However, this reduction is much more accentuated when the electron correlation effect is introduced in the Hartree-Fock wave functions. By far, the corr main effect is the most important one on the H bond C and C tbond C frequency values. The MP2 electron correlation effect provokes an increment of -157.4 cm-1 and -283.8 cm-1 on the H bond C and C tbond C stretching frequencies, respectively, whereas the dif effect produces only a reduction of -9.1 cm-1 and -12.9 cm-1 on these frequencies, respectively. The inclusion of Møller-Plesset 2 perturbation in the Hartree-Fock wave functions also produces an important pol-corr interaction effect on the H bond C and C tbond C stretching frequencies, increasing their values by +45.2 cm-1 and +17.3 cm-1, respectively. Algebraic models were then established to explain how calculated H bond C and C tbond C stretching frequencies depend on characteristics of the molecular orbital wave functions. These models were successful in reproducing calculated H bond C and C tbond C frequency values for the H bond CN and CH3C tbond CCH3 molcules, which were not included in the training set. The principal component analysis has revealed that the calculated H bond C and C tbond C stretching frequencies can be

  11. The Effectiveness of Cognitive Bias Modification Interventions for Substance Addictions: A Meta-Analysis

    PubMed Central

    Kok, Robin N.; Cuijpers, Pim

    2016-01-01

    Background and Aims Cognitive bias modification (CBM) interventions, presumably targeting automatic processes, are considered particularly promising for addictions. We conducted a meta-analysis examining randomized controlled trials (RCTs) of CBM for substance addiction outcomes. Methods Studies were identified through systematic searches in bibliographical databases. We included RCTs of CBM interventions, alone or in combination with other treatments, for any type of addiction. We examined trial risk of bias, publication bias and possible moderators. Effects sizes were computed for post-test and follow-up, using a random-effects model. We grouped outcome measures and reported results for addiction (all related measures), craving and cognitive bias. Results We identified 25 trials, 18 for alcohol problems, and 7 for smoking. At post-test, there was no significant effect of CBM for addiction, g = 0.08 (95% CI -0.02 to 0.18) or craving, g = 0.05 (95% CI -0.06 to 0.16), but there was a significant, moderate effect on cognitive bias, g = 0.60 (95% CI 0.39 to 0.79). Results were similar for alcohol and smoking outcomes taken separately. Follow-up addiction outcomes were reported in 7 trials, resulting in a small but significant effect of CBM, g = 0.18 (95% CI 0.03 to 0.32). Results for addiction and craving did not differ by substance type, sample type, delivery setting, bias targeted or number of sessions. Risk of bias was high or uncertain in most trials, for most criteria considered. Meta-regression analyses revealed significant inverse relationships between risk of bias and effect sizes for addiction outcomes and craving. The relationship between cognitive bias and respectively addiction ESs was not significant. There was consistent evidence of publication bias in the form of funnel plot asymmetry. Conclusions Our results cast serious doubts on the clinical utility of CBM interventions for addiction problems, but sounder methodological trials are necessary before

  12. The Effectiveness of Cognitive Bias Modification Interventions for Substance Addictions: A Meta-Analysis.

    PubMed

    Cristea, Ioana A; Kok, Robin N; Cuijpers, Pim

    2016-01-01

    Cognitive bias modification (CBM) interventions, presumably targeting automatic processes, are considered particularly promising for addictions. We conducted a meta-analysis examining randomized controlled trials (RCTs) of CBM for substance addiction outcomes. Studies were identified through systematic searches in bibliographical databases. We included RCTs of CBM interventions, alone or in combination with other treatments, for any type of addiction. We examined trial risk of bias, publication bias and possible moderators. Effects sizes were computed for post-test and follow-up, using a random-effects model. We grouped outcome measures and reported results for addiction (all related measures), craving and cognitive bias. We identified 25 trials, 18 for alcohol problems, and 7 for smoking. At post-test, there was no significant effect of CBM for addiction, g = 0.08 (95% CI -0.02 to 0.18) or craving, g = 0.05 (95% CI -0.06 to 0.16), but there was a significant, moderate effect on cognitive bias, g = 0.60 (95% CI 0.39 to 0.79). Results were similar for alcohol and smoking outcomes taken separately. Follow-up addiction outcomes were reported in 7 trials, resulting in a small but significant effect of CBM, g = 0.18 (95% CI 0.03 to 0.32). Results for addiction and craving did not differ by substance type, sample type, delivery setting, bias targeted or number of sessions. Risk of bias was high or uncertain in most trials, for most criteria considered. Meta-regression analyses revealed significant inverse relationships between risk of bias and effect sizes for addiction outcomes and craving. The relationship between cognitive bias and respectively addiction ESs was not significant. There was consistent evidence of publication bias in the form of funnel plot asymmetry. Our results cast serious doubts on the clinical utility of CBM interventions for addiction problems, but sounder methodological trials are necessary before this issue can be settled. We found no indication

