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

Science.gov (United States)

Vetter, Thomas R; Mascha, Edward J

2017-09-01

Epidemiologists seek to make a valid inference about the causal effect between an exposure and a disease in a specific population, using representative sample data from a specific population. Clinical researchers likewise seek to make a valid inference about the association between an intervention and outcome(s) in a specific population, based upon their randomly collected, representative sample data. Both do so by using the available data about the sample variable to make a valid estimate about its corresponding or underlying, but unknown population parameter. Random error in an experiment can be due to the natural, periodic fluctuation or variation in the accuracy or precision of virtually any data sampling technique or health measurement tool or scale. In a clinical research study, random error can be due to not only innate human variability but also purely chance. Systematic error in an experiment arises from an innate flaw in the data sampling technique or measurement instrument. In the clinical research setting, systematic error is more commonly referred to as systematic bias. The most commonly encountered types of bias in anesthesia, perioperative, critical care, and pain medicine research include recall bias, observational bias (Hawthorne effect), attrition bias, misclassification or informational bias, and selection bias. A confounding variable is a factor associated with both the exposure of interest and the outcome of interest. A confounding variable (confounding factor or confounder) is a variable that correlates (positively or negatively) with both the exposure and outcome. Confounding is typically not an issue in a randomized trial because the randomized groups are sufficiently balanced on all potential confounding variables, both observed and nonobserved. However, confounding can be a major problem with any observational (nonrandomized) study. Ignoring confounding in an observational study will often result in a "distorted" or incorrect estimate of

Quantitative assessment of unobserved confounding is mandatory in nonrandomized intervention studies

NARCIS (Netherlands)

Groenwold, R H H; Hak, E; Hoes, A W

OBJECTIVE: In nonrandomized intervention studies unequal distribution of patient characteristics in the groups under study may hinder comparability of prognosis and therefore lead to confounding bias. Our objective was to review methods to control for observed confounding, as well as unobserved

Confounding and exposure measurement error in air pollution epidemiology.

Science.gov (United States)

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.

CONFOUNDING STRUCTURE OF TWO-LEVEL NONREGULAR FACTORIAL DESIGNS

Institute of Scientific and Technical Information of China (English)

Ren Junbai

2012-01-01

In design theory,the alias structure of regular fractional factorial designs is elegantly described with group theory.However,this approach cannot be applied to nonregular designs directly. For an arbitrary nonregular design,a natural question is how to describe the confounding relations between its effects,is there any inner structure similar to regular designs? The aim of this article is to answer this basic question.Using coefficients of indicator function,confounding structure of nonregular fractional factorial designs is obtained as linear constrains on the values of effects.A method to estimate the sparse significant effects in an arbitrary nonregular design is given through an example.

The performance of random coefficient regression in accounting for residual confounding.

Science.gov (United States)

Gustafson, Paul; Greenland, Sander

2006-09-01

Greenland (2000, Biometrics 56, 915-921) describes the use of random coefficient regression to adjust for residual confounding in a particular setting. We examine this setting further, giving theoretical and empirical results concerning the frequentist and Bayesian performance of random coefficient regression. Particularly, we compare estimators based on this adjustment for residual confounding to estimators based on the assumption of no residual confounding. This devolves to comparing an estimator from a nonidentified but more realistic model to an estimator from a less realistic but identified model. The approach described by Gustafson (2005, Statistical Science 20, 111-140) is used to quantify the performance of a Bayesian estimator arising from a nonidentified model. From both theoretical calculations and simulations we find support for the idea that superior performance can be obtained by replacing unrealistic identifying constraints with priors that allow modest departures from those constraints. In terms of point-estimator bias this superiority arises when the extent of residual confounding is substantial, but the advantage is much broader in terms of interval estimation. The benefit from modeling residual confounding is maintained when the prior distributions employed only roughly correspond to reality, for the standard identifying constraints are equivalent to priors that typically correspond much worse.

Propensity score methodology for confounding control in health care utilization databases

Directory of Open Access Journals (Sweden)

Elisabetta Patorno

2013-06-01

Full Text Available Propensity score (PS methodology is a common approach to control for confounding in nonexperimental studies of treatment effects using health care utilization databases. This methodology offers researchers many advantages compared with conventional multivariate models: it directly focuses on the determinants of treatment choice, facilitating the understanding of the clinical decision-making process by the researcher; it allows for graphical comparisons of the distribution of propensity scores and truncation of subjects without overlapping PS indicating a lack of equipoise; it allows transparent assessment of the confounder balance achieved by the PS at baseline; and it offers a straightforward approach to reduce the dimensionality of sometimes large arrays of potential confounders in utilization databases, directly addressing the “curse of dimensionality” in the context of rare events. This article provides an overview of the use of propensity score methodology for pharmacoepidemiologic research with large health care utilization databases, covering recent discussions on covariate selection, the role of automated techniques for addressing unmeasurable confounding via proxies, strategies to maximize clinical equipoise at baseline, and the potential of machine-learning algorithms for optimized propensity score estimation. The appendix discusses the available software packages for PS methodology. Propensity scores are a frequently used and versatile tool for transparent and comprehensive adjustment of confounding in pharmacoepidemiology with large health care databases.

Overlapping neural systems represent cognitive effort and reward anticipation.

Science.gov (United States)

Vassena, Eliana; Silvetti, Massimo; Boehler, Carsten N; Achten, Eric; Fias, Wim; Verguts, Tom

2014-01-01

Anticipating a potential benefit and how difficult it will be to obtain it are valuable skills in a constantly changing environment. In the human brain, the anticipation of reward is encoded by the Anterior Cingulate Cortex (ACC) and Striatum. Naturally, potential rewards have an incentive quality, resulting in a motivational effect improving performance. Recently it has been proposed that an upcoming task requiring effort induces a similar anticipation mechanism as reward, relying on the same cortico-limbic network. However, this overlapping anticipatory activity for reward and effort has only been investigated in a perceptual task. Whether this generalizes to high-level cognitive tasks remains to be investigated. To this end, an fMRI experiment was designed to investigate anticipation of reward and effort in cognitive tasks. A mental arithmetic task was implemented, manipulating effort (difficulty), reward, and delay in reward delivery to control for temporal confounds. The goal was to test for the motivational effect induced by the expectation of bigger reward and higher effort. The results showed that the activation elicited by an upcoming difficult task overlapped with higher reward prospect in the ACC and in the striatum, thus highlighting a pivotal role of this circuit in sustaining motivated behavior.

On the biomechanical function of scaffolds for engineering load-bearing soft tissues.

Science.gov (United States)

Stella, John A; D'Amore, Antonio; Wagner, William R; Sacks, Michael S

2010-07-01

Replacement or regeneration of load-bearing soft tissues has long been the impetus for the development of bioactive materials. While maturing, current efforts continue to be confounded by our lack of understanding of the intricate multi-scale hierarchical arrangements and interactions typically found in native tissues. The current state of the art in biomaterial processing enables a degree of controllable microstructure that can be used for the development of model systems to deduce fundamental biological implications of matrix morphologies on cell function. Furthermore, the development of computational frameworks which allow for the simulation of experimentally derived observations represents a positive departure from what has mostly been an empirically driven field, enabling a deeper understanding of the highly complex biological mechanisms we wish to ultimately emulate. Ongoing research is actively pursuing new materials and processing methods to control material structure down to the micro-scale to sustain or improve cell viability, guide tissue growth, and provide mechanical integrity, all while exhibiting the capacity to degrade in a controlled manner. The purpose of this review is not to focus solely on material processing but to assess the ability of these techniques to produce mechanically sound tissue surrogates, highlight the unique structural characteristics produced in these materials, and discuss how this translates to distinct macroscopic biomechanical behaviors. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Assessing mediation using marginal structural models in the presence of confounding and moderation

OpenAIRE

Coffman, Donna L.; Zhong, Wei

2012-01-01

This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and ou...

Confounding in statistical mediation analysis: What it is and how to address it.

Science.gov (United States)

Valente, Matthew J; Pelham, William E; Smyth, Heather; MacKinnon, David P

2017-11-01

Psychology researchers are often interested in mechanisms underlying how randomized interventions affect outcomes such as substance use and mental health. Mediation analysis is a common statistical method for investigating psychological mechanisms that has benefited from exciting new methodological improvements over the last 2 decades. One of the most important new developments is methodology for estimating causal mediated effects using the potential outcomes framework for causal inference. Potential outcomes-based methods developed in epidemiology and statistics have important implications for understanding psychological mechanisms. We aim to provide a concise introduction to and illustration of these new methods and emphasize the importance of confounder adjustment. First, we review the traditional regression approach for estimating mediated effects. Second, we describe the potential outcomes framework. Third, we define what a confounder is and how the presence of a confounder can provide misleading evidence regarding mechanisms of interventions. Fourth, we describe experimental designs that can help rule out confounder bias. Fifth, we describe new statistical approaches to adjust for measured confounders of the mediator-outcome relation and sensitivity analyses to probe effects of unmeasured confounders on the mediated effect. All approaches are illustrated with application to a real counseling intervention dataset. Counseling psychologists interested in understanding the causal mechanisms of their interventions can benefit from incorporating the most up-to-date techniques into their mediation analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cardiovascular health, traffic-related air pollution and noise: are associations mutually confounded? A systematic review.

Science.gov (United States)

Tétreault, Louis-François; Perron, Stéphane; Smargiassi, Audrey

2013-10-01

This review assessed the confounding effect of one traffic-related exposure (noise or air pollutants) on the association between the other exposure and cardiovascular outcomes. A systematic review was conducted with the databases Medline and Embase. The confounding effects in studies were assessed by using change in the estimate with a 10 % cutoff point. The influence on the change in the estimate of the quality of the studies, the exposure assessment methods and the correlation between road noise and air pollutions were also assessed. Nine publications were identified. For most studies, the specified confounders produced changes in estimates noise and pollutants, the quality of the study and of the exposure assessment do not seem to influence the confounding effects. Results from this review suggest that confounding of cardiovascular effects by noise or air pollutants is low, though with further improvements in exposure assessment, the situation may change. More studies using pollution indicators specific to road traffic are needed to properly assess if noise and air pollution are subjected to confounding.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

Science.gov (United States)

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Confounder selection in environmental epidemiology: Assessment of health effects of prenatal mercury exposure

DEFF Research Database (Denmark)

Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe

2007-01-01

PURPOSE: The purpose of the study is to compare different approaches to the identification of confounders needed for analyzing observational data. Whereas standard analysis usually is conducted as if the confounders were known a priori, selection uncertainty also must be taken into account. METHO...

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

Science.gov (United States)

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

2018-06-01

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).

Control principles of confounders in ecological comparative studies: standardization and regressive modelss

Directory of Open Access Journals (Sweden)

Varaksin Anatoly

2014-03-01

Full Text Available The methods of the analysis of research data including the concomitant variables (confounders associated with both the response and the current factor are considered. There are two usual ways to take into account such variables: the first, at the stage of planning the experiment and the second, in analyzing the received data. Despite the equal effectiveness of these approaches, there exists strong reason to restrict the usage of regression method to accounting for confounders by ANCOVA. Authors consider the standardization by stratification as a reliable method to account for the effect of confounding factors as opposed to the widely-implemented application of logistic regression and the covariance analysis. The program for the automation of standardization procedure is proposed, it is available at the site of the Institute of Industrial Ecology.

Confounding of three binary-variables counterfactual model

OpenAIRE

Liu, Jingwei; Hu, Shuang

2011-01-01

Confounding of three binary-variables counterfactual model is discussed in this paper. According to the effect between the control variable and the covariate variable, we investigate three counterfactual models: the control variable is independent of the covariate variable, the control variable has the effect on the covariate variable and the covariate variable affects the control variable. Using the ancillary information based on conditional independence hypotheses, the sufficient conditions...

An introduction to sensitivity analysis for unobserved confounding in nonexperimental prevention research.

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Liu, Weiwei; Kuramoto, S Janet; Stuart, Elizabeth A

2013-12-01

Despite the fact that randomization is the gold standard for estimating causal relationships, many questions in prevention science are often left to be answered through nonexperimental studies because randomization is either infeasible or unethical. While methods such as propensity score matching can adjust for observed confounding, unobserved confounding is the Achilles heel of most nonexperimental studies. This paper describes and illustrates seven sensitivity analysis techniques that assess the sensitivity of study results to an unobserved confounder. These methods were categorized into two groups to reflect differences in their conceptualization of sensitivity analysis, as well as their targets of interest. As a motivating example, we examine the sensitivity of the association between maternal suicide and offspring's risk for suicide attempt hospitalization. While inferences differed slightly depending on the type of sensitivity analysis conducted, overall, the association between maternal suicide and offspring's hospitalization for suicide attempt was found to be relatively robust to an unobserved confounder. The ease of implementation and the insight these analyses provide underscores sensitivity analysis techniques as an important tool for nonexperimental studies. The implementation of sensitivity analysis can help increase confidence in results from nonexperimental studies and better inform prevention researchers and policy makers regarding potential intervention targets.

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

Science.gov (United States)

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

Correction of confounding bias in non-randomized studies by appropriate weighting.

Science.gov (United States)

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams.

Science.gov (United States)

Yu, Yuanyuan; Li, Hongkai; Sun, Xiaoru; Su, Ping; Wang, Tingting; Liu, Yi; Yuan, Zhongshang; Liu, Yanxun; Xue, Fuzhong

2017-12-28

Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM) were compared. The "do-calculus" was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal strategy was to adjust for the parent nodes of outcome, which

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams

Directory of Open Access Journals (Sweden)

Yuanyuan Yu

2017-12-01

Full Text Available Abstract Background Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Methods Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM were compared. The “do-calculus” was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Results Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal

Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

Directory of Open Access Journals (Sweden)

Enrica Migliore

Full Text Available Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR and 95% confidence intervals (CI were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10 [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache revealed no increased risk of wheezing in children.The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.

Investigating the Idoho oil spillage into Lagos: Some confounding ...

African Journals Online (AJOL)

... caused by these spillages must consider the socio-economic characteristics of the population as this may reveal a true picture of the event and facilitate proper interpretation of the result. Keywords: Toxicity, Idoho Oil Spillage, Confounders, Socio economic factors. Nigerian Journal of Health and Biomedical Sciences Vol.

Assessment of Confounding in Studies of Delay and Survival

DEFF Research Database (Denmark)

Tørring, Marie Louise; Vedsted, Peter; Frydenberg, Morten

BACKGROUND: Whether longer time to diagnosis (diagnostic delay) in patients with cancer symptoms is directly and independently associated with poor prognosis cannot be determined in randomised controlled trials. Analysis of observational data is therefore necessary. Many previous studies of the i......BACKGROUND: Whether longer time to diagnosis (diagnostic delay) in patients with cancer symptoms is directly and independently associated with poor prognosis cannot be determined in randomised controlled trials. Analysis of observational data is therefore necessary. Many previous studies......) Clarify which factors are considered confounders or intermediate variables in the literature. 2) Assess how and to what extent these factors bias survival estimates. CONSIDERATIONS: As illustrated in Figure 1, symptoms of cancer may alert patients, GP's, and hospital doctors differently and influence both...... delay and survival time in different ways. We therefore assume that the impact of confounding factors depends on the type of delay studied (e.g., patient delay, GP delay, referral delay, or treatment delay). MATERIALS & METHODS: The project includes systematic review and methodological developments...

Hypnotics and mortality – confounding by disease and socioeconomic position

DEFF Research Database (Denmark)

Kriegbaum, Margit; Hendriksen, Carsten; Vass, Mikkel

2015-01-01

Purpose The aim of this Cohort study of 10 527 Danish men was to investigate the extent to which the association between hypnotics and mortality is confounded by several markers of disease and living conditions. Methods Exposure was purchases of hypnotics 1995–1999 (“low users” (150 or less defined......% confidence intervals (CI). Results When covariates were entered one at a time, the changes in HR estimates showed that psychiatric disease, socioeconomic position and substance abuse reduced the excess risk by 17–36% in the low user group and by 45–52% in the high user group. Somatic disease, intelligence...... point at psychiatric disease, substance abuse and socioeconomic position as potential confounding factors partly explaining the association between use of hypnotics and all-cause mortality....

An Introduction to Sensitivity Analysis for Unobserved Confounding in Non-Experimental Prevention Research

Science.gov (United States)

Kuramoto, S. Janet; Stuart, Elizabeth A.

2013-01-01

Despite that randomization is the gold standard for estimating causal relationships, many questions in prevention science are left to be answered through non-experimental studies often because randomization is either infeasible or unethical. While methods such as propensity score matching can adjust for observed confounding, unobserved confounding is the Achilles heel of most non-experimental studies. This paper describes and illustrates seven sensitivity analysis techniques that assess the sensitivity of study results to an unobserved confounder. These methods were categorized into two groups to reflect differences in their conceptualization of sensitivity analysis, as well as their targets of interest. As a motivating example we examine the sensitivity of the association between maternal suicide and offspring’s risk for suicide attempt hospitalization. While inferences differed slightly depending on the type of sensitivity analysis conducted, overall the association between maternal suicide and offspring’s hospitalization for suicide attempt was found to be relatively robust to an unobserved confounder. The ease of implementation and the insight these analyses provide underscores sensitivity analysis techniques as an important tool for non-experimental studies. The implementation of sensitivity analysis can help increase confidence in results from non-experimental studies and better inform prevention researchers and policymakers regarding potential intervention targets. PMID:23408282

Effect decomposition in the presence of an exposure-induced mediator-outcome confounder

Science.gov (United States)

VanderWeele, Tyler J.; Vansteelandt, Stijn; Robins, James M.

2014-01-01

Methods from causal mediation analysis have generalized the traditional approach to direct and indirect effects in the epidemiologic and social science literature by allowing for interaction and non-linearities. However, the methods from the causal inference literature have themselves been subject to a major limitation in that the so-called natural direct and indirect effects that are employed are not identified from data whenever there is a variable that is affected by the exposure, which also confounds the relationship between the mediator and the outcome. In this paper we describe three alternative approaches to effect decomposition that give quantities that can be interpreted as direct and indirect effects, and that can be identified from data even in the presence of an exposure-induced mediator-outcome confounder. We describe a simple weighting-based estimation method for each of these three approaches, illustrated with data from perinatal epidemiology. The methods described here can shed insight into pathways and questions of mediation even when an exposure-induced mediator-outcome confounder is present. PMID:24487213

Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

Directory of Open Access Journals (Sweden)

Anne-Christin Hauschild

2015-06-01

Full Text Available 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

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols.

Science.gov (United States)

Reveiz, Ludovic; Haby, Michelle M; Martínez-Vega, Ruth; Pinzón-Flores, Carlos E; Elias, Vanessa; Smith, Emma; Pinart, Mariona; Broutet, Nathalie; Becerra-Posada, Francisco; Aldighieri, Sylvain; Van Kerkhove, Maria D

2017-01-01

Given the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV. We conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols. Observational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design. Observational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols.

Directory of Open Access Journals (Sweden)

Ludovic Reveiz

Full Text Available Given the severity and impact of the current Zika virus (ZIKV outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV.We conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols.Observational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome. Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design.Observational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to

Tissue Engineering of the Penis

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Manish N. Patel

2011-01-01

Full Text Available Congenital disorders, cancer, trauma, or other conditions of the genitourinary tract can lead to significant organ damage or loss of function, necessitating eventual reconstruction or replacement of the damaged structures. However, current reconstructive techniques are limited by issues of tissue availability and compatibility. Physicians and scientists have begun to explore tissue engineering and regenerative medicine strategies for repair and reconstruction of the genitourinary tract. Tissue engineering allows the development of biological substitutes which could potentially restore normal function. Tissue engineering efforts designed to treat or replace most organs are currently being undertaken. Most of these efforts have occurred within the past decade. However, before these engineering techniques can be applied to humans, further studies are needed to ensure the safety and efficacy of these new materials. Recent progress suggests that engineered urologic tissues and cell therapy may soon have clinical applicability.

