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Sample records for confounding effect modification

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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).

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. [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.

  5. 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.

  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. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  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. 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.

  15. 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

  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. 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.

  18. 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

  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. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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.

  14. 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

  15. '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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. [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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

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

    DTIC Science & Technology

    2010-05-01

    Metoclopramide A03FA01 12/5 12/ 1 Ondansetron A04AA01 2/0 0/0 Antifungal Terbinafine D01BA02 0/2 0/ 1 Antiarrythmia Flecainid C01BC04 1 /0 0/0 Amiodarone...AD_________________ AWARD NUMBER: W81XWH-08- 1 -0300 TITLE: Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs...No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for

  2. 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…

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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,…

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. [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.

  9. 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.

  10. 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

  11. [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.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. Effect of cavity fore wall modifications in supersonic flow

    NASA Astrophysics Data System (ADS)

    Jeyakumar, S.; Yuvaraj, K. Arun; Jayaraman, K.; Cardona, F.; Sultan, M. T. H.

    2016-10-01

    Understanding the complex behaviour of the cavity flow is essential for the design of supersonic combustor. The characteristics of the axisymmetric aft ramp cavity with fore wall modification have been experimentally studied in a blow-down type supersonic flow facility. The facility consists of a conventional CD nozzle that issues a flow Mach number of 1.88 to a supersonic combustor of circular cross section, which is placed immediately downstream of the nozzle. The axisymmetric cavities are incorporated within the combustor. The cavities are of open type and their length is kept constant while their depth varies. The aft wall of the cavities is inclined with three ramp angles and the fore wall is provided with a constant fillet radius of 3 mm. The performance of the cavity is analysed based on wall static pressures, momentum flux distribution at the exit of the combustor and stagnation pressure loss across the combustor. The study reveals that fore wall fillet cavities provide less cavity drag and stagnation pressure loss for various aft ramp angles under identical operating conditions.

  17. 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.

  18. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  19. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  20. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  1. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  2. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  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. 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.

  5. 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.

  6. 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…

  7. 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

  8. 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

  9. 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.

  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. 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.

  12. 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.

  13. 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…

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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>

  11. 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.

  12. 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…

  13. 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…

  14. 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

    2017-03-06

    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.

  15. "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.

  16. 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.

  17. 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.

  18. 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

  19. 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…

  20. 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.

  1. Distribution-free mediation analysis for nonlinear models with confounding.

    PubMed

    Albert, Jeffrey M

    2012-11-01

    Recently, researchers have used a potential-outcome framework to estimate causally interpretable direct and indirect effects of an intervention or exposure on an outcome. One approach to causal-mediation analysis uses the so-called mediation formula to estimate the natural direct and indirect effects. This approach generalizes the classical mediation estimators and allows for arbitrary distributions for the outcome variable and mediator. A limitation of the standard (parametric) mediation formula approach is that it requires a specified mediator regression model and distribution; such a model may be difficult to construct and may not be of primary interest. To address this limitation, we propose a new method for causal-mediation analysis that uses the empirical distribution function, thereby avoiding parametric distribution assumptions for the mediator. To adjust for confounders of the exposure-mediator and exposure-outcome relationships, inverse-probability weighting is incorporated based on a supplementary model of the probability of exposure. This method, which yields the estimates of the natural direct and indirect effects for a specified reference group, is applied to data from a cohort study of dental caries in very-low-birth-weight adolescents to investigate the oral-hygiene index as a possible mediator. Simulation studies show low bias in the estimation of direct and indirect effects in a variety of distribution scenarios, whereas the standard mediation formula approach can be considerably biased when the distribution of the mediator is incorrectly specified.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  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. 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.

  13. 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.

  14. 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

  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. 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

  17. 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

  18. 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

  19. 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.

  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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  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. 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.

  11. 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

  12. 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.

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  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. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

    SciTech Connect

    Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

    2007-07-01

    We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extent to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.

  13. 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.

  14. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction-Having Your Cake and Eating It Two.

    PubMed

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L; Haneuse, Sebastien

    2016-07-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis-in which detailed high-quality confounding data are obtained among a small subsample-can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake.

  15. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction—Having Your Cake and Eating It Two

    PubMed Central

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L.; Haneuse, Sebastien

    2016-01-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis—in which detailed high-quality confounding data are obtained among a small subsample—can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake. PMID:27285260

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. [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.

  2. Effect of sulfated modification on the molecular characteristics and biological activities of polysaccharides from Hypsizigus marmoreus.

    PubMed

    Bao, HongHui; Choi, Won-Seok; You, SangGuan

    2010-01-01

    The effect of sulfated modification on polysaccharides from Hypsizigus marmoreus was examined by determining their molecular structures and bioactivities. The sulfation, which was implemented by using an orthogonal array design, produced polysaccharides with varying degrees of substitution (DS) ranging from 0.11 to 1.06. The sulfated polysaccharides exhibited a lower average molecular weight (M(w)) and considerably higher radius of gyration (R(g)) than those of native polysaccharide, suggesting that the conformation of the sulfated polysaccharides had been changed towards a more extended type. The inhibitory activity toward cancer cell growth was enhanced by treating with the sulfated polysaccharides by up to 34%, as compared to the native polysaccharide. In addition, treating with the sulfated polysaccharides increased the nitric oxide (NO) and cytokine (IL-1beta and TNF-alpha) release to levels comparable to those detected in the positive control, lipopolysaccharide (LPS), suggesting that the sulfated polysaccharides might have strong immunomodulatory activity.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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)

  14. 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.

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  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. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  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. Applications of the propensity score weighting method in psychogeriatric research: correcting selection bias and adjusting for confounders.

    PubMed

    Chang, Chung-Chou H

    2017-05-01

    The propensity score (PS) weighting method is an analytic technique that has been applied in multiple fields for a number of purposes. Here, we discuss two common applications, which are (1) to correct for selection bias and (2) to adjust for confounding variables when estimating the effect of an exposure variable on the outcome of interest.

  11. Removal of Potentially Confounding Phenotypes from a Siamese-Derived Feline Glaucoma Breeding Colony

    PubMed Central

    Rutz-Mendicino, Michelle M; Snella, Elizabeth M; Jens, Jackie K; Gandolfi, Barbara; Carlson, Steven A; Kuehn, Markus H; McLellan, Gillian J; Ellinwood, N Matthew

    2011-01-01

    Feline breeding colonies face genetic constraints involving founder effects. A Siamese-founded colony used to study primary congenital glaucoma displayed coat colors additional to the Siamese coat. Genes affecting pigment can exhibit pleiotropy on ocular development and function. To remove potentially confounding phenotypes from our colony, we documented the source and frequency of the Siamese allele at the gene for tyrosinase (TYR), the dilution allele at melanophilin (MLPH), and the brown allele at tyrosinase-related protein 1 (TYRP1). We used PCR–RFLP diagnostics to genotype cats in our colony for the published alleles. A commercially acquired phenotypically normal tom was the source of the dilute allele. A founding Siamese queen was the source of the brown allele. Founders also were blood-typed and screened for disease-associated alleles segregating in Siamese cats at 3 loci (ASB, GLB1, and CEP290). Siamese founders were normal at all loci except ASB, at which both animals carried the hypomorphic allele. Current stock is being managed to limit production of glaucomatous cats with brown, dilute, or Siamese phenotypes or homozygosity for the ASB hypomorphic allele. Genotyping will aid in the elimination of these alleles. The clinical effect of these phenotypes and alleles on the glaucoma phenotype is uncertain, but their elimination will remove potentially confounding effects. In conclusion, when founding a colony, stock should be selected or screened to limit potentially confounding phenotypes. When studying the immune, nervous, and visual systems, screening stock for alleles known to be associated with coat color may be warranted. PMID:21819695

  12. Role of Environmental Confounding in the Association between FKBP5 and First-Episode Psychosis

    PubMed Central

    Ajnakina, Olesya; Borges, Susana; Di Forti, Marta; Patel, Yogen; Xu, Xiaohui; Green, Priscilla; Stilo, Simona A.; Kolliakou, Anna; Sood, Poonam; Marques, Tiago Reis; David, Anthony S.; Prata, Diana; Dazzan, Paola; Powell, John; Pariante, Carmine; Mondelli, Valeria; Morgan, Craig; Murray, Robin M.; Fisher, Helen L.; Iyegbe, Conrad

    2014-01-01

    Background: Failure to account for the etiological diversity that typically occurs in psychiatric cohorts may increase the potential for confounding as a proportion of genetic variance will be specific to exposures that have varying distributions in cases. This study investigated whether minimizing the potential for such confounding strengthened the evidence for a genetic candidate currently unsupported at the genome-wide level. Methods: Two hundred and ninety-one first-episode psychosis cases from South London, UK and 218 unaffected controls were evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. The relationship between FKBP5 and psychosis was modeled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire) and parental separation (Childhood Experience of Care and Abuse Questionnaire) were included as confounders in the analysis. Results: Association at rs1360780 was not detected until the effects of the two environmental factors had been adjusted for in the model (OR = 2.81, 95% CI 1.23–6.43, p = 0.02). A statistical interaction between rs1360780 and parental separation was confirmed by stratified tests (OR = 2.8, p = 0.02 vs. OR = 0.89, p = 0.80). The genetic main effect was directionally consistent with findings in other (stress-related) clinical phenotypes. Moreover, the variation in effect magnitude was explained by the level of power associated with different cannabis constructs used in the model (r = 0.95). Conclusion: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on other etiological factors. This finding requires further validation in large independent cohorts. Potentially this work could have translational implications; the ability to discriminate between genetic etiologies based on a case-by-case understanding of previous environmental exposures would confer an important clinical advantage that would

  13. 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.

  14. 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

  15. Structural and physico-chemical properties of insoluble rice bran fiber: effect of acid–base induced modifications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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.

  17. 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.

  18. 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

  19. 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

  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.

  1. 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

  2. Pulsed laser cleaning of aluminium-magnesium alloys: effect of surface modifications on adhesion

    NASA Astrophysics Data System (ADS)

    Autric, Michel; Oltra, Roland

    2008-05-01

    Surface cleaning is a key step in many industrial processes and especially in laser surface treatments. During laser cleaning of metallic alloys using pulsed lasers, surface modification can be induced due to transient thermal effect. In ambient atmospheric conditions, an oxidation of the cleaned surface can be detected. The aim of this work was to characterize this transient oxidation that can occur below the laser energy domain leading to any phase change (melting, ablation) of the cleaned substrate. A Q-switched Nd:YAG laser (1.06 μm) with 10 ns pulse duration was used for this study. X-ray photoelectron spectroscopy and secondary ion mass spectroscopy were used for surface analysis of irradiated samples. Thermal oxidation took place on the aluminium-magnesium alloy (5000 series) during the irradiation in air (fluence range 0.6-1.4 Jcm-2). It has been demonstrated that this 10 ns laser thermal oxidation and the steady state thermal oxidation have the same mechanism. When the laser fluence reached 1 J cm -2 , the oxide formed by the thermal oxidation became in a large extent crystalline and its outer part was entirely covered by a continuous magnesium oxide layer.

  3. Effectiveness of a behavior modification program for older people with uncontrolled type 2 diabetes.

    PubMed

    Ounnapiruk, Liwan; Wirojratana, Virapun; Meehatchai, Nitaya; Turale, Sue

    2014-06-01

    This quasi-experimental study examined the effectiveness of a behavior modification program for diabetic control in Thai elders with uncontrolled Type 2 Diabetes. Purposive sampling was used to select 30 elders from one community as an intervention group, and 30 from a neighboring community as a control group. The intervention group participated in a program of 12 weeks' duration involving activities related to group counseling, group discussion, and an empowerment process that enhanced appropriate consumption of healthy diet, medication taking, and exercise. Data were collected by interviews using a questionnaire to assess knowledge of diabetes, perceived self-efficacy, and diabetes control behavior, including fasting blood glucose and glycosylated hemoglobin, were examined at the baseline and three months thereafter. At program completion, the intervention group had significantly higher scores of knowledge, self-efficacy, and health behaviors than those in the control group, but blood glucose and glycosylated hemoglobin were not significantly different. Although nurses can use aspects of this program to benefit elders with diabetes who require support and education, further research is required to provide improved health outcomes such as better glycemic control.

  4. Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines.

    PubMed

    Vzorov, Andrei N; Wang, Li; Chen, Jianjun; Wang, Bao-Zhong; Compans, Richard W

    2016-02-01

    We investigated the effects on assembly and antigenic properties of specific modifications of the transmembrane spanning (TMS) and cytoplasmic tail (CT) domains of HIV-1 Env from a transmitted/founder (T/F) ZM53 Env glycoprotein. A construct containing a short version of the TMS domain derived from the mouse mammary tumor virus (MMTV) Env with or without a GCN4 trimerization sequence in the CT exhibited the highest levels of incorporation into VLPs and induced the highest titers of anti-Env IgG immune responses in a VLP context. Sera from guinea pigs immunized by VLPs with high Env content, and containing the CT trimerization sequence, had increased neutralization activity and antibody avidity. A cross-clade prime-boost regimen with clade B SF162 or clade C ZM53 Env DNA priming and boosting with VLPs containing modified ZM53 Env further enhanced these immune responses. The modified VLPs demonstrate improved potential as HIV-1 vaccine antigens.

  5. Towards a methodology for the effective surface modification of porous polymer scaffolds.

    PubMed

    Safinia, Laleh; Datan, Nathalie; Höhse, Marek; Mantalaris, Athanassios; Bismarck, Alexander

    2005-12-01

    A novel low-pressure radio-frequency plasma treatment protocol was developed to achieve the effective through-thickness surface modification of large porous poly (D,L-lactide) (PDLLA) polymer scaffolds using air or water: ammonia plasma treatments. Polymer films were modified as controls. Scanning electron micrographs and maximum bubble point measurements demonstrated that the PDLLA foams have the high porosity, void fraction and interconnected pores required for use as tissue engineering scaffolds. The polymer surface of the virgin polymer does contain acidic functional groups but is hydrophobic. Following exposure to air or water: ammonia plasma, an increased number of polar functional groups and improved wetting behaviour, i.e. hydrophilicity, of wet surfaces was detected. The number of polar surface functional groups increased (hence the decrease in water contact angles) with increasing exposure time to plasma. The change in surface composition and wettablility of wet polymer constructs was characterised by zeta potential and contact angle measurements. The hydrophobic recovery of the treated PDLLA polymer surfaces was also studied. Storage of the treated polymer constructs in ambient air caused an appreciable hydrophobic recovery, whereas in water only partial hydrophobic recovery occurred. However, in both cases the initial surface characteristics decay as function of time.

  6. Diet modification and metformin have a beneficial effect in a fly model of obesity and mucormycosis.

    PubMed

    Shirazi, Fazal; Farmakiotis, Dimitrios; Yan, Yuanqing; Albert, Nathaniel; Do, Kim-Anh; Kim-Anh, Do; Kontoyiannis, Dimitrios P

    2014-01-01

    In an experimental model of obesity and hyperglycemia in Drosophila melanogaster we studied the effect of diet modification and administration of metformin on systemic infection with Rhizopus, a common cause of mucormycosis in diabetic patients. Female Wt-type Drosophila flies were fed regular (RF) or high-fat diet (HFD; 30% coconut oil) food with or without metformin for 48 h and then injected with R. oryzae. Survival rates, glucose and triglyceride levels were compared between 1) normal-weight flies (RF), 2) obese flies (HFD), 3) obese flies fed with RF, 4) flies continuously fed on HFD + metformin, 5) flies fed on HFD + metformin, then transferred to RF, and 6) obese flies administered metformin after infection [corrected].Glucose levels were compared across groups of non-infected flies and across groups of infected flies. Survival was significantly decreased (P = 0.003) in obese flies, while post-infection glucose levels were significantly increased (P = 0.0001), compared to normal-weight flies. Diet and administration of metformin led to weight loss, normalized glucose levels during infection, and were associated with decreased mortality and tissue fungal burden. In conclusion, diet and metformin help control infection-associated hyperglycemia and improve survival in Drosophila flies with mucormycosis. Fly models of obesity bear intriguing similarities to the pathophysiology of insulin resistance and diabetes in humans, and can provide new insights into the pathogenesis and treatment of infections in obese and diabetic patients.

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. The effect of surface modification on initial ice formation on aluminum surfaces

    NASA Astrophysics Data System (ADS)

    Rahimi, M.; Afshari, A.; Fojan, P.; Gurevich, L.

    2015-11-01

    One of the most promising energy saving methods in cold climate areas is heat recovery in ventilation system by using air-to-air heat exchangers. However, due to a higher humidity in the exhaust air, there is a risk of ice formation on the heat exchanger fins at subzero temperatures. Since the main material of heat exchanger fins is aluminum, this paper focuses on the effect of aluminum wettability on the initial stages of ice formation. The ice growth was studied on bare as well as hydrophilically and hydrophobically modified surfaces of aluminum (8011A) sheets, commonly used in heat exchangers, at different psychrometric parameters. The obtained results show that the surface modification of aluminum plays a crucial role in the ice formation. We demonstrated that flat hydrophobic surfaces exhibit slower ice growth and denser ice layers, hence making this type of treatment preferable for aluminum heat exchangers. Furthermore we provide an explanation for a commonly observed phenomenon that bare aluminum surfaces are characterized by a faster ice growth and less dense ice layer as compared to both hydrophilically and hydrophobically modified surfaces.

  12. The effects of threat and nonthreat word lead stimuli on blink modification.

    PubMed

    Aitken, C J; Siddle, D A; Lipp, O V

    1999-11-01

    Two experiments examined the effects of visually presented threat and nonthreat word lead stimuli on blink modification among unselected young adults (Experiment 1, N = 35) and participants selected for low and high trait anxiety (Experiment 2, N = 60). The blink reflex was elicited by a white noise probe of 105 dB. Lead stimulus intervals of 60, 120, 240, and 2000 ms were used in both experiments. Prepulse inhibition was observed at the 240-ms interval and prepulse facilitation was observed at the 60-ms interval in both experiments. Also, greater facilitation was found in both experiments during threat words at the 60-ms interval and greater inhibition during threat words at the 240-ms interval. Experiment 2 provided some evidence that the greater facilitation during threat words than during nonthreat words at the 60-ms probe interval may be found in high trait anxious participants, but not in low trait anxious participants. The results are discussed in relation to contemporary information processing theories of anxiety.

  13. Comprehensive characterization of well-defined silk fibroin surfaces: Toward multitechnique studies of surface modification effects.

    PubMed

    Amornsudthiwat, Phakdee; Nitschke, Mirko; Zimmermann, Ralf; Friedrichs, Jens; Grundke, Karina; Pöschel, Kathrin; Damrongsakkul, Siriporn; Werner, Carsten

    2015-06-21

    The study aims at a comprehensive surface characterization of untreated and oxygen plasma-treated silk fibroin with a particular focus on phenomena relevant to biointeraction and cell adhesion. For that purpose, a range of advanced surface diagnostic techniques is employed to thoroughly investigate well-defined and especially clean silk fibroin samples in a comparable setting. This includes surface chemistry and surface charges as factors, which control protein adsorption, but also hydration and swelling of the material as important parameters, which govern the mechanical stiffness at the interface with aqueous media. Oxygen plasma exposure of silk fibroin surfaces reveals that material ablation strongly predominates over the introduction of functional groups even for mild plasma conditions. A substantial increase in mechanical stiffness is identified as the most prominent effect upon this kind of plasma treatment. Regarding the experimental approach and the choice of techniques, the work goes beyond previous studies in this field and paves the way for well-founded investigations of other surface-selective modification procedures that enhance the applicability of silk fibroin in biomedical applications.

  14. Effect of genomic deficiencies on sexual size dimorphism through modification of developmental time in Drosophila melanogaster

    PubMed Central

    Takahashi, K H; Blanckenhorn, W U

    2015-01-01

    Sexual size dimorphism (SSD), a difference in body size between sexes, is common in many taxa. In insects, females are larger than males in >70% of all taxa in most orders. The fruit fly, Drosophila melanogaster is one prominent model organism to investigate SSD since its clear and representative female-biased SSD and its growth regulation are well studied. Elucidating the number and nature of genetic elements that can potentially influence SSD would be helpful in understanding the evolutionary potential of SSD. Here, we investigated the SSD pattern caused by artificially introduced genetic variation in D. melanogaster, and examined whether variation in SSD was mediated by the sex-specific modification of developmental time. To map the genomic regions that had effects on sexual wing size and/or developmental time differences (SDtD), we reanalyzed previously published genome-wide deficiency mapping data to evaluate the effects of 376 isogenic deficiencies covering a total of ~67% of the genomic regions of the second and third chromosomes of D. melanogaster. We found genetic variation in SSD and SDtD generated by genomic deficiencies, and a negative genetic correlation between size and development time. We also found SSD and SDtD allometries that are not qualitatively congruent, which however overall at best only partly help in explaining the patterns found. We identified several genomic deficiencies with the tendency to either exaggerate or suppress SSD, in agreement with quantitative genetic null expectations of many loci with small effects. These novel findings contribute to a better understanding of the evolutionary potential of sexual dimorphism. PMID:25899012

  15. Different methods of balancing covariates leading to different effect estimates in the presence of effect modification.

    PubMed

    Lunt, Mark; Solomon, Daniel; Rothman, Kenneth; Glynn, Robert; Hyrich, Kimme; Symmons, Deborah P M; Stürmer, Til

    2009-04-01

    A number of covariate-balancing methods, based on the propensity score, are widely used to estimate treatment effects in observational studies. If the treatment effect varies with the propensity score, however, different methods can give very different answers. The authors illustrate this effect by using data from a United Kingdom-based registry of subjects treated with anti-tumor necrosis factor drugs for rheumatoid arthritis. Estimates of the effect of these drugs on mortality varied from a relative risk of 0.4 (95% confidence interval: 0.16, 0.91) to a relative risk of 1.3 (95% confidence interval: 0.8, 2.25), depending on the balancing method chosen. The authors show that these differences were due to a combination of an interaction between propensity score and treatment effect and to differences in weighting subjects with different propensity scores. Thus, the methods are being used to calculate average treatment effects in populations with very different distributions of effect-modifying variables, resulting in different overall estimates. This phenomenon highlights the importance of careful selection of the covariate-balancing method so that the overall estimate has a meaningful interpretation.

  16. Behavior modification.

    PubMed

    Pelham, W E; Fabiano, G A

    2000-07-01

    Attention deficit/hyperactivity disorder (ADHD) is a chronic and substantially impairing disorder. This means that treatment must also be chronic and substantial. Behavior Modification, and in many cases, the combination of behavior modification and stimulant medication, is a valid, useful treatment for reducing the pervasive impairment experienced by children with ADHD. Based on the research evidence reviewed, behavior modification should be the first line of treatment for children with ADHD.

  17. The effects of early grade retention: Effect modification by prior achievement and age.

    PubMed

    Vandecandelaere, Machteld; Vansteelandt, Stijn; De Fraine, Bieke; Van Damme, Jan

    2016-02-01

    This study examines the effects of early grade retention and different effects according to prior achievement and age. Within a population of children at risk of early retention, we compared the development throughout primary school in mathematics achievement after kindergarten retention, first-grade retention, and continuous promotion. Analyzing data from a large-scale longitudinal study using covariate balancing propensity score weighting, the findings revealed that early grade repeaters would score higher in mathematics if they were promoted each year instead. However, the effects diminished or even disappeared in the long term. Compared to kindergarten retention, first-grade retention was found to be more harmful for the mathematics development of younger children specifically.

  18. Airfoil modification effects on subsonic and transonic pressure distributions and performance for the EA-6B airplane

    NASA Technical Reports Server (NTRS)

    Allison, Dennis O.; Sewall, William G.

    1995-01-01

    Longitudinal characteristics and wing-section pressure distributions are compared for the EA-6B airplane with and without airfoil modifications. The airfoil modifications were designed to increase low-speed maximum lift for maneuvering, while having a minimal effect on transonic performance. Section contour changes were confined to the leading-edge slat and trailing-edge flap regions of the wing. Experimental data are analyzed from tests in the Langley 16-Foot Transonic Tunnel on the baseline and two modified wing-fuselage configurations with the slats and flaps in their retracted positions. Wing modification effects on subsonic and transonic performance are seen in wing-section pressure distributions of the various configurations at similar lift coefficients. The modified-wing configurations produced maximum lift coefficients which exceeded those of the baseline configuration at low-speed Mach numbers (0.300 and 0.400). This benefit was related to the behavior of the wing upper surface leading-edge suction peak and the behavior of the trailing-edge pressure. At transonic Mach numbers (0.725 to 0.900), the wing modifications produced a somewhat stronger nose-down pitching moment, a slightly higher drag at low-lift levels, and a lower drag at higher lift levels.