  13. Triggering of Myocardial Infarction by Increased Ambient Fine Particle Concentration: Effect Modification by Source Direction

    PubMed Central

    Hopke, Philip K.; Kane, Cathleen; Utell, Mark J.; Chalupa, David C.; Kumar, Pramod; Ling, Frederick; Gardner, Blake; Rich, David Q.

    2015-01-01

    Background Previously, we reported a 18% increased odds of ST-elevation myocardial infarction (STEMI) associated with each 7.1 µg/m3 increase in PM2.5 concentration in the hour prior to MI onset. We found no association with non-ST elevation myocardial infarction (NSTEMI). We examined if this association was modified by PM2.5 source direction. Methods We used the NOAA HYbrid Single-Particle Lagrangian Trajectory (HYSPLIT) model to calculate each hourly air mass location for the 24 hours before each case or control time period in our previous PM2.5/STEMI case-crossover analysis. Using these data on patients with STEMI (n=338), hourly PM2.5 concentrations, and case-crossover methods, we evaluated whether our PM2.5/STEMI association was modified by whether the air mass passed through each of the 8 cardinal wind direction sectors in the previous 24 hours. Results When the air mass passed through the West-Southwest direction (WSW) any time in the past 24 hours, the odds of STEMI associated with each 7.1 µg/m3 increase in PM2.5 concentration in the previous hour (OR=1.27; 95% CI=1.08, 1.22) was statistically significantly (p=0.01) greater than the relative odds of STEMI associated with increased PM2.5 concentration when the wind arrived from any other direction (OR=0.99; 95% CI=0.80, 1.22). We found no other effect modification by any other source direction. Further, relative odds estimates were largest when the time spent in the WSW was 8-16 hours, compared to ≤7 hours or 17-24 hours, suggesting that particles arising from sources in this direction were more potent in triggering STEMIs. Conclusions Since relative odds estimates were higher when the air mass passed through the WSW octant in the past 24 hours, there may be specific components of the ambient aerosol that are more potent in triggering STEMIs. This direction is associated with substantial emissions from coal-fired power plants and other industrial sources of the Ohio River Valley, many of which are

  14. Breast-feeding and health consequences in early childhood: is there an impact of time-dependent confounding?

    PubMed

    Groenwold, R H H; Tilling, K; Moons, K G M; Hoes, A W; van der Ent, C K; Kramer, M S; Martin, R M; Sterne, J A C

    2014-01-01

    Estimated effects of breast-feeding on childhood health vary between studies, possibly due to confounding by baseline maternal and child characteristics. Possible time-dependent confounding has received little consideration. Our aim was to evaluate the impact of such confounding. We estimated the relationship between cumulative exclusive breast-feeding up to 6 months and wheezing, rash and body mass index (BMI) at 12 months [in the Whistler cohort (n = 494) and PROBIT (n = 11,463)], and wheezing, rash, asthma, hay fever, eczema, allergy and BMI at age 6.5 years (PROBIT). We adjusted for time-dependent confounding by weight, length, rash, respiratory illness and day care attendance using marginal structural models (MSMs). Weight and day care attendance appeared potential time-dependent confounders, since these predicted breast-feeding status and were influenced by previous breast-feeding. However, adjustment for time-dependent confounders did not markedly change the estimated associations. For example, in PROBIT the adjusted increase in BMI at 12 months per 1-month increase in exclusive breast-feeding was 0.04 (95% CI -0.09 to 0.01) using logistic regression and -0.06 (95% CI -0.11 to -0.01) using MSM. In Whistler, these estimates were each -0.05 (95% CI -0.10 to 0.00). In two cohort studies, there was little evidence of time-dependent confounding by weight, length, rash, respiratory illness or day care attendance of the effects of breast-feeding on early childhood health. © 2014 S. Karger AG, Basel.