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

Science.gov (United States)

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 ...

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

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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 ...

Interpretational confounding is due to misspecification, not to type of indicator: comment on Howell, Breivik, and Wilcox (2007).

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Bollen, Kenneth A

2007-06-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.

Using ecological propensity score to adjust for missing confounders in small area studies.

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Wang, Yingbo; Pirani, Monica; Hansell, Anna L; Richardson, Sylvia; Blangiardo, Marta

2017-11-09

Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. © The Author 2017. Published by Oxford University Press.

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms.

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van der Meer, Hedwig A; Speksnijder, Caroline M; Engelbert, Raoul H H; Lobbezoo, Frank; Nijhuis-van der Sanden, Maria W G; Visscher, Corine M

2017-09-01

The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. Several subtypes of headaches have been diagnosed: self-reported headache, (probable) migraine, (probable) tension-type headache, and secondary headache attributed to TMD. The presence of TMD was subdivided into 2 subtypes: painful TMD and function-related TMD. The associations between the subtypes of TMD and headaches were evaluated by single regression models. To study the influence of possible confounding factors on this association, the regression models were extended with age, sex, bruxism, stress, depression, and somatic symptoms. Of the included patients (n=203), 67.5% experienced headaches. In the subsample of patients with a painful TMD (n=58), the prevalence of self-reported headaches increased to 82.8%. The associations found between self-reported headache and (1) painful TMD and (2) function-related TMD were confounded by the presence of somatic symptoms. For probable migraine, both somatic symptoms and bruxism confounded the initial association found with painful TMD. The findings of this study imply that there is a central working mechanism overlapping TMD and headache. Health care providers should not regard these disorders separately, but rather look at the bigger picture to appreciate the complex nature of the diagnostic and therapeutic process.

Which Propensity Score Method Best Reduces Confounder Imbalance? An Example From a Retrospective Evaluation of a Childhood Obesity Intervention.

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Schroeder, Krista; Jia, Haomiao; Smaldone, Arlene

Propensity score (PS) methods are increasingly being employed by researchers to reduce bias arising from confounder imbalance when using observational data to examine intervention effects. The purpose of this study was to examine PS theory and methodology and compare application of three PS methods (matching, stratification, weighting) to determine which best improves confounder balance. Baseline characteristics of a sample of 20,518 school-aged children with severe obesity (of whom 1,054 received an obesity intervention) were assessed prior to PS application. Three PS methods were then applied to the data to determine which showed the greatest improvement in confounder balance between the intervention and control group. The effect of each PS method on the outcome variable-body mass index percentile change at one year-was also examined. SAS 9.4 and Comprehensive Meta-analysis statistical software were used for analyses. Prior to PS adjustment, the intervention and control groups differed significantly on seven of 11 potential confounders. PS matching removed all differences. PS stratification and weighting both removed one difference but created two new differences. Sensitivity analyses did not change these results. Body mass index percentile at 1 year decreased in both groups. The size of the decrease was smaller in the intervention group, and the estimate of the decrease varied by PS method. Selection of a PS method should be guided by insight from statistical theory and simulation experiments, in addition to observed improvement in confounder balance. For this data set, PS matching worked best to correct confounder imbalance. Because each method varied in correcting confounder imbalance, we recommend that multiple PS methods be compared for ability to improve confounder balance before implementation in evaluating treatment effects in observational data.

Leading Efforts to Increase Organ Donation Through Professionalization of Organ Procurement Organizations and Establishment of Organ and Tissue Donor Registries.

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Vertanous, T; Czer, L S C; de Robertis, M; Kiankhooy, A; Kobashigawa, J; Esmailian, F; Trento, A

2016-01-01

The influence of new donor registrations through the California Organ and Tissue Donor Registry on the local OneLegacy Organ Procurement Organization (OPO) was examined during a 6-year period. Publicly available data from Donate Life America for California were examined for the 6 calendar years of 2009-2014. Performance data from OneLegacy for the same 6 years for organ donors and number of transplants were also examined. The donor designation rate (DDR) was defined as the rate at which new individuals joined the state donor registry as a percentage of all driver licenses and ID cards issued within a calendar year. The total donor designation (TDD) was defined as the sum of the new and existing people who were registered organ donors. Donor designation share (DDS) was the total number of designated donors as a percentage of all residents of the state who were ≥18 years old. The business practices and educational efforts of the OneLegacy OPO were examined as well. In California, from 2009 through 2014, the DDR was 25.5%-28%. When added to the existing donor registrations, the TDD and DDS increased each year from 2009 through 2014. With the current level of growth, it is projected that California will be able to reach a DDS of 50% by 2017. For the OneLegacy OPO, designated donors from the California Organ and Tissue Donor Registry made up 15% of the total donations in 2009, and 39% of the total donations in 2014, increasing by ∼5% each year since 2009. By increasing professionalization and transparency, and widening its educational and training efforts, OneLegacy was able to take advantage of an increasing percentage of donors who were designated donors and to increase the overall number of donors and organs transplanted, becoming one of the largest OPOs in the nation. This can be a model for OPOs in other donor service areas, and it may set the stage for the United States to serve as an example to the global community in the practice of organ donation. Copyright

Musculoskeletal pain and effort-reward imbalance--a systematic review.

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Koch, Peter; Schablon, Anja; Latza, Ute; Nienhaus, Albert

2014-01-15

Musculoskeletal pain may be triggered by physical strains and psychosocial risk factors. The effort-reward imbalance model (ERI model) is a stress model which measures psychosocial factors in the working world. The question is whether workers with an effort-reward imbalance report musculoskeletal pain more frequently than those with no effort-reward imbalance. A systematic review using a best evidence synthesis approach was conducted to answer this question. A literature search was conducted for the period from 1996 to 2012, using three databases (Pubmed, Embase and PsycINFO). The research criteria related to psychosocial, work-related stress as per the ERI model and to musculoskeletal pain. A quality score was developed using various quality criteria to assess the standard of the studies. The level of evidence was graded as in (Am J Ind Med 39:180-193, 2001). After applying the inclusion criteria, a total of 19 studies were included in the review: 15 cross-sectional studies, three prospective studies and one case-control study. 74% of all studies exhibited good methodological quality, 53% collected data using the original ERI questionnaire, and in 42% of the studies, there was adequate control for physical working conditions. Furthermore, different cut-off points were used to classify exposed and non-exposed individuals. On the basis of 13 studies with a positive, statistically significant association, a moderate level of evidence was inferred for the association between effort-reward imbalance and musculoskeletal pain. The evidence for a role of over-commitment and for its interaction with effort-reward imbalance was rated as inconclusive - on the basis of eight and five studies, respectively. On the basis of the available evidence, no reliable conclusion may be drawn about any association between the psychosocial factors ascertained using the ERI model and musculoskeletal pain. Before a reliable statement can be made on the association between ERI and

LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

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Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary K.

2015-01-01

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from...

Marine oils: Complex, confusing, confounded?

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Benjamin B. Albert

2016-09-01

Full Text Available Marine oils gained prominence following the report that Greenland Inuits who consumed a high-fat diet rich in long-chain n-3 polyunsaturated fatty acids (PUFAs also had low rates of cardiovascular disease. Marine n-3 PUFAs have since become a billion dollar industry, which will continue to grow based on current trends. However, recent systematic reviews question the health benefits of marine oil supplements, particularly in the prevention of cardiovascular disease. Marine oils constitute an extremely complex dietary intervention for a number of reasons: i the many chemical compounds they contain; ii the many biological processes affected by n-3 PUFAs; iii their tendency to deteriorate and form potentially toxic primary and secondary oxidation products; and iv inaccuracy in the labelling of consumer products. These complexities may confound the clinical literature, limiting the ability to make substantive conclusions for some key health outcomes. Thus, there is a pressing need for clinical trials using marine oils whose composition has been independently verified and demonstrated to be minimally oxidised. Without such data, it is premature to conclude that n-3 PUFA rich supplements are ineffective.

Quantifying the potential role of unmeasured confounders : the example of influenza vaccination

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Groenwold, R H H; Hoes, A W; Nichol, K L; Hak, E

2008-01-01

BACKGROUND: The validity of non-randomized studies using healthcare databases is often challenged because they lack information on potentially important confounders, such as functional health status and socioeconomic status. In a study quantifying the effects of influenza vaccination among

External adjustment of unmeasured confounders in a case-control study of benzodiazepine use and cancer risk

DEFF Research Database (Denmark)

Thygesen, Lau Caspar; Pottegård, Anton; Ersbøll, Annette Kjaer

2017-01-01

AIMS: Previous studies have reported diverging results on the association between benzodiazepine use and cancer risk. METHODS: We investigated this association in a matched case-control study including incident cancer cases during 2002-2009 in the Danish Cancer Registry (n = 94 923) and age......% confidence interval 1.00-1.19) and for smoking-related cancers from 1.20 to 1.10 (95% confidence interval 1.00-1.21). CONCLUSION: We conclude that the increased risk observed in the solely register-based study could partly be attributed to unmeasured confounding....... PSs were used: The error-prone PS using register-based confounders and the calibrated PS based on both register- and survey-based confounders, retrieved from the Health Interview Survey. RESULTS: Register-based data showed that cancer cases had more diagnoses, higher comorbidity score and more co...

The relationship between urinary tract infection during pregnancy and preeclampsia: causal, confounded or spurious?

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Karmon, Anatte; Sheiner, Eyal

2008-06-01

Preeclampsia is a major cause of maternal morbidity, although its precise etiology remains elusive. A number of studies suggest that urinary tract infection (UTI) during the course of gestation is associated with elevated risk for preeclampsia, while others have failed to prove such an association. In our medical center, pregnant women who were exposed to at least one UTI episode during pregnancy were 1.3 times more likely to have mild preeclampsia and 1.8 times more likely to have severe preeclampsia as compared to unexposed women. Our results are based on univariate analyses and are not adjusted for potential confounders. This editorial aims to discuss the relationship between urinary tract infection and preeclampsia, as well as examine the current problems regarding the interpretation of this association. Although the relationship between UTI and preeclampsia has been demonstrated in studies with various designs, carried-out in a variety of settings, the nature of this association is unclear. By taking into account timeline, dose-response effects, treatment influences, and potential confounders, as well as by neutralizing potential biases, future studies may be able to clarify the relationship between UTI and preeclampsia by determining if it is causal, confounded, or spurious.

The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model.

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Fritz, Matthew S; Kenny, David A; MacKinnon, David P

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator-to-outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. To explore the combined effect of measurement error and omitted confounders in the same model, the effect of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect.

The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model

Science.gov (United States)

Fritz, Matthew S.; Kenny, David A.; MacKinnon, David P.

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903

Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

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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. © 2016 The British Psychological Society.

Adipose tissue Fatty Acid patterns and changes in antrhropometry

DEFF Research Database (Denmark)

Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

2011-01-01

Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...... in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men...

Cryptic confounding compounds: A brief consideration of the influences of anthropogenic contaminants on courtship and mating behavior

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Blocker, Tomica D.; Ophir, Alexander G.

2012-01-01

Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals, and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have, and promote caution when interpreting results where the potential for cryptic affects are possible. PMID:24244068

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

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Liu, Tianyi; Nie, Xiaolu; Wu, Zehao; Zhang, Ying; Feng, Guoshuang; Cai, Siyu; Lv, Yaqi; Peng, Xiaoxia

2017-12-29

Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind

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

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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 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. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of Bayesian and Monte Carlo sensitivity analysis for unmeasured confounding.

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McCandless, Lawrence C; Gustafson, Paul

2017-08-15

Bias from unmeasured confounding is a persistent concern in observational studies, and sensitivity analysis has been proposed as a solution. In the recent years, probabilistic sensitivity analysis using either Monte Carlo sensitivity analysis (MCSA) or Bayesian sensitivity analysis (BSA) has emerged as a practical analytic strategy when there are multiple bias parameters inputs. BSA uses Bayes theorem to formally combine evidence from the prior distribution and the data. In contrast, MCSA samples bias parameters directly from the prior distribution. Intuitively, one would think that BSA and MCSA ought to give similar results. Both methods use similar models and the same (prior) probability distributions for the bias parameters. In this paper, we illustrate the surprising finding that BSA and MCSA can give very different results. Specifically, we demonstrate that MCSA can give inaccurate uncertainty assessments (e.g. 95% intervals) that do not reflect the data's influence on uncertainty about unmeasured confounding. Using a data example from epidemiology and simulation studies, we show that certain combinations of data and prior distributions can result in dramatic prior-to-posterior changes in uncertainty about the bias parameters. This occurs because the application of Bayes theorem in a non-identifiable model can sometimes rule out certain patterns of unmeasured confounding that are not compatible with the data. Consequently, the MCSA approach may give 95% intervals that are either too wide or too narrow and that do not have 95% frequentist coverage probability. Based on our findings, we recommend that analysts use BSA for probabilistic sensitivity analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

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Walz, Johanna M; Boehringer, Daniel; Deissler, Heidrun L; Faerber, Lothar; Goepfert, Jens C; Heiduschka, Peter; Kleeberger, Susannah M; Klettner, Alexa; Krohne, Tim U; Schneiderhan-Marra, Nicole; Ziemssen, Focke; Stahl, Andreas

2016-01-01

Vascular endothelial growth factor-A (VEGF-A) is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements. Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center) twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD), cannula (butterfly vs. neonatal), type of centrifuge (swing-out vs. fixed-angle), time before and after centrifugation, filling level (completely filled vs. half-filled tubes) and analyzing method (ELISA vs. multiplex bead array). Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model. The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes. VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

Directory of Open Access Journals (Sweden)

Johanna M Walz

Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

Effort-reward imbalance at work and self-rated health of Las Vegas hotel room cleaners.

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Krause, Niklas; Rugulies, Reiner; Maslach, Christina

2010-04-01

This study investigates the relationship between effort-reward-imbalance (ERI) at work and self-rated health (SF-36) among 941 Las Vegas hotel room cleaners (99% female, 84% immigrant). Logistic regression models adjust for age, health behaviors, physical workload and other potential confounders. 50% reported ERI and 60% poor or fair general health. Significant associations were found between ERI and all SF-36 health measures. Workers in the upper quartile of the efforts/rewards ratio were 2-5 times more likely to experience poor or fair general health, low physical function, high levels of pain, fatigue, and role limitations due to physical and mental health problems. The cross-sectional design limits causal interpretation of these associations. However, the development of interventions to reduce ERI and to improve general health among room cleaners deserves high priority considering that both high ERI and low self-rated health have predicted chronic diseases and mortality in prospective studies. (c) 2009 Wiley-Liss, Inc.

Multisample adjusted U-statistics that account for confounding covariates.

Science.gov (United States)

Satten, Glen A; Kong, Maiying; Datta, Somnath

2018-06-19

Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.

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

Science.gov (United States)

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental regulation of valvulogenesis:implications for tissue engineering

NARCIS (Netherlands)

Riem Vis, P.W.; Kluin, J.; Sluijter, J.P.G.; Herwerden, van L.A.; Bouten, C.V.C.

2011-01-01

Ongoing research efforts aim at improving the creation of tissue-engineered heart valves for in vivo systemic application. Hence, in vitro studies concentrate on optimising culture protocols incorporating biological as well as biophysical stimuli for tissue development. Important lessons can be

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies

DEFF Research Database (Denmark)

Jackson, D.; White, I.; Kostis, J.B.

2009-01-01

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an...

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies

NARCIS (Netherlands)

Jackson, D.; White, I.; Kostis, J.B.; Wilson, A.C.; Folsom, A.R.; Feskens, E.J.M.

2009-01-01

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an

The Effort Paradox: Effort Is Both Costly and Valued.

Science.gov (United States)

Inzlicht, Michael; Shenhav, Amitai; Olivola, Christopher Y

2018-04-01

According to prominent models in cognitive psychology, neuroscience, and economics, effort (be it physical or mental) is costly: when given a choice, humans and non-human animals alike tend to avoid effort. Here, we suggest that the opposite is also true and review extensive evidence that effort can also add value. Not only can the same outcomes be more rewarding if we apply more (not less) effort, sometimes we select options precisely because they require effort. Given the increasing recognition of effort's role in motivation, cognitive control, and value-based decision-making, considering this neglected side of effort will not only improve formal computational models, but also provide clues about how to promote sustained mental effort across time. Copyright © 2018 Elsevier Ltd. All rights reserved.

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

Science.gov (United States)

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.

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors

International Nuclear Information System (INIS)

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-01-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors.

Science.gov (United States)

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-02-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations.

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables

DEFF Research Database (Denmark)

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær

2016-01-01

STUDY DESIGN: Cross-sectional analyses on a consecutive, prospective cohort. OBJECTIVE: To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible...... to confounding. However, age group and aetiology had individual significant effects. CONCLUSION: The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained...... confounding variables. SUMMARY OF BACKGROUND DATA: The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal...

Overview of potential procedural and participant-related confounds for neuroimaging of the resting state

Science.gov (United States)

Duncan, Niall W.; Northoff, Georg

2013-01-01

Studies of intrinsic brain activity in the resting state have become increasingly common. A productive discussion of what analysis methods are appropriate, of the importance of physiologic correction and of the potential interpretations of results has been ongoing. However, less attention has been paid to factors other than physiologic noise that may confound resting-state experiments. These range from straightforward factors, such as ensuring that participants are all instructed in the same manner, to more obscure participant-related factors, such as body weight. We provide an overview of such potentially confounding factors, along with some suggested approaches for minimizing their impact. A particular theme that emerges from the overview is the range of systematic differences between types of study groups (e.g., between patients and controls) that may influence resting-state study results. PMID:22964258

Prostate-Specific Antigen Velocity Before and After Elimination of Factors That Can Confound the Prostate-Specific Antigen Level

International Nuclear Information System (INIS)

Park, Jessica J.; Chen, Ming-Hui; Loffredo, Marian; D’Amico, Anthony V.

2012-01-01

Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y. Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders. Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09). Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels.

Everything that you have ever been told about assessment center ratings is confounded.

Science.gov (United States)

Jackson, Duncan J R; Michaelides, George; Dewberry, Chris; Kim, Young-Jae

2016-07-01

Despite a substantial research literature on the influence of dimensions and exercises in assessment centers (ACs), the relative impact of these 2 sources of variance continues to raise uncertainties because of confounding. With confounded effects, it is not possible to establish the degree to which any 1 effect, including those related to exercises and dimensions, influences AC ratings. In the current study (N = 698) we used Bayesian generalizability theory to unconfound all of the possible effects contributing to variance in AC ratings. Our results show that ≤1.11% of the variance in AC ratings was directly attributable to behavioral dimensions, suggesting that dimension-related effects have no practical impact on the reliability of ACs. Even when taking aggregation level into consideration, effects related to general performance and exercises accounted for almost all of the reliable variance in AC ratings. The implications of these findings for recent dimension- and exercise-based perspectives on ACs are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Adiposity signals predict vocal effort in Alston's singing mice.

Science.gov (United States)

Burkhard, Tracy T; Westwick, Rebecca R; Phelps, Steven M

2018-04-25

Advertisement displays often seem extravagant and expensive, and are thought to depend on the body condition of a signaller. Nevertheless, we know little about how signallers adjust effort based on condition, and few studies find a strong relationship between natural variation in condition and display. To examine the relationship between body condition and signal elaboration more fully, we characterized physiological condition and acoustic displays in a wild rodent with elaborate vocalizations, Alston's singing mouse, Scotinomys teguina We found two major axes of variation in condition-one defined by short-term fluctuations in caloric nutrients, and a second by longer-term variation in adiposity. Among acoustic parameters, song effort was characterized by high rates of display and longer songs. Song effort was highly correlated with measures of adiposity. We found that leptin was a particularly strong predictor of display effort. Leptin is known to influence investment in other costly traits, such as immune function and reproduction. Plasma hormone levels convey somatic state to a variety of tissues, and may govern trait investment across vertebrates. Such measures offer new insights into how animals translate body condition into behavioural and life-history decisions. © 2018 The Author(s).