  19. Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

    PubMed

    Philbrook, Nicola A; Winn, Louise M

    2015-11-15

    Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted.

  20. Current practices for modification of paving asphalts

    SciTech Connect

    Bahia, H.U.; Perdomo, D.

    1996-12-31

    The Superpave binder specification, AASHTO MP1, has introduced new concepts for selecting paving asphalt binders. The specification, in addition to using rheological and failure measurements that are more related to performance, is based on the idea that the criteria to maintain a satisfactory contribution of asphalt binders to the resistance of pavement failures remains the same but have to be satisfied at critical application temperatures. The test procedures require that the material be characterized within certain ranges of strains or stresses to ensure that material and geometric non-linearities are not confounded in the measurements. These new specification concepts have resulted in re-evaluation of asphalt modification by the majority of modified asphalt suppliers. The philosophy of asphalt modification is expected to change, following these new concepts, from a general improvement of quality to more focus on using modifiers based on the most critical need as defined by two factors: (1) The application temperature domain and (2) the type of distress to be remedied. The new specification requirements should result in a more effective use of modifiers as the amount and type of modifier will be directly related to the application environment and the engineering requirements.

  1. Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation.

    PubMed

    Mills, Martin; Arimondo, Paola B; Lacroix, Laurent; Garestier, Thérèse; Klump, Horst; Mergny, Jean-Louis

    2002-01-08

    DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple-helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on the chemical nature of the triplex-forming strands and the stability of the corresponding triplexes.

  2. Effect of alcohol-acid modification on physicochemical, rheological and morphological properties of glutinous rice starch.

    PubMed

    Gope, Sangeeta; Samyor, Duyi; Paul, Atanu Kumar; Das, Amit Baran

    2016-12-01

    In the present study chemical modification of glutinous rice starch was carried out using 1-Buatnol-hydrochloric acid with varying time and temperature. The changes in physico-chemical, dynamic rheological and morphological properties of starch during hydrolysis was investigated. There was a significant increase in water solubility of starch due to modification; however, swelling and sedimentation value decrease after modification. The peak, hold and final viscosity of modified starches were decreased significantly as compared to native starch. Thermal properties and dynamic rheological properties of rice starch were changed with the change in time and temperature during modification. The storage (G') modulus, loss (G″) modulus, dynamic viscosity (η') and complex viscosity (η*) of modified starches were varied significantly. Analysis of microstructure revealed that the hydrolysis altered morphology of starch granules. The hydrolysis was affected the surface properties and granule size of rice starch. These results suggested that 1-butanol-HCl hydrolysis of glutinous rice starch can be a preferred way of modification.

  3. Effect of goal attainment theory based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: Randomized study.

    PubMed

    Park, Moonkyoung; Song, Rhayun; Jeong, Jin-Ok

    2017-02-24

    Effect of goal-attainment-theory-based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: randomized study BACKGROUND: The behavioral modification strategies should be explored at the time of admission to lead the maximum effect of cardiovascular risk management.

  4. Hamilton study: distribution of factors confounding the relationship between air quality and respiratory health

    SciTech Connect

    Pengelly, L.D.; Kerigan, A.T.; Goldsmith, C.H.; Inman, E.M.

    1984-10-01

    Hamilton, Ontario is an industrial city with a population of 300,000 which is situated at the western end of Lake Ontario. Canada's two largest iron and steel mills are located here; the city historically has had relatively poor air quality, which has improved markedly in the last 25 years. Concern about the health effects of current air quality recently led us to carry out an epidemiological study of the effects of air pollution on the respiratory health of over 3500 school children. Respiratory health was measured by pulmonary function testing of each child, and by an assessment of each child's respiratory symptoms via a questionnaire administered to the parents. Previous studies had shown that other environmental factors (e.g. parental smoking, parental cough, socioeconomic level, housing, and gas cooking) might also affect respiratory health, and thus confound any potential relationships between health and air pollution. The questionnaire also collected information on many of these confounding factors. For the purposes of initial analysis, the city was divided into five areas in which differences in air quality were expected. In general, factors which have been associated with poor respiratory health were observed to be more prevalent in areas of poorer air quality.

  5. Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

    PubMed

    Lester, Kathryn J; Field, Andy P; Muris, Peter

    2011-01-01

    This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

  6. Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts.

    PubMed

    Chorro, Francisco J; Trapero, Isabel; Such-Miquel, Luis; Pelechano, Francisca; Mainar, Luis; Cánoves, Joaquín; Tormos, Alvaro; Alberola, Antonio; Hove-Madsen, Leif; Cinca, Juan; Such, Luis

    2009-11-01

    Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.

  7. Clustering and Residual Confounding in the Application of Marginal Structural Models: Dialysis Modality, Vascular Access, and Mortality.

    PubMed

    Kasza, Jessica; Polkinghorne, Kevan R; Marshall, Mark R; McDonald, Stephen P; Wolfe, Rory

    2015-09-15

    In the application of marginal structural models to compare time-varying treatments, it is rare that the hierarchical structure of a data set is accounted for or that the impact of unmeasured confounding on estimates is assessed. These issues often arise when analyzing data sets drawn from clinical registries, where patients may be clustered within health-care providers, and the amount of data collected from each patient may be limited by design (e.g., to reduce costs or encourage provider participation). We compared the survival of patients undergoing treatment with various dialysis types, where some patients switched dialysis modality during the course of their treatment, by estimating a marginal structural model using data from the Australia and New Zealand Dialysis and Transplant Registry, 2003-2011. The number of variables recorded by the registry is limited, and patients are clustered within the dialysis centers responsible for their treatment, so we assessed the impact of accounting for unmeasured confounding or clustering on estimated treatment effects. Accounting for clustering had limited impact, and only unreasonable levels of unmeasured confounding would have changed conclusions about treatment comparisons. Our analysis serves as a case study in assessing the impact of unmeasured confounding and clustering in the application of marginal structural models.

  8. Are We Missing Something Pertinent? A Bias Analysis of Unmeasured Confounding in the Firearm-Suicide Literature.

    PubMed

    Miller, M; Swanson, S A; Azrael, D

    2016-01-01

    Despite the magnitude and consistency of risk estimates in the peer-reviewed literature linking firearm availability and suicide, inferring causality has been questioned on the theoretical basis that existing studies may have failed to account for the possibility that members of households with firearms differ from members of households without firearms in important ways related to suicide risk. The current bias analysis directly addresses this concern by describing the salient characteristics that such an unmeasured confounder would need to possess in order to yield the associations between firearm availability and suicide observed in the literature when, in fact, the causal effect is null. Four US studies, published between 1992 and 2003, met our eligibility criteria. We find that any such unmeasured confounder would need to possess an untenable combination of characteristics, such as being not only 1) as potent a suicide risk factor as the psychiatric disorders most tightly linked to suicide (e.g., major depressive and substance use disorders) but also 2) an order of magnitude more imbalanced across households with versus without firearms than is any known risk factor. No such confounder has been found or even suggested. The current study strongly suggests that unmeasured confounding alone is unlikely to explain the association between firearms and suicide.

  9. Differential dietary nutrient intake according to hormone replacement therapy use: an underestimated confounding factor in epidemiologic studies?

    PubMed

    Vercambre, Marie-Noël; Fournier, Agnès; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Ringa, Virginie; Berr, Claudine

    2007-12-15

    Observational studies and randomized controlled trials have produced divergent results concerning the effect of hormone replacement therapy (HRT) on cardiovascular disease and, to a lesser extent, dementia. Residual confounding (confounding that remains even after adjustment for various socioeconomic and lifestyle factors) is one explanation that has been offered for these divergent results. The authors used data collected between 1990 and 1995 from 6,697 French women aged 61-72 years participating in a prospective cohort study to explore the hypothesis that nutritional intake varies according to HRT use and thus may be a source of residual confounding. After the authors adjusted for health and lifestyle factors, HRT users, compared with never users, had significantly higher intakes of alcohol; omega3 fatty acids; vitamins B6, B12, and D; and phosphorus and a lower intake of starch. These differential nutrient intakes were related to differences in eating habits. In particular, HRT users in the studied sample, compared with nonusers, ate significantly more fish. Most of the dietary differences were seen in both early users and delayers of HRT. To limit residual confounding in observational studies, dietary factors may be important parameters to be taken into account in analyses of HRT use and health outcomes.

  10. Heterogeneity Confounds Establishment of "a" Model Microbial Strain.

    PubMed

    Keller, Nancy P

    2017-02-21

    Aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al. (mBio 7:e01515-16, 2016, https://doi.org/10.1128/mBio.01515-16) demonstrated that variation in 16 environmental and clinical isolates of A. fumigatus correlated virulence with fitness in low oxygen, whereas Fuller et al. (mBio 7:e01517-16, 2016, https://doi.org/10.1128/mBio.01517-16) showed wide variation in light responses at a physiological and protein functionality level in 15 A. fumigatus isolates. In both studies, two commonly used type strains, Af293 and CEA10, displayed significant differences in physiological responses to abiotic stimuli and virulence in a murine model of IPA.

  11. Heterogeneity Confounds Establishment of “a” Model Microbial Strain

    PubMed Central

    2017-01-01

    ABSTRACT Aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al. (mBio 7:e01515-16, 2016, https://doi.org/10.1128/mBio.01515-16) demonstrated that variation in 16 environmental and clinical isolates of A. fumigatus correlated virulence with fitness in low oxygen, whereas Fuller et al. (mBio 7:e01517-16, 2016, https://doi.org/10.1128/mBio.01517-16) showed wide variation in light responses at a physiological and protein functionality level in 15 A. fumigatus isolates. In both studies, two commonly used type strains, Af293 and CEA10, displayed significant differences in physiological responses to abiotic stimuli and virulence in a murine model of IPA. PMID:28223452

  12. Diagnostic and therapeutic strategy for confounding radiation myelitis.

    PubMed

    Higashida, Tetsuhiro; Colen, Chaim B; Guthikonda, Murali

    2010-05-01

    We report a case of confounding radiation myelitis to demonstrate the usefulness of surgical biopsy in ensuring the correct diagnosis and to avoid unnecessary treatment. The patient was a 40-year-old man with a history of epiglottis carcinoma and sarcoidosis. Six months after radiation therapy and chemotherapy for epiglottis carcinoma, he noticed paresthesia and dysesthesia in the left arm and leg. Two months after that, he complained of severe neck pain and rapidly progressing weakness in all extremities. MRI showed an enhanced intramedullary lesion with extensive edema in the cervical spinal cord. Radiation myelitis, intramedullary spinal tumor, and neurosarcoidosis were considered as differential diagnoses. Spinal cord biopsy with laminectomy was performed and radiation myelitis was diagnosed. After the surgery, the lesion was significantly decreased in size even though corticosteroid therapy was rapidly tapered. We emphasize that a spinal cord biopsy is indicated to obtain a pathological diagnosis and to make a clear treatment strategy for patients with associated diseases causing lesions of the spinal cord.

  13. New covalent modifications of phosphatidylethanolamine by alkanals: mass spectrometry based structural characterization and biological effects.

    PubMed

    Annibal, Andrea; Schubert, Kristin; Wagner, Ulf; Hoffmann, Ralf; Schiller, Jürgen; Fedorova, Maria

    2014-07-01

    The pathophysiology of numerous human disorders, such as atherosclerosis, diabetes, obesity and Alzheimer's disease, is accompanied by increased production of reactive oxygen species (ROS). ROS can oxidatively damage nearly all biomolecules, including lipids, proteins and nucleic acids. In particular, (poly)unsaturated fatty acids within the phospholipid (PL) structure are easily oxidized by ROS to lipid peroxidation products (LPP) carrying reactive carbonyl groups. Carbonylated LPP are characterized by high in vivo toxicity due to their reactivity with nucleophilic substrates (Lys-, Cys-and His-residues in proteins or amino groups of phosphatidylethanolamines [PE]). Adducts of unsaturated LPP with PE amino groups have been reported before, whereas less is known about the reactivity of saturated alkanals - which are significantly increased in vivo under oxidative stress conditions - towards nucleophilic groups of PLs. Here, we present a study of new alkanal-dipalmitoyl-phosphatidylethanolamine (DPPE) adducts by MS-based approaches, using consecutive fragmentation (MS(n)) and multiple reaction monitoring techniques. At least eight different DPPE-hexanal adducts were identified, including Schiff base and amide adducts, six of which have not been reported before. The structures of these new compounds were determined by their fragmentation patterns using MS(n) experiments. The new PE-hexanal adducts contained dimeric and trimeric hexanal conjugates, including cyclic adducts. A new pyridine ring containing adduct of DPPE and hexanal was purified by HPLC, and its biological effects were investigated. Incubation of peripheral blood mononuclear cells and monocytes with modified DPPE did not result in increased production of TNF-α as one selected inflammation marker. However, incorporation of modified DPPE into 1,2-dipalmitoleoyl-sn-phosphatidylethanolamine multilamellar vesicles resulted in a negative shift of the transition temperature, indicating a possible role of

  14. Staphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation

    PubMed Central

    Hansenová Maňásková, Silvie; Nazmi, Kamran; van ‘t Hof, Wim; van Belkum, Alex; Martin, Nathaniel I.; Bikker, Floris J.; van Wamel, Willem J. B.; Veerman, Enno C. I.

    2016-01-01

    The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITC)LPETG-amide) into the bacterial cell wall, albeit at high concentrations of 500 μM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i) by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 μM, 100 μM and 250 μM; (ii) Substituting aspartic acid (E) for methionine increased the incorporation of the resulting K(FITC)LPMTG-amide approximately three times at all concentrations tested; (iii) conjugation of the lipid II binding antibiotic vancomycin to K(FITC)LPMTG-amide resulted in the same incorporation levels as K(FITC)LPETG-amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall. PMID:26799839

  15. New covalent modifications of phosphatidylethanolamine by alkanals: mass spectrometry based structural characterization and biological effects

    PubMed Central

    Annibal, Andrea; Schubert, Kristin; Wagner, Ulf; Hoffmann, Ralf; Schiller, Jürgen; Fedorova, Maria

    2014-01-01

    The pathophysiology of numerous human disorders, such as atherosclerosis, diabetes, obesity and Alzheimer's disease, is accompanied by increased production of reactive oxygen species (ROS). ROS can oxidatively damage nearly all biomolecules, including lipids, proteins and nucleic acids. In particular, (poly)unsaturated fatty acids within the phospholipid (PL) structure are easily oxidized by ROS to lipid peroxidation products (LPP) carrying reactive carbonyl groups. Carbonylated LPP are characterized by high in vivo toxicity due to their reactivity with nucleophilic substrates (Lys-, Cys-and His-residues in proteins or amino groups of phosphatidylethanolamines [PE]). Adducts of unsaturated LPP with PE amino groups have been reported before, whereas less is known about the reactivity of saturated alkanals – which are significantly increased in vivo under oxidative stress conditions – towards nucleophilic groups of PLs. Here, we present a study of new alkanal-dipalmitoyl-phosphatidylethanolamine (DPPE) adducts by MS-based approaches, using consecutive fragmentation (MSn) and multiple reaction monitoring techniques. At least eight different DPPE–hexanal adducts were identified, including Schiff base and amide adducts, six of which have not been reported before. The structures of these new compounds were determined by their fragmentation patterns using MSn experiments. The new PE-hexanal adducts contained dimeric and trimeric hexanal conjugates, including cyclic adducts. A new pyridine ring containing adduct of DPPE and hexanal was purified by HPLC, and its biological effects were investigated. Incubation of peripheral blood mononuclear cells and monocytes with modified DPPE did not result in increased production of TNF-α as one selected inflammation marker. However, incorporation of modified DPPE into 1,2-dipalmitoleoyl-sn-phosphatidylethanolamine multilamellar vesicles resulted in a negative shift of the transition temperature, indicating a possible role of

  16. Precipitation Effects on Microbial Pollution in a River: Lag Structures and Seasonal Effect Modification

    PubMed Central

    Tornevi, Andreas; Bergstedt, Olof; Forsberg, Bertil

    2014-01-01

    Background The river Göta Älv is a source of freshwater for 0.7 million swedes. The river is subject to contamination from sewer systems discharge and runoff from agricultural lands. Climate models projects an increase in precipitation and heavy rainfall in this region. This study aimed to determine how daily rainfall causes variation in indicators of pathogen loads, to increase knowledge of variations in river water quality and discuss implications for risk management. Methods Data covering 7 years of daily monitoring of river water turbidity and concentrations of E. coli, Clostridium and coliforms were obtained, and their short-term variations in relation with precipitation were analyzed with time series regression and non-linear distributed lag models. We studied how precipitation effects varied with season and compared different weather stations for predictive ability. Results Generally, the lowest raw water quality occurs 2 days after rainfall, with poor raw water quality continuing for several more days. A rainfall event of >15 mm/24-h (local 95 percentile) was associated with a three-fold higher concentration of E. coli and 30% higher turbidity levels (lag 2). Rainfall was associated with exponential increases in concentrations of indicator bacteria while the effect on turbidity attenuated with very heavy rainfall. Clear associations were also observed between consecutive days of wet weather and decreased water quality. The precipitation effect on increased levels of indicator bacteria was significant in all seasons. Conclusions Rainfall elevates microbial risks year-round in this river and freshwater source and acts as the main driver of varying water quality. Heavy rainfall appears to be a better predictor of fecal pollution than water turbidity. An increase of wet weather and extreme events with climate change will lower river water quality even more, indicating greater challenges for drinking water producers, and suggesting better control of sources of

  17. Limit of detection of field effect transistor biosensors: Effects of surface modification and size dependence

    NASA Astrophysics Data System (ADS)

    Rajan, Nitin K.; Brower, Kara; Duan, Xuexin; Reed, Mark A.

    2014-02-01

    Field-effect transistor biosensors have shown great promise in the detection of biomolecules. However, a quantitative understanding of what limits the smallest measurable concentration of analyte (limit of detection or LOD) is still missing. By considering the signal-to-noise ratio (SNR), extracted from a combination of noise and I-V characterization, we are able to accurately predict and experimentally confirm a LOD of 0.01 pH. Our results also show that devices with larger area and with amine functionalized surfaces have larger SNR. We are able to extract the associated oxide trap densities and, thus, quantify the improvements in LOD.

  18. Surface modification as an effective approach to enhance the microwave absorbing properties of hollow carbon spheres

    NASA Astrophysics Data System (ADS)

    Zhu, Hui-Ling; Xu, Zhen-Fu; Cui, Hong-Zhi; Wu, Jie; Dang, Jun-Fan; Wang, Tian-Fang; Zhang, Li-Dong

    2016-10-01

    The microwave absorbing properties of hollow carbon spheres modified by KOH were measured using a transmission/reflection coaxial method in the range of 2-18 GHz. The modification could result in a significant enhancement in the properties, including both the increment in absorbing intensity and bandwidth and the decrease in absorber thickness, which can be well explained by the high concentration of dangling bonds in per unit volume or per unit weight introduced during the modification. This dangling bond dominated mechanism could be used to instruct the design of absorbers with outstanding performances.

  19. The effect of RGD fluorosurfactant polymer modification of ePTFE on endothelial cell adhesion, growth, and function

    PubMed Central

    Larsen, Coby C.; Kligman, Faina; Kottke-Marchant, Kandice; Marchant, Roger E.

    2007-01-01

    We have synthesized and characterized a novel peptide fluorosurfactant polymer (PFSP) modification that facilitates the adhesion and growth of endothelial cells on ePTFE vascular graft material. This PFSP consists of a poly(vinyl amine) (PVAm) backbone with integrin binding Arg-Gly-Asp (RGD) peptides and perfluorocarbon pendant branches for adsorption and stable adhesion to underlying ePTFE. Aqueous PFSP solution was used to modify the surface of fluorocarbon substrates. Following subconfluent seeding, endothelial cell (EC) adhesion and growth on PFSP was assessed by determining cell population at different time points. Spectroscopic results indicated successful synthesis of PFSP. PFSP modification of ePTFE reduced the receding water contact angle measurement from 120° to 6°, indicating successful surface modification. Quantification of cell population demonstrated reduced EC attachment efficiency but increased growth rate on RGD PFSP compared with fibronectin (FN). Actin staining revealed a well-developed cytoskeleton for ECs on RGD PFSP indicative of stable adhesion. Uptake of acetylated low-density lipoprotein and positive staining for VE-Cadherin confirm EC phenotype for adherent cells. Production of prostacyclin, a potent antiplatelet agent, was equivalent between ECs on FN and RGD PFSP surfaces. Our results indicate successful synthesis and surface modification with PFSP; this is a simple, quantitative, and effective approach to modifying ePTFE to encourage endothelial cell attachment, growth, and function. PMID:16762410

  20. Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

    PubMed

    Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

    2005-06-01

    Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

  1. The effect of RGD fluorosurfactant polymer modification of ePTFE on endothelial cell adhesion, growth, and function.

    PubMed

    Larsen, Coby C; Kligman, Faina; Kottke-Marchant, Kandice; Marchant, Roger E

    2006-10-01

    We have synthesized and characterized a novel peptide fluorosurfactant polymer (PFSP) modification that facilitates the adhesion and growth of endothelial cells on expanded polytetrafluoroetheylene (ePTFE) vascular graft material. This PFSP consists of a poly(vinyl amine) (PVAm) backbone with integrin binding Arg-Gly-Asp (RGD) peptides and perfluorocarbon pendant branches for adsorption and stable adhesion to underlying ePTFE. Aqueous PFSP solution was used to modify the surface of fluorocarbon substrates. Following subconfluent seeding, endothelial cell (EC) adhesion and growth on PFSP was assessed by determining cell population at different time points. Spectroscopic results indicated successful synthesis of PFSP. PFSP modification of ePTFE reduced the receding water contact angle measurement from 120 degrees to 6 degrees , indicating successful surface modification. Quantification of cell population demonstrated reduced EC attachment efficiency but increased growth rate on RGD PFSP compared with fibronectin (FN). Actin staining revealed a well-developed cytoskeleton for ECs on RGD PFSP indicative of stable adhesion. Uptake of acetylated low-density lipoprotein and positive staining for VE-Cadherin confirm EC phenotype for adherent cells. Production of prostacyclin, a potent antiplatelet agent, was equivalent between ECs on FN and RGD PFSP surfaces. Our results indicate successful synthesis and surface modification with PFSP; this is a simple, quantitative, and effective approach to modifying ePTFE to encourage endothelial cell attachment, growth, and function.

  2. Endwall shape modification using vortex generators and fences to improve gas turbine cooling and effectiveness

    NASA Astrophysics Data System (ADS)

    Gokce, Zeki Ozgur

    The gas turbine is one of the most important parts of the air-breathing jet engine. Hence, improving its efficiency and rendering it operable under high temperatures are constant goals for the aerospace industry. Two types of flow within the gas turbine are of critical relevance: The flow around the first row of stator blades (also known as the nozzle guide vane blade - NGV) and the cooling flow inside the turbine blade cooling channel. The subject of this thesis work was to search for methods that could improve the characteristics of these two types of flows, thus enabling superior engine performance. The innovative aspect of our work was to apply an endwall shape modification previously employed by non-aerospace industries for cooling applications, to the gas turbine cooling flow which is vital to aerospace propulsion. Since the costs of investigating the possible benefits of any idea via extensive experiments could be quite high, we decided to use computational fluid dynamics (CFD) followed by experimentation as our methodology. We decided to analyze the potential benefits of using vortex generators (VGs) as well as the rectangular endwall fence. Since the pin-fins used in cooling flow are circular cylinders, and since the boundary layer flow is mainly characterized by the leading edge diameter of the NGV blade, we modeled both the pin-fins and the NGV blade as vertical circular cylinders. The baseline case consisted of the cylinder(s) being subjected to cross flow and a certain amount of freestream turbulence. The modifications we made on the endwall consisted of rectangular fences. In the case of the cooling flow, we used triangular shaped, common flow up oriented, delta winglet type vortex generators as well as rectangular endwall fences. The channel contained singular cylinders as well as staggered rows of multiple cylinders. For the NGV flow, a rectangular endwall fence and a singular cylinder were utilized. Using extensive CFD modeling and analysis, we

  3. The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders.

    PubMed

    Dettenborn, L; Tietze, A; Kirschbaum, C; Stalder, T

    2012-11-01

    To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex.