  15. Effect of sports modification on clinical outcome in children and adolescent athletes with symptomatic lumbar spondylolysis.

    PubMed

    El Rassi, Georges; Takemitsu, Masakazu; Glutting, Joseph; Shah, Suken A

    2013-12-01

    This cohort study aimed to report the compliance of young athletes with nonoperative treatment and to clarify the role of sports modification on clinical outcome of symptomatic spondylolysis. This study included patients with a chief complaint of low back pain participating in regular sports activity, having spondylolysis, and being treated and followed up between 1990 and 2002 in the authors' hospital. One hundred thirty-two athletes were included in this study: 78 males and 54 females. The mean age of the patients was 13 yrs (range, 7-18 yrs). Only 56 patients (42.4%) were compliant to nonoperative treatment. Eighty-six patients (65%) stopped all sports activities for at least 3 mos, and 46 patients (35%) stopped exercising for a variable period of less than 3 mos. The grading of clinical outcome after nonoperative treatment was as follows: excellent in 48 patients (36.4%), good in 74 patients (56.1), fair in 6 patients (4.5%), and poor in 4 patients (3%). The patients who stopped sports for at least 3 mos were 16.39 times more likely to have an excellent result than those who did not stop sports. Bony healing on radiographs did not correlate with clinical outcome. Timely cessation of sports activity for 3 mos is considered an effective method of nonoperative treatment for young athletes with symptomatic lumbar spondylolysis.

  16. A Review about the Effect of Life style Modification on Diabetes and Quality of Life

    PubMed Central

    Shrestha, Prabha; Ghimire, Laxmi

    2012-01-01

    The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required. PMID:23121755

  17. Effect of radiation light characteristics on surface hardness of paint-on resin for shade modification.

    PubMed

    Arikawa, Hiroyuki; Kanie, Takahito; Fujii, Koichi; Ban, Seiji

    2005-12-01

    The purpose of this study was to investigate the effect of radiation light characteristics--of different types of clinical light-curing unit--on polymerization efficiency, as determined by the surface hardness of light-cured paint-on resins. Four shades of paint-on resin for shade modification of restorative resins were used. Materials were cured using one laboratory and three clinical light-curing units with different light sources, namely tungsten-halogen, LED, plasma arc, and xenon flash lamps. Knoop hardness measurements were taken at both the top and bottom surfaces of the specimens to assess the mechanical properties and degree of polymerization. Both LED and plasma arc light units caused significantly poorer surface hardness than the halogen and laboratory xenon lights. In addition, the transparent shade was more sensitive to surface hardness than other chromatic shades. Our results indicated that the polymerization efficiency of paint-on resin was significantly influenced by the radiation light characteristics of clinical light-curing units.

  18. Effect of chemical modification on molecular structure and functional properties of Musa AAB starch.

    PubMed

    Koteswara Reddy, Chagam; Vidya, P V; Haripriya, Sundaramoorthy

    2015-11-01

    Starch extracted from Musa AAB (poovan banana) was subjected to acetylation, acid-thinning and oxidation. The effect of the treatments on molecular structure and functional properties of starch were analysed. Chemical composition revealed that non-starch components were reduced after chemical treatment. Amylose content of starch decreased on acetylation from 24.16% to 20.90%, whereas it increased to 24.50% and 25.5% on oxidation and acid-thinning, respectively. X-ray diffraction pattern of modified starches showed B-type crystalline structure with peaks at 2θ=5.5°, 15.0°, 17.1° and 23.5°; which were parallel with the pattern observed in case of native starch. Swelling capacity of starch granules was found to reduce by acid-thinning and oxidation but acetylation induced to increase it. The percentage of colour (L*, a* and b*), solubility and water absorption capacities varied significantly from native starch after chemical modification. Changes in gelatinisation temperatures and enthalpy value of starches were observed in modified starches and it is varied according to reaction conditions. Pasting properties of the starches was increased by acetylation and oxidation while acid-thinning reduced it (P<0.05).