Engineering complex orthopaedic tissues via strategic biomimicry.

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

2015-03-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

2014-01-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Assessing Mediation Using Marginal Structural Models in the Presence of Confounding and Moderation

Science.gov (United States)

Coffman, Donna L.; Zhong, Wei

2012-01-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW…

The Application of Tissue Engineering Procedures to Repair the Larynx

Science.gov (United States)

Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

2006-01-01

The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer.

Science.gov (United States)

Di Sebastiano, Katie M; Mourtzakis, Marina

2012-10-01

The majority of cancer patients experience some form of body composition change during the disease trajectory. For example, breast cancer patients undergoing chemotherapy and prostate cancer patients undergoing androgen deprivation therapy gain fat and lose skeletal muscle, which are associated with increased risk of cancer recurrence and clinical comorbidities. In contrast, advanced cancer patients, such as lung and colorectal cancer patients, experience symptoms of cancer cachexia (accelerated loss of skeletal muscle with or without adipose tissue loss), which are associated with decreased treatment response and poorer survival rates in advanced cancers. The heterogeneity of body composition features and their diverse implications across different cancer populations supports the need for accurate quantification of muscle and adipose tissue. Use of appropriate body composition modalities will facilitate an understanding of the complex relationship between body composition characteristics and clinical outcomes. This will ultimately support the development and evaluation of future therapeutic interventions that aim to counter muscle loss and fat gain in cancer populations. Despite the various metabolic complications that may confound the accurate body composition measurement in cancer patients (i.e., dehydration may confound lean tissue measurement), there are no guidelines for selecting the most appropriate modalities to make these measurements. In this review we outline specific considerations for choosing the most optimal approaches of lean and adipose tissue measurements among different cancer populations. Anthropometric measures, bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging will be discussed.

Discriminating between Interstitial and Circulating Leukocytes in Tissues of the Murine Oral Mucosa Avoiding Nasal-Associated Lymphoid Tissue Contamination.

Science.gov (United States)

Bittner-Eddy, Peter D; Fischer, Lori A; Tu, Andy A; Allman, Daniel A; Costalonga, Massimo

2017-01-01

Periodontitis is a chronic inflammatory response to a microbial biofilm that destroys bone and soft tissues supporting the teeth. Murine models of periodontitis based on Porphyromonas gingivalis ( Pg ) colonization have shown that extravasation of leukocytes into oral tissue is critical to driving alveolar bone destruction. Identifying interstitial leukocytes is key to understanding the immunopathogenesis of periodontitis. Here, we describe a robust flow cytometry assay based on intravenous FITC-conjugated anti-mouse CD45 mAb that distinguishes interstitial leukocytes in the oral mucosa of mice from those circulating within the vasculature or in post-dissection contaminating blood. Unaccounted circulating leukocytes skewed the relative frequency of B cells and granulocytes and inflated the numbers of all leukocyte cell types. We also describe a dissection technique that avoids contamination of oral mucosal tissues with nasal-associated lymphoid tissues (NALT), a B cell rich organ that can inflate leukocyte numbers at least 10-fold and skew the assessment of interstitial CD4 T cell phenotypes. Unlike circulating CD4 T cells, interstitial CD4 T cells were almost exclusively antigen-experienced cells (CD44 hi ). We report for the first time the presence of antigen-experienced Pg -specific CD4 T cells in NALT following oral feeding of mice with Pg . This new combined flow cytometry and dissection approach allows identification of leukocytes infiltrating the connective tissues of the murine oral mucosa and avoids confounding analyses of leukocytes not recruited to inflamed oral mucosal tissues in disease conditions like periodontitis, candidiasis, or sialadenitis.

Confounding Underlies the Apparent Month of Birth Effect in Multiple Sclerosis

OpenAIRE

Fiddes, Barnaby; Wason, James; Kemppinen, Anu; Ban, Maria; Compston, Alastair; Sawcer, Stephen

2013-01-01

Objective Several groups have reported apparent association between month of birth and multiple sclerosis. We sought to test the extent to which such studies might be confounded by extraneous variables such as year and place of birth. Methods Using national birth statistics from 2 continents, we assessed the evidence for seasonal variations in birth rate and tested the extent to which these are subject to regional and temporal variation. We then established the age and regional origin distrib...

The Association between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Complaints

NARCIS (Netherlands)

van der Meer, Hedwig A.; Speksnijder, Caroline M.; Engelbert, Raoul; Lobbezoo, Frank; Nijhuis – van der Sanden, Maria W G; Visscher, Corine M.

OBJECTIVES:: The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. METHODS:: Several subtypes of headaches were

Test anxiety in medical school is unrelated to academic performance but correlates with an effort/reward imbalance.

Science.gov (United States)

Hahn, Henry; Kropp, Peter; Kirschstein, Timo; Rücker, Gernot; Müller-Hilke, Brigitte

2017-01-01

During their early years at medical school, students repeatedly criticize their workload, time constraints and test associated stress. At the same time, depressiveness and anxiety among first and second year medical students are on the rise. We therefore hypothesized that test anxiety may be related to depressiveness and considered cognitive and academic performances as confounders for the former and psychosocial distress for the latter. A whole class of 200 second year students was invited to participate in the study. Anxiety as a trait, depressiveness, crystallized intelligence, verbal fluency and psychosocial distress were assessed using validated tests and questionnaires. Acute state anxiety and sympathetic stress parameters were measured in real life situations immediately before an oral and a written exam and paired tests were used to compare the individual anxieties at the various time points. Previous academic performances were self-reported, the results of the impending exams were monitored. Finally, correlations were performed to test for interrelatedness between academic performances and the various personal, cognitive and psychosocial factors. Acute test anxiety did not correlate with depressiveness nor did it correlate with previous nor impending academic performances nor any of the expected confounders on academic performance. However both, depressiveness and test anxiety strongly correlated with the perceived imbalance between efforts spent and rewards received. Moreover, anxiety as a trait not only correlated with acute state anxiety before an exam but was also significantly correlated to the feeling of over-commitment. Depressiveness during the early years of medical school seems unrelated to test anxiety and academic performance. Instead, it strongly correlated with the psychosocial distress emanating from attending medical school and points at a perceived imbalance between efforts spent and rewards received.

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

Science.gov (United States)

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

2017-12-01

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

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms

NARCIS (Netherlands)

Meer, H.A. van der; Speksnijder, C.M.; Engelbert, R.H.; Lobbezoo, F.; Nijhuis-Van der Sanden, M.W.G.; Visscher, C.M.

2017-01-01

OBJECTIVES: The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. MATERIALS AND METHODS: Several subtypes of headaches

Effort-Reward Imbalance at Work and Incident Coronary Heart Disease: A Multicohort Study of 90,164 Individuals.

Science.gov (United States)

Dragano, Nico; Siegrist, Johannes; Nyberg, Solja T; Lunau, Thorsten; Fransson, Eleonor I; Alfredsson, Lars; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Erbel, Raimund; Fahlén, Göran; Goldberg, Marcel; Hamer, Mark; Heikkilä, Katriina; Jöckel, Karl-Heinz; Knutsson, Anders; Madsen, Ida E H; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Schupp, Jürgen; Singh-Manoux, Archana; Steptoe, Andrew; Theorell, Töres; Vahtera, Jussi; Westerholm, Peter J M; Westerlund, Hugo; Virtanen, Marianna; Zins, Marie; Batty, G David; Kivimäki, Mika

2017-07-01

Epidemiologic evidence for work stress as a risk factor for coronary heart disease is mostly based on a single measure of stressful work known as job strain, a combination of high demands and low job control. We examined whether a complementary stress measure that assesses an imbalance between efforts spent at work and rewards received predicted coronary heart disease. This multicohort study (the "IPD-Work" consortium) was based on harmonized individual-level data from 11 European prospective cohort studies. Stressful work in 90,164 men and women without coronary heart disease at baseline was assessed by validated effort-reward imbalance and job strain questionnaires. We defined incident coronary heart disease as the first nonfatal myocardial infarction or coronary death. Study-specific estimates were pooled by random effects meta-analysis. At baseline, 31.7% of study members reported effort-reward imbalance at work and 15.9% reported job strain. During a mean follow-up of 9.8 years, 1,078 coronary events were recorded. After adjustment for potential confounders, a hazard ratio of 1.16 (95% confidence interval, 1.00-1.35) was observed for effort-reward imbalance compared with no imbalance. The hazard ratio was 1.16 (1.01-1.34) for having either effort-reward imbalance or job strain and 1.41 (1.12-1.76) for having both these stressors compared to having neither effort-reward imbalance nor job strain. Individuals with effort-reward imbalance at work have an increased risk of coronary heart disease, and this appears to be independent of job strain experienced. These findings support expanding focus beyond just job strain in future research on work stress.

When can efforts to control nuisance and invasive species backfire?

Science.gov (United States)

Zipkin, Elise F; Kraft, Clifford E; Cooch, Evan G; Sullivan, Patrick J

2009-09-01

Population control through harvest has the potential to reduce the abundance of nuisance and invasive species. However, demographic structure and density-dependent processes can confound removal efforts and lead to undesirable consequences, such as overcompensation (an increase in abundance in response to harvest) and instability (population cycling or chaos). Recent empirical studies have demonstrated the potential for increased mortality (such as that caused by harvest) to lead to overcompensation and instability in plant, insect, and fish populations. We developed a general population model with juvenile and adult stages to help determine the conditions under which control harvest efforts can produce unintended outcomes. Analytical and simulation analyses of the model demonstrated that the potential for overcompensation as a result of harvest was significant for species with high fecundity, even when annual stage-specific survivorship values were fairly low. Population instability as a result of harvest occurred less frequently and was only possible with harvest strategies that targeted adults when both fecundity and adult survivorship were high. We considered these results in conjunction with current literature on nuisance and invasive species to propose general guidelines for assessing the risks associated with control harvest based on life history characteristics of target populations. Our results suggest that species with high per capita fecundity (over discrete breeding periods), short juvenile stages, and fairly constant survivorship rates are most likely to respond undesirably to harvest. It is difficult to determine the extent to which overcompensation and instability could occur during real-world removal efforts, and more empirical removal studies should be undertaken to evaluate population-level responses to control harvests. Nevertheless, our results identify key issues that have been seldom acknowledged and are potentially generic across taxa.

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

Science.gov (United States)

Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

Science.gov (United States)

Sitterle, Valerie B.; Roberts, David W.

2003-06-01

The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

'Mechanical restraint-confounders, risk, alliance score': testing the clinical validity of a new risk assessment instrument.

Science.gov (United States)

Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise; Alkier Gildberg, Frederik

2017-08-01

Unstructured risk assessment, as well as confounders (underlying reasons for the patient's risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients. To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical restraint. The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. The three sub-scales (Confounders, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. MR-CRAS contains 18 clinically valid items, and the instrument can be used to support the clinical decision-making regarding the possibility of releasing the patient from mechanical restraint. The present three studies have clinically validated a short MR-CRAS scale that is currently being psychometrically tested in a larger study.

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

Science.gov (United States)

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 interpersonal discrimination remained a positive predictor of depressive symptoms (beta: 0.1176, p 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

Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort

Science.gov (United States)

Kouvonen, A; Kivimäki, M; Elovainio, M; Pentti, J; Linna, A; Virtanen, M; Vahtera, J

2006-01-01

Objectives To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle. Methods Cross sectional data from the ongoing Finnish Public Sector Study related to 30 433 women and 7718 men aged 17–64 were used (n = 35 918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as sedentary lifestyle. High individual level ERI was associated with a higher likelihood of sedentary lifestyle both among women (odds ratio (OR) = 1.08, 95% CI 1.01 to 1.16) and men (OR = 1.17, 95% CI 1.02 to 1.33). These associations were not explained by relevant confounders and they were also independent of work unit level job strain measured as a ratio of job demands and control. Conclusions A mismatch between high occupational effort spent and low reward received in turn seems to be associated with an increased risk of sedentary lifestyle, although this association is relatively weak. PMID:16497854

Medical versus surgical abortion: comparing satisfaction and potential confounders in a partly randomized study

DEFF Research Database (Denmark)

Rørbye, Christina; Nørgaard, Mogens; Nilas, Lisbeth

2005-01-01

BACKGROUND: The aim of the study was to compare satisfaction with medical and surgical abortion and to identify potential confounders affecting satisfaction. METHODS: 1033 women with gestational age (GA) < or = 63 days had either a medical (600 mg mifepristone followed by 1 mg gemeprost) or a sur...

Effort--reward imbalance and medically certified absence for mental health problems: a prospective study of white-collar workers.

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Ndjaboué, R; Brisson, C; Vézina, M; Blanchette, C; Bourbonnais, R

2014-01-01

Little is known about the effects of psychosocial work factors on objectively assessed mental health problems leading to medically certified absence. Only one study has evaluated the prospective effects of effort-reward imbalance (ERI) at work with regards to this outcome. The present study aimed to evaluate the effects of ERI on the incidence of medically certified absence for mental health problems. The study included 2086 white-collar workers (63.3% women) employed in public organisations in Quebec city. Participants were followed over a 9-year period. Medical absences from work were collected from employers' files and psychosocial factors were measured using the ERI questionnaire. Cox regression models were used to estimate the incidence of certified sickness absence due to mental health problems that lasted 5 workdays or more, while controlling for confounders. Workers exposed to ERI had a higher risk of a first spell of medically certified absence for mental health problems (HR=1.38, 95% CI 1.08 to 1.76) compared with unexposed workers. Low reward was significantly associated with a high risk among men (HR=2.80, 95% CI 1.34 to 5.89) but not in women. (HR=1.24, 95% CI 0.90 to 1.73). Effort at work had no effect on certified absence. All these effects were adjusted for potential confounders. ERI and low reward at work were prospectively associated with medically certified absence for mental health problems. These effects seem to differ by gender. Primary prevention that is aimed at reducing these stressors should be considered to help reduce the incidence of such severe mental health problems.

Consequences of exposure measurement error for confounder identification in environmental epidemiology

DEFF Research Database (Denmark)

Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe

2003-01-01

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true...... exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse...

Sensitivity analysis for unobserved confounding of direct and indirect effects using uncertainty intervals.

Science.gov (United States)

Lindmark, Anita; de Luna, Xavier; Eriksson, Marie

2018-05-10

To estimate direct and indirect effects of an exposure on an outcome from observed data, strong assumptions about unconfoundedness are required. Since these assumptions cannot be tested using the observed data, a mediation analysis should always be accompanied by a sensitivity analysis of the resulting estimates. In this article, we propose a sensitivity analysis method for parametric estimation of direct and indirect effects when the exposure, mediator, and outcome are all binary. The sensitivity parameters consist of the correlations between the error terms of the exposure, mediator, and outcome models. These correlations are incorporated into the estimation of the model parameters and identification sets are then obtained for the direct and indirect effects for a range of plausible correlation values. We take the sampling variability into account through the construction of uncertainty intervals. The proposed method is able to assess sensitivity to both mediator-outcome confounding and confounding involving the exposure. To illustrate the method, we apply it to a mediation study based on the data from the Swedish Stroke Register (Riksstroke). An R package that implements the proposed method is available. Copyright © 2018 John Wiley & Sons, Ltd.

Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy

Energy Technology Data Exchange (ETDEWEB)

Skuladottir, Margret; Ramel, Alfons [Faculty of Food Science and Nutrition, University of Iceland, Reykjavik (Iceland); Unit for Nutrition Research, Landspitali National University Hospital, Reykjavik (Iceland); Rytter, Dorte [Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus (Denmark); Haug, Line Småstuen; Sabaredzovic, Azemira [Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo (Norway); Bech, Bodil Hammer [Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus (Denmark); Henriksen, Tine Brink [Pediatric Department, Aarhus University Hospital, Aarhus (Denmark); Olsen, Sjurdur F. [Center for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen (Denmark); Department of Nutrition, Harvard School of Public Health, Boston, MA (United States); Halldorsson, Thorhallur I., E-mail: tih@hi.is [Faculty of Food Science and Nutrition, University of Iceland, Reykjavik (Iceland); Unit for Nutrition Research, Landspitali National University Hospital, Reykjavik (Iceland); Center for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen (Denmark)

2015-11-15

Background: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. Objective: To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. Methods: 854 Danish women who gave birth in 1988–89 and provided a blood sample and reported their diet in week 30 of gestation. Results: Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. Conclusion: In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol. - Highlights: • PFOS and PFOA have consistently been linked with raised serum cholesterol • Clinical relevance remains uncertain and confounding by diet has been suggested • The aim of this study was to address these issues in

Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy

International Nuclear Information System (INIS)

Skuladottir, Margret; Ramel, Alfons; Rytter, Dorte; Haug, Line Småstuen; Sabaredzovic, Azemira; Bech, Bodil Hammer; Henriksen, Tine Brink; Olsen, Sjurdur F.; Halldorsson, Thorhallur I.

2015-01-01

Background: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. Objective: To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. Methods: 854 Danish women who gave birth in 1988–89 and provided a blood sample and reported their diet in week 30 of gestation. Results: Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. Conclusion: In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol. - Highlights: • PFOS and PFOA have consistently been linked with raised serum cholesterol • Clinical relevance remains uncertain and confounding by diet has been suggested • The aim of this study was to address these issues in

Mesenchymal Stem Cells in Tissue Repair

Directory of Open Access Journals (Sweden)

Amy M DiMarino

2013-09-01

Full Text Available The advent of mesenchymal stem cell (MSC based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC and quality assurance (QA are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

Clinical and evoked pain, personality traits, and emotional states: can familial confounding explain the associations?

Science.gov (United States)

Strachan, Eric; Poeschla, Brian; Dansie, Elizabeth; Succop, Annemarie; Chopko, Laura; Afari, Niloofar

2015-01-01

Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2014-01-01

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

Role of environmental confounding in the association between FKBP5 and first-episode psychosis

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Olesya eAjnakina

2014-07-01

Full Text Available 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 variable distribution 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: 291 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 modelled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire and parental separation (Childhood Experience of Care and Abuse Questionnaire were modelled 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.Conclusions: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on the other etiological factors involved. This finding requires further validation in other large independent cohorts. Potentially this work could have translational implications, as the ability to discriminate between genetic etiologies, based on a case-by-case understanding of exposure history would confer an important clinical advantage that would benefit the delivery of personalizable treatment

phMRI: methodological considerations for mitigating potential confounding factors

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Julius H Bourke

2015-05-01

Full Text Available Pharmacological Magnetic Resonance Imaging (phMRI is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g. clinical neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome.

A New Paradigm for Tissue Diagnostics: Tools and Techniques to Standardize Tissue Collection, Transport, and Fixation.

Science.gov (United States)

Bauer, Daniel R; Otter, Michael; Chafin, David R

2018-01-01

Studying and developing preanalytical tools and technologies for the purpose of obtaining high-quality samples for histological assays is a growing field. Currently, there does not exist a standard practice for collecting, fixing, and monitoring these precious samples. There has been some advancement in standardizing collection for the highest profile tumor types, such as breast, where HER2 testing drives therapeutic decisions. This review examines the area of tissue collection, transport, and monitoring of formalin diffusion and details a prototype system that could be used to help standardize tissue collection efforts. We have surveyed recent primary literature sources and conducted several site visits to understand the most error-prone processes in histology laboratories. This effort identified errors that resulted from sample collection techniques and subsequent transport delays from the operating room (OR) to the histology laboratories. We have therefore devised a prototype sample collection and transport concept. The system consists of a custom data logger and cold transport box and takes advantage of a novel cold + warm (named 2 + 2) fixation method. This review highlights the beneficial aspects of standardizing tissue collection, fixation, and monitoring. In addition, a prototype system is introduced that could help standardize these processes and is compatible with use directly in the OR and from remote sites.

Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

International Nuclear Information System (INIS)

Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S.; Donard, O.F.X.; Krupp, Eva A.; Point, David; Horvat, Milena; Gibicar, D.; Kljakovic-Gaspic, Z.; Porter, Barbara J.; Schantz, Michele M.

2007-01-01

This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

Energy Technology Data Exchange (ETDEWEB)

Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S. [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); Donard, O.F.X.; Krupp, Eva A. [LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Point, David [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Horvat, Milena; Gibicar, D. [Jozef Stefan Institute, Ljubljana (Slovenia); Kljakovic-Gaspic, Z. [Jozef Stefan Institute, Ljubljana (Slovenia); Institute for Medical Research and Occupational Health, Zagreb (Croatia); Porter, Barbara J.; Schantz, Michele M. [National Institute of Standards and Technology (NIST), Analytical Chemistry Division, Gaithersburg, MD (United States)

2007-04-15

This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

Growing tissues in real and simulated microgravity: new methods for tissue engineering.

Science.gov (United States)

Grimm, Daniela; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E; Infanger, Manfred; Bauer, Johann

2014-12-01

Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

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

OpenAIRE

Hunte, Haslyn ER; King, Katherine; Hicken, Margaret; Lee, Hedwig; Lewis, Ten? T

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 ...

Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort.

Science.gov (United States)

Kouvonen, A; Kivimäki, M; Elovainio, M; Pentti, J; Linna, A; Virtanen, M; Vahtera, J

2006-06-01

To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle. Cross sectional data from the ongoing Finnish Public Sector Study related to 30,433 women and 7718 men aged 17-64 were used (n = 35,918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as work unit level predictors in the models. Adjustments were made for age, marital status, occupational status, job contract, smoking, and heavy drinking. Twenty five per cent of women and 27% of men had a sedentary lifestyle. High individual level ERI was associated with a higher likelihood of sedentary lifestyle both among women (odds ratio (OR) = 1.08, 95% CI 1.01 to 1.16) and men (OR = 1.17, 95% CI 1.02 to 1.33). These associations were not explained by relevant confounders and they were also independent of work unit level job strain measured as a ratio of job demands and control. A mismatch between high occupational effort spent and low reward received in turn seems to be associated with an increased risk of sedentary lifestyle, although this association is relatively weak.

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

Science.gov (United States)

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

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

Directory of Open Access Journals (Sweden)

Mashhood Ahmed Sheikh

2017-08-01

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

Effort-reward imbalance at work and the risk of antidepressant treatment in the Danish workforce

DEFF Research Database (Denmark)

Nielsen, Maj Britt D.; Madsen, Ida E. H.; Aust, Birgit

2016-01-01

Background: Previous studies have shown that high effort-reward imbalance (ERI) at work is a risk factor for the onset of self-reported depressive symptoms. In this study, we examined whether ERI predicts risk of treatment with antidepressant medication in a representative sample of the Danish...... workforce. Methods: We linked survey data on ERI and covariates of 4541 participants from the Danish Work Environment Cohort Study 2000 with the Danish National Prescription Registry that includes all legally purchased prescription drugs at pharmacies in Denmark since 1995. Participants with a history....... Results: A total of 309 (6.8%) participants started antidepressant treatment during follow-up. Exposure to ERI at baseline was not related to risk of antidepressant treatment (hazard ratio: 0.91, 95% CI=0.81–1.03 after adjustment for potential confounders). Limitations: The use of antidepressant treatment...

Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors

Science.gov (United States)

Schiekirka, Sarah; Feufel, Markus A.; Herrmann-Lingen, Christoph; Raupach, Tobias

2015-01-01

Background and objective: Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors. Methods: We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the “grey literature”. Results are presented as a narrative review. Results: We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards. Conclusion: The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors. PMID:26421003

Nanotopography-guided tissue engineering and regenerative medicine☆

Science.gov (United States)

Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S.; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

2017-01-01

Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end. PMID:22921841

The growth of tissue engineering.

Science.gov (United States)

Lysaght, M J; Reyes, J

2001-10-01

This report draws upon data from a variety of sources to estimate the size, scope, and growth rate of the contemporary tissue engineering enterprise. At the beginning of 2001, tissue engineering research and development was being pursued by 3,300 scientists and support staff in more than 70 startup companies or business units with a combined annual expenditure of over $600 million. Spending by tissue engineering firms has been growing at a compound annual rate of 16%, and the aggregate investment since 1990 now exceeds $3.5 billion. At the beginning of 2001, the net capital value of the 16 publicly traded tissue engineering startups had reached $2.6 billion. Firms focusing on structural applications (skin, cartilage, bone, cardiac prosthesis, and the like) comprise the fastest growing segment. In contrast, efforts in biohybrid organs and other metabolic applications have contracted over the past few years. The number of companies involved in stem cells and regenerative medicine is rapidly increasing, and this area represents the most likely nidus of future growth for tissue engineering. A notable recent trend has been the emergence of a strong commercial activity in tissue engineering outside the United States, with at least 16 European or Australian companies (22% of total) now active.

Neighbourhood social and built environment factors and falls in community-dwelling canadian older adults: A validation study and exploration of structural confounding

Directory of Open Access Journals (Sweden)

Afshin Vafaei

2016-12-01

Full Text Available Older persons are vulnerable to the ill effects of their social and built environment due to age-related limitations in mobility and bio-psychological vulnerability. Falls are common in older adults and result from complex interactions between individual, social, and contextual determinants. We addressed two methodological issues of neighbourhood-health and social epidemiological studies in this analysis: (1 validity of measures of neighbourhood contexts, and (2 structural confounding resulting from social sorting mechanisms. Baseline data from International Mobility in Aging Study were used. Samples included community-dwelling Canadians older than 65 living in Kingston (Ontario and St-Hyacinthe (Quebec. We performed factor analysis and ecometric analysis to assess the validity of measures of neighbourhood social capital, socioeconomic status, and the built environment and stratified tabular analyses to explore structural confounding. The scales all demonstrated good psychometric and ecometric properties. There was an evidence of the existence of structural confounding in this sample of Canadian older adults as some combinations of strata for the three neighbourhood measures had no population. This limits causal inference in studying relationships between neighbourhood factors and falls and should be taken into account in aetiological aging research. Keywords: Ecometric analysis, Falls, Social and built environment, Neighbourhoods, Older adults, Social Capital, Structural confounding, Validity

Correlated responses in tissue weights measured in vivo by computer tomography in Dorset Down sheep selected for lean tissue growth

International Nuclear Information System (INIS)

Nsoso, S.J.; Young, M.J.; Beatson, P.R.

2003-01-01

The aim of this study was to estimate correlated responses in lean, fat and bone weights in vivo in Dorset Down sheep selected for lean tissue growth. Over the period 1986-1992 inclusive, the lean tissue growth line had been selected using two economic indices for an increased aggregate breeding value incorporating predicted lean and fat weights with positive and negative economic weightings, respectively. The control line was selected for no change in lean tissue growth each year. Animals were born and run on pasture all year round. X-ray computer tomography was used to estimate the weights of lean, fat and bone in vivo in the 1994-born sheep, aged 265-274 days and selected randomly into 12 rams and 12 ewes from the selected line and 10 rams and 9 ewes from the control line. The lean tissue growth line had significantly greater responses in lean weight (+0.65 + 0.10 kg) and lean percentage (+1.19 + 0.17%) and significantly lesser fat weight (-0.36 + 0.08 kg) and fat percentage (-1.88 + 0.20%) compared to the control line. There was a significant increase in bone weight (+0.27 + 0.03 kg) and bone percentage (+0.69 + 0.09%) in the lean tissue growth line compared to the control line. Responses differed significantly between sexes of the lean tissue growth line, rams having a greater response in weight of lean (+1.22 + 0.20 vs. +0.08 + 0.22 kg) and bone (+0.45 + 0.06 vs. +0.09 + 0.07 kg), and a lesser response in weight of fat (-0.03 + 0.15 vs. -0.70 + 0.16 kg) than the ewes. Selection led to significant changes in lean (increase) and fat weights (decrease), and bone weight increased. Although responses in the lean tissue growth line differed significantly between sexes, there were confounding factors due to differences in management and lack of comparison at equal stage of development. Therefore, to assess real genetic differences further studies should be conducted taking these factors into consideration

Time-Dependent Confounding in the Study of the Effects of Regular Physical Activity in Chronic Obstructive Pulmonary Disease: An Application of the Marginal Structural Model

DEFF Research Database (Denmark)

Garcia-Aymerich, J.; Lange, P.; Serra, I.

2008-01-01

this type of confounding. We sought to assess the presence of time-dependent confounding in the association between physical activity and COPD development and course by comparing risk estimates between standard statistical methods and MSMs. METHODS: By using the population-based cohort Copenhagen City Heart...

Damage Models for Soft Tissues: A Survey.

Science.gov (United States)

Li, Wenguang

Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.

Electrospun nanofiber scaffolds: engineering soft tissues

International Nuclear Information System (INIS)

Kumbar, S G; Nukavarapu, S P; Laurencin, C T; James, R

2008-01-01

Electrospinning has emerged to be a simple, elegant and scalable technique to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetics have been successfully electrospun into nanofiber matrices. Physiochemical properties of nanofiber matrices can be controlled by manipulating electrospinning parameters to meet the requirements of a specific application. Such efforts include the fabrication of fiber matrices containing nanofibers, microfibers, combination of nano-microfibers and also different fiber orientation/alignments. Polymeric nanofiber matrices have been extensively investigated for diversified uses such as filtration, barrier fabrics, wipes, personal care, biomedical and pharmaceutical applications. Recently electrospun nanofiber matrices have gained a lot of attention, and are being explored as scaffolds in tissue engineering due to their properties that can modulate cellular behavior. Electrospun nanofiber matrices show morphological similarities to the natural extra-cellular matrix (ECM), characterized by ultrafine continuous fibers, high surface-to-volume ratio, high porosity and variable pore-size distribution. Efforts have been made to modify nanofiber surfaces with several bioactive molecules to provide cells with the necessary chemical cues and a more in vivo like environment. The current paper provides an overlook on such efforts in designing nanofiber matrices as scaffolds in the regeneration of various soft tissues including skin, blood vessel, tendon/ligament, cardiac patch, nerve and skeletal muscle

Electrospun nanofiber scaffolds: engineering soft tissues

Energy Technology Data Exchange (ETDEWEB)

Kumbar, S G; Nukavarapu, S P; Laurencin, C T [Department of Orthopaedic Surgery, University of Virginia, VA 22908 (United States); James, R [Department of Biomedical Engineering, University of Virginia, VA 22908 (United States)], E-mail: laurencin@virginia.edu

2008-09-01

Electrospinning has emerged to be a simple, elegant and scalable technique to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetics have been successfully electrospun into nanofiber matrices. Physiochemical properties of nanofiber matrices can be controlled by manipulating electrospinning parameters to meet the requirements of a specific application. Such efforts include the fabrication of fiber matrices containing nanofibers, microfibers, combination of nano-microfibers and also different fiber orientation/alignments. Polymeric nanofiber matrices have been extensively investigated for diversified uses such as filtration, barrier fabrics, wipes, personal care, biomedical and pharmaceutical applications. Recently electrospun nanofiber matrices have gained a lot of attention, and are being explored as scaffolds in tissue engineering due to their properties that can modulate cellular behavior. Electrospun nanofiber matrices show morphological similarities to the natural extra-cellular matrix (ECM), characterized by ultrafine continuous fibers, high surface-to-volume ratio, high porosity and variable pore-size distribution. Efforts have been made to modify nanofiber surfaces with several bioactive molecules to provide cells with the necessary chemical cues and a more in vivo like environment. The current paper provides an overlook on such efforts in designing nanofiber matrices as scaffolds in the regeneration of various soft tissues including skin, blood vessel, tendon/ligament, cardiac patch, nerve and skeletal muscle.

Modelling Cardiac Signal as a Confound in EEG-fMRI and its Application in Focal Epilepsy

DEFF Research Database (Denmark)

Liston, Adam David; Salek-Haddadi, Afraim; Hamandi, Khalid

2005-01-01

Cardiac noise has been shown to reduce the sensitivity of functional Magnetic Resonance Imaging (fMRI) to an experimental effect due to its confounding presence in the blood oxygenation level-dependent (BOLD) signal. Its effect is most severe in particular regions of the brain and a method is yet...

Tissue-engineered trachea: History, problems and the future

OpenAIRE

Tan, Qiang; Steiner, Rudolf; Hoerstrup, Simon P.; Weder, Walter

2017-01-01

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of ‘in vivo bioreactor', defined a...

Negative confounding by essential fatty acids in methylmercury neurotoxicity associations

DEFF Research Database (Denmark)

Choi, Anna L; Mogensen, Ulla Brasch; Bjerve, Kristian S

2014-01-01

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...... 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...

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

Science.gov (United States)

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

2015-03-15

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

Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering

Science.gov (United States)

Nau, Thomas; Teuschl, Andreas

2015-01-01

Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon. PMID:25621217

Comparison of cardiovascular response to combined static-dynamic effort, postprandial dynamic effort and dynamic effort alone in patients with chronic ischemic heart disease

International Nuclear Information System (INIS)

Hung, J.; McKillip, J.; Savin, W.; Magder, S.; Kraus, R.; Houston, N.; Goris, M.; Haskell, W.; DeBusk, R.

1982-01-01

The cardiovascular responses to combined static-dynamic effort, postprandial dynamic effort and dynamic effort alone were evaluated by upright bicycle ergometry during equilibrium-gated blood pool scintigraphy in 24 men, mean age 59 +/- 8 years, with chronic ischemic heart disease. Combined static-dynamic effort and the postprandial state elicited a peak cardiovascular response similar to that of dynamic effort alone. Heart rate, intraarterial systolic and diastolic pressures, rate-pressure product and ejection fraction were similar for the three test conditions at the onset of ischemia and at peak effort. The prevalence and extent of exercise-induced ischemic left ventricular dysfunction, ST-segment depression, angina pectoris and ventricular ectopic activity were also similar during the three test conditions. Direct and indirect measurements of systolic and diastolic blood pressure were highly correlated. The onset of ischemic ST-segment depression and angina pectoris correlated as strongly with heart rate alone as with the rate-pressure product during all three test conditions. The cardiovascular response to combined static-dynamic effort and to postprandial dynamic effort becomes more similar to that of dynamic effort alone as dynamic effort reaches a symptom limit. If significant ischemic and arrhythmic abnormalities are absent during symptom-limited dynamic exercise testing, they are unlikely to appear during combined static-dynamic or postprandial dynamic effort

Effort in Multitasking: Local and Global Assessment of Effort.

Science.gov (United States)

Kiesel, Andrea; Dignath, David

2017-01-01

When performing multiple tasks in succession, self-organization of task order might be superior compared to external-controlled task schedules, because self-organization allows optimizing processing modes and thus reduces switch costs, and it increases commitment to task goals. However, self-organization is an additional executive control process that is not required if task order is externally specified and as such it is considered as time-consuming and effortful. To compare self-organized and externally controlled task scheduling, we suggest assessing global subjective and objectives measures of effort in addition to local performance measures. In our new experimental approach, we combined characteristics of dual tasking settings and task switching settings and compared local and global measures of effort in a condition with free choice of task sequence and a condition with cued task sequence. In a multi-tasking environment, participants chose the task order while the task requirement of the not-yet-performed task remained the same. This task preview allowed participants to work on the previously non-chosen items in parallel and resulted in faster responses and fewer errors in task switch trials than in task repetition trials. The free-choice group profited more from this task preview than the cued group when considering local performance measures. Nevertheless, the free-choice group invested more effort than the cued group when considering global measures. Thus, self-organization in task scheduling seems to be effortful even in conditions in which it is beneficiary for task processing. In a second experiment, we reduced the possibility of task preview for the not-yet-performed tasks in order to hinder efficient self-organization. Here neither local nor global measures revealed substantial differences between the free-choice and a cued task sequence condition. Based on the results of both experiments, we suggest that global assessment of effort in addition to

Patch esophagoplasty using an in-body-tissue-engineered collagenous connective tissue membrane.

Science.gov (United States)

Okuyama, Hiroomi; Umeda, Satoshi; Takama, Yuichi; Terasawa, Takeshi; Nakayama, Yasuhide

2018-02-01

Although many approaches to esophageal replacement have been investigated, these efforts have thus far only met limited success. In-body-tissue-engineered connective tissue tubes have been reported to be effective as vascular replacement grafts. The aim of this study was to investigate the usefulness of an In-body-tissue-engineered collagenous connective tissue membrane, "Biosheet", as a novel esophageal scaffold in a beagle model. We prepared Biosheets by embedding specially designed molds into subcutaneous pouches in beagles. After 1-2months, the molds, which were filled with ingrown connective tissues, were harvested. Rectangular-shaped Biosheets (10×20mm) were then implanted to replace defects of the same size that had been created in the cervical esophagus of the beagle. An endoscopic evaluation was performed at 4 and 12weeks after implantation. The esophagus was harvested and subjected to a histological evaluation at 4 (n=2) and 12weeks (n=2) after implantation. The animal study protocols were approved by the National Cerebral and Cardiovascular Centre Research Institute Committee (No. 16048). The Biosheets showed sufficient strength and flexibility to replace the esophagus defect. All animals survived with full oral feeding during the study period. No anastomotic leakage was observed. An endoscopic study at 4 and 12weeks after implantation revealed that the anastomotic sites and the internal surface of the Biosheets were smooth, without stenosis. A histological analysis at 4weeks after implantation demonstrated that stratified squamous epithelium was regenerated on the internal surface of the Biosheets. A histological analysis at 12weeks after implantation showed the regeneration of muscle tissue in the implanted Biosheets. The long-term results of patch esophagoplasty using Biosheets showed regeneration of stratified squamous epithelium and muscular tissues in the implanted sheets. These results suggest that Biosheets may be useful as a novel esophageal

Controlled drug release for tissue engineering.

Science.gov (United States)

Rambhia, Kunal J; Ma, Peter X

2015-12-10

Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthetic aperture tissue and flow ultrasound imaging

DEFF Research Database (Denmark)

Nikolov, Svetoslav

imaging applied to medical ultrasound. It is divided into two major parts: tissue and blood flow imaging. Tissue imaging using synthetic aperture algorithms has been investigated for about two decades, but has not been implemented in medical scanners yet. Among the other reasons, the conventional scanning...... and beamformation methods are adequate for the imaging modalities in clinical use - the B-mode imaging of tissue structures, and the color mapping of blood flow. The acquisition time, however, is too long, and these methods fail to perform real-time three-dimensional scans. The synthetic transmit aperture......, on the other hand, can create a Bmode image with as little as 2 emissions, thus significantly speeding-up the scan procedure. The first part of the dissertation describes the synthetic aperture tissue imaging. It starts with an overview of the efforts previously made by other research groups. A classification...

Estimation of inspection effort

International Nuclear Information System (INIS)

Mullen, M.F.; Wincek, M.A.