  4. Child welfare clients have higher risks for teenage childbirths: which are the major confounders?

    PubMed Central

    Vinnerljung, Bo; Hjern, Anders

    2016-01-01

    Background: Aiming to support effective social intervention strategies targeting high-risk groups for teenage motherhood, this study examined to what extent the elevated crude risks of teenage childbirth among child welfare groups were attributable to the uneven distribution of adverse individual and family background factors. Methods: Comprehensive longitudinal register data for more than 700 000 Swedish females born 1973–1989 (including around 29 000 child welfare clients) were analysed by means of binary logistic regression. The Karlson/Holm/Breen-method was used to decompose each confounding factor’s relative contribution to the difference between crude and adjusted odds ratios (ORs). Results: Elevated crude risks for teenage childbirth are to a large extent attributable to selection on observables. Girls’ school failure was the most potent confounder, accounting for 28–35% of the difference between crude and adjusted ORs. Conclusion: As in majority populations, girls’ school failure was a strong risk factor for teenage childbirth among former child welfare children. At least among pre-adolescents, promoting school performance among children in the child welfare system seems to be a viable intervention path. PMID:27085195

  5. The effects of magnetic field modifications on the solar modulation of cosmic rays with a SDE-based model

    NASA Astrophysics Data System (ADS)

    Raath, J. L.; Potgieter, M. S.; Strauss, R. D.; Kopp, A.

    2016-05-01

    A numerical model for the solar modulation of cosmic rays, based on the solution of a set of stochastic differential equations (SDEs), is used to illustrate the effects of modifying the heliospheric magnetic field, particularly in the polar regions of the heliosphere. SDE-based models are well suited for such studies so that new insights are gained. To this end, the differences in the modulation brought about by each of three choices for the heliospheric magnetic field, i.e. the unmodified Parker field, the Smith-Bieber modified field, and the Jokipii-Kóta modified field, are studied as typical well-known cases. It is illustrated that although both these modifications change the Parker field satisfactorily in the polar regions of the heliosphere, the Smith-Bieber modification is more effective in reducing cosmic ray drift effects in these regions. The features of these two modifications, as well as the effects on the solar modulation of cosmic rays, are illustrated qualitatively and quantitatively. In particular, it is shown how the Smith-Bieber modified field is applied in a cosmic ray modulation model to reproduce observational proton spectra from the PAMELA mission during the solar minimum of 2006-2009. These SDE-based results are compared with those obtained in previous studies of this unusual solar minimum activity period and found to be in good qualitative agreement.

  6. Evaluation of surface sensible heat flux effects on the generation and modification of mesoscale circulations

    NASA Technical Reports Server (NTRS)

    Segal, M.; Pielke, R. A.; Mahrer, Y.

    1984-01-01

    Mesoscale thermal-induced circulations generated by horizontal gradients in surface characteristics as well as significant perturbations on land and sea breezes and mountain-valley winds due to substantial modifications in the thermal forcing are introduced. It is suggested that these types of mesoscale situations are generally ignored in forecasting but that they may have important implications in very short range predictions.

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

    ERIC Educational Resources Information Center

    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…

  8. Effect of dual modification with hydroxypropylation and cross-linking on physicochemical properties of taro starch.

    PubMed

    Hazarika, Bidyut Jyoti; Sit, Nandan

    2016-04-20

    Dual modification of taro starch by hydroxypropylation and cross-linking was carried out and the properties of the modified starches were investigated. Two different levels of hydroxypropylation (5 and 10%) and cross-linking (0.05 and 0.10%) were used in different sequences. The amylose contents of the starch decreased due to single and dual modification. For the dual-modified starches, the swelling, solubility and clarity was found to increase with level of hydroxypropylation and decrease with level of cross-linking. The freeze-thaw stability of the dual-modified starches was also affected by the sequence of modification. The viscosities of the cross-linked and dual-modified starches were more than native and hydroxypropylated starches. The firmness of the dual-modified starches was also higher than native and single modified starches. The dual-modified starches have benefits of both type of modifications and could be used for specific purposes e.g. food products requiring high viscosity as well as freeze-thaw stability.

  9. Effects of modification of the tyrosine residues of bacteriorhodopsin with tetranitromethane.

    PubMed Central

    Campos-Cavieres, M; Moore, T A; Perham, R N

    1979-01-01

    Treatment of the purple membrane of Halobacterium halobium with tetranitromethane led to modification of tyrosine residues. Modification of more than 3-4 tyrosine residues per bacteriorhodopsin monomer caused a decrease in the light-induced proton-pumping ability of purple membrane in synthetic lipid vesicles, loss of the sharp X-ray-diffraction patterns characteristic of the crystal lattice, loss of the absorbance maximum at 560 nm, and change in the buoyant density of the membrane. No modification of lipid was detected. These changes were interpreted as a gradual denaturation of the protein component such that when 8-9 tyrosine residues are modified, no proton pumping is observed. Modification of less than 3-4 tyrosine residues with tetranitromethane caused an increse in light-induced proton pumping. It was possible to generate partly modified purple membrane which had completely lost the property of diffracting X-rays into the sharp pattern observed with native purple membrane, but which still retained the ability to pump protons in a vectorial manner. Retention of crystal lattice is not essential for proton pumping. Images Fig. 3. PMID:475758

  10. Characterization of organo-modified bentonite sorbents: The effect of modification conditions on adsorption performance

    NASA Astrophysics Data System (ADS)

    Parolo, María E.; Pettinari, Gisela R.; Musso, Telma B.; Sánchez-Izquierdo, María P.; Fernández, Laura G.

    2014-11-01

    The organic modification of a natural bentonite was evaluated using two methods: exchanging the interlayer cations by hexadecyltrimethylammonium (HDTMA) and grafting with vinyltrimethoxysilane (VTMS) and γ-methacryloyloxy propyl trimethoxysilane (TMSPMA) on montmorillonite surface. The physicochemical characterization of all materials was made by X-ray diffraction (XRD), IR spectroscopy, thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET) surface area techniques. HDTMA cations and organosilanes were intercalated into the interlayer space of montmorillonite, as deduced from the increase of the basal spacing. IR spectroscopy, TGA and BET area give evidence of successful organic modification. The studies show a decrease in the IR absorption band intensity at 3465 cm-1 with surfactant modification, and also a decrease of mass loss due to adsorbed water observed in two samples: the organoclay and functionalized bentonites, which are evidences of a lower interlayer hydrophilicity. The efficiency of aniline removal onto natural bentonite, organobentonite and functionalized bentonites from aqueous solutions was evaluated. Aniline sorption on natural bentonite was studied using batch experiments, XRD and IR spectroscopy. The hydrophobic surface of organobentonite and functionalized bentonites increased the retention capacity for nonionic organic substances such as aniline on bentonites. The sorption properties of modified bentonite, through different modification methods, enhanced the potential industrial applications of bentonites in water decontamination.

  11. Effect of Subliminal Stimulation of Symbiotic Fantasies on Behavior Modification Treatment of Obesity.

    ERIC Educational Resources Information Center

    And Others; Silverman, Lloyd H.

    1978-01-01

    Obese women were treated in behavior modification programs for overeating. Behavior programs were accompanied by subliminal stimulation and by symbiotic and control messages. The symbiotic condition gave evidence of enhancing weight loss. This finding supports the proposition that subliminal stimulation of symbiotic fantasies can enhance the…

  12. A Meta-Analysis of the Effect of Cognitive Bias Modification on Anxiety and Depression

    ERIC Educational Resources Information Center

    Hallion, Lauren S.; Ruscio, Ayelet Meron

    2011-01-01

    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…

  13. Organizational Behavior Change: The Effectiveness of Behavior Modification Techniques with and without Participatory Management.

    ERIC Educational Resources Information Center

    Sweeney, Mary M.; Goldstein, Marc B.

    This study examines a naturally occurring experiment in a large urban hospital faced with budget cuts, in which departments were ordered to reduce employees' overtime without jeopardizing service quality. The study focuses on two departments that chose to use behavior modification techniques. In one department (Radiology) the intervention combined…

  14. Effect of polymer surface modification on polymer-protein interaction via hydrophilic polymer grafting

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surface modification of flat sheet ultrafiltration membranes, polyethersulfone (PES) was investigated to improve the hydrophilicity of the membrane surface thereby reducing adsorption of the proteins onto the membrane. Grafting of hydrophilic polymers onto UV/ozone treated PES was used to improve t...

  15. Sampling Modification Effects in the Subgingival Microbiome Profile of Healthy Children

    PubMed Central

    Santigli, Elisabeth; Trajanoski, Slave; Eberhard, Katharina; Klug, Barbara

    2017-01-01

    grouping by sampling modes (p = 0.914 by R2 = 0.09). Conclusion: A slight modification of sampling mode has minor effects corresponding to a natural variability in the microbiome profiles of healthy children. The inter-individual variability in subgingival microprints is greater than intra-individual differences. Statistical analyses of microbial populations should consider this baseline variability and move beyond mere quantification with input from visual analytics. Comparative results are difficult to summarize as methods for studying huge datasets are still evolving. Advanced approaches are needed for sample size calculations in clinical settings. PMID:28149291

  16. Effect of surface modification on single-walled carbon nanotube retention and transport in saturated and unsaturated porous media.

    PubMed

    Tian, Yuan; Gao, Bin; Morales, Verónica L; Wang, Yu; Wu, Lei

    2012-11-15

    This work investigated the effect of different surface modification methods, including oxidization, surfactant coating, and humic acid coating, on single-walled carbon nanotube (SWNT) stability and their mobility in granular porous media under various conditions. Characterization and stability studies demonstrated that the three surface modification methods were all effective in solubilizing and stabilizing the SWNTs in aqueous solutions. Packed sand column experiments showed that although the three surface medication methods showed different effect on the retention and transport of SWNTs in the columns, all the modified SWNTs were highly mobile. Compared with the other two surface modification methods, the humic acid coating method introduced the highest mobility to the SWNTs. While reductions in moisture content in the porous media could promote the retention of the surface modified SWNTs in some sand columns, results from bubble column experiment suggested that only oxidized SWNTs were retention in unsaturated porous media through attachment on air-water interfaces. Other mechanisms such as grain surface attachment and thin-water film straining could also be responsible for the retention of the SWNTs in unsaturated porous media. An advection-dispersion model was successfully applied to simulate the experimental data of surface modified SWNT retention and transport in porous media.

  17. Proteomic Investigation of Protein Profile Changes and Amino Acid Residue Level Modification in Cooked Lamb Meat: The Effect of Boiling.

    PubMed

    Yu, Tzer-Yang; Morton, James D; Clerens, Stefan; Dyer, Jolon M

    2015-10-21

    Hydrothermal treatment (heating in water) is a common method of general food processing and preparation. For red-meat-based foods, boiling is common; however, how the molecular level effects of this treatment correlate to the overall food properties is not yet well-understood. The effects of differing boiling times on lamb meat and the resultant cooking water were here examined through proteomic evaluation. The longer boiling time was found to result in increased protein aggregation involving particularly proteins such as glyceraldehyde-3-phosphate dehydrogenase, as well as truncation in proteins such as in α-actinin-2. Heat-induced protein backbone cleavage was observed adjacent to aspartic acid and asparagine residues. Side-chain modifications of amino acid residues resulting from the heating, including oxidation of phenylalanine and formation of carboxyethyllysine, were characterized in the cooked samples. Actin and myoglobin bands from the cooked meat per se remained visible on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, even after significant cooking time. These proteins were also found to be the major source of observed heat-induced modifications. This study provides new insights into molecular-level modifications occurring in lamb meat proteins during boiling and a protein chemistry basis for better understanding the effect of this common treatment on the nutritional and functional properties of red-meat-based foods.

  18. Interpersonal discrimination and depressive symptomatology: examination of several personality-related characteristics as potential confounders in a racial/ethnic heterogeneous adult sample

    PubMed Central

    2013-01-01

    Background Research suggests that reports of interpersonal discrimination result in poor mental health. Because personality characteristics may either confound or mediate the link between these reports and mental health, there is a need to disentangle its role in order to better understand the nature of discrimination-mental health association. We examined whether hostility, anger repression and expression, pessimism, optimism, and self-esteem served as confounders in the association between perceived interpersonal discrimination and CESD-based depressive symptoms in a race/ethnic heterogeneous probability-based sample of community-dwelling adults. Methods We employed a series of ordinary least squares regression analyses to examine the potential confounding effect of hostility, anger repression and expression, pessimism, optimism, and self-esteem between interpersonal discrimination and depressive symptoms. Results Hostility, anger repression, pessimism and self-esteem were significant as possible confounders of the relationship between interpersonal discrimination and depressive symptoms, together accounting for approximately 38% of the total association (beta: 0.1892, p < 0.001). However, interpersonal discrimination remained a positive predictor of depressive symptoms (beta: 0.1176, p < 0.001). Conclusion As one of the first empirical attempts to examine the potential confounding role of personality characteristics in the association between reports of interpersonal discrimination and mental health, our results suggest that personality-related characteristics may serve as potential confounders. Nevertheless, our results also suggest that, net of these characteristics, reports of interpersonal discrimination are associated with poor mental health. PMID:24256578

  19. Homophily and Contagion Are Generically Confounded in Observational Social Network Studies

    PubMed Central

    Shalizi, Cosma Rohilla; Thomas, Andrew C.

    2012-01-01

    The authors consider processes on social networks that can potentially involve three factors: homophily, or the formation of social ties due to matching individual traits; social contagion, also known as social influence; and the causal effect of an individual’s covariates on his or her behavior or other measurable responses. The authors show that generically, all of these are confounded with each other. Distinguishing them from one another requires strong assumptions on the parametrization of the social process or on the adequacy of the covariates used (or both). In particular the authors demonstrate, with simple examples, that asymmetries in regression coefficients cannot identify causal effects and that very simple models of imitation (a form of social contagion) can produce substantial correlations between an individual’s enduring traits and his or her choices, even when there is no intrinsic affinity between them. The authors also suggest some possible constructive responses to these results. PMID:22523436

  20. Assessing quality of nursing care as a confounding variable in an outcome study on neurodevelopmental treatment.

    PubMed

    Hafsteinsdóttir, Thóra B; Kruitwagen, Cas; Strijker, Karin; van der Weide, Lies; Grypdonck, Maria H F

    2007-01-01

    When planning a study measuring the effects of a neurodevelopmental treatment (NDT), we were confronted with the methodological problem that while measuring the effects of NDT, a rival hypothesis is that the decision to implement the NDT might be related to the quality of nursing care. Therefore, we measured the quality of nursing care as a possible confounding variable in relation to this outcome study. The quality of nursing care was measured on 12 wards participating in the experimental and control groups of the outcome study. Data were collected from 125 patients and 71 nurses and patients' records. The findings showed no significant differences in the quality of nursing care between the 2 groups of wards (P = .49). This method may be useful to other researchers conducting outcome research and who are confronted with a similar methodological problem.

  1. Missing variables: how exclusion of human resources policy information confounds research connecting health and business outcomes.

    PubMed

    Lynch, Wendy D; Sherman, Bruce W

    2014-01-01

    When corporate health researchers examine the effects of health on business outcomes or the effect of health interventions on health and business outcomes, results will necessarily be confounded by the corporate environment(s) in which they are studied. In this research setting, most studies control for factors traditionally identified in public health, such as demographics and health status. Nevertheless, often overlooked is the extent to which company policies can also independently impact health care cost, work attendance, and productivity outcomes. With changes in employment and benefits practices resulting from health care reform, including incentives and plan design options, consideration of these largely neglected variables in research design has become increasingly important. This commentary summarizes existing knowledge regarding the implications of policy variations in research outcomes and provides a framework for incorporating them into future employer-based research.

  2. Home Modification

    MedlinePlus

    ... it is important to consider certain safety modifications. Adaptations such as those in the following list can ... The importance of a Consumer Perspective in Home Adaptation of Alzheimer’s Households” (Chapter 6 pp 91-112) ...

  3. Effects of activity modification on the patients with osteoarthritis of the knee.

    PubMed

    Shakoor, M A; Taslim, Md Abu; Hossain, Md Shahadat

    2007-08-01

    A prospective randomized clinical trial was conducted on 162 patients of osteoarthritis of knee were included in the study. The patients were divided into two groups- Group A and Group B. The Group A was treated with shortwave diathermy, exercise, naproxen and activity modification and the Group B was treated with shortwave diathermy, exercise and naproxen. Improvement was found more in Group A than Group B after 4th week (95% CI was -2.59 to 6.56). Then it was found that the improvement was gradually increased in Group A than Group B and finally, it was found that there was highly significant improvement in Group A than Group B after 6th week (95% CI was -3.45 to -0.70). This study suggests that activity modification play an important role for the treatment of the patients with osteoarthritis of knee.

  4. The effects of magnetic field modifications on the solar modulation of cosmic rays with a SDE-based model

    NASA Astrophysics Data System (ADS)

    Raath, Jan-Louis; Toit Strauss, Du; Kopp, Andreas; Potgieter, Marius

    2016-07-01

    The effects of modifying the heliospheric magnetic field, particularly in the polar regions of the heliosphere, are illustrated by utilizing a numerical model based on the solution of a set of stochastic differential equations (SDEs). Because SDE-based models are especially well suited for such studies, we are able to gain new insights into this subject. The differences in the modulation brought about by each of three choices for the heliospheric magnetic field are studied as typical well-known cases; they are the unmodified Parker field, and the Smith-Bieber and Jokipii-Kóta modified fields. It is illustrated that both these modifications change the Parker field satisfactorily in the heliospheric polar regions, but that the modification of Smith and Bieber affects a larger reduction in cosmic ray drift effects in these regions. The general features of these two modifications are illustrated and the Smith-Bieber modified field is applied in a cosmic ray modulation model to reproduce observational proton spectra from the PAMELA mission during the solar minimum of 2006 - 2009. These SDE-based results are compared to the results from other studies and found to be in good qualitative agreement.

  5. Effect of micro-arc oxidation surface modification on the properties of the NiTi shape memory alloy.

    PubMed

    Xu, J L; Zhong, Z C; Yu, D Z; Liu, F; Luo, J M

    2012-12-01

    In this paper, the effects of micro-arc oxidation (MAO) surface modification (alumina coatings) on the phase transformation behavior, shape memory characteristics, in vitro haemocopatibility and cytocompatibility of the biomedical NiTi alloy were investigated respectively by differential scanning calorimetry, bending test, hemolysis ratio test, dynamic blood clotting test, platelet adhesion test and cytotoxicity testing by human osteoblasts (Hobs). The results showed that there were no obvious changes of the phase transformation temperatures and shape memory characteristics of the NiTi alloy after the MAO surface modification and the coating could withstand the thermal shock and volume change caused by martensite-austenite phase transformation. Compared to the uncoated NiTi alloys, the MAO surface modification could effectively improve the haemocopatibility of the coated NiTi alloys by the reduced hemolysis ratio, the prolonged dynamic clotting time and the decreased number of platelet adhesion; and the rough and porous alumina coatings could obviously promote the adherence, spread and proliferation of the Hobs with the significant increase of proliferation number of Hobs adhered on the surface of the coated NiTi alloys (P < 0.05).

  6. Effects of ultraviolet nanosecond laser irradiation on structural modification and optical transmission of single layer graphene

    NASA Astrophysics Data System (ADS)

    Li, Chunhong; Kang, Xiaoli; Zhu, Qihua; Zheng, Wanguo

    2017-03-01

    Structural modifications and optical transmission change of single layer graphene (SLG) on transparent SiO2 substrate induced by nanosecond 355 nm laser irradiation were systematically studied by scanning electron microscopy (SEM), laser-excited Raman, X-ray photon spectroscopy (XPS) and UV-vis transmission spectra. In this study, to avoid damage to graphene, the selected irradiation fluence was set to be smaller than the laser damage threshold of SLG. Laser-driven formation of nano-dots, carbon clusters and spherical carbon morphologies were clearly presented using SEM magnification images, and the formation mechanism of such structures were discussed. Raman spectra revealed formation of D' peak and the continuously increasing of ID/IG intensity ratio with the concurrent increase of laser fluence, indicating the increase in amount of structural defects and disordering in SLG. XPS results disclosed that the oxygen content in SLG increases with laser fluence. The formation and relative content increase of Cdbnd O, Csbnd Osbnd C and Osbnd Cdbnd O bonds in SLG induced by laser irradiation were also revealed by XPS. Laser-driven micro-structure modifications of crystalline graphene to nano-crystalline graphene and photo-chemical reactions between graphene and O2 and H2O in air environment were suggested to be responsible for the Raman and XPS revealed modifications in SLG. It is worthy to point out that the above mentioned structural modifications only caused a slight decrease (<2% @ 550 nm) in the optical transmittance of SLG. These results may provide more selections for the batch processing of large scale graphene aiming at modifying its structure and thus taiorling its properties.

  7. Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds to low levels of arsenite

    SciTech Connect

    Hirano, Seishiro; Watanabe, Takayuki; Kobayashi, Yayoi

    2013-12-15

    Inorganic arsenite (iAs{sup 3+}) is a two-edged sword. iAs{sup 3+} is a well-known human carcinogen; nevertheless, it has been used as a therapeutic drug for acute promyelocytic leukemia (APL), which is caused by a fusion protein comprising retinoic acid receptor-α and promyelocytic leukemia (PML). PML, a nuclear transcription factor, has a RING finger domain with densely positioned cysteine residues. To examine PML-modulated cellular responses to iAs{sup 3+}, CHO-K1 and HEK293 cells were each used to establish cell lines that expressed ectopic human PML. Overexpression of PML increased susceptibility to iAs{sup 3+} in CHO-K1 cells, but not in HEK293 cells. Exposure of PML-transfected cells to iAs{sup 3+} caused PML to change from a soluble form to less soluble forms, and this modification of PML was observable even with just 0.1 μM iAs{sup 3+} (7.5 ppb). Western blot and immunofluorescent microscopic analyses revealed that the biochemical changes of PML were caused at least in part by conjugation with small ubiquitin-like modifier proteins (SUMOylation). A luciferase reporter gene was used to investigate whether modification of PML was caused by oxidative stress or activation of antioxidant response element (ARE) in CHO-K1 cells. Modification of PML protein occurred faster than activation of the ARE in response to iAs{sup 3+}, suggesting that PML was not modified as a consequence of oxidative stress-induced ARE activation. - Highlights: • PML was found in nuclear microspecles in response to arsenite. • Arsenite triggers SUMOylation of PML. • Arsenite modifies PML at as low as 0.1 μM. • Modification of PML is not caused by ARE activation.

  8. Ubiquitin modifications

    PubMed Central

    Swatek, Kirby N; Komander, David

    2016-01-01

    Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation. PMID:27012465

  9. Effect of Hybrid Surface Modifications on Tensile Properties of Polyacrylonitrile- and Pitch-Based Carbon Fibers

    NASA Astrophysics Data System (ADS)

    Naito, Kimiyoshi

    2016-05-01

    Recent interest has emerged in techniques that modify the surfaces of carbon fibers, such as carbon nanotube (CNT) grafting or polymer coating. Hybridization of these surface modifications has the potential to generate highly tunable, high-performance materials. In this study, the mechanical properties of surface-modified polyacrylonitrile (PAN)-based and pitch-based carbon fibers were investigated. Single-filament tensile tests were performed for fibers modified by CNT grafting, dipped polyimide coating, high-temperature vapor deposition polymerized polyimide coating, grafting-dipping hybridization, and grafting-vapor deposition hybridization. The Weibull statistical distributions of the tensile strengths of the surface-modified PAN- and pitch-based carbon fibers were examined. All surface modifications, especially hybrid modifications, improved the tensile strengths and Weibull moduli of the carbon fibers. The results exhibited a linear relationship between the Weibull modulus and average tensile strength on a log-log scale for all surface-modified PAN- and pitch-based carbon fibers.

  10. Effects of channel modification on fish habitat in the upper Yellowstone River: Final report to the USACE, Omaha

    USGS Publications Warehouse

    Bowen, Zachary H.; Bovee, Ken D.; Waddle, Terry J.

    2003-01-01

    A two-dimensional hydrodynamic simulation model was coupled with a geographic information system (GIS) to produce a variety of habitat classification maps for three study reaches in the upper Yellowstone River basin in Montana. Data from these maps were used to examine potential effects of channel modification on shallow, slow current velocity (SSCV) habitats that are important refugia and nursery areas for young salmonids. At low flows, channel modifications were found to contribute additional SSCV habitat, but this contribution was negligible at higher discharges. During runoff, when young salmonids are most vulnerable to downstream displacement, the largest areas of SSCV habitat occurred in side channels, point bars, and overbank areas. Because of the diversity of elevations in the existing Yellowstone River, SSCV habitat tends to be available over a wide range of discharges. Based on simulations in modified and unmodified sub-reaches, channel simplification results in decreased availability of SSCV habitat, particularly during runoff. The combined results of the fish population and fish habitat studies present strong evidence that during runoff, SSCV habitat is most abundant in side channel and overbank areas and that juvenile salmonids use these habitats as refugia. Channel modifications that result in reduced availability of side channel and overbank habitats, particularly during runoff, will probably cause local reductions in juvenile abundances during the runoff period. Effects of reduced juvenile abundances during runoff on adult numbers later in the year will depend on (1) the extent of channel modification, (2) patterns of fish displacement and movement, (3) longitudinal connectivity between reaches that contain refugia and those that do not, and (4) the relative importance of other limiting factors.