  19. [Chemical modification of chymopapain with monomethoxypolyethylene glycol and its effect on enzymic activity and antigenicity].

    PubMed

    Shu, Wei; Fang, Shi-Song; Cui, Tang-Bing; Guo, Yong

    2006-05-01

    To study the effect of chemical modification of chymopapain with monomethoxypolyethylene glycol on enzymic activity and antigenicity. Under the substrate protecting and non-substrate protecting, the chymopapain (Cp) was modified with two types of mPEG derivatives mPEG1 and mPEG2. The average ratio of modified-NH2 was tested by trinitrobenzenesulfonic acid (TNBS) method, the enzymic activity was tested with macromolecular casein and ATEE as substrates, the antigenicity of modified enzyme was determined by ELISA method. (1) Both mPEG1 and mPEG2 can reduce and eliminate antigenicity of Cp, the mPEG2 was better than mPEG1. (2) The enzymic activities of modified Cp were reduced, the enzymic activities of mPEG1-modified Cp were higher than that of mPEG2-modified Cp (especially macromolecular protein as its substrate). (3) The enzymic activities in present of ATEE were obviously higher than that in absent of substrate. When mPEG1 as the modifier and in present of ATEE, the antigenicity of Cp was completely eliminated, and the enzymic activities were still higher.

  20. Effects of single and dual physical modifications on pinhão starch.

    PubMed

    Pinto, Vânia Zanella; Vanier, Nathan Levien; Deon, Vinicius Gonçalves; Moomand, Khalid; El Halal, Shanise Lisie Mello; Zavareze, Elessandra da Rosa; Lim, Loong-Tak; Dias, Alvaro Renato Guerra

    2015-11-15

    Pinhão starch was modified by annealing (ANN), heat-moisture (HMT) or sonication (SNT) treatments. The starch was also modified by a combination of these treatments (ANN-HMT, ANN-SNT, HMT-ANN, HMT-SNT, SNT-ANN, SNT-HMT). Whole starch and debranched starch fractions were analyzed by gel-permeation chromatography. Moreover, crystallinity, morphology, swelling power, solubility, pasting and gelatinization characteristics were evaluated. Native and single ANN and SNT-treated starches exhibited a CA-type crystalline structure while other modified starches showed an A-type structure. The relative crystallinity increased in ANN-treated starches and decreased in single HMT- and SNT-treated starches. The ANN, HMT and SNT did not provide visible cracks, notches or grooves to pinhão starch granule. SNT applied as second treatment was able to increase the peak viscosity of single ANN- and HMT-treated starches. HMT used alone or in dual modifications promoted the strongest effect on gelatinization temperatures and enthalpy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A review about the effect of life style modification on diabetes and quality of life.

    PubMed

    Shrestha, Prabha; Ghimire, Laxmi

    2012-10-10

    The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required.

  2. Birth defects risk associated with maternal sport fish consumption: potential effect modification by sex of offspring.

    PubMed

    Mendola, Pauline; Robinson, Luther K; Buck, Germaine M; Druschel, Charlotte M; Fitzgerald, Edward F; Sever, Lowell E; Vena, John E

    2005-02-01

    Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infants born to members of the New York State (NYS) Angler Cohort between 1986 and 1991 (n=2237 births). Birth defects (n=125 cases) were ascertained from both newborn medical records and the NYS Congenital Malformations Registry. For sport fish meals eaten during pregnancy, the odds ratio (OR) for all major malformations combined was slightly elevated for < or =1 meal/month (OR=1.26, 95% confidence interval (CI): 0.84, 1.89) and > or =2 meals/month (OR=1.51, CI=0.74, 3.09), with no meals during pregnancy as the reference category. Higher ORs were consistently observed among male offspring compared with females. For > or =2 meals/month, the risk for males was significantly elevated (males: OR=3.01, CI: 1.2, 7.5; females: OR=0.73, CI: 0.2, 2.4). Exposure during pregnancy and effect modification by infants sex could be important considerations for future studies of birth outcomes associated with endocrine disruptors.