1979-06-01

An overview of IAEA inspection activities is presented, and the problem of evaluating the effectiveness of an inspection is discussed. Two models are described - an effort model and an effectiveness model. The effort model breaks the IAEA's inspection effort into components; the amount of effort required for each component is estimated; and the total effort is determined by summing the effort for each component. The effectiveness model quantifies the effectiveness of inspections in terms of probabilities of detection and quantities of material to be detected, if diverted over a specific period. The method is applied to a 200 metric ton per year low-enriched uranium fuel fabrication facility. A description of the model plant is presented, a safeguards approach is outlined, and sampling plans are calculated. The required inspection effort is estimated and the results are compared to IAEA estimates. Some other applications of the method are discussed briefly. Examples are presented which demonstrate how the method might be useful in formulating guidelines for inspection planning and in establishing technical criteria for safeguards implementation

Effects of honey to mobilize endogenous stem cells in efforts intestinal and ovarian tissue regeneration in rats with protein energy malnutrition

Directory of Open Access Journals (Sweden)

R. Heru Prasetyo

2016-05-01

Conclusions: Expression of CD34+ and CD45+, which significantly different in treatment 2 (2. Furthermore, increase of immune response (decrease Hsp70 expression and increased PGE2 in intestinal tissue. Increased immune response causes expression of GDF-9 in ovarian tissue. Decreased of Hsp70 expression, increased PGE2 and increased GDF-9 followed the process of regeneration of the intestinal and ovarian tissue.

Challenges and opportunities for tissue-engineering polarized epithelium.

Science.gov (United States)

Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

Energy Technology Data Exchange (ETDEWEB)

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

2016-07-01

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

Effortful echolalia.

Science.gov (United States)

Hadano, K; Nakamura, H; Hamanaka, T

1998-02-01

We report three cases of effortful echolalia in patients with cerebral infarction. The clinical picture of speech disturbance is associated with Type 1 Transcortical Motor Aphasia (TCMA, Goldstein, 1915). The patients always spoke nonfluently with loss of speech initiative, dysarthria, dysprosody, agrammatism, and increased effort and were unable to repeat sentences longer than those containing four or six words. In conversation, they first repeated a few words spoken to them, and then produced self initiated speech. The initial repetition as well as the subsequent self initiated speech, which were realized equally laboriously, can be regarded as mitigated echolalia (Pick, 1924). They were always aware of their own echolalia and tried to control it without effect. These cases demonstrate that neither the ability to repeat nor fluent speech are always necessary for echolalia. The possibility that a lesion in the left medial frontal lobe, including the supplementary motor area, plays an important role in effortful echolalia is discussed.

Bioreactors in tissue engineering - principles, applications and commercial constraints.

Science.gov (United States)

Hansmann, Jan; Groeber, Florian; Kahlig, Alexander; Kleinhans, Claudia; Walles, Heike

2013-03-01

Bioreactor technology is vital for tissue engineering. Usually, bioreactors are used to provide a tissue-specific physiological in vitro environment during tissue maturation. In addition to this most obvious application, bioreactors have the potential to improve the efficiency of the overall tissue-engineering concept. To date, a variety of bioreactor systems for tissue-specific applications have been developed. Of these, some systems are already commercially available. With bioreactor technology, various functional tissues of different types were generated and cultured in vitro. Nevertheless, these efforts and achievements alone have not yet led to many clinically successful tissue-engineered implants. We review possible applications for bioreactor systems within a tissue-engineering process and present basic principles and requirements for bioreactor development. Moreover, the use of bioreactor systems for the expansion of clinically relevant cell types is addressed. In contrast to cell expansion, for the generation of functional three-dimensional tissue equivalents, additional physical cues must be provided. Therefore, bioreactors for musculoskeletal tissue engineering are discussed. Finally, bioreactor technology is reviewed in the context of commercial constraints. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic Regression Models.

Science.gov (United States)

Schmidt, Amand F; Klungel, Olaf H; Groenwold, Rolf H H

2016-01-01

Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification. We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding. Model misspecification was induced in the independent derivation dataset. We evaluated performance using relative bias confidence interval coverage of the true effect, among other metrics. At low events per coefficient (1.0 and 0.5), the logistic regression estimates had a large relative bias (greater than -100%). Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the propensity score model, this was 8.74% and >100%, respectively. At events per coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or reduced to a crude regression, resulting in biases of -8.49% and 24.55%. Coverage of logistic regression estimates became less than the nominal level at events per coefficient ≤5. For the disease risk score, inverse probability weighting, and propensity score, coverage became less than nominal at events per coefficient ≤2.5, ≤1.0, and ≤1.0, respectively. Bias of misspecified disease risk score models was 16.55%. In settings with low events/exposed subjects per coefficient, disease risk score methods can be useful alternatives to logistic regression models, especially when propensity score models cannot be used. Despite better performance of disease risk score methods than logistic regression and propensity score models in small events per coefficient settings, bias, and coverage still deviated from nominal.

Bayesian inference in a discrete shock model using confounded common cause data

International Nuclear Information System (INIS)

Kvam, Paul H.; Martz, Harry F.

1995-01-01

We consider redundant systems of identical components for which reliability is assessed statistically using only demand-based failures and successes. Direct assessment of system reliability can lead to gross errors in estimation if there exist external events in the working environment that cause two or more components in the system to fail in the same demand period which have not been included in the reliability model. We develop a simple Bayesian model for estimating component reliability and the corresponding probability of common cause failure in operating systems for which the data is confounded; that is, the common cause failures cannot be distinguished from multiple independent component failures in the narrative event descriptions

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

Science.gov (United States)

Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

No evidence for thermal transgenerational plasticity in metabolism when minimizing the potential for confounding effects.

Science.gov (United States)

Kielland, Ø N; Bech, C; Einum, S

2017-01-11

Environmental change may cause phenotypic changes that are inherited across generations through transgenerational plasticity (TGP). If TGP is adaptive, offspring fitness increases with an increasing match between parent and offspring environment. Here we test for adaptive TGP in somatic growth and metabolic rate in response to temperature in the clonal zooplankton Daphnia pulex Animals of the first focal generation experienced thermal transgenerational 'mismatch' (parental and offspring temperatures differed), whereas conditions of the next two generations matched the (grand)maternal thermal conditions. Adjustments of metabolic rate occurred during the lifetime of the first generation (i.e. within-generation plasticity). However, no further change was observed during the subsequent two generations, as would be expected under TGP. Furthermore, we observed no tendency for increased juvenile somatic growth (a trait highly correlated with fitness in Daphnia) over the three generations when reared at new temperatures. These results are inconsistent with existing studies of thermal TGP, and we describe how previous experimental designs may have confounded TGP with within-generation plasticity and selective mortality. We suggest that the current evidence for thermal TGP is weak. To increase our understanding of the ecological and evolutionary role of TGP, future studies should more carefully identify possible confounding factors. © 2017 The Author(s).

Non-Immunogenic Structurally and Biologically Intact Tissue Matrix Grafts for the Immediate Repair of Ballistic-Induced Vascular and Nerve Tissue Injury in Combat Casualty Care

National Research Council Canada - National Science Library

Bachrach, Nathaniel

2003-01-01

.... This past year the source of he defects was determined to be the freeze-drying process. Ongoing efforts toward process optimization and design modifications that will provide undamaged tissue grafts are presented in this report...

Epithelium percentage estimation facilitates epithelial quantitative protein measurement in tissue specimens.

Science.gov (United States)

Chen, Jing; Toghi Eshghi, Shadi; Bova, George Steven; Li, Qing Kay; Li, Xingde; Zhang, Hui

2013-12-01

The rapid advancement of high-throughput tools for quantitative measurement of proteins has demonstrated the potential for the identification of proteins associated with cancer. However, the quantitative results on cancer tissue specimens are usually confounded by tissue heterogeneity, e.g. regions with cancer usually have significantly higher epithelium content yet lower stromal content. It is therefore necessary to develop a tool to facilitate the interpretation of the results of protein measurements in tissue specimens. Epithelial cell adhesion molecule (EpCAM) and cathepsin L (CTSL) are two epithelial proteins whose expressions in normal and tumorous prostate tissues were confirmed by measuring staining intensity with immunohistochemical staining (IHC). The expressions of these proteins were measured by ELISA in protein extracts from OCT embedded frozen prostate tissues. To eliminate the influence of tissue heterogeneity on epithelial protein quantification measured by ELISA, a color-based segmentation method was developed in-house for estimation of epithelium content using H&E histology slides from the same prostate tissues and the estimated epithelium percentage was used to normalize the ELISA results. The epithelium contents of the same slides were also estimated by a pathologist and used to normalize the ELISA results. The computer based results were compared with the pathologist's reading. We found that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly affected by epithelium content in the tissue specimens. Without adjusting for epithelium percentage, both EpCAM and CTSL levels appeared significantly higher in tumor tissues than normal tissues with a p value less than 0.001. However, after normalization by the epithelium percentage, ELISA measurements of both EpCAM and CTSL were in agreement with IHC staining results, showing a significant increase only in EpCAM with no difference in CTSL expression in cancer tissues. These results

External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure.

Science.gov (United States)

Fournier, L; Laurent, O; Samson, E; Caër-Lorho, S; Laroche, P; Le Guen, B; Laurier, D; Leuraud, K

2016-11-01

French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat à l'Energie Atomique), AREVA NC, or EDF (Electricité de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

External radiation dose and cancer mortality among French nuclear workers. Considering potential confounding by internal radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Fournier, L.; Laurent, O.; Samson, E.; Caer-Lorho, S.; Laurier, D.; Leuraud, K. [Institute for Radiological Protection and Nuclear Safety, Fontenay aux Roses (France). Ionizing Radiation Epidemiology Lab.; Laroche, P. [AREVA, Paris (France); Le Guen, B. [EDF, Saint Denis (France)

2016-11-15

French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat a l'Energie Atomique), AREVA NC, or EDF (Electricite de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

Directory of Open Access Journals (Sweden)

Aimee L. Dordevic

2015-07-01

Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

Science.gov (United States)

Keogh, Ruth H; Daniel, Rhian M; VanderWeele, Tyler J; Vansteelandt, Stijn

2018-05-01

Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time-dependent confounding, to estimate the total effect of an exposure on a subsequent outcome by controlling appropriately for prior exposures, outcomes, and time-varying covariates. We refer to the resulting estimation approach as sequential conditional mean models (SCMMs), which can be fitted using generalized estimating equations. We outline this approach and describe how including propensity score adjustment is advantageous. We compare the causal effects being estimated using SCMMs and marginal structural models, and we compare the two approaches using simulations. SCMMs enable more precise inferences, with greater robustness against model misspecification via propensity score adjustment, and easily accommodate continuous exposures and interactions. A new test for direct effects of past exposures on a subsequent outcome is described.

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

Science.gov (United States)

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

Maximum effort in the minimum-effort game

Czech Academy of Sciences Publication Activity Database

Engelmann, Dirk; Normann, H.-T.

2010-01-01

Roč. 13, č. 3 (2010), s. 249-259 ISSN 1386-4157 Institutional research plan: CEZ:AV0Z70850503 Keywords : minimum-effort game * coordination game * experiments * social capital Subject RIV: AH - Economics Impact factor: 1.868, year: 2010

Time-Dependent Confounding in the Study of the Effects of Regular Physical Activity in Chronic Obstructive Pulmonary Disease: An Application of the Marginal Structural Model

DEFF Research Database (Denmark)

Garcia-Aymerich, Judith; Lange, Peter; Serra, Ignasi

2008-01-01

PURPOSE: Results from longitudinal studies about the association between physical activity and chronic obstructive pulmonary disease (COPD) may have been biased because they did not properly adjust for time-dependent confounders. Marginal structural models (MSMs) have been proposed to address...... this type of confounding. We sought to assess the presence of time-dependent confounding in the association between physical activity and COPD development and course by comparing risk estimates between standard statistical methods and MSMs. METHODS: By using the population-based cohort Copenhagen City Heart...... Study, 6,568 subjects selected from the general population in 1976 were followed up until 2004 with three repeated examinations. RESULTS: Moderate to high compared with low physical activity was associated with a reduced risk of developing COPD both in the standard analysis (odds ratio [OR] 0.76, p = 0...

Bioactive polymeric scaffolds for tissue engineering

Directory of Open Access Journals (Sweden)

Scott Stratton

2016-12-01

Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Indoor biofuel air pollution and respiratory health: the role of confounding factors among women in highland Guatemala.

Science.gov (United States)

Bruce, N; Neufeld, L; Boy, E; West, C

1998-06-01

A number of studies have reported associations between indoor biofuel air pollution in developing countries and chronic obstructive lung disease (COLD) in adults and acute lower respiratory infection (ALRI) in children. Most of these studies have used indirect measures of exposure and generally dealt inadequately with confounding. More reliable, quantified information about this presumed effect is an important pre-requisite for prevention, not least because of the technical, economic and cultural barriers to achieving substantial exposure reductions in the world's poorest households, where ambient pollution levels are typically between ten and a hundred times higher than recommended standards. This study was carried out as part of a programme of research designed to inform the development of intervention studies capable of providing quantified estimates of health benefits. The association between respiratory symptoms and the use of open fires and chimney woodstoves ('planchas'), and the distribution of confounding factors, were examined in a cross-sectional study of 340 women aged 15-45 years, living in a poor rural area in the western highlands of Guatemala. The prevalence of reported cough and phlegm was significantly higher for three of six symptom measures among women using open fires. Although this finding is consistent with a number of other studies, none has systematically examined the extent to which strong associations with confounding variables in these settings limit the ability of observational studies to define the effect of indoor air pollution adequately. Very strong associations (P air pollution and health, although there is a reasonable case for believing that the observed association is causal. Intervention studies are required for stronger evidence of this association, and more importantly, to determine the size of health benefit achievable through feasible exposure reductions.

Adipose tissue trans fatty acids and changes in body weight and waist circumference

DEFF Research Database (Denmark)

Hansen, Camilla P.; Berentzen, Tina L.; Østergaard, Jane N.

2014-01-01

). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50–64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after...... enrolment. The exposure measures were total trans-octadecenoic acids (18 : 1t), 18 : 1 D6-10t, vaccenic acid (18 : 1 D11t) and rumenic acid (18 : 2 D9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18 : 1t was 1·52% (90......% central range 0·98, 2·19) in men and 1·47% (1·01, 2·19) in women. No significant associations were observed between the proportions of total 18 : 1t, 18:1 D6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue...

On Estimation of the Survivor Average Causal Effect in Observational Studies when Important Confounders are Missing Due to Death

Science.gov (United States)

Egleston, Brian L.; Scharfstein, Daniel O.; MacKenzie, Ellen

2008-01-01

We focus on estimation of the causal effect of treatment on the functional status of individuals at a fixed point in time t* after they have experienced a catastrophic event, from observational data with the following features: (1) treatment is imposed shortly after the event and is non-randomized, (2) individuals who survive to t* are scheduled to be interviewed, (3) there is interview non-response, (4) individuals who die prior to t* are missing information on pre-event confounders, (5) medical records are abstracted on all individuals to obtain information on post-event, pre-treatment confounding factors. To address the issue of survivor bias, we seek to estimate the survivor average causal effect (SACE), the effect of treatment on functional status among the cohort of individuals who would survive to t* regardless of whether or not assigned to treatment. To estimate this effect from observational data, we need to impose untestable assumptions, which depend on the collection of all confounding factors. Since pre-event information is missing on those who die prior to t*, it is unlikely that these data are missing at random (MAR). We introduce a sensitivity analysis methodology to evaluate the robustness of SACE inferences to deviations from the MAR assumption. We apply our methodology to the evaluation of the effect of trauma center care on vitality outcomes using data from the National Study on Costs and Outcomes of Trauma Care. PMID:18759833

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

Science.gov (United States)

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

2016-05-01

Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the

Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems.

Science.gov (United States)

D'Onofrio, Brian M; Rickert, Martin E; Langström, Niklas; Donahue, Kelly L; Coyne, Claire A; Larsson, Henrik; Ellingson, Jarrod M; Van Hulle, Carol A; Iliadou, Anastasia N; Rathouz, Paul J; Lahey, Benjamin B; Lichtenstein, Paul

2012-11-01

Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring. To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design. We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding. Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2). Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1,187,360). Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2). The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17-1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31]; HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant. The association between maternal SDP and offspring substance use/problems is likely due to familial background

Biomarker discovery in heterogeneous tissue samples -taking the in-silico deconfounding approach

Directory of Open Access Journals (Sweden)

Parida Shreemanta K

2010-01-01

Full Text Available Abstract Background For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues. Results Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available. Conclusions The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in

Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers

DEFF Research Database (Denmark)

del Campo, Marta; Mollenhauer, Brit; Bertolotto, Antonio

2012-01-01

Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging...... the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized...

Tissue banking: public awareness in Indonesia

International Nuclear Information System (INIS)

Nazly Hilmy

1999-01-01

Public awareness and acceptance on the benefit of Tissue Bank (TB) and its products in Indonesia are still very low, however four productive TBs are in operation by using mostly tissues from living donors. Except for medical doctors, nurses and experts who are involved in the establishment of the TB as well as who applied the products, almost nobody else understand what kind of bank this tissue bank is. Ethical in collecting tissues from non- living donors and using of this human tissues for safe medical application has several considerations that should be overcome, such as religious, legal and medical considerations. Legal and medical considerations are not very difficult to be faced. People are reluctant to give up by cutting off the needed tissue of a dead relative to help someone else who is suffering from a life threatening disease. Our duty is to enlighten the public about this bank by means of seminars, exposition, writings and discussions. We can use the electronic mass- media or printed one to explain the necessity of this tissue bank. We also need to involve leaders of religions, government high ranking officials as well as related Government institutions. Otherwise the tissues that are needed can only be obtained from the poor, the homeless whose health condition we do not know and no relatives who can give their permission for the taking of parts of the body. This is a very unethical way. Since January 1998, Batan Research Tissue Bank together with several hospitals in Indonesia have done four seminars, two discussions, two expositions, producing leaflets and carried out training in this matter. But it is not enough. More efforts should be done

Articular cartilage: from formation to tissue engineering.

Science.gov (United States)

Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

2016-05-26

Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

Chasing the effects of Pre-analytical Confounders - a Multicentre Study on CSF-AD biomarkers

Directory of Open Access Journals (Sweden)

Maria Joao Leitao

2015-07-01

Full Text Available Core cerebrospinal fluid (CSF biomarkers-Aβ42, Tau and pTau–have been recently incorporated in the revised criteria for Alzheimer’s disease (AD. However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. In this study, we aim to surpass the efforts from previous studies, by employing a multicentre approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Four different centres participated in this study and followed the same established protocol. CSF samples were analysed for three biomarkers (Aβ42, Tau and pTau and tested for different spinning conditions (temperature: Room temperature (RT vs. 4oC; speed: 500g vs. 2000g vs. 3000g, storage volume variations (25%, 50% and 75% of tube total volume as well as freezing-thaw cycles (up to 5 cyles. The influence of sample routine parameters, inter-centre variability and relative value of each biomarker (reported as normal/abnormal, was analysed. Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non centrifugation or centrifugation at RT, compared to 4ºC, led to higher Aβ42 levels. Reducing CSF storage volume from 75% to 50% of total tube capacity, decreased Aβ42 concentration (within analytical CV of the assay, whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to 5 freeze-thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than 3 times. This systematic study reinforces the need for CSF centrifugation at 4ºC prior to storage and highlights the influence of storage conditions in Aβ42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF

Do patient and practice characteristics confound age-group differences in preferences for general practice care? A quantitative study

Science.gov (United States)

2013-01-01

Background Previous research showed inconsistent results regarding the relationship between the age of patients and preference statements regarding GP care. This study investigates whether elderly patients have different preference scores and ranking orders concerning 58 preference statements for GP care than younger patients. Moreover, this study examines whether patient characteristics and practice location may confound the relationship between age and the categorisation of a preference score as very important. Methods Data of the Consumer Quality Index GP Care were used, which were collected in 32 general practices in the Netherlands. The rank order and preference score were calculated for 58 preference statements for four age groups (0–30, 31–50, 51–74, 75 years and older). Using chi-square tests and logistic regression analyses, it was investigated whether a significant relationship between age and preference score was confounded by patient characteristics and practice location. Results Elderly patients did not have a significant different ranking order for the preference statements than the other three age groups (r = 0.0193; p = 0.41). However, in 53% of the statements significant differences were found in preference score between the four age groups. Elderly patients categorized significantly less preference statements as ‘very important’. In most cases, the significant relationships were not confounded by gender, education, perceived health, the number of GP contacts and location of the GP practice. Conclusion The preferences of elderly patients for GP care concern the same items as younger patients. However, their preferences are less strong, which cannot be ascribed to gender, education, perceived health, the number of GP contacts and practice location. PMID:23800156

[COMPUTER TECHNOLOGY FOR ACCOUNTING OF CONFOUNDERS IN THE RISK ASSESSMENT IN COMPARATIVE STUDIES ON THE BASE OF THE METHOD OF STANDARDIZATION].