  11. Control of confounding in the analysis phase – an overview for clinicians

    PubMed Central

    Kahlert, Johnny; Gribsholt, Sigrid Bjerge; Gammelager, Henrik; Dekkers, Olaf M; Luta, George

    2017-01-01

    In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and

  12. Effects of modification of calcium hydroxyapatites by trivalent metal ions on the protein adsorption behavior.

    PubMed

    Kandori, Kazuhiko; Toshima, Satoko; Wakamura, Masato; Fukusumi, Masao; Morisada, Yoshiaki

    2010-02-25

    The effects of modification of calcium hydroxyapatites (Hap; Ca10(PO4)6(OH)2) by trivalent metal ions (Al(III), La(III), and Fe(III)) on protein adsorption behavior were examined using bovine serum albumin (BSA; isoelectric point (iep) = 4.7 and molecular mass (M(s)) = 67,200 Da). The Al(III)-, La(III)-, and Fe(III)-substituted Hap particles were prepared by the coprecipitation method with different atomic ratios, metal/(Ca + metal), abbreviated as X(metal). The particles precipitated at X(metal) = 0 (original-Hap) were rod-like and 10 x 36 nm2 in size. The short, rod-like original-Hap particles were elongated upon adding metal ions up to X(metal) = 0.10, and the extent of the particle growth was in the order of La(III) < Al(III) < Fe(III). The crystallinity of the materials was slightly lowered by increasing X(metal) for all systems. The adsorption isotherms of BSA onto the Al(III)-, La(III)-, and Fe(III)-substituted Hap particles showed the Langmuirian type. The saturated amounts of adsorbed BSA (n(s)(BSA)) values were strongly dependent on X(metal) in each system. The n(s)(BSA) values for the Fe(III)-substituted Hap system were increased with an increase in X(Fe) (X(metal) value of Hap particles substituted with Fe(III)); the n(s)(BSA) value obtained at X(Fe) = 0.10 was 2.7-fold more than that for the original-Hap particle, though those for the La(III) system were decreased to ca. 1/5. On the other hand, the n(s)(BSA) values for the Al(III) system were decreased with substitution of small amounts of Al(III), showing a minimum point at X(Al) = 0.01, but they were increased again at X(Al) over 0.03. Since the concentrations of hetero metal ions dissolved from the particles exhibited extremely low values, the possibility of binder effects of trivalent cations dissolved from the particle surface for adsorbing BSA to trivalent-ion-substituted Hap particles was excluded. The increase of n(s)(BSA) by an increase in X(Fe) was explained by elongation of mean particle

  13. Residential proximity to electromagnetic field sources and birth weight: Minimizing residual confounding using multiple imputation and propensity score matching.

    PubMed

    de Vocht, Frank; Lee, Brian

    2014-08-01

    Studies have suggested that residential exposure to extremely low frequency (50 Hz) electromagnetic fields (ELF-EMF) from high voltage cables, overhead power lines, electricity substations or towers are associated with reduced birth weight and may be associated with adverse birth outcomes or even miscarriages. We previously conducted a study of 140,356 singleton live births between 2004 and 2008 in Northwest England, which suggested that close residential proximity (≤ 50 m) to ELF-EMF sources was associated with reduced average birth weight of 212 g (95%CI: -395 to -29 g) but not with statistically significant increased risks for other adverse perinatal outcomes. However, the cohort was limited by missing data for most potentially confounding variables including maternal smoking during pregnancy, which was only available for a small subgroup, while also residual confounding could not be excluded. This study, using the same cohort, was conducted to minimize the effects of these problems using multiple imputation to address missing data and propensity score matching to minimize residual confounding. Missing data were imputed using multiple imputation using chained equations to generate five datasets. For each dataset 115 exposed women (residing ≤ 50 m from a residential ELF-EMF source) were propensity score matched to 1150 unexposed women. After doubly robust confounder adjustment, close proximity to a residential ELF-EMF source remained associated with a reduction in birth weight of -116 g (95% confidence interval: -224:-7 g). No effect was found for proximity ≤ 100 m compared to women living further away. These results indicate that although the effect size was about half of the effect previously reported, close maternal residential proximity to sources of ELF-EMF remained associated with suboptimal fetal growth.

  14. Confounding by dietary pattern of the inverse association between alcohol consumption and type 2 diabetes risk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as ...

  15. Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

  16. Non-Chemical Distant Cellular Interactions as a potential confounder of cell biology experiments

    PubMed Central

    Farhadi, Ashkan

    2014-01-01

    Distant cells can communicate with each other through a variety of methods. Two such methods involve electrical and/or chemical mechanisms. Non-chemical, distant cellular interactions may be another method of communication that cells can use to modify the behavior of other cells that are mechanically separated. Moreover, non-chemical, distant cellular interactions may explain some cases of confounding effects in Cell Biology experiments. In this article, we review non-chemical, distant cellular interactions studies to try to shed light on the mechanisms in this highly unconventional field of cell biology. Despite the existence of several theories that try to explain the mechanism of non-chemical, distant cellular interactions, this phenomenon is still speculative. Among candidate mechanisms, electromagnetic waves appear to have the most experimental support. In this brief article, we try to answer a few key questions that may further clarify this mechanism. PMID:25368582

  17. The Effect of a Lifestyle Modification Education on Adiposity Measures in Overweight and Obese Nonalcoholic Fatty Liver Disease Patients

    PubMed Central

    Arab, Arman; Askari, Gholamreza; Golshiri, Parastoo; Feizi, Awat; Hekmatnia, Ali; Iraj, Bijan; Nourian, Mojgan

    2017-01-01

    Background: Obesity is increasingly associated with nonalcoholic fatty liver disease (NAFLD) and weight loss through a combination of dietary modifications and increased physical activity is a primary goal of therapy in this disease. Therefore, this study was conducted to evaluate the effects of a lifestyle modification education on adiposity measures, physical activity, and total calorie intake in overweight and obese NAFLD patients. Methods: During 8 weeks, 82 obese patients were randomly assigned into either an intervention group (n = 41) receiving a lifestyle modification education or to a control group (n = 41) receiving usual care. Total calorie intake, physical activity, and body composition indices were measured before and after the intervention. Results: Thirty-six patients in intervention group and 33 in control group completed the study. The analysis of body composition variables did not show any significant reduction for percent of body fat, abdominal circumference, waist to hip ratio, visceral fat area, age matched of body, and soft lean mass (SLM) of the trunk (P > 0.05). On the other hand, a significant reduction in weight, body mass index, mass of body fat (MBF), SLM, and MBF of the trunk was observed after 2 months of intervention compared to the controls (P < 0.05). A significant reduction was observed in total calorie intake of intervention group as compared to the control group. Physical activity status did not show any significant improvements after 2 months of intervention. Conclusions: Our lifestyle modification education and its guidelines could be used in obese patients with NAFLD to improve their body composition measurements and to lose weight. This could result in significant long-term benefits in NAFLD patients. PMID:28299034

  18. Dietary Soy May Not Confound Acute Experimental Stroke Infarct Volume Outcomes In Ovariectomized Female Rats

    PubMed Central

    Prongay, Kamm D.; Lewis, Anne D.; Hurn, Patricia D.; Murphy, Stephanie J.

    2009-01-01

    Estrogen administration can alter experimental stroke outcomes. Soy as a source of phytoestrogens may therefore modulate responses in “estrogen-sensitive” stroke models, thus potentially confounding results. We evaluated the effects of dietary soy on acute infarct volumes in a pilot study using a rat focal stroke model. We hypothesized that ovariectomized (OVX) rats fed a soy-rich diet would have smaller acute infarct volumes than rats fed a soy-free diet. OVX rats were randomly assigned to a soy-free (n=6) or a soy-rich (n=6) diet for 4 weeks and weighed weekly. Following the dietary trial, rats underwent 2 hours of middle cerebral artery occlusion (MCAO). Mean arterial blood pressure, rectal and temporalis muscle temperatures, arterial blood gases, and blood glucose were recorded peri-ischemia. Rats were euthanized 22 hours following 2 hours of MCAO. Brains were stained with 2,3,5-triphenyl tetrazolium chloride for acute infarct volume analysis. Uterine weight and histology were also evaluated as additional internal estrogen-sensitive controls. Rats on the soy-free diet had greater gains in body weight (259±6% baseline body weight) than rats on the soy-rich diet (238±4% baseline body weight). No differences were seen in uterine weight and histology, peri-ischemic physiological parameters, and infarct volumes between the treatment groups. Results of this pilot study suggest that the dietary soy level tested may not alter acute infarct volumes in ischemic female rat brain. More studies addressing the potential confounding effects of dietary soy in “estrogen-sensitive” stroke models are needed if investigators are to make informed choices regarding diets used in experimental stroke research. PMID:20147341

  19. Evaluation of cloud shading effects on the generation and modification of mesoscale circulations

    NASA Technical Reports Server (NTRS)

    Segal, M.; Song, J. L.; Pielke, R. A.; Purdom, J. F. W.; Mahrer, Y.

    1986-01-01

    This study presents scale analysis and numerical model evaluations of the impact of cloud shading on (1) the development of sea breeze and thermally induced upslope flows and (2) the generation of mesoscale circulations between cloudy areas adjacent to clear areas. Based on the assumption of modifications of solar and longwave radiation which are typical for some overcast conditions, it was found that the reduction in the first type of circulation is significant and most noticeable in the vertical velocities. In the second case, thermally induced circulations in favorable conditions appear to approach the typical intensity of the sea breeze.

  20. Influence the loading effect on modification of PET film and fiber by Argon Plasma

    NASA Astrophysics Data System (ADS)

    Vasilkin, D. P.; Shikova, T. G.; Titov, V. A.; Smirnov, S. A.; Kuzmicheva, L. A.

    2017-01-01

    Poly(ethylene terepthalate) films and fabrics were modified by low-pressure argon plasma at different area of samples been treated. Contact angles for water and glycerol were measured and surface energy was calculated for film surface characterization. Height of water capillary rise was measured for fabric. The changes in chemical structure of surface layer were analyzed by ATR-FTIR method. Influence of sample area on non-homogeneity of plasma modification was shown. Some experiments were performed with polypropylene treatment in flowing plasma afterglow to confirm the reactions of oxygen active species originated from gas products of poly(ethylene terepthalate) etching in argon plasma.

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

    SciTech Connect

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

    1996-12-31

    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} combustion. 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 & Electric`s (LG&E) Cane Run Station and at Jamestown Board of Public Utilities (JBPU). This paper will discuss the method and results of these burner modifications.

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

    SciTech Connect

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

    1996-12-31

    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} combustion. 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 will discuss the method and results of these burner modifications.

  3. Mini-Society vs. Token Economy: An Experimental Comparison of the Effects on Learning and Autonomy of Socially Emergent and Imposed Behavior Modification

    ERIC Educational Resources Information Center

    Kourilsky, Marilyn; Hirshleifer, Jack

    1976-01-01

    This study compares the effects of two teacher training programs designed to emphasize one of two forms of behavior modification in teaching economics to fourth-, fifth-, and sixth-grade pupils. (DMT)

  4. Effects of hydrophobic and hydrophilic modifications on gene delivery of amphiphilic chitosan based nanocarriers.

    PubMed

    Wang, Bingqing; He, Chunbai; Tang, Cui; Yin, Chunhua

    2011-07-01

    The structure-activity relationships between hydrophobic and hydrophilic modification on chitosan and resultant physicochemical properties along with performances in dealing with critical gene delivery barriers were investigated through amphiphilic linoleic acid(LA) and poly (β-malic acid) (PMLA) double grafted chitosan (LMC)/plasmid DNA (pDNA) nanocomplexes. LMC polymers with various LA and PMLA substitution degrees were synthesized and their hydrophilicity/hydrophobicity was characterized. Compared to chitosan, LMC nanoparticles retained the pDNA binding ability at pH 5.5 when they formed nanocomplexes with pDNA encoding enhanced green fluorescence protein (pEGFP) and the resultant complexes showed diameters below 300 nm. Hydrophobic LA and hydrophilic PMLA substitution contributed to suppressed non-specific adsorption, reduced interactions inside LMC/pDNA nanocomplexes, and enhanced pDNA dissociation. However, enzymatic degradation resistance, cell adsorption, and cellular uptake through clathrin-mediated pathway were promoted by hydrophobic LA grafting while being inhibited by hydrophilic PMLA substitution. In vitro transfection assay suggested the optimal LMC/pEGFP nanocomplexes mediated an 8.0-fold improved transfection compared to chitosan/pEGFP nanocomplexes. The 4.2-fold and 2.2-fold higher intramuscular gene expression in mice compared to chitosan/pEGFP and polyethyleneimine (PEI)/pEGFP nanocomplexes further demonstrated the superiority of LMC/pDNA nanocomplexes. Therefore, amphiphilic chitosan derivates with appropriate combination of hydrophobic and hydrophilic modification would be promising gene delivery nanocarriers.

  5. Sediment organic matter content as a confounding factor in toxicity tests with Chironomus tentans

    SciTech Connect

    Lacey, R.; Watzin, M.C.; McIntosh, A.W.

    1999-02-01

    Physicochemical characteristics of sediment unrelated to contaminant levels and bioavailability may influence the outcome of toxicity tests. In particular, sediment organic matter content has the potential to be a confounding factor in toxicity tests using the midge larva Chironomus tentans because the larvae are infaunal and feed on organic matter in the sediments. To examine the possibility, the authors conducted a series of tests using formulated sediments with varying organic matter contents following the standard US Environmental Protection Agency (US EPA) 10-day C. tentans growth and survival protocol. Formulated sediments made with peat moss, {alpha}-cellulose, and maple leaves were tested. An organic-rich natural sediment diluted with formulated sediment to achieve a range of organic matter contents was also examined. In a final experiment, sediments containing each of the four organic matter sources at the same concentration were tested against one another. Survival was not greatly affected by concentration of organic matter, except at the lowest concentrations in natural sediment, where survival dipped below 70%. In experiments using peat moss, {alpha}-cellulose, and maple leaves, significant differences in C. tentans growth were found at different organic matter concentrations. In contrast, concentration of organic matter in the natural sediment dilution series had little effect on growth, perhaps because much of this material was highly refractory. In the comparison experiment, growth differed significantly among the four sediments, with best growth achieved with {alpha}-cellulose and leaves. These results suggest that both organic matter quantity and quality can be confounding factors in toxicity tests using C. tentans.

  6. PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances

    PubMed Central

    Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V.

    2016-01-01

    Motivation: Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. Results: We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. Availability and Implementation: miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile. Contact: z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics

  7. The Effectiveness of an Attention Bias Modification Program as an Adjunctive Treatment for Post-Traumatic Stress Disorder

    PubMed Central

    Kuckertz, Jennie M.; Amir, Nader; Boffa, Joseph W.; Warren, Ciara K.; Rindt, Susan E. M.; Norman, Sonya; Ram, Vasudha; Ziajko, Lauretta; Webb-Murphy, Jennifer; McLay, Robert

    2014-01-01

    Attention bias modification (ABM) may be an effective treatment for anxiety disorders (Beard, Sawyer, & Hofmann, 2012). As individuals with PTSD possess an attentional bias towards threat-relevant information ABM may prove effective in reducing PTSD symptoms. We examined the efficacy of ABM as an adjunct treatment for PTSD in a real-world setting. We administered ABM in conjunction with prolonged exposure or cognitive-processing therapy and medication in a community inpatient treatment facility for military personnel diagnosed with PTSD. Participants were randomized to either ABM or an attention control condition (ACC). While all participants experienced reductions in PTSD symptoms, participants in the ABM group experienced significantly fewer PTSD and depressive symptoms at post-treatment when compared to the ACC group. Moreover, change in plasticity of attentional bias mediated this change in symptoms and initial attentional bias moderated the effects of the treatment. These results suggest that ABM may be an effective adjunct treatment for PTSD. PMID:25277496

  8. Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

    PubMed

    Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

    2015-03-01

    Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen.

  9. Effect of hierarchical porosity and phosphorus modification on the catalytic properties of zeolite Y

    NASA Astrophysics Data System (ADS)

    Li, Wenlin; Zheng, Jinyu; Luo, Yibin; Da, Zhijian

    2016-09-01

    The zeolite Y is considered as a leading catalyst for FCC industry. The acidity and porosity modification play important roles in determining the final catalytic properties of zeolite Y. The alkaline treatment of zeolite Y by dealumination and alkaline treatment with NaOH and NaOH&TBPH was investigated. The zeolites were characterized by X-ray diffraction, low-temperature adsorption of nitrogen, transmission electron microscope, NMR, NH3-TPD and IR study of acidity. Accordingly, the hierarchical porosity and acidity property were discussed systematically. Finally, the catalytic performance of the zeolites Y was evaluated in the cracking of 1,3,5-TIPB. It was found that desilication with NaOH&TBPH ensured the more uniform intracrystalline mesoporosity with higher microporosity, while preserving higher B/L ratio and moderate Brønsted acidities resulting in catalysts with the most appropriated acidity and then with better catalytic performance.

  10. Physiological effects of a modification of the construction of impermeable protective clothing.

    PubMed

    Marszałek, Anna; Bartkowiak, Grazyna; Lezak, Krzysztof

    2009-01-01

    This study was conducted to improve the construction of impermeable clothing protecting against liquid chemical agents in order to lower the thermal strain caused by the clothing during work. Previous studies indicated that light work in a hot environment in this kind of clothing could last 30 min only. We propose a modification of the construction; new models of protective clothing were tested in wear trials. Then the results were compared with a basic model of impermeable protective clothing. Results indicated that all new models of protective clothing allowed workers to work 39-64% longer than in a basic model of protective clothing. Thus new clothing significantly improved comfort of work in impermeable protective clothing because of the lower thermal strain that it imposed on the user.

  11. Effects of the order of addition of reagents and alkali on modification of wheat starches.

    PubMed

    Sui, Zhongquan; Huber, Kerry C; BeMiller, James N

    2015-07-10

    The objective of this research was to determine if adding reactive reagents to wheat starch granules before addition of alkali (the TRF method) would produce products that are different than those obtained with the conventional procedure (adding alkali before addition of reagent). Laboratory-isolated (LI) and commercial (C) normal (NWS) and waxy (WWS) wheat starches were each reacted with 6 reagents (acetic-adipic mixed anhydride (AAMA), phosphoryl chloride (POCl3), sodium trimetaphosphate (STMP), acetic anhydride (AA), succinic anhydride (SA), octenylsuccinic anhydride (OSA)). Data obtained were similar to those previously obtained with maize starches (Sui, Huber, & BeMiller, 2013). Almost no starch polymer molecule modification occurred when the TRF method and AAMA or AA were used; less than a third as much reaction when SA was the reagent used, and about the same amount of reaction when POCl3, STMP, or OSA were the reagents used (for different reasons).

  12. Direct tunneling through high-κ amorphous HfO{sub 2}: Effects of chemical modification

    SciTech Connect

    Wang, Yin Yu, Zhizhou; Zahid, Ferdows; Wang, Jian; Liu, Lei; Zhu, Yu; Guo, Hong

    2014-07-14

    We report first principles modeling of quantum tunneling through amorphous HfO{sub 2} dielectric layer of metal-oxide-semiconductor (MOS) nanostructures in the form of n-Si/HfO{sub 2}/Al. In particular, we predict that chemically modifying the amorphous HfO{sub 2} barrier by doping N and Al atoms in the middle region—far from the two interfaces of the MOS structure—can reduce the gate-to-channel tunnel leakage by more than one order of magnitude. Several other types of modification are found to enhance tunneling or induce substantial band bending in the Si, both are not desired from leakage point of view. By analyzing transmission coefficients and projected density of states, the microscopic physics of electron traversing the tunnel barrier with or without impurity atoms in the high-κ dielectric is revealed.

  13. Effects of hydrothermal pretreatment on subsequent octenylsuccinic anhydride (OSA) modification of cornstarch.

    PubMed

    Chen, Xu; He, Xiaowei; Huang, Qiang

    2014-01-30

    Cornstarch granules were hydrothermally pretreated and then esterified with octenylsuccinic anhydride (OSA). The physicochemical properties of cornstarch and hydrothermally pretreated OS-starch (H-OS-starch) were investigated. Results showed that hydrothermal pretreatments significantly increased the degree of substitution (DS) and reaction efficiency (RE) of H-OS-starch compared with the control. The higher the pretreatment temperature was, the more the OSA could go deep into the internal starch granules. The optimal pretreatment temperature for the OSA modification was 60°C. In addition, the OS groups appeared to be distributed throughout the OS-starch granules, especially on the surface, as shown by confocal laser scanning microscopy (CLSM). H-OS-starch had a slightly higher peak viscosity (Pv) and break down (BD) values, but lower pasting temperature (Tp) compared with the control OS-starch.

  14. Angular momentum effects and barrier modification in sub-barrier fusion reactions using the proximity potential in the Wong formula

    SciTech Connect

    Kumar, Raj; Bansal, Manie; Arun, Sham K.; Gupta, Raj K.

    2009-09-15

    Using the capture cross-section data from {sup 48}Ca+{sup 238}U, {sup 48}Ca+{sup 244}Pu, and {sup 48}Ca+{sup 248}Cm reactions in the superheavy mass region, and fusion-evaporation cross sections from {sup 58}Ni+{sup 58}Ni, {sup 64}Ni+{sup 64}Ni, and {sup 64}Ni+{sup 100}Mo reactions known for fusion hindrance phenomenon in coupled-channels calculations, the Wong formula is assessed for its angular momentum and barrier-modification effects at sub-barrier energies. The simple, l=0 barrier-based Wong formula is shown to ignore the modifications of the barrier due to its inbuilt l dependence via l summation, which is found to be adequate enough to explain the capture cross sections for all the three above-mentioned {sup 48}Ca-based reactions forming superheavy systems. For the capture (equivalently, quasifission) reactions, the complete l-summed Wong formula is shown to be the same as the dynamical cluster-decay model expression, of one of us (R.K.G.) and collaborators, with the condition of fragment preformation probability P{sub 0}{sup l}=1 for all the angular momentum l values. In the case of fusion-evaporation cross sections, however, a further modification of barriers is required for below-barrier energies, affected in terms of either the barrier 'lowering' or barrier 'narrowing' via the curvature constant. Calculations are made for use of nuclear proximity potential, with effects of multipole deformations included up to hexadecapole, and orientation degrees of freedom integrated for both the coplanar and noncoplanar configurations.

  15. Modification of Leaf Glucosinolate Contents in Brassica oleracea by Divergent Selection and Effect on Expression of Genes Controlling Glucosinolate Pathway

    PubMed Central

    Sotelo, Tamara; Velasco, Pablo; Soengas, Pilar; Rodríguez, Víctor M.; Cartea, María E.

    2016-01-01

    Modification of the content of secondary metabolites opens the possibility of obtaining vegetables enriched in these compounds related to plant defense and human health. We report the first results of a divergent selection for glucosinolate (GSL) content of the three major GSL in leaves: sinigrin (SIN), glucoiberin (GIB), and glucobrassicin (GBS) in order to develop six kale genotypes (Brassica oleracea var. acephala) with high (HSIN, HIGIB, HGBS) and low (LSIN, LGIB, LGBS) content. The aims were to determine if the three divergent selections were successful in leaves, how each divergent selection affected the content of the same GSLs in flower buds and seeds and to determine which genes would be involved in the modification of the content of the three GSL studied. The content of SIN and GIB after three cycles of divergent selection increased 52.5% and 77.68%, and decreased 51.9% and 45.33%, respectively. The divergent selection for GBS content was only successful and significant for decreasing the concentration, with a reduction of 39.04%. Mass selection is an efficient way of modifying the concentration of individual GSLs. Divergent selections realized in leaves had a side effect in the GSL contents of flower buds and seeds due to the novo synthesis in these organs and/or translocation from leaves. The results obtained suggest that modification in the SIN and GIB concentration by selection is related to the GSL-ALK locus. We suggest that this locus could be related with the indirect response found in the GBS concentration. Meantime, variations in the CYP81F2 gene expression could be the responsible of the variations in GBS content. The genotypes obtained in this study can be used as valuable materials for undertaking basic studies about the biological effects of the major GSLs present in kales. PMID:27471510

  16. Modification of Leaf Glucosinolate Contents in Brassica oleracea by Divergent Selection and Effect on Expression of Genes Controlling Glucosinolate Pathway.