  3. Morphological modifications of electrodeposited calcium phosphate coatings under amino acids effect

    NASA Astrophysics Data System (ADS)

    Drevet, R.; Lemelle, A.; Untereiner, V.; Manfait, M.; Sockalingum, G. D.; Benhayoune, H.

    2013-03-01

    Calcium phosphate coatings are synthesized on titanium alloy (Ti6Al4V) substrates by pulsed electrodeposition. This work aims to observe the morphological modifications of the coating when an amino acid is added to the electrolytic solution used in the process. The effects of two amino acids (glutamic acid and aspartic acid) are studied at a low and a high concentration. The coating morphology is observed at a nanometer scale by field emission gun-scanning electron microscopy (FEG-SEM). The structural characterization of the coating is performed by Fourier transformed infrared spectroscopy (FT-IR), Raman spectroscopy and X-ray diffraction (XRD). Moreover, corrosion measurements of the prosthetic surfaces are carried out by potentiodynamic polarization experiments in a physiological solution named Dulbecco's modified eagle medium (DMEM). The results show that the addition of an amino acid to the electrolytic solution leads to the decrease of the size of the crystallites which compose the prosthetic calcium phosphate coating that becomes denser and less porous than the coatings obtained without amino acid. Consequently, the corrosion behavior of the prosthetic material immersed in DMEM is improved.

  4. Susceptibility to mortality in weather extremes: effect modification by personal and small-area characteristics.

    PubMed

    Zanobetti, Antonella; O'Neill, Marie S; Gronlund, Carina J; Schwartz, Joel D

    2013-11-01

    Extremes of temperature have been associated with short-term increases in daily mortality. We identified subpopulations with increased susceptibility to dying during temperature extremes, based on personal demographics, small-area characteristics, and preexisting medical conditions. We examined Medicare participants in 135 US cities and identified preexisting conditions based on hospitalization records before their deaths, from 1985 to 2006. Personal characteristics were obtained from the Medicare records, and area characteristics were assigned based on zip code of residence. We conducted a case-only analysis of over 11 million deaths and evaluated modification of the risk of dying associated with extremely hot days and extremely cold days, continuous temperatures, and water vapor pressure. Modifiers included preexisting conditions, personal characteristics, zip code-level population characteristics, and land cover characteristics. For each effect modifier, a city-specific logistic regression model was fitted and then an overall national estimate was calculated using meta-analysis. People with certain preexisting conditions were more susceptible to extreme heat, with an additional 6% (95% confidence interval = 4%-8%) increase in the risk of dying on an extremely hot day in subjects with previous admission for atrial fibrillation, an additional 8% (4%-12%) in subjects with Alzheimer disease, and an additional 6% (3%-9%) in subjects with dementia. Zip code level and personal characteristics were also associated with increased susceptibility to temperature. We identified several subgroups of the population who are particularly susceptible to temperature extremes, including persons with atrial fibrillation.

  5. Effects of genetic modifications to flax (Linum usitatissimum) on arbuscular mycorrhiza and plant performance.

    PubMed

    Wróbel-Kwiatkowska, Magdalena; Turnau, Katarzyna; Góralska, Katarzyna; Anielska, Teresa; Szopa, Jan

    2012-10-01

    Although arbuscular mycorrhizal fungi (AMF) are known for their positive effect on flax growth, the impact of genetic manipulation in this crop on arbuscular mycorrhiza and plant performance was assessed for the first time. Five types of transgenic flax that were generated to improve fiber quality and resistance to pathogens, through increased levels of either phenylpropanoids (W92.40), glycosyltransferase (GT4, GT5), or PR2 beta-1,3-glucanase (B14) or produce polyhydroxybutyrate (M50), were used. Introduced genetic modifications did not change the degree of mycorrhizal colon