Science.gov (United States)

Shalaumova, Yu V; Varaksin, A N; Panov, V G

2016-01-01

There was performed an analysis of the accounting of the impact of concomitant variables (confounders), introducing a systematic error in the assessment of the impact of risk factors on the resulting variable. The analysis showed that standardization is an effective method for the reduction of the shift of risk assessment. In the work there is suggested an algorithm implementing the method of standardization based on stratification, providing for the minimization of the difference of distributions of confounders in groups on risk factors. To automate the standardization procedures there was developed a software available on the website of the Institute of Industrial Ecology, UB RAS. With the help of the developed software by numerically modeling there were determined conditions of the applicability of the method of standardization on the basis of stratification for the case of the normal distribution on the response and confounder and linear relationship between them. Comparison ofresults obtained with the help of the standardization with statistical methods (logistic regression and analysis of covariance) in solving the problem of human ecology, has shown that obtaining close results is possible if there will be met exactly conditions for the applicability of statistical methods. Standardization is less sensitive to violations of conditions of applicability.

Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

OpenAIRE

Strahler, Jana

2010-01-01

Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

Survey of public knowledge in tissue banking in Malaysia

International Nuclear Information System (INIS)

Norimah Yusof; Asnah Hassan

1998-01-01

A survey was conducted with the objective to determine the level of public knowledge and awareness in tissue banking. From 233 respondents of 62.2% male and 37.8% female, only 44.6% have heard about tissue banking in Malaysia, mainly from newspapers and mass media, and only 11.6% realised the existence of the two tissue banks i.e at MINT, Bangi and USM, Kubang Kerian. However, higher percentage of respondents were aware of donation for both organs (56.2%) and tissues (51.1%). When asked about donating, 54.5% were willing to donate after death and surprisingly only 39.9% as life donors. On the contrary, 71.7% were willing to accept tissue grafts for clinical treatment and transplantation. The findings suggest that more aggressive publicity on tissue banking is necessary and more detailed information have to be made known especially regarding the 'fatwa' in particular for the Muslims and the Human Tissue Act 1974 for the general public. This may lead to even better response to the tissue donation programme which is being planned. Most of the respondents congratulated both tissue banks in our effort to develop indigenous expertise in this interesting new venture with high appreciation to our social and welfare obligations

Respiratory effort from the photoplethysmogram.

Science.gov (United States)

Addison, Paul S

2017-03-01

The potential for a simple, non-invasive measure of respiratory effort based on the pulse oximeter signal - the photoplethysmogram or 'pleth' - was investigated in a pilot study. Several parameters were developed based on a variety of manifestations of respiratory effort in the signal, including modulation changes in amplitude, baseline, frequency and pulse transit times, as well as distinct baseline signal shifts. Thirteen candidate parameters were investigated using data from healthy volunteers. Each volunteer underwent a series of controlled respiratory effort maneuvers at various set flow resistances and respiratory rates. Six oximeter probes were tested at various body sites. In all, over three thousand pleth-based effort-airway pressure (EP) curves were generated across the various airway constrictions, respiratory efforts, respiratory rates, subjects, probe sites, and the candidate parameters considered. Regression analysis was performed to determine the existence of positive monotonic relationships between the respiratory effort parameters and resulting airway pressures. Six of the candidate parameters investigated exhibited a distinct positive relationship (poximeter probe and an ECG (P2E-Effort) and the other using two pulse oximeter probes placed at different peripheral body sites (P2-Effort); and baseline shifts in heart rate, (BL-HR-Effort). In conclusion, a clear monotonic relationship was found between several pleth-based parameters and imposed respiratory loadings at the mouth across a range of respiratory rates and flow constrictions. The results suggest that the pleth may provide a measure of changing upper airway dynamics indicative of the effort to breathe. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Use of gel zymography to examine matrix metalloproteinase (gelatinase) expression in brain tissue or in primary glial cultures.

Science.gov (United States)

Frankowski, Harald; Gu, Yu-Huan; Heo, Ji Hoe; Milner, Richard; Del Zoppo, Gregory J

2012-01-01

Glia synthesize, package, and secrete several species of matrix proteases, including the gelatinases (pro-)MMP-2 and (pro-)MMP-9. In appropriate settings (e.g., experimental ischemia), these MMPs can be assayed from cerebral tissues or from astrocytes and microglia in culture by enzymatic substrate-dependent assays and by gelatin-based zymography. We describe the methodologies for the sensitive quantitative development of the inactive and active forms of both MMP-2 and MMP-9 from tissues and cells, by means of lysis of the collagen substrate in collagen-impregnated gel electropheresis by the zymogen and active gelatinases. These methodologies are a refinement of those used commonly, with instructions to increase sensitivity. Serious and often overlooked issues regarding sources of sample contamination and elements confounding the MMP band development and their interpretation are discussed.

An electromechanical based deformable model for soft tissue simulation.

Science.gov (United States)

Zhong, Yongmin; Shirinzadeh, Bijan; Smith, Julian; Gu, Chengfan

2009-11-01

Soft tissue deformation is of great importance to surgery simulation. Although a significant amount of research efforts have been dedicated to simulating the behaviours of soft tissues, modelling of soft tissue deformation is still a challenging problem. This paper presents a new deformable model for simulation of soft tissue deformation from the electromechanical viewpoint of soft tissues. Soft tissue deformation is formulated as a reaction-diffusion process coupled with a mechanical load. The mechanical load applied to a soft tissue to cause a deformation is incorporated into the reaction-diffusion system, and consequently distributed among mass points of the soft tissue. Reaction-diffusion of mechanical load and non-rigid mechanics of motion are combined to govern the simulation dynamics of soft tissue deformation. An improved reaction-diffusion model is developed to describe the distribution of the mechanical load in soft tissues. A three-layer artificial cellular neural network is constructed to solve the reaction-diffusion model for real-time simulation of soft tissue deformation. A gradient based method is established to derive internal forces from the distribution of the mechanical load. Integration with a haptic device has also been achieved to simulate soft tissue deformation with haptic feedback. The proposed methodology does not only predict the typical behaviours of living tissues, but it also accepts both local and large-range deformations. It also accommodates isotropic, anisotropic and inhomogeneous deformations by simple modification of diffusion coefficients.

High blood pressure and sedentary behavior in adolescents are associated even after controlling for confounding factors.

Science.gov (United States)

Christofaro, Diego Giulliano Destro; De Andrade, Selma Maffei; Cardoso, Jefferson Rosa; Mesas, Arthur Eumann; Codogno, Jamile Sanches; Fernandes, Rômulo Araújo

2015-01-01

The aim of this study was to determine whether high blood pressure (HBP) is associated with sedentary behavior in young people even after controlling for potential confounders (gender, age, socioeconomic level, tobacco, alcohol, obesity and physical activity). In this epidemiological study, 1231 adolescents were evaluated. Blood pressure was measured with an oscillometric device and waist circumference with an inextensible tape. Sedentary behavior (watching television, computer use and playing video games) and physical activity were assessed by a questionnaire. We used mean and standard deviation to describe the statistical analysis, and the association between HBP and sedentary behavior was assessed by the chi-squared test. Binary logistic regression was used to observe the magnitude of association and cluster analyses (sedentary behavior and abdominal obesity; sedentary behavior and physical inactivity). HBP was associated with sedentary behaviors [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.41-3.96], even after controlling for various confounders (OR = 1.68, CI = 1.03-2.75). In cluster analysis the combination of sedentary behavior and elevated abdominal obesity contributed significantly to an increased likelihood of having HBP (OR = 13.51, CI 7.21-23.97). Sedentary behavior was associated with HBP, and excess fat in the abdominal region contributed to the modulation of this association.

Fresh fruit intake and asthma symptoms in young British adults: confounding or effect modification by smoking?

Science.gov (United States)

Butland, B K; Strachan, D P; Anderson, H R

1999-04-01

Antioxidant vitamins have been postulated as a protective factor in asthma. The associations between the frequency of fresh fruit consumption in summer, and the prevalence of self-reported asthma symptoms were investigated. The analysis was based on 5,582 males and 5,770 females, born in England, Wales and Scotland between March 3-9, 1958 and aged 33 yrs at the time of survey. The 12-month period prevalence of wheeze and frequent wheeze were inversely associated with frequent intakes of fresh fruit and salad/raw vegetables and positively associated with smoking and lower social class. After adjustment for mutual confounding and sex, associations with smoking persisted, but those with social class and salad/raw vegetable consumption lost significance. The frequency of fresh fruit intake was no longer associated with wheeze after adjustment, but was inversely associated with frequent wheeze and speech-limiting attacks. The association with frequent wheeze differed significantly between smoking groups (never, former, current) and appeared to be confined to exsmokers and current smokers. These findings support postulated associations between infrequent fresh fruit consumption and the prevalence of frequent or severe asthma symptoms in adults. Associations appeared to be restricted to smokers, with effect modification as a more likely explanation of this pattern than residual confounding by smoking.

Comparison of soft and hard tissue ablation with sub-ps and ns pulse lasers

Energy Technology Data Exchange (ETDEWEB)

Da Silva, L.B.; Stuart, B.C.; Celliers, P.M.; Feit, M.D.; Glinsky, M.E.; Heredia, N.J.; Herman, S.; Lane, S.M.; London, R.A.; Matthews, D.L.; Perry, M.D.; Rubenchik, A.M. [Lawrence Livermore National Lab., CA (United States); Chang, T.D. [Veterans Administration Hospital, Martinez, CA (United States); Neev, J. [Beckman Laser Inst. and Medical Clinic, Irvine, CA (United States)

1996-05-01

Tissue ablation with ultrashort laser pulses offers several unique advantages. The nonlinear energy deposition is insensitive to tissue type, allowing this tool to be used for soft and hard tissue ablation. The localized energy deposition lead to precise ablation depth and minimal collateral damage. This paper reports on efforts to study and demonstrate tissue ablation using an ultrashort pulse laser. Ablation efficiency and extent of collateral damage for 0.3 ps and 1000 ps duration laser pulses are compared. Temperature measurements of the rear surface of a tooth section is also presented.

Cognitive effort: A neuroeconomic approach

Science.gov (United States)

Braver, Todd S.

2015-01-01

Cognitive effort has been implicated in numerous theories regarding normal and aberrant behavior and the physiological response to engagement with demanding tasks. Yet, despite broad interest, no unifying, operational definition of cognitive effort itself has been proposed. Here, we argue that the most intuitive and epistemologically valuable treatment is in terms of effort-based decision-making, and advocate a neuroeconomics-focused research strategy. We first outline psychological and neuroscientific theories of cognitive effort. Then we describe the benefits of a neuroeconomic research strategy, highlighting how it affords greater inferential traction than do traditional markers of cognitive effort, including self-reports and physiologic markers of autonomic arousal. Finally, we sketch a future series of studies that can leverage the full potential of the neuroeconomic approach toward understanding the cognitive and neural mechanisms that give rise to phenomenal, subjective cognitive effort. PMID:25673005

Choice of Illumination System & Fluorophore for Multiplex Immunofluorescence on FFPE Tissue Sections.

Directory of Open Access Journals (Sweden)

Sandrine Prost

Full Text Available The recent availability of novel dyes and alternative light sources to facilitate complex tissue immunofluorescence studies such as multiplex labelling has not been matched by reports critically evaluating the considerations and relative benefits of these new tools, particularly in combination. Product information is often limited to wavelengths used for older fluorophores (FITC, TRITC & corresponding Alexa dyes family. Consequently, novel agents such as Quantum dots are not widely appreciated or used, despite highly favourable properties including extremely bright emission, stability and potentially reduced tissue autofluorescence at the excitation wavelength. Using spectral analysis, we report here a detailed critical appraisal and comparative evaluation of different light sources and fluorophores in multiplex immunofluorescence of clinical biopsy sections. The comparison includes mercury light, metal halide and 3 different LED-based systems, using 7 Qdots (525, 565, 585, 605, 625, 705, Cy3 and Cy5. We discuss the considerations relevant to achieving the best combination of light source and fluorophore for accurate multiplex fluorescence quantitation. We highlight practical limitations and confounders to quantitation with filter-based approaches.

Interpretational Confounding Is Due to Misspecification, Not to Type of Indicator: Comment on Howell, Breivik, and Wilcox (2007)

Science.gov (United States)

Bollen, Kenneth A.

2007-01-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal…

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

DEFF Research Database (Denmark)

Møller, P; Knudsen, Lisbeth E.; Loft, S

2000-01-01

appeared to have less power than the positive studies. Also, there were poor dose-response relationships in many of the biomonitoring studies. Many factors have been reported to produce effects by the comet assay, e.g., age, air pollution exposure, diet, exercise, gender, infection, residential radon...... be used as criteria for the selection of populations and that data on exercise, diet, and recent infections be registered before blood sampling. Samples from exposed and unexposed populations should be collected at the same time to avoid seasonal variation. In general, the comet assay is considered...... exposure, smoking, and season. Until now, the use of the comet assay has been hampered by the uncertainty of the influence of confounding factors. We argue that none of the confounding factors are unequivocally positive in the majority of the studies. We recommend that age, gender, and smoking status...

Effort rights-based management

DEFF Research Database (Denmark)

Squires, Dale; Maunder, Mark; Allen, Robin

2017-01-01

Effort rights-based fisheries management (RBM) is less widely used than catch rights, whether for groups or individuals. Because RBM on catch or effort necessarily requires a total allowable catch (TAC) or total allowable effort (TAE), RBM is discussed in conjunction with issues in assessing fish...... populations and providing TACs or TAEs. Both approaches have advantages and disadvantages, and there are trade-offs between the two approaches. In a narrow economic sense, catch rights are superior because of the type of incentives created, but once the costs of research to improve stock assessments...

Reducing confounding and suppression effects in TCGA data: an integrated analysis of chemotherapy response in ovarian cancer

Directory of Open Access Journals (Sweden)

Hsu Fang-Han

2012-10-01

Full Text Available Abstract Background Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms. Results To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

Science.gov (United States)

Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

2017-08-24

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

In-effort perfusion pulmonary tomo-scintigraphies for pre-surgery evaluation of severe emphysema

International Nuclear Information System (INIS)

Poiseau, E.; Roue, C.; Bonnin, F.; Stievenart, J.L.; Fournier, M.; Bok, B.

1997-01-01

The pulmonary reduction surgery improves the in-effort tolerance of certain severe emphysema, possibly by the compression of zones of adjacent healthy pulmonary parenchyma. Six patients afflicted with severe emphysema (5 M and 1 F, 20 to 63 years old) benefited at each 3 days by an at-rest and in-effort perfusion pulmonary tomo-scintigraphy (PPTS), after a trial interval of 6 minutes. After injection IV of 6 mCi of MAA- 99m Tc, in sitting position, 120 projection images were acquired with a single-head camera on a 128 x 128 matrix, with a high resolution collimator. After reconstruction with a Metz filter, without corrections of attenuations, the coronal and cross sections were recorded on films in a standard procedure. These were visually interpreted by two independent senior physicians. The procedure has been tolerated by all the patients. Differences of pulmonary perfusion occurred at rest in comparison with the in-effort condition in 4 patients. In all the cases concerned were the zones of pulmonary parenchyma appearing as strongly injured in tomodensitometry. The in-effort pulmonary perfusion improves in 3 patients and impairs in one patient. The role of bubble and implied pulmonary diseases in the deterioration of pulmonary function, respectively, is difficult to estimate. The improvement of in-effort pulmonary perfusion could suggest the persistence of functional pulmonary tissue. On the other side, its deterioration could express the compressive character of bubbles and thus could be an indicator of severity. The observation during this pilot study of the differences between at-rest and in-effort pulmonary perfusion urges utilisation of a tool of analysis of image superposition (PPTS and scans) to study in a group of patients the correlations between the perfusion variations and the post-surgery development, in order to know better the pathophysiology of diseases and select better the patients

Effort-reward imbalance and one-year change in neck-shoulder and upper extremity pain among call center computer operators.

Science.gov (United States)

Krause, Niklas; Burgel, Barbara; Rempel, David

2010-01-01

The literature on psychosocial job factors and musculoskeletal pain is inconclusive in part due to insufficient control for confounding by biomechanical factors. The aim of this study was to investigate prospectively the independent effects of effort-reward imbalance (ERI) at work on regional musculoskeletal pain of the neck and upper extremities of call center operators after controlling for (i) duration of computer use both at work and at home, (ii) ergonomic workstation design, (iii) physical activities during leisure time, and (iv) other individual worker characteristics. This was a one-year prospective study among 165 call center operators who participated in a randomized ergonomic intervention trial that has been described previously. Over an approximate four-week period, we measured ERI and 28 potential confounders via a questionnaire at baseline. Regional upper-body pain and computer use was measured by weekly surveys for up to 12 months following the implementation of ergonomic interventions. Regional pain change scores were calculated as the difference between average weekly pain scores pre- and post intervention. A significant relationship was found between high average ERI ratios and one-year increases in right upper-extremity pain after adjustment for pre-intervention regional mean pain score, current and past physical workload, ergonomic workstation design, and anthropometric, sociodemographic, and behavioral risk factors. No significant associations were found with change in neck-shoulder or left upper-extremity pain. This study suggests that ERI predicts regional upper-extremity pain in -computer operators working >or=20 hours per week. Control for physical workload and ergonomic workstation design was essential for identifying ERI as a risk factor.

HIV Persistence in Adipose Tissue Reservoirs.

Science.gov (United States)

Couturier, Jacob; Lewis, Dorothy E

2018-02-01

The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

Variation in faecal water content may confound estimates of gastro-intestinal parasite intensity in wild African herbivores.

Science.gov (United States)

Turner, W C; Cizauskas, C A; Getz, W M

2010-03-01

Estimates of parasite intensity within host populations are essential for many studies of host-parasite relationships. Here we evaluated the seasonal, age- and sex-related variability in faecal water content for two wild ungulate species, springbok (Antidorcas marsupialis) and plains zebra (Equus quagga). We then assessed whether or not faecal water content biased conclusions regarding differences in strongyle infection rates by season, age or sex. There was evidence of significant variation in faecal water content by season and age for both species, and by sex in springbok. Analyses of faecal egg counts demonstrated that sex was a near-significant factor in explaining variation in strongyle parasite infection rates in zebra (P = 0.055) and springbok (P = 0.052) using wet-weight faecal samples. However, once these intensity estimates were re-scaled by the percent of dry matter in the faeces, sex was no longer a significant factor (zebra, P = 0.268; springbok, P = 0.234). These results demonstrate that variation in faecal water content may confound analyses and could produce spurious conclusions, as was the case with host sex as a factor in the analysis. We thus recommend that researchers assess whether water variation could be a confounding factor when designing and performing research using faecal indices of parasite intensity.