    PubMed

    Sotelo, Tamara; Velasco, Pablo; Soengas, Pilar; Rodríguez, Víctor M; Cartea, María E

    2016-01-01

    Modification of the content of secondary metabolites opens the possibility of obtaining vegetables enriched in these compounds related to plant defense and human health. We report the first results of a divergent selection for glucosinolate (GSL) content of the three major GSL in leaves: sinigrin (SIN), glucoiberin (GIB), and glucobrassicin (GBS) in order to develop six kale genotypes (Brassica oleracea var. acephala) with high (HSIN, HIGIB, HGBS) and low (LSIN, LGIB, LGBS) content. The aims were to determine if the three divergent selections were successful in leaves, how each divergent selection affected the content of the same GSLs in flower buds and seeds and to determine which genes would be involved in the modification of the content of the three GSL studied. The content of SIN and GIB after three cycles of divergent selection increased 52.5% and 77.68%, and decreased 51.9% and 45.33%, respectively. The divergent selection for GBS content was only successful and significant for decreasing the concentration, with a reduction of 39.04%. Mass selection is an efficient way of modifying the concentration of individual GSLs. Divergent selections realized in leaves had a side effect in the GSL contents of flower buds and seeds due to the novo synthesis in these organs and/or translocation from leaves. The results obtained suggest that modification in the SIN and GIB concentration by selection is related to the GSL-ALK locus. We suggest that this locus could be related with the indirect response found in the GBS concentration. Meantime, variations in the CYP81F2 gene expression could be the responsible of the variations in GBS content. The genotypes obtained in this study can be used as valuable materials for undertaking basic studies about the biological effects of the major GSLs present in kales.

  17. Effects of functional group modification on the thermal properties of nano-carbon clusters

    NASA Astrophysics Data System (ADS)

    Wu, Zhenyi; Cai, Xueying; Yang, Zhiquan

    2015-08-01

    In this paper, the thermal properties including thermal stability, thermal decomposition activation energy and the thermal enthalpy of nano-carbon clusters (NCCs, including fullerene[60](C60, with a diameter of 0.71 nm), multi-walled carbon nanotubes(MWCNTs, with a diameter of 10-30 nm and a length of 1-2 µm), single-walled carbon nanotubes (SWCNTs, with a diameter of 2 nm and a length of 5-15 µm), ligands of NCC-based terpyridine (NCC-tpy), and NCC-based ruthenium complexes (NCC-tpyRuCl3) were systematically studied by method of simultaneous thermogravimetric and differential thermal analysis. The results show that the modification of NCCs with terpyridine leads to a decrease in the thermal stability and in the thermal decomposition activation energy (the thermal decomposition activation energy decreased from 174.4 for C60, 144.9 for MWCNTs and 161.2 kJ/mol for SWCNTs to 166.2 for C60-tpy, 119.7 for MWCNT-tpy and 85.0 kJ/mol for SWCNT-tpy). But the modification of NCCs with terpyridine results in an increase in the enthalpy change of NCC thermal decomposition reaction. The introduction of the metal ions through complexation further decreases the thermal stability and the thermal decomposition activation energy of NCC-tpyRuCl3 due to the catalytic oxidation of Ru(III) ions (the activation energy decreases to 124.1 for C60-tpyRuCl3, 106.4 for MWCNT-tpyRuCl3 and 41.2 kJ/mol for SWCNT-tpyRuCl3). The introduction of the metal ions also leads to a decrease in the enthalpy change of the thermal decomposition reaction.

  18. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

  19. Effects of Wutou Decoction on DNA Methylation and Histone Modifications in Rats with Collagen-Induced Arthritis

    PubMed Central

    Wen, Cai-Yu-Zhu; Chen, Zhe; Wang, Yu; Huang, Ying; Hu, Yong-Hong; Tu, Sheng-Hao

    2016-01-01

    Background. Wutou decoction (WTD) has been wildly applied in the treatment of rheumatoid arthritis and experimental arthritis in rats for many years. Epigenetic deregulation is associated with the aetiology of rheumatoid arthritis; however, the effects of WTD on epigenetic changes are unclear. This study is set to explore the effects of WTD on DNA methylation and histone modifications in rats with collagen-induced arthritis (CIA). Methods. The CIA model was established by the stimulation of collagen and adjuvant. The knee synovium was stained with hematoxylin and eosin. The DNA methyltransferase 1 (DNMT1) and methylated CpG binding domain 2 (MBD2) expression of peripheral blood mononuclear cells (PBMCs) were determined by Real-Time PCR. The global DNA histone H3-K4/H3-K27 methylation and total histones H3 and H4 acetylation of PBMCs were detected. Results. Our data demonstrated that the DNMT1 mRNA expression was significantly lowered in group WTD compared to that in group CIA (P < 0.05). The DNA methylation level was significantly reduced in group WTD compared to that in group CIA (P < 0.05). Moreover, H3 acetylation of PBMCs was overexpressed in WTD compared with CIA (P < 0.05). Conclusions. WTD may modulate DNA methylation and histone modifications, functioning as anti-inflammatory potential. PMID:27042192

  20. The effect of modification procedures on rigid gas permeable contact lenses: the UM-St. Louis Study.

    PubMed

    Morgan, B W; Henry, V A; Bennett, E S; Caroline, P J

    1992-03-01

    The purpose of this study is to evaluate the effect of frequently performed modification procedures on quality of vision, surface wettability, optical quality and subjective response. One subject was optimally fitted with both silicone/acrylate (S/A) and fluoro-silicone/acrylate (F-S/A) lens materials of identical design. Two methods of surface polishing, edge polishing and repowering were used in addition to three different spindle speeds. Each pair of lenses was worn by the subject for a period of 4 hours and the subjective response was then compared to the baseline or premodification data. In addition, both low magnification photography and Scanning Electron Microscopy (S.E.M.) were performed on each lens. The results showed that the addition of 0.50D minus power reduced visual acuity, contrast sensitivity function and optical quality with one of the methods used. Front surface polish and edge polish procedures did not appear to affect short-term performance. Controlling polish, application and tool pressure on certain procedures resulted in similar findings. Further studies would be beneficial to evaluate the effect of longer wearing periods and the use of other modification procedures. The authors conclude that S/A and F-S/A lens materials can be successfully modified in-office with adherence to recommended guidelines.

  1. The effect of activated carbon support surface modification on characteristics of carbon nanospheres prepared by deposition precipitation of Fe-catalyst

    NASA Astrophysics Data System (ADS)

    Kristianto, H.; Arie, A. A.; Susanti, R. F.; Halim, M.; Lee, J. K.

    2016-11-01

    In this study the effect of activated carbon support modification to synthesis of CNSs was observed. Modification of activated carbon was done by using nitric acid. The effect of modification was analyzed from its FTIR spectra. The Fe catalysts were deposited on to the support by using urea deposition precipitation method at various initial catalysts concentration. CNSs was synthesized by utilizing cooking palm oil as renewable carbon source, and pyrolized at 700°C for 1 hour under nitrogen atmosphere. The products obtained then analyzed using SEM-EDS, TEM, XRD, and Raman spectroscopy. The modification of activated carbon support had increased the oxygen functional group. This increase resulted on increase of metal catalysts deposited on activated carbon surface. Peak of C (100) was observed, while ID/IG of samples were obtained around 0.9, which is commonly obtained for CNSs. High catalysts loading on modified activated carbon support caused decomposition of CNSs and formation carbon onion.

  2. Evaluation of AUSDRISK as a screening tool for lifestyle modification programs: international implications for policy and cost-effectiveness

    PubMed Central

    Malo, Jonathan A; Versace, Vincent L; Janus, Edward D; Laatikainen, Tiina; Peltonen, Markku; Vartiainen, Erkki; Coates, Michael J; Dunbar, James A

    2015-01-01

    Objective To evaluate the current use of Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK) as a screening tool to identify individuals at high risk of developing type 2 diabetes for entry into lifestyle modification programs. Research Design and Methods AUSDRISK scores were calculated from participants aged 40–74 years in the Greater Green Triangle Risk Factor Study, a cross-sectional population survey in 3 regions of Southwest Victoria, Australia, 2004–2006. Biomedical profiles of AUSDRISK risk categories were determined along with estimates of the Victorian population included at various cut-off scores. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and receiver operating characteristics were calculated for AUSDRISK in determining fasting plasma glucose (FPG) ≥6.1 mmol/L. Results Increasing AUSDRISK scores were associated with an increase in weight, body mass index, FPG, and metabolic syndrome. Increasing the minimum cut-off score also increased the proportion of individuals who were obese and centrally obese, had impaired fasting glucose (IFG) and metabolic syndrome. An AUSDRISK score of ≥12 was estimated to include 39.5% of the Victorian population aged 40–74 (916 000), while a score of ≥20 would include only 5.2% of the same population (120 000). At AUSDRISK≥20, the PPV for detecting FPG≥6.1 mmol/L was 28.4%. Conclusions AUSDRISK is powered to predict those with IFG and undiagnosed type 2 diabetes, but its effectiveness as the sole determinant for entry into a lifestyle modification program is questionable given the large proportion of the population screened-in using the current minimum cut-off of ≥12. AUSDRISK should be used in conjunction with oral glucose tolerance testing, fasting glucose, or glycated hemoglobin to identify those individuals at highest risk of progression to type 2 diabetes, who should be the primary targets for lifestyle modification. PMID:26468399

  3. Surface Modifications of Nanocarriers for Effective Intracellular Delivery of Anti-HIV Drugs

    PubMed Central

    Gunaseelan, Simi; Gunaseelan, Krishnan; Deshmukh, Manjeet; Zhang, Xiaoping; Sinko, Patrick J.

    2010-01-01

    A variety of nanocarriers such as bioconjugates, dendrimers, liposomes, and nanoparticles have been widely evaluated as potential targeted drug delivery systems. Passive targeting of nanoscale carriers is based on a size-flow-filtration phenomenon that is usually limited to tumors, the reticular endothelial system, and possibly lymph nodes (LN). In fact, targeting the delivery of drugs to pivotal physiological sites such as the lymph nodes has emerged as a promising strategy in treating HIV disease. Ligands for specific cell surface receptors can be displayed on nanocarriers in order to achieve active targeting. The approach has been extensively used preclinically in cancer where certain receptors are over-expressed at various stages of the disease. Unfortunately, markers of HIV infection are lacking and latently infected cells do not show any signs of infection on their surface. However, the disease naturally targets only a few cell types. The HIV receptor CD4, coreceptors (CCR5 and CXCR4), and some receptors relatively specific for macrophages provide potentially valuable surface targets for drug delivery to all susceptible cells in patients infected by HIV. This review focuses on nanoscale targeting with an emphasis on surface modifications of drug delivery nanocarriers for active targeting. A number of related issues, including HIV biology, targets, pharmacokinetics, and intracellular fate as well as literature-cited examples of emerging surface-modified targeted carrier systems are discussed. PMID:19941919

  4. Operation of marine diesel engines on biogenic fuels: modification of emissions and resulting climate effects.

    PubMed

    Petzold, Andreas; Lauer, Peter; Fritsche, Uwe; Hasselbach, Jan; Lichtenstern, Michael; Schlager, Hans; Fleischer, Fritz

    2011-12-15

    The modification of emissions of climate-sensitive exhaust compounds such as CO(2), NO(x), hydrocarbons, and particulate matter from medium-speed marine diesel engines was studied for a set of fossil and biogenic fuels. Applied fossil fuels were the reference heavy fuel oil (HFO) and the low-sulfur marine gas oil (MGO); biogenic fuels were palm oil, soybean oil, sunflower oil, and animal fat. Greenhouse gas (GHG) emissions related to the production of biogenic fuels were treated by means of a fuel life cycle analysis which included land use changes associated with the growth of energy plants. Emissions of CO(2) and NO(x) per kWh were found to be similar for fossil fuels and biogenic fuels. PM mass emission was reduced to 10-15% of HFO emissions for all low-sulfur fuels including MGO as a fossil fuel. Black carbon emissions were reduced significantly to 13-30% of HFO. Changes in emissions were predominantly related to particulate sulfate, while differences between low-sulfur fossil fuels and low-sulfur biogenic fuels were of minor significance. GHG emissions from the biogenic fuel life cycle (FLC) depend crucially on energy plant production conditions and have the potential of shifting the overall GHG budget from positive to negative compared to fossil fuels.

  5. Effect of cross-linking and enzymatic hydrolysis composite modification on the properties of rice starches.

    PubMed

    Xiao, Huaxi; Lin, Qinlu; Liu, Gao-Qiang

    2012-07-06

    Native rice starch lacks the versatility necessary to function adequately under rigorous industrial processing, so modified starches are needed to meet the functional properties required in food products. This work investigated the impact of enzymatic hydrolysis and cross-linking composite modification on the properties of rice starches. Rice starch was cross-linked with epichlorohydrin (EPI) with different concentrations (0.5%, 0.7%, 0.9% w/w, on a dry starch basis), affording cross-linked rice starches with the three different levels of cross-linking that were named R₁, R₂, and R₃, respectively. The cross-linked rice starches were hydrolyzed by α-amylase and native, hydrolyzed, and hydrolyzed cross-linked rice starches were comparatively studied. It was found that hydrolyzed cross-linked rice starches showed a lower the degree of amylase hydrolysis compared with hydrolyzed rice starch. The higher the degree of cross-linking, the higher the capacity to resist enzyme hydrolysis. Hydrolyzed cross-linked rice starches further increased the adsorptive capacities of starches for liquids and decreased the trend of retrogradation, and it also strengthened the capacity to resist shear compared to native and hydrolyzed rice starches.

  6. Time Evolution of Man-Made Harbour Modifications in San Diego: Effects on Tsunami Amplitudes and Currents

    NASA Astrophysics Data System (ADS)

    Barberopoulou, A.; Legg, M.; Gica, E.

    2014-12-01

    Harbors are typically modified to enhance operations and increase space in ports. Ports are usually designed to protect boats and docks against sudden vertical water fluctuations. Tsunami currents however are often ignored-current monitoring is usually not quantitative- in the design of harbor modifications. Damage from tsunami currents in ports has occurred in several recent tsunamis (Sea of Japan, 1983; Chile, 1960, 2010; Tohoku, 2011). Significant tsunami currents (>2 m/sec) often occur without substantial wave amplitudes (<1-2 meters). Because tsunami amplitudes are used as the basis to determine event "significance", the hazard from potentially strong currents may be overlooked. In order to evaluate the impact of anthropogenic effects on tsunami impact at ports, we examine the history of man-made modifications made to San Diego Bay since the late nineteenth century. Digital elevation models were created based on historic nautical charts of 1892, 1935, 1945 and at present. Tsunami simulations were conducted based on two distant events (1960 Chile and 2011 Tohoku) and two hypothetical severe local cases (San Clemente fault bend and Coronado Canyon landslide). The distant events provide historical comparisons with the model while the local events are based on offshore geology and tectonic activity. Most of the changes in San Diego Bay have included dredging, enlargement of the North Island/Coronado, widening of the Silver Strand, and creation of new marinas by enhancing already existing dunes or filling and creating breakwaters. Those changes mostly occurred during the first half of the 20th century. Post- 1965 the bay has sustained a similar appearance to the bathymetry/topography we know today. Early harbor configurations showed strong currents in the narrow channel between Point Loma and North Island/Coronado while overtopping of the narrow Silver Strand to the south occurred. The modern configuration finds increased currents at the harbor entrance and between

  7. Effect of graphene modification on thermo-mechanical and microwave absorption properties of polystyrene/graphene nanocomposites.

    PubMed

    Hatui, Goutam; Das, Chapal Kumar

    2012-10-01

    In the present study the effect of graphene percentage and graphene modification on the microwave absorption properties of the polystyrene/graphene nanocomposites was studied in detail. Acid modified graphene was prepared by the mixed acid route. Polystyrene/graphene nanocomposites with various percentages of graphene and modified graphene were prepared by solution mixing process. The dispersion of graphene sheets in the polystyrene matrix was analyzed by TEM and SEM and found to be uniform for the 1%, 2 wt% of graphene and 1 wt% of modified graphene loading. Microwave absorption of modified graphene containing nanocomposite was found to be superior among the nanocomposites. Incorporation of 1 wt% of ferrite particles enhanced the microwave absorption of the nanocomposite above all the nanocomposites, in the whole range of X-band, due to the effective cancellation of both electrical and magnetic components of the microwave. Incorporation of graphene enhanced the thermal and mechanical properties of the nanocomposites.

  8. Directly drawn poly(3-hexylthiophene) field-effect transistors by electrohydrodynamic jet printing: improving performance with surface modification.

    PubMed

    Jeong, Yong Jin; Lee, Hyungdong; Lee, Byoung-Sun; Park, Seonuk; Yudistira, Hadi Teguh; Choong, Chwee-Lin; Park, Jong-Jin; Park, Chan Eon; Byun, Doyoung

    2014-07-09

    In this study, direct micropatterning lines of poly(3-hexylthiophene) (P3HT) without any polymer binder were prepared by electrohydrodynamic jet printing to form organic field-effect transistors (OFETs). We controlled the dielectric surface by introducing self-assembled monolayers and polymer thin films to investigate the effect of surface modifications on the characteristics of printed P3HT lines and electrical performances of the OFETs. The morphology of the printed P3HT lines depended on the surface energy and type of substrate. The resulting OFETs exhibited high performance on octadecyltrichlorosilane-modified substrates, which was comparable to that of other printed P3HT OFETs. In order to realize the commercialization of the OFETs, we also fabricated a large-area transistor array, including 100 OFETs and low-operating-voltage flexible OFETs.

  9. Direct detection of thrombin binding to 8-bromodeoxyguanosine-modified aptamer: effects of modification on affinity and kinetics.

    PubMed

    Goji, Shou; Matsui, Jun

    2011-01-01

    The affinity of an 8-bromodeoxyguanosine- (8-BrdG-) substituted thrombin-binding aptamer (TBA-Br), which has the 1st and 10th guanosine residues replaced with 8-BrdG, was estimated using reflectometric interference spectroscopy (RIfS). When comparing TBA-Br with unmodified TBA (TBA-H), it was demonstrated that the modification effectively improved the affinity of TBA; dissociation constants (K(D)) of TBA-H and TBA-Br were 45.4 nM and 1.99 nM, respectively. These values, which were obtained by direct observation of thrombin binding using RIfS, have the same order of magnitude as those obtained in our previous study utilizing conformational changes in TBA to detect thrombin binding, thus confirming the validity of the obtained K(D) values. RIfS measurements also revealed that the 8-BrdG modification resulted in a lower dissociation rate constant (k(d)), which suggests that the enhancement of affinity can be attributed to the stabilization of the G-quadruplex structure on introduction of 8-BrdG.

  10. [The effect of methyl-containing supplements during pregnancy on the phenotypic modification of offspring hair color in rats].

    PubMed

    Prasolova, L A; Trut, L N; Os'kina, I N; Gulevich, R G; Pliusnina, I Z; Vsevolodov, E B; Latypov, I F

    2006-01-01

    The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.

  11. Assessment of safety effects for widening urban roadways in developing crash modification functions using nonlinearizing link functions.

    PubMed

    Park, Juneyoung; Abdel-Aty, Mohamed; Wang, Jung-Han; Lee, Chris

    2015-06-01

    Since a crash modification factor (CMF) represents the overall safety performance of specific treatments in a single fixed value, there is a need to explore the variation of CMFs with different roadway characteristics among treated sites over time. Therefore, in this study, we (1) evaluate the safety performance of a sample of urban four-lane roadway segments that have been widened with one through lane in each direction and (2) determine the relationship between the safety effects and different roadway characteristics over time. Observational before-after analysis with the empirical Bayes (EB) method was assessed in this study to evaluate the safety effects of widening urban four-lane roadways to six-lanes. Moreover, the nonlinearizing link functions were utilized to achieve better performance of crash modification functions (CMFunctions). The CMFunctions were developed using a Bayesian regression method including the estimated nonlinearizing link function to incorporate the changes in safety effects of the treatment over time. Data was collected for urban arterials in Florida, and the Florida-specific full SPFs were developed and used for EB estimation. The results indicated that the conversion of four-lane roadways to six-lane roadways resulted in a crash reduction of 15 percent for total crashes, and 24 percent for injury crashes on urban roadways. The results show that the safety effects vary across the sites with different roadway characteristics. In particular, LOS changes, time changes, and shoulder widths are significant parameters that affect the variation of CMFs. Moreover, it was found that narrowing shoulder and median widths to make space for an extra through lane shows a negative safety impact. It was also found that including the nonlinearizing link functions in developing CMFunctions shows more reliable estimates, if the variation of CMFs with specific parameters has a nonlinear relationship. The findings provide insights into the selection of

  12. Platelets confound the measurement of extracellular miRNA in archived plasma

    PubMed Central

    Mitchell, Adam J.; Gray, Warren D.; Hayek, Salim S.; Ko, Yi-An; Thomas, Sheena; Rooney, Kim; Awad, Mosaab; Roback, John D.; Quyyumi, Arshed; Searles, Charles D.

    2016-01-01

    Extracellular miRNAs are detectable in biofluids and represent a novel class of disease biomarker. Although many studies have utilized archived plasma for miRNA biomarker discovery, the effects of processing and storage have not been rigorously studied. Previous reports have suggested plasma samples are commonly contaminated by platelets, significantly confounding the measurement of extracellular miRNA, which was thought to be easily addressed by additional post-thaw plasma processing. In a case-control study of archived plasma, we noted a significant correlation between miRNA levels and platelet counts despite post-thaw processing. We thus examined the effects of a single freeze/thaw cycle on microparticles (MPs) and miRNA levels, and show that a single freeze/thaw cycle of plasma dramatically increases the number of platelet-derived MPs, contaminates the extracellular miRNA pool, and profoundly affects the levels of miRNAs detected. The measurement of extracellular miRNAs in archived samples is critically dependent on the removal of residual platelets prior to freezing plasma samples. Many previous clinical studies of extracellular miRNA in archived plasma should be interpreted with caution and future studies should avoid the effects of platelet contamination. PMID:27623086

  13. Platelets confound the measurement of extracellular miRNA in archived plasma.

    PubMed

    Mitchell, Adam J; Gray, Warren D; Hayek, Salim S; Ko, Yi-An; Thomas, Sheena; Rooney, Kim; Awad, Mosaab; Roback, John D; Quyyumi, Arshed; Searles, Charles D

    2016-09-13

    Extracellular miRNAs are detectable in biofluids and represent a novel class of disease biomarker. Although many studies have utilized archived plasma for miRNA biomarker discovery, the effects of processing and storage have not been rigorously studied. Previous reports have suggested plasma samples are commonly contaminated by platelets, significantly confounding the measurement of extracellular miRNA, which was thought to be easily addressed by additional post-thaw plasma processing. In a case-control study of archived plasma, we noted a significant correlation between miRNA levels and platelet counts despite post-thaw processing. We thus examined the effects of a single freeze/thaw cycle on microparticles (MPs) and miRNA levels, and show that a single freeze/thaw cycle of plasma dramatically increases the number of platelet-derived MPs, contaminates the extracellular miRNA pool, and profoundly affects the levels of miRNAs detected. The measurement of extracellular miRNAs in archived samples is critically dependent on the removal of residual platelets prior to freezing plasma samples. Many previous clinical studies of extracellular miRNA in archived plasma should be interpreted with caution and future studies should avoid the effects of platelet contamination.

  14. Effect of lipid structural modifications on their intermolecular hydrogen bonding interactions and membrane functions.

    PubMed

    Boggs, J M

    1986-01-01

    The large number of different membrane lipids with various structural modifications and properties and the characteristic lipid composition of different types of membranes suggest that different lipids have specific functions in the membrane. Many of the varying properties of lipids with different polar head groups and in different ionization states can be attributed to the presence of interactive or repulsive forces between the head groups in the bilayer. The interactive forces are hydrogen bonds between hydrogen bond donating groups such as --P--OH,--OH, and--NH3+ and hydrogen bond accepting groups such as --P--O- and --COO-. These interactions increase the lipid phase transition temperature and can account for the tendency of certain lipids to go into the hexagonal phase and the dependence of this tendency on the pH and ionization state of the lipid. The presence or absence of these interactions can also affect the penetration of hydrophobic substances into the bilayer, including hydrophobic residues of membrane proteins. Evidence for this suggestion has been gathered from studies of the myelin basic protein, a water-soluble protein with a number of hydrophobic residues. In this way the lipid composition can affect the conformation and activity of membrane proteins. Since hydrogen-bonding interactions depend on the ionization state of the lipid, they can be altered by changes in the environment which affect the pK of the ionizable groups. The formation of the hexagonal phase or inverted micelles, the conformation and activity of membrane proteins, and other functions mediated by lipids could thus be regulated in this way.

  15. Effect of nanodiamond modification of siloxane surfaces on stem cell behaviour

    NASA Astrophysics Data System (ADS)

    Keremidarska, M.; Hikov, T.; Radeva, E.; Pramatarova, L.; Krasteva, N.

    2014-12-01

    Mesenchymal stem cells (MSCs) hold a great promise for use in many cell therapies and tissue engineering due to their remarkable potential to replicate indefinitely and differentiate into various cell types. Many efforts have been put to study the factors controlling stem cell differentiation. However, still little knowledge has been gained to what extent biomaterials properties influence stem cell adhesion, growth and differentiation. Research utilizing bone marrow-derived MSCs has concentrated on development of specific materials which can enhance specific differentiation of stem cells e.g. osteogenic and chondrogenic. In the present work we have modified an organosilane, hexamethyldisiloxane (HMDS) with detonation nanodiamond (DND) particles aiming to improve adhesion, growth and osteodifferentiation of rat mesenchymal stem cells. HMDS/DND films were deposited on cover glass using two approaches: premixing of both compounds, followed by plasma polymerization (PP) and PP of HMDS followed by plasma deposition of DND particles. We did not observe however an increase in rMSCs adhesion and growth on DND-modified PPHMDS surfaces compared to unmodified PPHMDS. When we studied alkaline phosphatase (ALP) activity, which is a major sign for early osteodifferentiation, we found the highest ALP activity on the PPHMDS/DND material, prepared by consequent deposition while on the other composite material ALP activity was the lowest. These results suggested that DND-modified materials were able to control osteodifferention in MSCs depending on the deposition approach. Modification of HMDS with DND particles by consequent plasma deposition seems to be a promising approach to produce biomaterials capable to guide stem cell differentiation toward osteoblasts and thus to be used in bone tissue engineering.

  16. Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification.

    PubMed

    Korallus, U; Ulm, K; Steinmann-Steiner-Haldenstaett, W

    1993-01-01

    This study updates a 1982 report on mortality at two German chromate-producing factories. The main objective of the study was to establish whether the change-over to a production process using lime-free conversion of chromite ore, thus eliminating the formation of calcium chromate, had resulted in a distinct reduction in bronchial carcinoma mortality among workers exposed for the first time after the change-over (completed in 1958 in Leverkusen and 1964 in Uerdingen). A total of 1417 workers with at least 1 year of exposure were enrolled in the study. The observation period ended on 31 December 1988. The expected number of deaths was calculated using population statistics for North Rhine-Westphalia. The risk was determined in the form of a standardised mortality ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group of 739 workers exposed before the process change-over was completed, 432 died during the observation period, 66 of them from bronchial carcinoma. This significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85). Where the cause of death was unknown, cases were allocated to a cause of death on the basis of the percentage occurrence of various causes of death in the specific subcohort. The cohort of 678 workers first exposed after the process modification had been completed had a slightly increased SMR for lung cancer of 1.26 (95% confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. The Bayesian group lasso for confounded spatial data

    USGS Publications Warehouse

    Hefley, Trevor J.; Hooten, Mevin B.; Hanks, Ephraim M.; Russell, Robin E.; Walsh, Daniel P.

    2017-01-01

    Generalized linear mixed models for spatial processes are widely used in applied statistics. In many applications of the spatial generalized linear mixed model (SGLMM), the goal is to obtain inference about regression coefficients while achieving optimal predictive ability. When implementing the SGLMM, multicollinearity among covariates and the spatial random effects can make computation challenging and influence inference. We present a Bayesian group lasso prior with a single tuning parameter that can be chosen to optimize predictive ability of the SGLMM and jointly regularize the regression coefficients and spatial random effect. We implement the group lasso SGLMM using efficient Markov chain Monte Carlo (MCMC) algorithms and demonstrate how multicollinearity among covariates and the spatial random effect can be monitored as a derived quantity. To test our method, we compared several parameterizations of the SGLMM using simulated data and two examples from plant ecology and disease ecology. In all examples, problematic levels multicollinearity occurred and influenced sampling efficiency and inference. We found that the group lasso prior resulted in roughly twice the effective sample size for MCMC samples of regression coefficients and can have higher and less variable predictive accuracy based on out-of-sample data when compared to the standard SGLMM.

  18. Counterfactual Graphical Models for Longitudinal Mediation Analysis with Unobserved Confounding

    ERIC Educational Resources Information Center

    Shpitser, Ilya

    2013-01-01

    Questions concerning mediated causal effects are of great interest in psychology, cognitive science, medicine, social science, public health, and many other disciplines. For instance, about 60% of recent papers published in leading journals in social psychology contain at least one mediation test (Rucker, Preacher, Tormala, & Petty, 2011).…

  19. Effects of chemical modification on in vitro rate and extent of food starch digestion: an attempt to discover a slowly digested starch.

    PubMed

    Wolf, B W; Bauer, L L; Fahey, G C

    1999-10-01

    Differences in glycemic and insulinemic responses to dietary starch are directly related to the rate of starch digestion. Chemical modification of starch may allow for the production of a slowly digested starch that could be used for the treatment of certain medical modalities. An in vitro method was utilized to evaluate the effects of chemical modification on the rate and extent of raw and cooked starch digestion. The extent of starch digestion was significantly reduced by dextrinization, etherification, and oxidation. However, the rate of starch digestion was not significantly affected by chemical modification. For most modified starches, as the degree of modification increased, the extent of digestion decreased, suggesting an increase in the amount of resistant starch. The results of this study suggest that chemically modified starch has a metabolizable energy value of <16.7 kJ/g. Chemically modified starch ingredients may serve as a good source of resistant starch in human and animal diets.

  20. Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial

    PubMed Central

    Yamagata, Kunihiro; Makino, Hirofumi; Iseki, Kunitoshi; Ito, Sadayoshi; Kimura, Kenjiro; Kusano, Eiji; Shibata, Takanori; Tomita, Kimio; Narita, Ichiei; Nishino, Tomoya; Fujigaki, Yoshihide; Mitarai, Tetsuya; Watanabe, Tsuyoshi; Wada, Takashi; Nakamura, Teiji; Matsuo, Seiichi

    2016-01-01

    Objectives Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Design Stratified open cluster-randomized trial. Setting A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. Participants A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. Intervention All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. Main outcome measure The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. Results The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml

  1. Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions

    PubMed Central

    Chase, Herbert

    2016-01-01

    Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs. PMID:27716785

  2. Analysis of the Effect of Surface Modification on Polyimide Composites Coated with Erosion Resistant Materials

    NASA Technical Reports Server (NTRS)

    Ndalama, Tchinga; Hirschfeld, Deidre; Sutter, James K. (Technical Monitor)

    2003-01-01

    The aim of this research is to enhance performance of composite coatings through modification of graphite-reinforced polyimide composite surfaces prior to metal bond coat/ hard topcoat application for use in the erosive and/or oxidative environments of advanced engines. Graphite reinforced polyimide composites, PMR-15 and PMR-II-50, formed by sheet molding and pre-pregging will be surface treated, overlaid with a bond coat and then coated with WC-Co. The surface treatment will include cleaning, RF plasma or ultraviolet light- ozone etching, and deposition of SiO(x) groups. These surface treatments will be studied in order to investigate and improve adhesion and oxidation resistance. The following panels were provided by NASA-Glenn Research Center(NASA-GRC): Eight compression molded PMR-II-50; 6 x 6 x 0.125 in. Two vacuum-bagged PMR-II-50; 12 x 12 x 0.125 in. Eight compression molded PMR-15; 6 x 6 x 0.125 in. One vacuum-bagged PMR-15; 12 x 12 x 0.125 in. All panels were made using a 12 x 12 in. T650-35 8HS (3K-tow) graphite fabric. A diamond-wafering blade, with deionized water as a cutting fluid, was used to cut PMR-II-50 and PMR-15 panels into 1 x 1 in. pieces for surface tests. The panel edges exhibiting delamination were used for the preliminary surface preparation tests as these would be unsuitable for strength and erosion testing. PMR-15 neat resin samples were also provided by NASA GRC. Surface profiles of the as-received samples were determined using a Dektak III Surface profile measuring system. Two samples of compression molded PMR-II-50 and PMR-15, vacuum-bagged PMR-II-50 and PMR-15 were randomly chosen for surface profile measurement according to ANSI/ASME B46.1. Prior to each measurement, the samples were blasted with compressed air to remove any artifacts. Five 10 mm-long scans were made on each sample. The short and long wavelength cutoff filter values were set at 100 and 1000 m, diamond stylus radius was 12.5 microns. Table 1 is a summary of the

  3. A chronic bioassay with the estuarine amphipod Corophium volutator: test method description and confounding factors.

    PubMed

    van den Heuvel-Greve, Martine; Postma, Jaap; Jol, Johan; Kooman, Hanneke; Dubbeldam, Marco; Schipper, Cor; Kater, Belinda

    2007-01-01

    Methods of conducting a chronic sediment toxicity test with the estuarine amphipod Corophium volutator are described. They consist of a 49-day exposure, after which mortality, growth and reproduction are determined. Pilot experiments were used to optimize test design parameters such as temperature, duration, feeding and refreshing regimes, and effects of indigenous organisms. By way of further validation, the present study focused on the effects of four different parameters: oxygen saturation, salinity, ammonium and nitrite. These confounding factors might play an important role especially if the test is used for risk assessment of field-contaminated sediments. It is concluded that the present experimental design is well suited for chronic sediment exposures with C. volutator. The test can be performed at a broad range of salinity values, provided that controls are performed at the same salinity. Results further demonstrate that with the endpoints growth and reproduction this chronic test procedure is a factor 7-18 more sensitive to ammonium and nitrate than the standardized acute bioassay (endpoint mortality).

  4. The Scalp Confounds Near-Infrared Signal from Rat Brain Following Innocuous and Noxious Stimulation

    PubMed Central

    He, Ji-Wei; Liu, Hanli; Peng, Yuan Bo

    2015-01-01

    Functional near-infrared imaging (fNIRI) is a non-invasive, low-cost and highly portable technique for assessing brain activity and functions. Both clinical and experimental evidence suggest that fNIRI is able to assess brain activity at associated regions during pain processing, indicating a strong possibility of using fNIRI-derived brain activity pattern as a biomarker for pain. However, it remains unclear how, especially in small animals, the scalp influences fNIRI signal in pain processing. Previously, we have shown that the use of a multi-channel system improves the spatial resolution of fNIRI in rats (without the scalp) during pain processing. Our current work is to investigate a scalp effect by comparing with new data from rats with the scalp during innocuous or noxious stimulation (n = 6). Results showed remarkable stimulus-dependent differences between the no-scalp and intact-scalp groups. In conclusion, the scalp confounded the fNIRI signal in pain processing likely via an autonomic mechanism; the scalp effect should be a critical factor in image reconstruction and data interpretation. PMID:26426058

  5. Detection rates of geckos in visual surveys: Turning confounding variables into useful knowledge

    USGS Publications Warehouse

    Lardner, Bjorn; Rodda, Gordon H.; Yackel Adams, Amy A.; Savidge, Julie A.; Reed, Robert N.

    2016-01-01

    Transect surveys without some means of estimating detection probabilities generate population size indices prone to bias because survey conditions differ in time and space. Knowing what causes such bias can help guide the collection of relevant survey covariates, correct the survey data, anticipate situations where bias might be unacceptably large, and elucidate the ecology of target species. We used negative binomial regression to evaluate confounding variables for gecko (primarily Hemidactylus frenatus and Lepidodactylus lugubris) counts on 220-m-long transects surveyed at night, primarily for snakes, on 9,475 occasions. Searchers differed in gecko detection rates by up to a factor of six. The worst and best headlamps differed by a factor of at least two. Strong winds had a negative effect potentially as large as those of searchers or headlamps. More geckos were seen during wet weather conditions, but the effect size was small. Compared with a detection nadir during waxing gibbous (nearly full) moons above the horizon, we saw 28% more geckos during waning crescent moons below the horizon. A sine function suggested that we saw 24% more geckos at the end of the wet season than at the end of the dry season. Fluctuations on a longer timescale also were verified. Disturbingly, corrected data exhibited strong short-term fluctuations that covariates apparently failed to capture. Although some biases can be addressed with measured covariates, others will be difficult to eliminate as a significant source of error in longterm monitoring programs.

  6. Confounders in interpreting pathology for safety and risk assessment

    SciTech Connect

    Wolf, Douglas C. . E-mail: wolf.doug@epa.gov; Mann, Peter C.

    2005-02-01

    The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must be reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.

  7. Confounders in interpreting pathology for safety and risk assessment.

    PubMed

    Wolf, Douglas C; Mann, Peter C

    2005-02-01

    The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must be reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.

  8. Global climate change is confounding species conservation strategies.

    PubMed

    Koopowitz, Harold; Hawkins, Bradford A

    2012-06-01

    Most organisms face similar problems with respect to their conservation in the face of global climate change. Here, we examine probable effects of climate change on the hyperdiverse plant family Orchidaceae. In the 20th century, the major concerns for orchid conservation revolved around unsustainable harvest for the orchid trade and, more importantly, land conversion from natural ecosystems to those unable to support wild orchid populations. Land conversion included logging, fire regimes and forest conversions to agricultural systems. Although those forms of degradation continue, an additional suite of threats has emerged, fueled by global climate change. Global climate change involves more than responses of orchid populations to increases in ambient temperature. Increasing temperature induces secondary effects that can be more significant than simple changes in temperature. Among these new threats are extended and prolonged fire seasons, rising sea levels, increases in cyclonic storms, seasonal climate shifts, changes in orthographic wind dew point and increased drought. The long-term outlook for orchid biodiversity in the wild is dismal, as it is for many animal groups, and we need to start rethinking strategies for conservation in a rapidly changing world.

  9. Effect of starch type and its modifications on physicochemical properties of bologna-type sausage produced with sheep tail fat.

    PubMed

    Aktaş, N; Gençcelep, H

    2006-10-01

    Gelatinized, solubilized/dispersed and retrograded starches were produced from normal (unmodified) corn and potato starches, and were used with sheep tail fat for sausage batters. Emulsion stability, jelly and fat separation, water holding capacity (WHC), emulsion viscosity and batter pH were determined. Penetrometer reading after cooking of the batters, and tenderness of the end-product were determined. Modified starches statistically (p<0.01) affected emulsion stability and emulsion viscosity. The modification process was not significant for pH, WHC, jelly and fat separation and penetrometer values (p>0.05). While type of used starch had a significant effect on jelly and fat separation (p<0.05), for the other measurements it was not significant (p>0.05).

  10. Imaging nanostructural modifications induced by electronic metal-support interaction effects at Au||cerium-based oxide nanointerfaces.

    PubMed

    López-Haro, Miguel; Cíes, José M; Trasobares, Susana; Pérez-Omil, José A; Delgado, Juan J; Bernal, Serafín; Bayle-Guillemaud, Pascale; Stéphan, Odile; Yoshida, Kenta; Boyes, Edward D; Gai, Pratibha L; Calvino, José J

    2012-08-28

    A variety of advanced (scanning) transmission electron microscopy experiments, carried out in aberration-corrected equipment, provide direct evidence about subtle structural changes taking place at nanometer-sized Au||ceria oxide interfaces, which agrees with the occurrence of charge transfer effects between the reduced support and supported gold nanoparticles suggested by macroscopic techniques. Tighter binding of the gold nanoparticles onto the ceria oxide support when this is reduced is revealed by the structural analysis. This structural modification is accompanied by parallel deactivation of the CO chemisorption capacity of the gold nanoparticles, which is interpreted in exact quantitative terms as due to deactivation of the gold atoms at the perimeter of the Au||cerium oxide interface.

  11. Mental Health on the Go: Effects of a Gamified Attention Bias Modification Mobile Application in Trait Anxious Adults

    PubMed Central

    Dennis, Tracy A.; O’Toole, Laura

    2015-01-01

    Interest in the use of mobile technology to deliver mental health services has grown in light of the economic and practical barriers to treatment. Yet, research on alternative delivery strategies that are more affordable, accessible, and engaging is in its infancy. Attention bias modification training (ABMT), has potential to reduce treatment barriers as a mobile intervention for stress and anxiety, but the degree to which ABMT can be embedded in a mobile gaming format and its potential for transfer of benefits is unknown. The present study examined effects of a gamified ABMT mobile application in highly trait anxious participants (N = 78). A single session of the active compared to placebo training reduced subjective anxiety and observed stress reactivity. Critically, the long (45 minutes) but not short (25 minutes) active training condition reduced the core cognitive process implicated in ABMT (threat bias) as measured by an untrained, gold-standard protocol. PMID:26029490

  12. The Effect of Moment of Area Rule Modifications on the Drag, Lift and Pitching Moment Characteristics of an Unswept Aspect Ratio 6 Wing and Body Combination

    NASA Technical Reports Server (NTRS)

    Dickey, Robert R.

    1959-01-01

    An experimental investigation was conducted to determine the effect of moment-of-area-rule modifications on the drag, lift, and pitching-moment characteristics of a wing-body combination with a relatively high aspect-ratio unswept wing. The basic configuration consisted of an aspect-ratio-6 wing with a sharp leading edge and a thickness ratio of 0.06 mounted on a cut-off Sears-Haack body. The model with full moment-of-area-rule modifications had four contoured pods mounted on the wing and indentations in the body to improve the longitudinal distributions of area and moments of area. Also investigated were modifications employing pods and indentations that were only half the size of the full modifications and modifications with partial body indentations. The models were tested at angles of attack from -2 deg to +12 deg at Mach numbers from 0.6 to 1.4. In general, the moment-of-area-rule modifications had a large effect on the drag characteristics of the models but only a small effect on their lift and pitching-moment characteristics. The modifications provided substantial reductions in the zero-lift drag at transonic and low supersonic speeds, but at subsonic speeds the drag was increased. Near Mach number 1.0, the model with full modification provided the greatest reduction in drag, but at the highest test Mach numbers the half modification gave the largest drag reduction. In general, the percent reductions of zero- lift drag obtained with the aspect-ratio-6 wing were as great or greater than those previously obtained with aspect-ratio-3 wings. The effect of the modifications on the drag due to lift was small except at Mach num- bers below 0.9 where the modified models had higher drag-rise factors. Above Mach number 0.9, the modified models had higher lift-drag ratios than the basic model. The modified models also had higher lift curve slopes and generally were slightly more stable than the basic configuration.

  13. Structural and functional effects of selective chemical modifications of Scapharca inaequivalvis haemoglobins in relation to their unique assembly.

    PubMed Central

    Boffi, A; Gattoni, M; Santucci, R; Vecchini, P; Ascoli, F; Chiancone, E

    1987-01-01

    The structural and functional roles of lysyl and thiol groups in the dimeric (HbI) and tetrameric (HbII) haemoglobins from the mollusc Scapharca inaequivalvis have been assessed. In these haemoglobins a unique mode of assembly (the haem-carrying E and F helices form the intersubunit contact of the dimeric unit) is associated with co-operative oxygen binding. Extensive acylation is accompanied by significant haem oxidation. Modification of one or two lysyl residues per chain (corresponding to approximately 20% of the total residues) does not affect the structural and functional properties of both haemoglobins, in line with the proposal that the intersubunit contacts are rich in hydrophobic residues. The modification of the thiol groups does not influence the state of association in both HbI and HbII, despite the location of the cysteine residue common to all polypeptide chains in the vicinity of the major intersubunit contact. The effect on the functional properties depends on the size of the thiol reagent: p-chloromercuribenzoate and phenylmercuric acetate increase the oxygen affinity about 20-fold, but iodoacetamide and mercuric chloride have no effect. Moreover, electrophoresis experiments indicate that p-chloromercuribenzoate is bound in a co-operative fashion, the degree of co-operativity being much higher in the dimeric HbI. Thus, only in HbII are intermediates containing substoichiometric amounts of p-chloromercuribenzoate formed in significant amounts. Their oxygen binding properties show that reaction of only one thiol group/tetramer suffices to alter the oxygen affinity of the molecule. Images Fig. 1. Fig. 3. Fig. 4. PMID:3593205

  14. Prediction of effects of wing contour modifications on low-speed maximum lift and transonic performance for the EA-6B aircraft

    NASA Technical Reports Server (NTRS)

    Allison, Dennis O.; Waggoner, E. G.

    1990-01-01

    Computational predictions of the effects of wing contour modifications on maximum lift and transonic performance were made and verified against low speed and transonic wind tunnel data. This effort was part of a program to improve the maneuvering capability of the EA-6B electronics countermeasures aircraft, which evolved from the A-6 attack aircraft. The predictions were based on results from three computer codes which all include viscous effects: MCARF, a 2-D subsonic panel code; TAWFIVE, a transonic full potential code; and WBPPW, a transonic small disturbance potential flow code. The modifications were previously designed with the aid of these and other codes. The wing modifications consists of contour changes to the leading edge slats and trailing edge flaps and were designed for increased maximum lift with minimum effect on transonic performance. The prediction of the effects of the modifications are presented, with emphasis on verification through comparisons with wind tunnel data from the National Transonic Facility. Attention is focused on increments in low speed maximum lift and increments in transonic lift, pitching moment, and drag resulting from the contour modifications.

  15. Modification of digestive system microbiome of lactating dairy cows by feeding Bovamine: effect on ruminal fermentation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated the immune modulatory effects as well as effects on productivity of Bovamine® (Lactobacillus acidophilus strain NP51 and Probionibacterium freudenreichii) on the digestive system microbiome of dairy cattle during late lactation (average DIM = 202). To unveil the underlying mechanisms, ...

  16. Effects of nootropics on the EEG in conscious rats and their modification by glutamatergic inhibitors.

    PubMed

    Vorobyov, Vasily; Kaptsov, Vladimir; Kovalev, Georgy; Sengpiel, Frank

    2011-05-30

    To study the effects of acute and repeated injections of nootropics and to learn how glutamate receptors might be involved in their mediation, the frequency spectra of cortical and hippocampal electroencephalogram (EEG) were analyzed in non-narcotized rats subcutaneously injected repeatedly with Piracetam (400mg/kg) or its analogue, Noopept (0.2mg/kg), after intracerebroventricular infusions of saline (5 μl) or the antagonists of NMDA and quisqualate/AMPA receptors: CPP (0.1 nmol) and GDEE (1 μmol), respectively. Piracetam increased alpha/beta1 EEG activity in the left frontal cortex, and alpha activity in both the right cortex and hippocampus, with a 10-min latency and 40-min duration. Noopept increased alpha/beta1 activity, with 30-min latency and 40-min duration in all brain areas. CPP pretreatment eliminated Piracetam EEG effects; reduced Noopept effects in the cortex and completely suppressed them in the hippocampus. After four injections of Piracetam, EEG effects were very small in the cortex, and completely lacking in the hippocampus, while GDEE pretreatment partially recovered them. The effect of Noopept in the alpha/beta1 ranges was replaced by increased beta2 activity after the eighth injection, while no effects were observed after the ninth one. GDEE pretreatment restored the effect of Noopept in the beta2 frequency range. These results demonstrate similarities in EEG effects and their mediatory mechanisms for Piracetam and its much more effective analogue, Noopept. Activation of NMDA receptors is involved in the effects of a single injection of the nootropics, whereas activation of quisqualate/AMPA receptors is associated with the decrease in their efficacy after repeated use.

  17. Statistically Controlling for Confounding Constructs Is Harder than You Think

    PubMed Central

    Westfall, Jacob; Yarkoni, Tal

    2016-01-01

    Social scientists often seek to demonstrate that a construct has incremental validity over and above other related constructs. However, these claims are typically supported by measurement-level models that fail to consider the effects of measurement (un)reliability. We use intuitive examples, Monte Carlo simulations, and a novel analytical framework to demonstrate that common strategies for establishing incremental construct validity using multiple regression analysis exhibit extremely high Type I error rates under parameter regimes common in many psychological domains. Counterintuitively, we find that error rates are highest—in some cases approaching 100%—when sample sizes are large and reliability is moderate. Our findings suggest that a potentially large proportion of incremental validity claims made in the literature are spurious. We present a web application (http://jakewestfall.org/ivy/) that readers can use to explore the statistical properties of these and other incremental validity arguments. We conclude by reviewing SEM-based statistical approaches that appropriately control the Type I error rate when attempting to establish incremental validity. PMID:27031707

  18. Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?