Dopamine and Effort-Based Decision Making

Directory of Open Access Journals (Sweden)

Irma Triasih Kurniawan

2011-06-01

Full Text Available Motivational theories of choice focus on the influence of goal values and strength of reinforcement to explain behavior. By contrast relatively little is known concerning how the cost of an action, such as effort expended, contributes to a decision to act. Effort-based decision making addresses how we make an action choice based on an integration of action and goal values. Here we review behavioral and neurobiological data regarding the representation of effort as action cost, and how this impacts on decision making. Although organisms expend effort to obtain a desired reward there is a striking sensitivity to the amount of effort required, such that the net preference for an action decreases as effort cost increases. We discuss the contribution of the neurotransmitter dopamine (DA towards overcoming response costs and in enhancing an animal’s motivation towards effortful actions. We also consider the contribution of brain structures, including the basal ganglia (BG and anterior cingulate cortex (ACC, in the internal generation of action involving a translation of reward expectation into effortful action.

Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness

International Nuclear Information System (INIS)

Britten, R.A.; Evans, A.J.; Allalunis-Turner, M.J.; Franko, A.J.; Pearcey, R.G.

1996-01-01

The level of intra-tumoral heterogeneity of cellular radiosensitivity within primary cultures of three carcinomas of the cervix has been established. All three cultures contained clones that varied by as much as 3-fold in their clinically relevant radiosensitivity (SF 2 ). The level of intra-tumoral heterogeneity observed in these cervical tumour cultures was sufficient to be a major confounding factor to the use of pre-treatment assessments of radiosensitivity to predict for clinical radioresponsiveness. Mathematical modeling of the relative elimination of the tumour clones during fractionated radiotherapy indicates that, in two of the three biopsy samples, the use of pre-treatment derived SF 2 values from the heterogeneous tumour sample would significantly overestimate radioresponsiveness. We conclude that assays of cellular radiosensitivity that identify the radiosensitivity of the most radioresistant clones and measure their relative abundance could potentially increase the effectiveness of SF 2 values as a predictive marker of radioresponsiveness

Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

Science.gov (United States)

Yong, Chin-Khian

2013-09-01

A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

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

Science.gov (United States)

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

2016-09-01

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. 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. miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Tissue engineering and surgery: from translational studies to human trials

Directory of Open Access Journals (Sweden)

Vranckx Jan Jeroen

2017-06-01

Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination

International Nuclear Information System (INIS)

Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

2012-01-01

Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Highlights: ► Study of potential bias associated with the use of infected zebra mussels in ecotoxicological studies. ► Presence of infected mussels on banks and channels, up- and downstream a waste water treatment plant. ► Parasitism influence on biological responses dependent of mussel population history. ► Integrative index, an interesting tool to synthesize the set of biological data. - Parasitism influence on the host physiology would be strongly dependent on environmental conditions but remains a potential confounding factor in ecotoxicological studies.

Marital well-being and depression in Chinese marriage: Going beyond satisfaction and ruling out critical confounders.

Science.gov (United States)

Cao, Hongjian; Zhou, Nan; Fang, Xiaoyi; Fine, Mark

2017-09-01

Based on data obtained from 203 Chinese couples during the early years of marriage and utilizing the actor-partner interdependence model, this study examined the prospective associations between different aspects of marital well-being (i.e., marital satisfaction, instability, commitment, and closeness) and depressive symptoms (assessed 2 years later) while controlling for critical intrapersonal (i.e., neuroticism and self-esteem) and contextual (i.e., stressful life events) confounders. Results indicated that (a) when considering different aspects of marital well-being as predictors of depressive symptoms separately, each aspect was significantly associated with spouses' own subsequent depressive symptoms; (b) when examining various aspects of marital well-being simultaneously, only husbands' commitment, husbands' instability, and wives' instability were significantly associated with their own subsequent depressive symptoms above and beyond the other aspects; and (c) the associations between husbands' commitment, husbands' instability, and wives' instability and their own subsequent depressive symptoms remained significant even after controlling for potential major intrapersonal and contextual confounders. Such findings (a) provide evidence that the marital discord model of depression may apply to Chinese couples, (b) highlight the importance of going beyond marital (dis)satisfaction when examining the association between marital well-being and depression, and (c) demonstrate that marital well-being can account for unique variance in depressive symptoms above and beyond an array of intrapersonal and contextual risk factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Applying the Health Belief Model and an Integrated Behavioral Model to Promote Breast Tissue Donation Among Asian Americans.

Science.gov (United States)

Shafer, Autumn; Kaufhold, Kelly; Luo, Yunjuan

2018-07-01

An important part in the effort to prevent, treat, and cure breast cancer is research done with healthy breast tissue. The Susan G. Komen for the Cure Tissue Bank at Indiana University Simon Cancer Center (KTB) encourages women to donate a small amount of healthy breast tissue and then provides that tissue to researchers studying breast cancer. Although KTB has a large donor base, the volume of tissue samples from Asian women is low despite prior marketing efforts to encourage donation among this population. This study builds on prior work promoting breast cancer screenings among Asian women by applying constructs from the Health Belief Model (HBM) and the Integrated Behavioral Model (IBM) to investigate why Asian-American women are less inclined to donate their healthy breast tissue than non-Asian women and how this population may be motivated to donate in the future. A national online survey (N = 1,317) found Asian women had significantly lower perceived severity, some lower perceived benefits, and higher perceived barriers to tissue donation than non-Asian women under HBM and significantly lower injunctive norms supporting breast tissue donation, lower perceived behavioral control, and lower intentions to donate under IBM. This study also compares and discusses similarities and differences among East, Southeast, and South Asian women on these same constructs.

Cross-sectional analysis of food choice frequency, sleep confounding beverages, and psychological distress predictors of sleep quality.

Science.gov (United States)

Knowlden, Adam P; Burns, Maranda; Harcrow, Andy; Shewmake, Meghan E

2016-03-16

Poor sleep quality is a significant public health problem. The role of nutrition in predicting sleep quality is a relatively unexplored area of inquiry. The purpose of this study was to evaluate the capacity of 10 food choice categories, sleep confounding beverages, and psychological distress to predict the sleep quality of college students. A logistic regression model comprising 10 food choice variables (healthy proteins, unhealthy proteins, healthy dairy, unhealthy dairy, healthy grains, unhealthy grains, healthy fruits and vegetables, unhealthy empty calories, healthy beverages, unhealthy beverages), sleep confounding beverages (caffeinated/alcoholic beverages), as well as psychological distress (low, moderate, serious distress) was computed to determine the capacity of the variables to predict sleep quality (good/poor). The odds of poor sleep quality were 32.4% lower for each unit of increased frequency of healthy proteins consumed (pempty calorie food choices consumed (p=0.003; OR=1.131), and 107.3% higher for those classified in the moderate psychological distress (p=0.016; OR=2.073). Collectively, healthy proteins, healthy dairy, unhealthy empty calories, and moderate psychological distress were moderately predictive of sleep quality in the sample (Nagelkerke R2=23.8%). Results of the study suggested higher frequency of consumption of healthy protein and healthy dairy food choices reduced the odds of poor sleep quality, while higher consumption of empty calories and moderate psychological distress increased the odds of poor sleep quality.

A review of soft-tissue sarcomas: translation of biological advances into treatment measures

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Hoang NT

2018-05-01

Full Text Available Ngoc T Hoang,* Luis A Acevedo,* Michael J Mann, Bhairavi Tolani Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA *These authors contributed equally to this work Abstract: Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. Keywords: sarcoma, molecular pathways, immunotherapy, genomics

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

Science.gov (United States)

Lawn, Will; Freeman, Tom P; Pope, Rebecca A; Joye, Alyssa; Harvey, Lisa; Hindocha, Chandni; Mokrysz, Claire; Moss, Abigail; Wall, Matthew B; Bloomfield, Michael Ap; Das, Ravi K; Morgan, Celia Ja; Nutt, David J; Curran, H Valerie

2016-10-01

Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

Tissue Sampling Guides for Porcine Biomedical Models.

Science.gov (United States)

Albl, Barbara; Haesner, Serena; Braun-Reichhart, Christina; Streckel, Elisabeth; Renner, Simone; Seeliger, Frank; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

2016-04-01

This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. © The Author(s) 2016.

An Alternative Method of Evaluating 1540NM Exposure Laser Damage using an Optical Tissue Phantom

National Research Council Canada - National Science Library

Jindra, Nichole M; Figueroa, Manuel A; Rockwell, Benjamin A; Chavey, Lucas J; Zohner, Justin J

2006-01-01

An optical phantom was designed to physically and optically resemble human tissue, in an effort to provide an alternative for detecting visual damage resulting from inadvertent exposure to infrared lasers...

Mental effort affects vigilance enduringly: after-effects in EEG and behavior

NARCIS (Netherlands)

Smit, A.S.; Eling, P.A.T.M.; Coenen, A.M.L.

2004-01-01

Vigilance is assumed to decline with sustained task performance. The EEG-effects during performance on mental tasks, however, cannot be ascribed indisputably to vigilance decline per se. During task performance itself, effects of information processing and vigilance decline may be confounded. In

Incentive Design and Mis-Allocated Effort

OpenAIRE

Schnedler, Wendelin

2013-01-01

Incentives often distort behavior: they induce agents to exert effort but this effort is not employed optimally. This paper proposes a theory of incentive design allowing for such distorted behavior. At the heart of the theory is a trade-off between getting the agent to exert effort and ensuring that this effort is used well. The theory covers various moral-hazard models, ranging from traditional single-task to multi-task models. It also provides -for the first time- a formalization and proof...

High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions.

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Tianjiao Chu

Full Text Available Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV was used to determine the "Genomic Variants Frequency" (GVF for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically.

A systematic review on soft-to-hard tissue ratios in orthognathic surgery part II: Chin procedures.

Science.gov (United States)

San Miguel Moragas, Joan; Oth, Olivier; Büttner, Michael; Mommaerts, Maurice Y

2015-10-01

evidence level IIIb, three were evidence level IIb, and the rest were evidence level IV. Three studies were prospective in nature. A high variability of soft-to-hard tissue ratios regarding genioplasty seemed to disappear if data were stratified according to confounding factors. With the available data, a soft-to-hard pogonion ratio of 0.9:1 and 0.55:1 could be used for chin advancement and chin setback surgery, respectively. Advancement and extrusion movements of the chin segment show respectively a 0.9:1 of sPg:Pg horizontally and 0.95:1 of sMe:Me vertically. Setback and impaction movements show respectively a -0.52:1 of sPg:Pg horizontally and -0.43:1 of sMe:Me vertically. Prospective studies are needed that stratify by confounding factors such as type of osteotomy technique, magnitude of the movement, age, sex, race/ethnicity, and quantity and quality of the soft tissues. More specifically, studies are needed regarding soft-to-hard tissue changes after chin extrusion ("downgrafting"), intrusion ("impaction"), and widening and narrowing surgery. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Measurement of the tissue to A-150 tissue equivalent plastic kerma ratio at two p(66)Be neutron therapy facilities

International Nuclear Information System (INIS)

Langen, K M; Binns, P J; Schreuder, A N; Lennox, A J; Deluca, P M Jr.

2003-01-01

The ICRU tissue to A-150 tissue equivalent plastic kerma ratio is needed for neutron therapy dosimetry. The current ICRU protocol for neutron dosimetry recommends using a common conversion factor of 0.95 at all high-energy neutron therapy facilities. In an effort to determine facility specific ICRU tissue to A-150 plastic kerma ratios, an experimental approach was pursued. Four low pressure proportional counters that differed in wall materials (i.e. A-150, carbon, zirconium and zirconium-oxide) were used as dosimeters and integral kerma ratios were determined directly in the clinical beam. Measurements were performed at two p(66)Be facilities: iThemba LABS near Cape Town and Fermilab near Chicago. At the iThemba facility the clinical neutron beam is routinely filtered by a flattening and hardening filter combination. The influence of beam filtration on the kerma ratio was evaluated. Using two recent gas-to-wall dose conversion factor (r m,g value) evaluations a mean ICRU tissue to A-150 plastic kerma ratio of 0.93 ± 0.05 was determined for the clinical beam at iThemba LABS. The respective value for the Fermilab beam is 0.95 ± 0.05. The experimentally determined ICRU tissue to A-150 plastic kerma ratios for the two clinical beams are in agreement with theoretical evaluations. Beam filtration reduces the kerma ratio by 3 ± 2%

Estimation of total Effort and Effort Elapsed in Each Step of Software Development Using Optimal Bayesian Belief Network

Directory of Open Access Journals (Sweden)

Fatemeh Zare Baghiabad

2017-09-01

Full Text Available Accuracy in estimating the needed effort for software development caused software effort estimation to be a challenging issue. Beside estimation of total effort, determining the effort elapsed in each software development step is very important because any mistakes in enterprise resource planning can lead to project failure. In this paper, a Bayesian belief network was proposed based on effective components and software development process. In this model, the feedback loops are considered between development steps provided that the return rates are different for each project. Different return rates help us determine the percentages of the elapsed effort in each software development step, distinctively. Moreover, the error measurement resulted from optimized effort estimation and the optimal coefficients to modify the model are sought. The results of the comparison between the proposed model and other models showed that the model has the capability to highly accurately estimate the total effort (with the marginal error of about 0.114 and to estimate the effort elapsed in each software development step.

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

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Yuko Kurushima

Full Text Available 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.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.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.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.

The impact of bilinguism on cognitive aging and dementia:Finding a path through a forest of confounding variables

OpenAIRE

Bak, Thomas

2016-01-01

Within the current debates on cognitive reserve, cognitive aging and dementia, showing increasingly a positive effect of mental, social and physical activities on health in older age, bilingualism remains one of the most controversial issues. Some reasons for it might be social or even ideological. However, one of the most important genuine problems facing bilingualism research is the high number of potential confounding variables. Bilingual communities often differ from monolingual ones in a...

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

Science.gov (United States)

Sood, Sanjana; Gallagher, Iain J; Lunnon, Katie; Rullman, Eric; Keohane, Aoife; Crossland, Hannah; Phillips, Bethan E; Cederholm, Tommy; Jensen, Thomas; van Loon, Luc J C; Lannfelt, Lars; Kraus, William E; Atherton, Philip J; Howard, Robert; Gustafsson, Thomas; Hodges, Angela; Timmons, James A

2015-09-07

Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

Adipose tissue fatty acid patterns and changes in anthropometry: a cohort study.

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Christina Catherine Dahm

Full Text Available INTRODUCTION: Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA, but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA, may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue fatty acids and changes in anthropometry. METHODS: 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC, and WC controlled for changes in body mass index (WC(BMI, adjusting for confounders. RESULTS: 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men and women, respectively. Fatty acid patterns with high levels of TFA tended to be positively associated with changes in weight and WC for both sexes. Patterns with high levels of n-6 LC-PUFA tended to be negatively associated with changes in weight and WC in men, and positively associated in women. Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern. CONCLUSIONS: Adipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss. Associations depended on characteristics of the rest of the pattern.

Mental and physical effort affect vigilance differently

NARCIS (Netherlands)

Smit, A.S.; Eling, P.A.T.M.; Hopman, M.T.E.; Coenen, A.M.L.

2005-01-01

Both physical and mental effort are thought to affect vigilance. Mental effort is known for its vigilance declining effects, but the effects of physical effort are less clear. This study investigated whether these two forms of effort affect the EEG and subjective alertness differently. Participants

Mental and physical effort affect vigilance differently.

NARCIS (Netherlands)

Smit, A.S.; Eling, P.A.T.M.; Hopman, M.T.E.; Coenen, A.M.L.

2005-01-01

Both physical and mental effort are thought to affect vigilance. Mental effort is known for its vigilance declining effects, but the effects of physical effort are less clear. This study investigated whether these two forms of effort affect the EEG and subjective alertness differently. Participants

Low-effort thought promotes political conservatism.

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Eidelman, Scott; Crandall, Christian S; Goodman, Jeffrey A; Blanchar, John C

2012-06-01

The authors test the hypothesis that low-effort thought promotes political conservatism. In Study 1, alcohol intoxication was measured among bar patrons; as blood alcohol level increased, so did political conservatism (controlling for sex, education, and political identification). In Study 2, participants under cognitive load reported more conservative attitudes than their no-load counterparts. In Study 3, time pressure increased participants' endorsement of conservative terms. In Study 4, participants considering political terms in a cursory manner endorsed conservative terms more than those asked to cogitate; an indicator of effortful thought (recognition memory) partially mediated the relationship between processing effort and conservatism. Together these data suggest that political conservatism may be a process consequence of low-effort thought; when effortful, deliberate thought is disengaged, endorsement of conservative ideology increases.

Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance.

Science.gov (United States)

Freydefont, Laure; Gollwitzer, Peter M; Oettingen, Gabriele

2016-09-01

Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Childhood trauma is not a confounder of the overlap between autistic and schizotypal traits: A study in a non-clinical adult sample.

Science.gov (United States)

Gong, Jing-Bo; Wang, Ya; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K

2017-11-01

Childhood trauma has been shown to be a robust risk factor for mental disorders, and may exacerbate schizotypal traits or contribute to autistic trait severity. However, little is known whether childhood trauma confounds the overlap between schizotypal traits and autistic traits. This study examined whether childhood trauma acts as a confounding variable in the overlap between autistic and schizotypal traits in a large non-clinical adult sample. A total of 2469 participants completed the Autism Spectrum Quotient (AQ), the Schizotypal Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short Form. Correlation analysis showed that the majority of associations between AQ variables and SPQ variables were significant (p autistic and schizotypal traits could not be explained by shared variance in terms of exposure to childhood trauma. The findings point to important overlaps in the conceptualization of ASD and SSD, independent of childhood trauma. Copyright © 2017 Elsevier B.V. All rights reserved.

Is the association between general cognitive ability and violent crime caused by family-level confounders?

Science.gov (United States)

Frisell, Thomas; Pawitan, Yudi; Långström, Niklas

2012-01-01

Research has consistently found lower cognitive ability to be related to increased risk for violent and other antisocial behaviour. Since this association has remained when adjusting for childhood socioeconomic position, ethnicity, and parental characteristics, it is often assumed to be causal, potentially mediated through school adjustment problems and conduct disorder. Socioeconomic differences are notoriously difficult to quantify, however, and it is possible that the association between intelligence and delinquency suffer substantial residual confounding. We linked longitudinal Swedish total population registers to study the association of general cognitive ability (intelligence) at age 18 (the Conscript Register, 1980-1993) with the incidence proportion of violent criminal convictions (the Crime Register, 1973-2009), among all men born in Sweden 1961-1975 (N = 700,514). Using probit regression, we controlled for measured childhood socioeconomic variables, and further employed sibling comparisons (family pedigree data from the Multi-Generation Register) to adjust for shared familial characteristics. Cognitive ability in early adulthood was inversely associated to having been convicted of a violent crime (β = -0.19, 95% CI: -0.19; -0.18), the association remained when adjusting for childhood socioeconomic factors (β = -0.18, 95% CI: -0.18; -0.17). The association was somewhat lower within half-brothers raised apart (β = -0.16, 95% CI: -0.18; -0.14), within half-brothers raised together (β = -0.13, 95% CI: (-0.15; -0.11), and lower still in full-brother pairs (β = -0.10, 95% CI: -0.11; -0.09). The attenuation among half-brothers raised together and full brothers was too strong to be attributed solely to attenuation from measurement error. Our results suggest that the association between general cognitive ability and violent criminality is confounded partly by factors shared by brothers. However, most of the association remains even

Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment.

Science.gov (United States)

Barch, Deanna M; Treadway, Michael T; Schoen, Nathan

2014-05-01

One of the most debilitating aspects of schizophrenia is an apparent interest in or ability to exert effort for rewards. Such "negative symptoms" may prevent individuals from obtaining potentially beneficial outcomes in educational, occupational, or social domains. In animal models, dopamine abnormalities decrease willingness to work for rewards, implicating dopamine (DA) function as a candidate substrate for negative symptoms given that schizophrenia involves dysregulation of the dopamine system. We used the effort-expenditure for rewards task (EEfRT) to assess the degree to which individuals with schizophrenia were wiling to exert increased effort for either larger magnitude rewards or for rewards that were more probable. Fifty-nine individuals with schizophrenia and 39 demographically similar controls performed the EEfRT task, which involves making choices between "easy" and "hard" tasks to earn potential rewards. Individuals with schizophrenia showed less of an increase in effort allocation as either reward magnitude or probability increased. In controls, the frequency of choosing the hard task in high reward magnitude and probability conditions was negatively correlated with depression severity and anhedonia. In schizophrenia, fewer hard task choices were associated with more severe negative symptoms and worse community and work function as assessed by a caretaker. Consistent with patterns of disrupted dopamine functioning observed in animal models of schizophrenia, these results suggest that 1 mechanism contributing to impaired function and motivational drive in schizophrenia may be a reduced allocation of greater effort for higher magnitude or higher probability rewards.