    PubMed Central

    Karras, Spyridon; Rapti, Eleni; Matsoukas, Stauros; Kotsa, Kalliopi

    2016-01-01

    Fibromyalgia (FM) is a chronic syndrome with an increasing prevalence, characterized by widespread musculoskeletal pain in combination with a variety of cognitive symptoms and fatigue. A plethora of scientific evidence that has accumulated during the last decades, resulted in a significant improvement of the understanding of the pathophysiology of the disease. However, current therapeutic approaches in patients with FM remains a multidimensional approach including patient education, behavioral therapy, exercise, pain management, and relief of chronic symptoms, rather than the use drug therapies, based on the mechanisms of disease development. Vitamin D, a fat-soluble vitamin derived mainly from skin synthesis through ultraviolet radiation, has been recognized to manifest a plethora of extraskeletal actions, apart from its fundamental role in skeletal and calcium homeostasis, including modulation of cell growth, neuromuscular actions, and potential anti-inflammatory properties. Recent findings indicate that hypovitaminosis D to be highly prevalent in patients with FM. Supplementation studies are limited so far, indicating potential beneficial effects on pain and severity of the disease, however specific recommendations are lacking. This review aims to summarize and critically appraise data regarding the pathophysiological interplay between vitamin D and FM, available results from observational and supplementation studies so far, with a clinical discourse on current knowledge gaps and future research agenda. PMID:27271665

  19. Confounded winter and spring phenoclimatology on large herbivore ranges

    USGS Publications Warehouse

    Christianson, David; Klaver, Robert W.; Middleton, Arthur; Kauffman, Matthew

    2013-01-01

    Annual variation in winter severity and growing season vegetation dynamics appear to influence the demography of temperate herbivores but parsing winter from spring effects requires independent metrics of environmental conditions specific to each season. We tested for independence in annual variation amongst four common metrics used to describe winter severity and early growing season vegetation dynamics across the entire spatial distribution of elk (Cervus elaphus) in Wyoming from 1989 to 2006. Winter conditions and early growing season dynamics were correlated in a specific way. Winters with snow cover that ended early tended to be followed by early, but slow, rises in the normalized difference vegetation index (NDVI), while long winters with extended periods of snow cover were often followed by late and rapid rises in NDVI. Across the 35 elk ranges, 0.4–86.8 % of the variation in the rate of increase in NDVI’s in spring was explained by the date snow cover disappeared from SNOTEL stations. Because phenoclimatological metrics are correlated across seasons and shifting due to climate change, identifying environmental constraints on herbivore fitness, particularly migratory species, is more difficult than previously recognized.

  20. Do time-invariant confounders explain away the association between job stress and workers' mental health? Evidence from Japanese occupational panel data.

    PubMed

    Oshio, Takashi; Tsutsumi, Akizumi; Inoue, Akiomi

    2015-02-01

    It is well known that job stress is negatively related to workers' mental health, but most recent studies have not controlled for unobserved time-invariant confounders. In the current study, we attempted to validate previous observations on the association between job stress and workers' mental health, by removing the effects of unobserved time-invariant confounders. We used data from three to four waves of an occupational Japanese cohort survey, focusing on 31,382 observations of 9741 individuals who participated in at least two consecutive waves. We estimated mean-centered fixed effects models to explain psychological distress in terms of the Kessler 6 (K6) scores (range: 0-24) by eight job stress indicators related to the job demands-control, effort-reward imbalance, and organizational injustice models. Mean-centered fixed effects models reduced the magnitude of the association between jobs stress and K6 scores to 44.8-54.2% of those observed from pooled ordinary least squares. However, the association remained highly significant even after controlling for unobserved time-invariant confounders for all job stress indicators. In addition, alternatively specified models showed the robustness of the results. In all, we concluded that the validity of major job stress models, which link job stress and workers' mental health, was robust, although unobserved time-invariant confounders led to an overestimation of the association.

  1. Behavior Modification with Children

    ERIC Educational Resources Information Center

    Brown, Daniel G.

    1972-01-01

    The author urges wider use of positive reinforcement theories in helping emotionally disturbed and mentally handicapped children. Underlining the influence of environment on behavior, he also notes that behavior modification programs utilize fewer trained personnel more effectively and, like Tennessee's Re-Education Treatment, allow for therapy in…

  2. Diet Modification for Hyperlipidemia

    PubMed Central

    Mann, Heather D.; Piotrowski, Pamela

    1992-01-01

    Hyperlipidemia is a major risk factor associated with cardiovascular disease. Dietary modification is effective in achieving and maintaining improved serum lipid levels. Nutritional care provided by a dietitian includes individual dietary and lifestyle assessment, formulating an appropriate dietary regimen, education, and follow-up assessments. PMID:21221406

  3. Issues in risk assessment and modifications of the NRC health effects models

    SciTech Connect

    Gilbert, E.S.

    1992-06-01

    A report, Health Effects Models for Nuclear Power Plant Accident Consequence Analysis, was published by the US Nuclear Regulatory Commission, in 1985, and revised in 1989. These reports provided models for estimating health effects that would be expected to result from the radiation exposure received in a nuclear reactor accident. Separate models were given for early occurring effects, late somatic effects, and genetic effects; however, this paper addresses only late somatic effects, or the risk of cancer expected to occur in the lifetimes of exposed individuals. The 1989 revision was prepared prior to the publication of the BEIR V, 1988 UNSCEAR, and ICRP 60 reports. For this reason, an addendum was needed that would provide modified risk models that took into account these recent reports, and, more generally, any new evidence that had appeared since the 1989 publication. Of special importance was consideration of updated analyses of the Japanese A-bomb survivor study data based on revised DS86 dosimetry. The process of preparing the addendum required thorough review and evaluation of the models used by the BEIR V, UNSCEAR, and ICRP committees, and also required thorough consideration of the various decisions that must be made in any risk assessment effort. This paper emphasizes general issues and problems that arise in risk assessment, and also indicates areas where additional development and application of statistical methods may be fruitful.

  4. Issues in risk assessment and modifications of the NRC health effects models

    SciTech Connect

    Gilbert, E.S.

    1992-07-02

    A report, Health Effects Models for Nuclear Power Plant Accident Consequence Analysis, was published by the US Nuclear Regulatory Commission, in 1985, and revised in 1989. These reports provided models for estimating health effects that would be expected to result from the radiation exposure received in a nuclear reactor accident. Separate models were given for early occurring effects, late somatic effects, and genetic effects; however, this paper addresses only late somatic effects, or the risk of cancer expected to occur in the lifetimes of exposed individuals. The 1989 revision was prepared prior to the publication of the BEIR V, 1988 UNSCEAR, and ICRP 60 reports. For this reason, an addendum was needed that would provide modified risk models that took into account these recent reports, and, more generally, any new evidence that had appeared since the 1989 publication. Of special importance was consideration of updated analyses of the Japanese A-bomb survivor study data based on revised DS86 dosimetry. The process of preparing the addendum required thorough review and evaluation of the models used by the BEIR V, UNSCEAR, and ICRP committees, and also required thorough consideration of the various decisions that must be made in any risk assessment effort. This paper emphasizes general issues and problems that arise in risk assessment, and also indicates areas where additional development and application of statistical methods may be fruitful.

  5. Influence of potentially confounding factors on sea urchin porewater toxicity tests

    USGS Publications Warehouse

    Carr, R.S.; Biedenbach, J.M.; Nipper, M.

    2006-01-01

    The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

  6. Octopus visual system: a functional MRI model for detecting neuronal electric currents without a BOLD confound

    PubMed Central

    Jiang, Xia; Lu, Hanbing; Shigeno, Shuichi; Tan, Li-Hai; Yang, Yihong; Ragsdale, Clifton W.; Gao, Jia-Hong

    2014-01-01

    Purpose Despite the efforts that have been devoted to detecting the transient magnetic fields generated by neuronal firing, the conclusion that a functionally relevant signal can be measured with magnetic resonance imaging (MRI) is still controversial. For human studies of neuronal current MRI (nc-MRI), the blood-oxygen-level-dependent (BOLD) effect remains an irresolvable confound. For tissue studies where hemoglobin is removed, natural sensory stimulation is not possible. This study investigates the feasibility of detecting a physiologically induced nc-MRI signal in vivo in a BOLD-free environment. Methods The cephalopod mollusc Octopus bimaculoides has vertebrate-like eyes, large optic lobes (OLs) and blood that does not contain hemoglobin. Visually evoked potentials were measured in the octopus retina and OL by electroretinogram and local field potential. nc-MRI scans were conducted at 9.4 Tesla to capture these activities. Results Electrophysiological recording detected strong responses in the retina and OL in vivo; however, nc-MRI failed to demonstrate any statistically significant signal change with a detection threshold of 0.2° for phase and 0.2% for magnitude. Experiments in a dissected eye-OL preparation yielded similar results. Conclusion These findings in a large hemoglobin-free nervous system suggest that sensory evoked neuronal magnetic fields are too weak for direct detection with current MRI technology. PMID:24301336

  7. The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview.

    PubMed

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Jörg

    2006-03-01

    The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine -- MDMA) is neurotoxic upon central serotonergic neurons in laboratory animals and possibly also in humans. In recent years, several studies reported alterations of serotonergic transmission and neuropsychiatric abnormalities in ecstasy users which might be related to MDMA-induced neurotoxic brain damage. To date, the most consistent findings associate subtle cognitive, particularly memory, deficits with heavy ecstasy use. However, most studies have important inherent methodological problems. One of the most serious confounds is the widespread pattern of polydrug use which makes it dif.cult to relate the findings in user populations to one specific drug. The present paper represents a brief overview on this issue. The most commonly co-used substances are alcohol, cannabis and stimulants (amphetamines and cocaine). Stimulants are also neurotoxic upon both serotonergic and dopaminergic neurons. Hence, they may act synergistically with MDMA and enhance its long-term adverse effects. The interactions between MDMA and cannabis use may be more complex: cannabis use is a well-recognized risk factor for neuropsychiatric disorders and it was shown to contribute to psychological problems and cognitive failures in ecstasy users. However, at the cellular level, cannabinoids have neuroprotective actions and they were shown to (partially) block MDMA-induced neurotoxicity in laboratory animals. In future, longitudinal and prospective research designs should hopefully lead to a better understanding of the relation between drug use and subclinical psychological symptoms or neurocognitive failures and, also, of questions around interactions between the various substances of abuse.

  8. Peripheral neuropathy of the upper extremity: medical comorbidity that confounds common orthopedic pathology.

    PubMed

    Bales, Joshua G; Meals, Roy

    2009-10-01

    In the orthopedic patient, the diagnosis of a compression neuropathy may be straightforward. However, various medical comorbidities can obscure this diagnosis. It is paramount for the practicing orthopedic surgeon to have an appreciation for the medical pathology of common axonal neuropathies to properly diagnose, treat, and refer a patient with altered sensation in the upper extremity. The prevalence of diabetes in the United States is 10%, and roughly 20% of diabetic patients have peripheral neuropathy. In addition to diabetes, 32% of heavy alcohol users present with polyneuropathy. With advancements in the treatment of human immunodeficiency virus/acquired immunodeficiency syndrome clinicians may see the long-term effects of the virus manifested as axonal neuropathies and extreme allodynia. In some regions of the world, Hansen's disease usurps diabetes as the most common cause of polyneuropathy. Based on patient demographics and social habits, Lyme disease, multiple sclerosis, and syphilis can all manifest as polyneuropathies. Understanding the common medical causes of neuropathy will aid the orthopedic surgeon in differentiating simple compression neuropathies from diseases mimicking or confounding them.

  9. Is it patience or motivation? On motivational confounds in intertemporal choice tasks.

    PubMed

    Paglieri, Fabio; Addessi, Elsa; Sbaffi, Agnese; Tasselli, Maria Isabella; Delfino, Alexia

    2015-01-01

    Intertemporal choices create a tension between amount maximization, which would favor the larger and later option (LL), and delay minimization, which would promote the smaller and sooner reward (SS). Two common interpretations of intertemporal choice behavior are discussed: looking at LL responses as indicative of self-control, and using intertemporal choices to assess delay aversion. We argue that both interpretations need to take into account motivational confounds, in order to be warranted by data. In intertemporal choices with prepotent, salient stimuli (e.g., food amounts, typically used with nonhuman primates), LL responses could also be indicative of failed inhibition of a "go for more" impulsive response-the opposite of self-control. Similarly, intertemporal choices can be used to measure delay aversion only with respect to the subject's baseline motivation to maximize the reinforcer in question, and this baseline is not always assessed in current experimental protocols. This concern is especially crucial in comparing intertemporal choices across different groups or manipulation. We focus in particular on the effects of reward types on intertemporal choices, presenting two experimental studies where the difference in behavior with monetary versus food rewards is the product of different baseline motivation, rather than variations in delay aversion. We conclude discussing the implications of these and other similar recent findings, which are far-reaching.

  10. Modification of neurobehavioral effects of mercury by a genetic polymorphism of coproporphyrinogen oxidase in children.

    PubMed

    Woods, James S; Heyer, Nicholas J; Echeverria, Diana; Russo, Joan E; Martin, Michael D; Bernardo, Mario F; Luis, Henrique S; Vaz, Lurdes; Farin, Federico M

    2012-01-01

    Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents.

  11. Modification Of Gear Teeth To Reduce Vibrations

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Oswald, Fred B.; Lin, Hsiang Hsi

    1990-01-01

    Computer simulations yield data useful in designing for low noise. Effects of modifications in shape of gear teeth upon static transmission error and dynamic loading of gears now analyzed systematically. Design curves generated by conducting numerical simulations of dynamic effects at successive incremental modifications of gear systems operated at various applied loads. Modifications that result in minimum dynamic effect determined from design curves.

  12. Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists

    SciTech Connect

    Menon, M.K.; Dinovo, E.C.; Haddox, V.G.

    1987-09-28

    The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. 19 references, 8 figures, 2 tables.

  13. The effect of cognitive bias modification for interpretation on avoidance of pain during an acute experimental pain task.

    PubMed

    Jones, Emma Blaisdale; Sharpe, Louise

    2014-08-01

    Research confirms that patients with chronic pain show a tendency to interpret ambiguous stimuli as pain related. However, whether modifying these interpretive pain biases impacts pain outcomes is unknown. This study aimed to demonstrate that interpretation biases towards pain can be modified, and that changing these biases influences pain outcomes in the cold pressor task. One hundred and six undergraduate students were randomly allocated to receive either threatening or reassuring information regarding the cold pressor. They also were randomly allocated to 1 of 2 conditions in the Ambiguous Scenarios Task, in which they were trained to have either a threatening interpretation of pain (pain bias condition) or a nonthreatening interpretation of pain (no pain bias condition). Therefore, the study had a 2 (threat/reassuring)×2 (pain bias/no pain bias) design. Analyses showed that a bias was induced contingent on condition, and that the threat manipulation was effective. Participants in the pain bias condition hesitated more before doing the cold pressor task than those in the no pain bias condition, as did those in the threat compared with the reassurance condition. The major finding was that interpretive bias mediated the relationship between bias condition and hesitance time, supporting the causal role of interpretive biases for avoidance behaviors in current chronic pain models. No differences were found on other pain outcomes regarding bias or threat, and the efficacy of the bias modification was not impacted by different levels of threat. These results suggest that cognitive bias modification should be further explored as a potential intervention in pain.

  14. A case study on the identification of confounding factors for gene disease association analysis.

    PubMed

    Han, Bin; Xie, Ruifei; Wu, Shixiu; Li, Lihua; Zhu, Lei

    2015-01-01

    Variation in the expression of genes arises from a variety of sources. It is important to remove sources of variation between arrays of non-biological origin. Non-biological variation, caused by lurking confounding factors, usually attracts little attention, although it may substantially influence the expression profile of genes. In this study, we proposed a method which is able to identify the potential confounding factors and highlight the non-biological variations. We also developed methods and statistical tests to study the confounding factors and their influence on the homogeneity of microarray data, gene selection, and disease classification. We explored an ovarian cancer gene expression profile and showed that data batches and arraying conditions are two confounding factors. Their influence on the homogeneity of data, gene selection, and disease classification are statistically analyzed. Experiments showed that after normalization, their influences were removed. Comparative studies further showed that the data became more homogeneous and the classification quality was improved. This research demonstrated that identifying and reducing the impact of confounding factors is paramount in making sense of gene-disease association analysis.

  15. Assessment and indirect adjustment for confounding by smoking in cohort studies using relative hazards models.

    PubMed

    Richardson, David B; Laurier, Dominique; Schubauer-Berigan, Mary K; Tchetgen Tchetgen, Eric; Cole, Stephen R

    2014-11-01

    Workers' smoking histories are not measured in many occupational cohort studies. Here we discuss the use of negative control outcomes to detect and adjust for confounding in analyses that lack information on smoking. We clarify the assumptions necessary to detect confounding by smoking and the additional assumptions necessary to indirectly adjust for such bias. We illustrate these methods using data from 2 studies of radiation and lung cancer: the Colorado Plateau cohort study (1950-2005) of underground uranium miners (in which smoking was measured) and a French cohort study (1950-2004) of nuclear industry workers (in which smoking was unmeasured). A cause-specific relative hazards model is proposed for estimation of indirectly adjusted associations. Among the miners, the proposed method suggests no confounding by smoking of the association between radon and lung cancer--a conclusion supported by adjustment for measured smoking. Among the nuclear workers, the proposed method suggests substantial confounding by smoking of the association between radiation and lung cancer. Indirect adjustment for confounding by smoking resulted in an 18% decrease in the adjusted estimated hazard ratio, yet this cannot be verified because smoking was unmeasured. Assumptions underlying this method are described, and a cause-specific proportional hazards model that allows easy implementation using standard software is presented.

  16. Modification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in children.

    PubMed

    Woods, James S; Heyer, Nicholas J; Russo, Joan E; Martin, Michael D; Pillai, Pradeep B; Farin, Federico M

    2013-01-01

    Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that genetic variants of metallothionein (MT) that are reported to affect Hg toxicokinetics in adults would modify the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the completion of the clinical trial, we performed genotyping assays for variants of MT isoforms MT1M (rs2270837) and MT2A (rs10636) on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant interactions or independent main effects for Hg exposure and either of the MT gene variants were observed. In contrast, among boys, numerous significant interaction effects between variants of MT1M and MT2A, alone and combined, with Hg exposure were observed spanning multiple domains of neurobehavioral function. All dose-response associations between Hg exposure and test performance were restricted to boys and were in the direction of impaired performance. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with relatively common genetic variants of MT, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure. We note that because urinary Hg reflects a composite exposure index that cannot be attributed to a specific

  17. Magnetic Effects in the Heating and Modification of Flows in the Outer Stellar Atmospheres with Application to Early Type Star Case

    NASA Technical Reports Server (NTRS)

    Uchida, Y.

    1985-01-01

    Possible magnetic effects in the heating and modification of flows in early type star atmospheres are discussed by referring to the physically related phenomena dealt with for late type stars, young stars, and close binary systems. It is pointed out as the result of that the magnetic field may play important roles also in early type star atmospheres in converting the energy of the radiatively driven outflow into heat, or in modifying the outflow by nozzling or by initial modification of temperature and/or momentum by which the effect of the radiation pressure may be made the most of in accelerating the outflow.

  18. Evaluation of vegetation effects on the generation and modification of mesoscale circulations

    NASA Technical Reports Server (NTRS)

    Segal, M.; Avissar, R.; Pielke, R. A.; Mccumber, M. C.

    1988-01-01

    The effects of the presence of vegetation cover on modifying sea breeze and thermally induced upslope flows during daytime were investigated, and the possibility of the generation of mesoscale circulations due to nonuniform vegetation cover was evaluated. Scale analysis and numerical model simulations were used to provide quantitative evaluations of the circulations involved in the two vagetation effects, using several illustrative cases. The cases considered demonstrate that the impact of vegetated surfaces is highly dependent on the environmental conditions as well as vegetation characteristics.

  19. Modification of bactericidal effects of microwave heating and hyperthermia by hydrogen peroxide.

    PubMed

    Kuchma, T

    1997-01-01

    Two different approaches for studying of bactericidal effects of microwave heating and hyperthermia were introduced. Low concentration of hydrogen peroxide (0.05%) was used to modify the sensitivity of isogenous strains of Escherichia coli K-12 to microwave heating and hyperthermia with the following assessment of their combined action. This was carried out simulataneously and successively under equal conditions of temperature rise at 50 degrees C. A method of anomalous viscosity time dependencies (AVTD) was used for measurement of the changes in genome conformational state simultaneously with bacterial survival determination. Experiments were performed to study isolated effects of hyperthermia and microwave heating over a range of temperatures from 40 to 80 degrees C and hydrogen peroxide concentrations from 0.05 to 0.3% during 10-minute exposures and their combined action. No difference was found between isolated effects of microwave heating and hyperthermia when survival of E. coli AB 1157 cells was determined. It was shown by the AVTD method that microwave heating at a temperature increase of 6 degrees C per second caused greater damage to cell genome than hyperthermia. The synergistic interaction of microwave heating and low concentrations of hydrogen peroxide was found in simulataneous and successive exposures. The essential distinctions observed in recognition of the action of microwave heating and hyperthermia combined with hydrogen peroxide in various sequences on cellular and molecular levels were attributed to the different effects of microwave and conventional heating on the systems of DNA repair.

  20. Pharmacologic modification of the cytotoxic effects of cadmium in LLC-PK sub 1 cells

    SciTech Connect

    Battaglia, D.R.; Kahan, B.S.; Niewenhuis, R.J.; Prozialeck, W.C. )

    1989-02-09

    Recent results from our laboratories have shown that exposure to cadmium causes LLC-PK{sub 1} cells to shrink, detach and assume a spherical shape. The purpose of the present studies was to determine whether various pharmacologic agents can reduce or prevent these cytotoxic effects of Cd{sup 2+}. Confluent monolayers of LLC-PK{sub 1} cells were incubated with the drugs of interest (50 microM final concentration) for 2 hours. CadCl{sub 2} (final concentration = 75 microM) was then added and the cells were incubated for another 20 hours. Morphologic changes were assessed qualitatively by viewing the cells with a phase contrast microscope. The extent of Cd{sup 2+}-induced cellular damage was also quantified by staining the cells that remained on the growing surface with methylene blue, solubilizing the stained cells, and determining the absorbance at 660 nm. The results showed that several drugs, particularly the calmodulin antagonists trifluoperazine chlorpromazine, and the calcium channel blocker verapamil, significant reduced the severity of Cd{sup 2+}-induced cytotoxicity. By contrast, a variety of other agents, such as chlorpromazine sulfoxide, trifluoperazine sulfoxide, phenytoin and zinc, had no such protective effect. These findings indicate that Ca{sup 2+} antagonists can attenuate the cytotoxic effects of Cd{sup 2+} and that Cd{sup 2+} may produce some of its effects by activating Ca{sup 2+} -dependent systems.

  1. Modification of radiobiological effects of 171 MeV protons by elements of physical protection

    NASA Astrophysics Data System (ADS)

    Bulinina, Taisia; Shurshakov, Vyacheslav; Ivanov, Alexander; Molokanov, Alexander

    2016-07-01

    Space radiation includes protons of various energies. Physical protection is effective in the case of low energy protons (50-100 MeV) and becomes insufficient for radiation with a high part of high-energy protons. In the experiment performed on outbred mice, the purpose of the study was to evaluate the radiobiological effect of 171 MeV protons and protons modified by elements of physical protection of the spacecraft, on a complex of indicators of the functional condition of the system hematopoiesis and the central nervous system in 24 hours after irradiation at 20 cGy dose. The spacecraft radiation protection elements used in the experiment were a construction of wet hygiene wipes called a «protective curtain», and a glass plate imitating an ISS window. Mass thickness of the " protective curtain" in terms of water equivalent was ̴ 6,2 g/cm2. Physical shielding along the path of 171 MeV protons increases their linear energy transfer leading to the absorbed dose elevation and strengthening of the radiobiological effect. In the experiment, the two types of shielding together raised the absorbed dose from 20 to 23.2 cGy. Chemically different materials (glass and water in the wipes) were found to exert unequal modifying effects on physical and biological parameters of the proton-irradiated mice. There was a distinct dose-dependent reduction of bone marrow cellularity within the dose range from 20 cGy to 23.2 cGy in 24 hours after exposure. No modifying effect of the radiation protection elements on spontaneous motor activity was discovered when compared with entrance protons. The group of animals protected by the glass plate exhibited normal orientative-trying reactions and weakened grip with the forelimbs. The effects observed in the experiment indicate the necessity to carry out comprehensive radiobiological researches (physical, biological and mathematical) in assessing the effects of physical protection, that are actual for ensuring radiation safety of crews in

  2. Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy.

    PubMed

    Kitani, K; Kanai, S; Ivy, G O; Carrillo, M C

    1999-11-01

    Limited information is available on the upregulation of endogenous antioxidant enzymes by means of administering various pharmaceuticals and/or chemicals. It has been reported that ursodeoxycholic acid (UDCA), a bile acid originally identified from black bear bile (a Chinese medicine, Yutan) increased glutathione S-transferase (GST) activities in mouse livers, resulting in a decrease in systemic lethal toxicity of orally challenged 1-2-dichloro-4-nitrobenzene (DCNB). Also, ursolic acid found in herbal medicines (e.g. leaves of loquat) was reported to increase catalase (CAT) activities in mouse liver. Interestingly, the chemical structures of these two compounds are surprisingly similar to each other, despite the difference in their original sources. These results suggest that in the future, more and more compounds will be found to have effects on increasing endogenous antioxidant enzyme activities. Deprenyl is a monoamine oxidase B inhibitor but also possesses many other different pharmacological activities. Among these various pharmacological effects of deprenyl, a possible causal relationship between two effects of deprenyl, namely the prolongation of the survival of animals and upregulation of antioxidant enzymes in selective brain regions, has been postulated by the authors. In at least four different animal species (rats, mice, hamsters and dogs), a significant prolongation of survival by chronic administration of the drug has been reported by different groups including that of the authors. This group has reported that repeated administration of the drug for 2-3 weeks can significantly increase activities of both types of superoxide dismutase (SODs) (Cu, Zn-, and Mn-SODs) as well as of CAT selectively in brain dopaminergic regions. Both effects are dose dependent but excessive dosages become less effective and even cause an adverse effect (i.e. a decrease in enzyme activities and shortening of life span). The parallelism of the dose-effect relationship between

  3. Effectiveness of a Group Support Lifestyle Modification (GSLiM) Programme among Obese Adults in Workplace: A Randomised Controlled Trial

    PubMed Central

    Azmi Mohamed, Mohd Nahar; Mukhtar, Firdaus

    2016-01-01

    Background There was an increasing trend in the prevalence of obesity and its comorbidities over the past decades in Malaysia. Effective intervention for obesity remains limited. This study aimed to compare the effectiveness of a group based lifestyle modification programme amongst obese individuals with an existing dietary counseling programme. Methods We recruited one hundred and ninety four overweight and obese (BMI>27.5 kg/m2) employees from a local university. They were randomly allocated to either Group Support Lifestyle Modification (GSLiM) (intervention)(n = 97) or dietary counseling (comparison)(n = 97). The GSLIM activities included self monitoring, cognitive-behaviour sessions, exercise as well as dietary change advocacy, which were conducted through seminars and group sessions over 24 weeks. The comparison group was given dietary counselling once in 12 weeks. Both groups were followed up for additional 12 weeks to check for intervention effect sustenance. Anthropometric and biochemical parameters were measured at baseline, 12, 24 and 36 weeks; while dietary intake, physical activities, psychological measures and quality of life measured at baseline, 24 and 36 weeks. Data analysis was conducted using ANOVA repeated measures with intention to treat principle. Results The participants were predominantly women with mean (standard deviation) age of 40.5 (9.3) years. A total of 19.6% of the participants in GSLiM achieved 6% weight loss compared to 4.1% in the comparison group (Risk Ratio 4.75; 95% CI: 1.68, 13.45). At 24 weeks, the retention rate was 83.5% for GSLiM and 82.5% for comparison group. GSLiM participants also achieved significant improvement in total weight self-efficacy score, negative emotions and physical discomfort subscales, MDPSS friend subscale and all domains in quality of life. Participants in the comparison group experienced reduction in negative self-thoughts. Conclusion The GSLiM programme proved to be more effective in achieving

  4. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer.

    PubMed

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas Hg

    2011-06-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician's discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account.

  5. Chemical Modifications of PhTX-I Myotoxin from Porthidium hyoprora Snake Venom: Effects on Structural, Enzymatic, and Pharmacological Properties

    PubMed Central

    Huancahuire-Vega, Salomón; Corrêa, Daniel H. A.; Hollanda, Luciana M.; Lancellotti, Marcelo; Ramos, Carlos H. I.; Ponce-Soto, Luis Alberto; Marangoni, Sergio

    2013-01-01

    We recently described the isolation of a basic PLA2 (PhTX-I) from Porthidium hyoprora snake venom. This toxin exhibits high catalytic activity, induces in vivo myotoxicity, moderates footpad edema, and causes in vitro neuromuscular blockade. Here, we describe the chemical modifications of specific amino acid residues (His, Tyr, Lys, and Trp), performed in PhTX-I, to study their effects on the structural, enzymatic, and pharmacological properties of this myotoxin. After chemical treatment, a single His, 4 Tyr, 7 Lys, and one Trp residues were modified. The secondary structure of the protein remained unchanged as measured by circular dichroism; however other results indicated the critical role played by Lys and Tyr residues in myotoxic, neurotoxic activities and mainly in the cytotoxicity displayed by PhTX-I. His residue and therefore catalytic activity of PhTX-I are relevant for edematogenic, neurotoxic, and myotoxic effects, but not for its cytotoxic activity. This dissociation observed between enzymatic activity and some pharmacological effects suggests that other molecular regions distinct from the catalytic site may also play a role in the toxic activities exerted by this myotoxin. Our observations supported the hypothesis that both the catalytic sites as the hypothetical pharmacological sites are relevant to the pharmacological profile of PhTX-I. PMID:23484072

  6. Effect of modification to tongue and impeller geometry on unsteady flow, pressure fluctuations, and noise in a centrifugal pump

    SciTech Connect

    Dong, R.; Chu, S.; Katz, J.

    1997-07-01

    Particle Image Velocimetry (PIV), pressure, and noise measurements are used to study the effect of modifications to tongue and impeller geometries on the flow structure and resulting noise in a centrifugal pump. It is demonstrated that the primary sources of noise are associated with interactions of the nonuniform outflux from the impeller (jet/wake phenomenon) with the tongue. Consequently, significant reduction of noise is achieved by increasing the gap between the tongue and the impeller up to about 20% of the impeller radius. Further increase in the gap affects the performance adversely with minimal impact on the noise level. When the gap is narrow, the primary sources of noise are impingement of the wake on the tip of the tongue, and tongue oscillations when the pressure difference across it is high. At about 20% gap, the entire wake and its associated vorticity trains miss the tongue, and the only (quite weak) effect of nonuniform outflux is the impingement of the jet on the tongue. An attempt is also made to reduce the nonuniformity in outflux from the impeller by inserting short vanes between the blades. They cause reduction in the size of the original wakes, but generate an additional jet/wake phenomenon of their own. Both wakes are weak to a level that their impacts on local pressure fluctuations and noise are insignificant. The only remaining major contributor to noise is tongue oscillations. This effect is shown to be dependent on the stiffness of the tongue.

  7. Cold spells and ischaemic sudden cardiac death: effect modification by prior diagnosis of ischaemic heart disease and cardioprotective medication

    PubMed Central

    Ryti, Niilo R. I.; Mäkikyrö, Elina M. S.; Antikainen, Harri; Junttila, M. Juhani; Hookana, Eeva; Ikäheimo, Tiina M.; Kortelainen, Marja-Leena; Huikuri, Heikki V.; Jaakkola, Jouni J. K.

    2017-01-01

    Sudden cardiac death (SCD) is the leading cause of death. The current paradigm in SCD requires the presence of an abnormal myocardial substrate and an internal or external transient factor that triggers cardiac arrest. Based on prior mechanistic evidence, we hypothesized that an unusually cold weather event (a cold spell) could act as an external factor triggering SCD. We tested potential effect modification of prior diagnoses and select pharmacological agents disrupting pathological pathways between cold exposure and death. The home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of home-specific weather data. Based on conditional logistic regression, an increased risk of ischaemic SCD associated with a cold spell preceding death (OR 1.49; 95% CI: 1.06–2.09). Cases without a prior diagnosis of ischaemic heart disease seemed more susceptible to the effects of cold spells (OR 1.70; 95% CI: 1.13–2.56) than cases who had been diagnosed during lifetime (OR 1.14; 95% CI: 0.61–2.10). The use of aspirin, β-blockers, and/or nitrates, independently and in combinations decreased the risk of ischaemic SCD during cold spells. The findings open up new lines of research in mitigating the adverse health effects of weather. PMID:28106161

  8. The enhanced SERS effect of Ag/ZnO nanoparticles through surface hydrophobic modification

    NASA Astrophysics Data System (ADS)

    Li, Zhenjiang; Zhu, Kaixing; Zhao, Qian; Meng, Alan

    2016-07-01

    Ag/ZnO nanocomposites modified by a mixture of stearic acid (SA) and polyvinylpyrrolidone (PVP) were obtained using a heating reflux method. Fourier transform infrared spectroscopy (FT-IR) suggests that organic SA/PVP was bonded onto the surface of Ag/ZnO nanocrystals, converting the wettability property of the nanostructures from hydrophilic to hydrophobic. The modified Ag/ZnO nanostructures were confirmed as effective Raman substrates, with a 3-fold signal enhancement compared to the ordinary hydrophilic Ag/ZnO substrate for detecting Rh B molecules due to the hydrophobic condensation effect. It is expected that the modified Ag/ZnO nanoparticles have potential for SERS-based rapid detection of molecules.

  9. Effects of V-22 Blade Modifications on Whirl Flutter and Loads

    NASA Technical Reports Server (NTRS)

    Acree, C. W., Jr.

    2004-01-01

    A CAMRAD II model of the V-22 Osprey tiltrotor was constructed for the purpose of analyzing the effects of blade design changes on whirl flutter. The model incorporated a dual load-path grip/yoke assembly, a swashplate coupled to the transmission case, and a drive train. A multiple-trailer free wake was used for loads calculations. The effects of rotor design changes on whirl-mode stability were calculated for swept blades and offset tip masses. A rotor with swept tips and inboard tuning masses was examined in detail to reveal the mechanisms by which these design changes affect stability and loads. Certain combinations of design features greatly increased whirl-mode stability, with (at worst) moderate increases to loads.

  10. Effect of surface modification, microstructure, and trapping on hydrogen diffusion coefficients in high strength alloys

    NASA Astrophysics Data System (ADS)

    Jebaraj Johnley Muthuraj, Josiah

    Cathodic protection is widely used for corrosion prevention. However, this process generates hydrogen at the protected metal surface, and diffusion of hydrogen through the metal may cause hydrogen embrittlement or hydrogen induced stress corrosion cracking. Thus the choice of a metal for use as fasteners depends upon its hydrogen uptake, permeation, diffusivity and trapping. The diffusivity of hydrogen through four high strength alloys (AISI 4340, alloy 718, alloy 686, and alloy 59) was analyzed by an electrochemical method developed by Devanathan and Stachurski. The effect of plasma nitriding and microstructure on hydrogen permeation through AISI 4340 was studied on six different specimens: as-received (AR) AISI 4340, nitrided samples with and without compound layer, samples quenched and tempered (Q&T) at 320° and 520°C, and nitrided samples Q&T 520°C. Studies on various nitrided specimens demonstrate that both the gamma'-Fe 4N rich compound surface layer and the deeper N diffusion layer that forms during plasma nitriding reduce the effective hydrogen diffusion coefficient, although the gamma'-Fe4N rich compound layer has a larger effect. Multiple permeation transients yield evidence for the presence of only reversible trap sites in as-received, Q&T 320 and 520 AISI 4340 specimens, and the presence of both reversible and irreversible trap sites in nitrided specimens. Moreover, the changes in microstructure during the quenching and tempering process result in a significant decrease in the diffusion coefficient of hydrogen compared to as-received specimens. In addition, density functional theory-based molecular dynamics simulations yield hydrogen diffusion coefficients through gamma'- Fe4N one order of magnitude lower than through α-Fe, which supports the experimental measurements of hydrogen permeation. The effect of microstructure and trapping was also studied in cold rolled, solutionized, and precipitation hardened Inconel 718 foils. The effective hydrogen

  11. Modeling of Interfacial Modification Effects on Thermal Conductivity of Carbon Nanotube Composites

    NASA Technical Reports Server (NTRS)

    Clancy, Thomas C.; Gates, Thomas S.

    2006-01-01

    The effect of functionalization of carbon nanotubes on the thermal conductivity of nanocomposites has been studied using a multi-scale modeling approach. These results predict that grafting linear hydrocarbon chains to the surface of a single wall carbon nanotube with covalent chemical bonds should result in a significant increase in the thermal conductivity of these nanocomposites. This is due to the decrease in the interfacial thermal (Kapitza) resistance between the single wall carbon nanotube and the surrounding polymer matrix upon chemical functionalization. The nanocomposites studied here consist of single wall carbon nanotubes in a bulk poly(ethylene vinyl acetate) matrix. The nanotubes are functionalized by end-grafting linear hydrocarbon chains of varying length to the surface of the nanotube. The effect which this functionalization has on the interfacial thermal resistance is studied by molecular dynamics simulation. Interfacial thermal resistance values are calculated for a range of chemical grafting densities and with several chain lengths. These results are subsequently used in an analytical model to predict the resulting effect on the bulk thermal conductivity of the nanocomposite.

  12. Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

    SciTech Connect

    Fayerweather, W.E.

    2007-07-01

    The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimated by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.

  13. Examination of the Relationship between Oral Health and Arterial Sclerosis without Genetic Confounding through the Study of Older Japanese Twins

    PubMed Central

    Kurushima, Yuko; Ikebe, Kazunori; Matsuda, Ken-ichi; Enoki, Kaori; Ogata, Soshiro; Yamashita, Motozo; Murakami, Shinya; Maeda, Yoshinobu

    2015-01-01

    Objective Although researchers have recently demonstrated a relationship between oral health and arterial sclerosis, the genetic contribution to this relationship has been ignored even though genetic factors are expected to have some effect on various diseases. The aim of this study was to evaluate oral health as a significant risk factor related to arterial sclerosis after eliminating genetic confounding through study of older Japanese twins. Subjects and Methods Medical and dental surveys were conducted individually for 106 Japanese twin pairs over the age of 50 years. Maximal carotid intima-media thickness (IMT-Cmax) was measured as a surrogate marker of arterial sclerosis. IMT-Cmax > 1.0 mm was diagnosed as arterial sclerosis. All of the twins were examined for the number of remaining teeth, masticatory performance, and periodontal status. We evaluated each measurement related with IMT-Cmax and arterial sclerosis using generalized estimating equations analysis adjusted for potential risk factors. For non-smoking monozygotic twins, a regression analysis using a “between within” model was conducted to evaluate the relationship between IMT-Cmax and the number of teeth as the environmental factor controlling genetic and familial confounding. Results We examined 91 monozygotic and 15 dizygotic twin pairs (males: 42, females: 64) with a mean (± standard deviation) age of 67.4 ± 10.0 years. Out of all of the oral health-related measurements collected, only the number of teeth was significantly related to arterial sclerosis (odds ratio: 0.72, 95% confidence interval: 0.52-0.99 per five teeth). Regression analysis showed a significant association between the IMT-Cmax and the number of teeth as an environmental factor (p = 0.037). Conclusions Analysis of monozygotic twins older than 50 years of age showed that having fewer teeth could be a significant environmental factor related to arterial sclerosis, even after controlling for genetic and familial confounding

  14. Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use.

    PubMed Central

    Delfino, Ralph J; Zeiger, Robert S; Seltzer, James M; Street, Donald H; McLaren, Christine E

    2002-01-01

    Maxima of hourly data from outdoor monitors may capture adverse effects of outdoor particulate matter (PM) exposures in asthmatic children better than do 24-hr PM averages, which form the basis of current regulations in the United States. Also, asthmatic children on anti-inflammatory medications may be protected against the proinflammatory effects of air pollutants and aeroallergens. We examined strengths of pollutant associations with asthma symptoms between subgroups of asthmatic children who were on versus not on regularly scheduled anti-inflammatory medications, and tested associations for different particle averaging times. This is a daily panel study of 22 asthmatic children (9-19 years of age) followed March through April 1996 (1,248 person-days). They lived in nonsmoking households in a semirural area of Southern California within the air inversion mixing zone (range, 1,200-2,100 feet) with transported air pollution from urban areas of Southern California. The dependent variable derived from diary ordinal scores is episodes of asthma symptoms that interfered with daily activities. Minimum to 90th-percentile levels of exposures at the outdoor monitoring site were 12-63 microg/m(3) for 1-hr PM < 10 microm in aerodynamic diameter (PM(10)); 8-46 microg/m(3) for 8-hr PM(10); 7-32 microg/m(3) for 24-hr PM(10); 45-88 ppb for 1-hr O(3); 6-26 ppb for 8-hr NO(2); 70-4,714 particles/m(3) for 12-hr daytime fungi; and 12-744 particles/m(3) for 24-hr pollen. Data were analyzed with generalized estimating equations controlling for autocorrelation. There was no confounding by weather, day of week, or linear time trend. Associations were notably stronger in 12 asthmatic children who were not taking anti-inflammatory medications versus 10 subjects who were. Odds ratios (95% confidence intervals) for asthma episodes in relation to lag 0 minimum to 90th-percentile pollutant changes were, respectively, 1-hr maximum PM(10), 1.92 (1.22-3.02) versus 0.96 (0.25-3.69); 8-hr maximum

  15. Modification by ouabain of the electrical and mechanical effects of acetylcholine in isolated rabbit atria

    PubMed Central

    Kajimoto, N.; Toda, N.

    1970-01-01

    1. Left atrial preparations isolated from rabbits were stimulated electrically at frequencies between 6 and 240/min. Tension-frequency curves were obtained from control preparations and preparations treated with ouabain and acetylcholine. Transmembrane potentials were recorded from single cells of the left atrium stimulated at different frequencies. 2. The tension-frequency curve was moved downwards by acetylcholine (10-6 g/ml). Ouabain (10-6 g/ml) caused characteristic alterations in the tension-frequency relationship, enhancing the contractile tension at low but not high frequencies. The negative inotropic effect of acetylcholine was reduced by treatment with ouabain. 3. Action potential durations were significantly influenced by alterations in frequency of contraction. The 10% duration increased with frequency within the range between 6 and 60/min but decreased at frequencies higher than 120/min. The 50% duration increased with frequency between 6 and 120/min but decreased at frequencies higher than 180/min. The dependence of the 50% duration upon frequency paralleled that of contractile tension. The 90% duration, the overshoot and the resting potential were not affected by frequency of contraction. 4. Acetylcholine (10-6 g/ml) shifted the 10%, 50% and 90% duration-frequency curves downwards, but did not significantly alter the overshoot and the resting potential. Ouabain (10-6 g/ml) shifted the duration-frequency curves downwards and also reduced the size of the overshoot and the resting potential. Treatment of atrial preparations with 10-6 g/ml ouabain potentiated the membrane effects of acetylcholine. 5. The inhibition by ouabain of the negative inotropic effect of acetylcholine did not appear to be due to antagonism at the receptor level, but to interference with the mechanisms responsible for the mechanical events. PMID:5425273

  16. Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D

    PubMed Central

    Tse, Sze Man; Kelly, H. William; Litonjua, Augusto; Van Natta, Mark L.; Weiss, Scott T.; Tantisira, Kelan

    2012-01-01

    Background The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD). Objective To determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time. Methods Children aged 5–12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled and oral corticosteroids (OCS) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial and serial DEXA scans of the lumbar spine were performed. Annual BMA rates were defined as: [(BMD at 4 years follow-up − BMD at baseline)/4 years]. Results BMA was calculated for 780 subjects. In boys, baseline vitamin D levels significantly modified the relationship between OCS and BMA (vitamin D x OCS interaction, p=0.023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCS in vitamin D insufficient boys only (p<0.001). Compared to vitamin D sufficient boys, vitamin D insufficient boys exposed to more than 2 courses of oral corticosteroids per year had twice the decrease in BMA rate (relative to boys who were OCS-unexposed). Conclusions Vitamin D levels significantly modified the effect of oral corticosteroids on bone mineral accretion in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma may confer benefits to bone health. PMID:22608570

  17. Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

    PubMed Central

    Peters, Brandilyn A.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Slavkovich, Vesna; Siddique, Abu B.; Alam, Shafiul; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.

    2015-01-01

    Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (EhGSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs pWald = 0.03; bAs pWald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by EhGSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma EhGSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma EhGSH and reduces risk for As-induced diseases. PMID:25916185

  18. Modification of graphene/SiO2 interface by UV-irradiation: effect on electrical characteristics.

    PubMed

    Imamura, Gaku; Saiki, Koichiro

    2015-02-04

    Graphene is a promising material for next-generation electronic devices. The effect of UV-irradiation on the graphene devices, however, has not been fully explored yet. Here we investigate the UV-induced change of the field effect transistor (FET) characteristics of graphene/SiO2. UV-irradiation in a vacuum gives rise to the decrease in carrier mobility and a hysteresis in the transfer characteristics. Annealing at 160 °C in a vacuum eliminates the hysteresis, recovers the mobility partially, and moves the charge neutrality point to the negative direction. Corresponding Raman spectra indicated that UV-irradiation induced D band relating with defects and the annealing at 160 °C in a vacuum removed the D band. We propose a phenomenological model for the UV-irradiated graphene, in which photochemical reaction produces dangling bonds and the weak sp(3)-like bonds at the graphene/SiO2 interface, and the annealing restores the intrinsic graphene/SiO2 interface by removal of such bonds. Our results shed light to the nature of defect formation by UV-light, which is important for the practical performance of graphene based electronics.

  19. A Mixed Modeling Approach to Predict the Effect of Environmental Modification on Species Distributions

    PubMed Central

    Cozzoli, Francesco; Eelkema, Menno; Bouma, Tjeerd J.; Ysebaert, Tom; Escaravage, Vincent; Herman, Peter M. J.

    2014-01-01

    Human infrastructures can modify ecosystems, thereby affecting the occurrence and spatial distribution of organisms, as well as ecosystem functionality. Sustainable development requires the ability to predict responses of species to anthropogenic pressures. We investigated the large scale, long term effect of important human alterations of benthic habitats with an integrated approach combining engineering and ecological modelling. We focused our analysis on the Oosterschelde basin (The Netherlands), which was partially embanked by a storm surge barrier (Oosterscheldekering, 1986). We made use of 1) a prognostic (numerical) environmental (hydrodynamic) model and 2) a novel application of quantile regression to Species Distribution Modeling (SDM) to simulate both the realized and potential (habitat suitability) abundance of four macrozoobenthic species: Scoloplos armiger, Peringia ulvae, Cerastoderma edule and Lanice conchilega. The analysis shows that part of the fluctuations in macrozoobenthic biomass stocks during the last decades is related to the effect of the coastal defense infrastructures on the basin morphology and hydrodynamics. The methodological framework we propose is particularly suitable for the analysis of large abundance datasets combined with high-resolution environmental data. Our analysis provides useful information on future changes in ecosystem functionality induced by human activities. PMID:24586545

  20. Studying the effects of nucleating agents on texture modification of puffed corn-fish snack.

    PubMed

    Shahmohammadi, Hamid Reza; Bakar, Jamilah; Rahman, Russly Abdul; Adzhan, Noranizan Mohd

    2014-02-01

    To improve textural attributes of puffed corn-fish snack, the effects of 1%, 1.5%, and 2% of calcium carbonate, magnesium silicate (talc), sodium bicarbonate as well as 5% and 10% of wheat bran (as the nucleating materials) on textural attributes were studied. Sensory evaluation, bulk density, expansion ratio, maximum force, and count peaks were measured using the Kramer test. The results showed that all of the additives except bran significantly enhanced the texture. Among them, talc at 0.5% was the best to enhance the density and expansion ratio. Effects of using 0.5% talc on puffed corn-fish snack microstructure were studied using scanning electron microscopy. The average cell diameter of 109 ± 48 μm and cell numbers per square centimeter of 67.4 for talc-treated products were obtained, while for nontalc-treated extrudates, average cell diameter of 798 ± 361 μm and cell numbers per square centimeter of 13.9 were found. Incorporation of 0.5% w/w of magnesium silicate reduced (7-fold) the average cell diameter while increased (4-fold) the cell number.

  1. Biological effects of a root conditioning agent for dentin surface modification in vitro

    PubMed Central

    Lee, Jue-Yeon; Seol, Yang-Jo; Park, Jang-Ryul; Park, Yoon-Jeong

    2010-01-01

    Purpose Connective tissue reattachment to periodontally damaged root surfaces is one of the most important goals of periodontal therapy. The aim of this study was to develop a root conditioning agent that can demineralize and detoxify the infected root surface. Methods Dentin slices obtained from human teeth were treated with a novel root planing agent for 2 minutes and then washed with phosphate-buffered saline. Smear layer removal and type I collagen exposure were observed by scanning electron microscopy (SEM) and type I collagen immunostaining, respectively. Cell attachment and lipopolysaccharides (LPS) removal demonstrated the efficiency of the root conditioning agent. Results SEM revealed that the smear layer was entirely removed and the dentinal tubules were opened by the experimental gel. Type I collagen was exposed on the surfaces of the dentin slices treated by the experimental gel, which were compared with dentin treated with other root planing agents. Dentin slices treated with the experimental gel showed the highest number of attached fibroblasts and flattened cell morphology. The agar diffusion assay demonstrated that the experimental gel also has effective antimicrobial activity. Escherichia coli LPS were effectively removed from well plates by the experimental gel. Conclusions These results demonstrated that this experimental gel is a useful tool for root conditioning of infected root surfaces and can also be applied for detoxification of ailing implant surface threads. PMID:21246015