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

Science.gov (United States)

Borovjagin, Anton V.; Ogle, Brenda; Berry, Joel; Zhang, Jianyi

2016-01-01

Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional two-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and pre-clinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents. PMID:28057791

A short review: Recent advances in electrospinning for bone tissue regeneration

Directory of Open Access Journals (Sweden)

Song-Hee Shin

2012-12-01

Full Text Available Nanofibrous structures developed by electrospinning technology provide attractive extracellular matrix conditions for the anchorage, migration, and differentiation of tissue cells, including those responsible for the regeneration of hard tissues. Together with the ease of set up and cost-effectiveness, the possibility to produce nanofibers with a wide range of compositions and morphologies is the merit of electrospinning. Significant efforts have exploited the development of bone regenerative nanofibers, which includes tailoring of composite/hybrid compositions that are bone mimicking and the surface functionalization such as mineralization. Moreover, by utilizing bioactive molecules such as adhesive proteins, growth factors, and chemical drugs, in concert with the nanofibrous matrices, it is possible to provide artificial materials with improved cellular responses and therapeutic efficacy. These studies have mainly focused on the regulation of stem cell behaviors for use in regenerative medicine and tissue engineering. While there are some challenges in achieving controllable delivery of bioactive molecules and complex-shaped three-dimensional scaffolds for tissue engineering, the electrospun nanofibrous matrices can still have a beneficial impact in the area of hard-tissue regeneration.

Non-Chemical Distant Cellular Interactions as a potential confounder of Cell Biology Experiments

Directory of Open Access Journals (Sweden)

Ashkan eFarhadi

2014-10-01

Full Text Available 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.

Tissue engineering by self-assembly and bio-printing of living cells

International Nuclear Information System (INIS)

Jakab, Karoly; Marga, Francoise; Forgacs, Gabor; Norotte, Cyrille; Murphy, Keith; Vunjak-Novakovic, Gordana

2010-01-01

Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion. (topical review)

Tissue engineering by self-assembly and bio-printing of living cells

Energy Technology Data Exchange (ETDEWEB)

Jakab, Karoly; Marga, Francoise; Forgacs, Gabor [Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211 (United States); Norotte, Cyrille [Department of Biology, University of Missouri, Columbia, MO 65211 (United States); Murphy, Keith [Organovo, Inc., 5871 Oberlin Drive, San Diego, CA 92121 (United States); Vunjak-Novakovic, Gordana, E-mail: forgacsg@missouri.ed [Department of Biomedical Engineering, Columbia University, New York, NY 10032 (United States)

2010-06-15

Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion. (topical review)

Recent advancements in electrospinning design for tissue engineering applications: A review.

Science.gov (United States)

Kishan, Alysha P; Cosgriff-Hernandez, Elizabeth M

2017-10-01

Electrospinning, a technique used to fabricate fibrous scaffolds, has gained popularity in recent years as a method to produce tissue engineered grafts with architectural similarities to the extracellular matrix. Beyond its versatility in material selection, electrospinning also provides many tools to tune the fiber morphology and scaffold geometry. Recent efforts have focused on extending the capabilities of electrospinning to produce scaffolds that better recapitulate tissue properties and enhance regeneration. This review highlights these advancements by providing an overview of the processing variables and setups used to modulate scaffold architecture, discussing strategies to improve cellular infiltration and guide cell behavior, and providing a summary of electrospinning applications in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2892-2905, 2017. © 2017 Wiley Periodicals, Inc.

Raman Spectroscopy of Ocular Tissue

Science.gov (United States)

Ermakov, Igor V.; Sharifzadeh, Mohsen; Gellermann, Warner

The optically transparent nature of the human eye has motivated numerous Raman studies aimed at the non-invasive optical probing of ocular tissue components critical to healthy vision. Investigations include the qualitative and quantitative detection of tissue-specific molecular constituents, compositional changes occurring with development of ocular pathology, and the detection and tracking of ocular drugs and nutritional supplements. Motivated by a better understanding of the molecular mechanisms leading to cataract formation in the aging human lens, a great deal of work has centered on the Raman detection of proteins and water content in the lens. Several protein groups and the hydroxyl response are readily detectable. Changes of protein compositions can be studied in excised noncataractous tissue versus aged tissue preparations as well as in tissue samples with artificially induced cataracts. Most of these studies are carried out in vitro using suitable animal models and conventional Raman techniques. Tissue water content plays an important role in optimum light transmission of the outermost transparent ocular structure, the cornea. Using confocal Raman spectroscopy techniques, it has been possible to non-invasively measure the water to protein ratio as a measure of hydration status and to track drug-induced changes of the hydration levels in the rabbit cornea at various depths. The aqueous humor, normally supplying nutrients to cornea and lens, has an advantageous anterior location for Raman studies. Increasing efforts are pursued to non-invasively detect the presence of glucose and therapeutic concentrations of antibiotic drugs in this medium. In retinal tissue, Raman spectroscopy proves to be an important tool for research into the causes of macular degeneration, the leading cause of irreversible vision disorders and blindness in the elderly. It has been possible to detect the spectral features of advanced glycation and advanced lipooxydation end products in

Quality-oriented efforts in IPD, - a framework

DEFF Research Database (Denmark)

Andreasen, Mogens Myrup

1998-01-01

It is generally expected that modern quality efforts like TQM and ISO9000 should deliver a sufficient framework for quality efforts in industrial companies. Our findings in Danish industry shows a fragmented picture of islands of efforts and a weak understanding of basic quality concepts between...... designers. The paper propose a framework for quality efforts, illustrated by simple metaphors....

Learning Environment and Student Effort

Science.gov (United States)

Hopland, Arnt O.; Nyhus, Ole Henning

2016-01-01

Purpose: The purpose of this paper is to explore the relationship between satisfaction with learning environment and student effort, both in class and with homework assignments. Design/methodology/approach: The authors use data from a nationwide and compulsory survey to analyze the relationship between learning environment and student effort. The…

Tissue banking in Hungary: legal, ethical and technical frame

International Nuclear Information System (INIS)

Pellet, S.; Ternesi, A.

1999-01-01

Hungary is a small country in the middle of Europe with a population of 10 million. Many religions are represented in the country but the majority of the population is Christian. The Hungarian medical education and practice based on the 'German School' and the modem medicine has been started more than 200 years ago. At the same time some of the medical school have been established first in Nagyszombat and the school for surgery in Kolozsyar, later in Debrecen 80 years ago. Recently we have four medical faculties. From the beginning of implementation of modern medicine many efforts were taken to establish the relevant legal frame and ethical rules to help and make understandable and acceptable for the society of various medical interventions. The previous mentioned structure was before and presently conformed with the political and social structure of the country. The initial of tissue for transplantation in medicine was widely accepted by medical fraternity since the middle of the century. Recently tissue grafts are performed daily is in burn, reconstructive surgery, in bone and nerve surgery, unfortunately we use commercial products in heart surgery. At the initial phase of our tissue banking activity, we first followed the American Association Tissue Banking procedures based on our personal contact with leading US Tissue Bank and the American Association of Tissue Banks. Later after joining the Europe Association of Tissue Bank we played an active role in the establishing of the Europe recommendations related to legal, ethical and technical rules of tissue banking. In this presentation the legal frame and the recent ethical concept for tissue donation as well as the technical possibilities and the donor recreation programme of tissue banks will be introduced to the audience. Also the problems of legal harmonization will be mentioned to which we are facing as an associated country to the European Union

Fluid mechanics as a driver of tissue-scale mechanical signaling in organogenesis.

Science.gov (United States)

Gilbert, Rachel M; Morgan, Joshua T; Marcin, Elizabeth S; Gleghorn, Jason P

2016-12-01

Organogenesis is the process during development by which cells self-assemble into complex, multi-scale tissues. Whereas significant focus and research effort has demonstrated the importance of solid mechanics in organogenesis, less attention has been given to the fluid forces that provide mechanical cues over tissue length scales. Fluid motion and pressure is capable of creating spatial gradients of forces acting on cells, thus eliciting distinct and localized signaling patterns essential for proper organ formation. Understanding the multi-scale nature of the mechanics is critically important to decipher how mechanical signals sculpt developing organs. This review outlines various mechanisms by which tissues generate, regulate, and sense fluid forces and highlights the impact of these forces and mechanisms in case studies of normal and pathological development.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

Science.gov (United States)

Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

2016-11-25

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Effort-Based Decision-Making in Schizophrenia.

Science.gov (United States)

Culbreth, Adam J; Moran, Erin K; Barch, Deanna M

2018-08-01

Motivational impairment has long been associated with schizophrenia but the underlying mechanisms are not clearly understood. Recently, a small but growing literature has suggested that aberrant effort-based decision-making may be a potential contributory mechanism for motivational impairments in psychosis. Specifically, multiple reports have consistently demonstrated that individuals with schizophrenia are less willing than healthy controls to expend effort to obtain rewards. Further, this effort-based decision-making deficit has been shown to correlate with severity of negative symptoms and level of functioning, in many but not all studies. In the current review, we summarize this literature and discuss several factors that may underlie aberrant effort-based decision-making in schizophrenia.

Effort Estimation in BPMS Migration

Directory of Open Access Journals (Sweden)

Christopher Drews

2018-04-01

Full Text Available Usually Business Process Management Systems (BPMS are highly integrated in the IT of organizations and are at the core of their business. Thus, migrating from one BPMS solution to another is not a common task. However, there are forces that are pushing organizations to perform this step, e.g. maintenance costs of legacy BPMS or the need for additional functionality. Before the actual migration, the risk and the effort must be evaluated. This work provides a framework for effort estimation regarding the technical aspects of BPMS migration. The framework provides questions for BPMS comparison and an effort evaluation schema. The applicability of the framework is evaluated based on a simplified BPMS migration scenario.

The tissue microarray OWL schema: An open-source tool for sharing tissue microarray data

Directory of Open Access Journals (Sweden)

Hyunseok P Kang

2010-01-01

Full Text Available Background: Tissue microarrays (TMAs are enormously useful tools for translational research, but incompatibilities in database systems between various researchers and institutions prevent the efficient sharing of data that could help realize their full potential. Resource Description Framework (RDF provides a flexible method to represent knowledge in triples, which take the form Subject- Predicate-Object. All data resources are described using Uniform Resource Identifiers (URIs, which are global in scope. We present an OWL (Web Ontology Language schema that expands upon the TMA data exchange specification to address this issue and assist in data sharing and integration. Methods: A minimal OWL schema was designed containing only concepts specific to TMA experiments. More general data elements were incorporated from predefined ontologies such as the NCI thesaurus. URIs were assigned using the Linked Data format. Results: We present examples of files utilizing the schema and conversion of XML data (similar to the TMA DES to OWL. Conclusion: By utilizing predefined ontologies and global unique identifiers, this OWL schema provides a solution to the limitations of XML, which represents concepts defined in a localized setting. This will help increase the utilization of tissue resources, facilitating collaborative translational research efforts.

Dopamine, behavioral economics, and effort

Directory of Open Access Journals (Sweden)

John D Salamone

2009-09-01

Full Text Available Abstract. There are numerous problems with the hypothesis that brain dopamine (DA systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding to other concepts and lines of inquiry. The present review is focused upon the involvement of nucleus accumbens DA in behavioral activation and effort-related processes. Viewed from the framework of behavioral economics, the effects of accumbens DA depletions and antagonism on food-reinforced behavior are highly dependent upon the work requirements of the instrumental task, and DA depleted rats are more sensitive to increases in response costs (i.e., ratio requirements. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related choice behavior. Rats with accumbens DA depletions or antagonism reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead these rats select a less-effortful type of food-seeking behavior. Nucleus accumbens DA and adenosine interact in the regulation of effort-related functions, and other brain structures (anterior cingulate cortex, amygdala, ventral pallidum also are involved. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue or anergia in depression and other neurological disorders.

Compromised Motor Dexterity Confounds Processing Speed Task Outcomes in Stroke Patients

Directory of Open Access Journals (Sweden)

Essie Low

2017-09-01

Full Text Available Most conventional measures of information processing speed require motor responses to facilitate performance. However, although not often addressed clinically, motor impairment, whether due to age or acquired brain injury, would be expected to confound the outcome measure of such tasks. The current study recruited 29 patients (20 stroke and 9 transient ischemic attack with documented reduction in dexterity of the dominant hand, and 29 controls, to investigate the extent to which 3 commonly used processing speed measures with varying motor demands (a Visuo-Motor Reaction Time task, and the Wechsler Adult Intelligence Scale-IV Symbol Search and Coding subtests may be measuring motor-related speed more so than cognitive speed. Analyses include correlations between indices of cognitive and motor speed obtained from two other tasks (Inspection Time and Pegboard task, respectively with the three speed measures, followed by hierarchical regressions to determine the relative contribution of cognitive and motor speed indices toward task performance. Results revealed that speed outcomes on tasks with relatively high motor demands, such as Coding, were largely reflecting motor speed in individuals with reduced dominant hand dexterity. Thus, findings indicate the importance of employing measures with minimal motor requirements, especially when the assessment of speed is aimed at understanding cognitive rather than physical function.

Some confounding factors in the study of mortality and occupational exposures

International Nuclear Information System (INIS)

Gilbert, E.S.

1982-01-01

With the recent interest in the study of occupational exposures, the impact of certain selective biases in the groups studied is a matter of some concern. In this paper, data from the Hanford nuclear facility population (southeastern Washington State, 1947-1976), which includes many radiation workers, are used to illustrate a method for examining the effect on mortality of such potentially confounding variables as calendar year, length of time since entering the industry, employment status, length of employment, job category, and initial employment year. The analysis, which is based on the Mantel-Haenszel procedure as adapted for a prospective study, differs from most previous studies of occupational variables which have relied primarily on comparing standardized mortality ratios (utilizing an external control) for various subgroups of the population. Results of this analysis confirm other studies in that reduced death rates are observed for early years of follow-up and for those with higher socioeconomic status (as indicated by job category). In addition, workers employed less than two years and especially terminated workers are found to have elevated death rates as compared with the remainder of the study population. It is important that such correlations be taken into account in planning and interpreting analyses of the effects of occupational exposure

"I put in effort, therefore I am passionate": Investigating the path from effort to passion in entrepreneurship

OpenAIRE

Gielnik, Michael Marcus; Spitzmuller, Matthias; Schmitt, Antje; Klemann, Katharina; Frese, Michael

2015-01-01

Most theoretical frameworks in entrepreneurship emphasize that entrepreneurial passion drives entrepreneurial effort. We hypothesize that the reverse effect is also true, and investigate changes in passion as an outcome of effort. Based on theories of self-regulation and self-perception, we hypothesize that making new venture progress and free choice are two factors that help to explain why and under which conditions entrepreneurial effort affects entrepreneurial passion. We undertook two stu...

Computational Modeling for Enhancing Soft Tissue Image Guided Surgery: An Application in Neurosurgery.

Science.gov (United States)

Miga, Michael I

2016-01-01

With the recent advances in computing, the opportunities to translate computational models to more integrated roles in patient treatment are expanding at an exciting rate. One area of considerable development has been directed towards correcting soft tissue deformation within image guided neurosurgery applications. This review captures the efforts that have been undertaken towards enhancing neuronavigation by the integration of soft tissue biomechanical models, imaging and sensing technologies, and algorithmic developments. In addition, the review speaks to the evolving role of modeling frameworks within surgery and concludes with some future directions beyond neurosurgical applications.

Evaluating ex vivo fluorescence confocal microscopy images of basal cell carcinomas in Mohs excised tissue.

Science.gov (United States)

Longo, C; Rajadhyaksha, M; Ragazzi, M; Nehal, K; Gardini, S; Moscarella, E; Lallas, A; Zalaudek, I; Piana, S; Argenziano, G; Pellacani, G

2014-09-01

Fluorescence confocal microscopy (FCM) is an emerging technology for rapid imaging of excised tissue, without the need for frozen- or fixed-section processing. Basal cell carcinomas (BCCs) can be detected in Mohs excisions although few studies have described the major BCC findings as seen on FCM. To describe the major BCC findings of excised tissue during Mohs surgery and to correlate them with histopathology. Freshly excised tumours and frozen-thawed discarded tissue of BCC during Mohs surgery were analysed by means of FCM. A side-by-side correlation between FCM images and histological sections was performed. The FCM features of overlying skin and adnexal structures were also described. Sixty-four BCC cases were analysed. Distinct BCC types appeared unique in terms of shape and size of tumour islands [bigger in nodular (18/25), smaller and rounded in micronodular (7/7) and tiny cords for infiltrative ones (24/30)] and for the presence of clefting, palisading and increased nucleus/cytoplasm ratio. An excellent correlation was found between FCM and histological findings (Cohen's κ statistics = 0·9). In six cases, the presence of sebaceous glands and intense stroma reaction represented possible confounders. Fluorescence confocal microscopy is a fast and new imaging technique that allows an excellent visualization of skin structures and BCC findings during Mohs surgery. © 2014 British Association of Dermatologists.

Multidisciplinary Efforts Driving Translational Theranostics

Science.gov (United States)

Hu, Tony Y.

2014-01-01

This themed issue summarizes significant efforts aimed at using “biological language” to discern between “friends” and “foes” in the context of theranostics for true clinical application. It is expected that the success of theranostics depends on multidisciplinary efforts, combined to expedite our understanding of host responses to “customized” theranostic agents and formulating individualized therapies. PMID:25285169

HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities.

Science.gov (United States)

Thompson, Corbin G; Gay, Cynthia L; Kashuba, Angela D M

2017-06-01

An increasing amount of evidence suggests that HIV replication persists in gut-associated lymphoid tissues (GALT), despite treatment with combination antiretroviral therapy (cART). Residual replication in this compartment may propagate infection at other sites in the body and contribute to sustained immune dysregulation and delayed immune recovery. Therefore, it is important to focus efforts on eliminating residual replication at this site. There are several challenges to accomplishing this goal, including low antiretroviral (ARV) exposure at specific tissue locations within GALT, which might be overcome by using the tools of clinical pharmacology. Here, we summarize the evidence for GALT as a site of residual HIV replication, highlight the consequences of persistent infection in tissues, identify current pharmacologic knowledge of drug exposure in GALT, define the challenges that hinder eradication from this site, and propose several avenues for pharmacologic intervention.

Effort levels of the partners in networked manufacturing

Science.gov (United States)

Chai, G. R.; Cai, Z.; Su, Y. N.; Zong, S. L.; Zhai, G. Y.; Jia, J. H.

2017-08-01

Compared with traditional manufacturing mode, could networked manufacturing improve effort levels of the partners? What factors will affect effort level of the partners? How to encourage the partners to improve their effort levels? To answer these questions, we introduce network effect coefficient to build effort level model of the partners in networked manufacturing. The results show that (1) with the increase of the network effect in networked manufacturing, the actual effort level can go beyond the ideal level of traditional manufacturing. (2) Profit allocation based on marginal contribution rate would help improve effort levels of the partners in networked manufacturing. (3) The partners in networked manufacturing who wishes to have a larger distribution ratio must make a higher effort level, and enterprises with insufficient effort should be terminated in networked manufacturing.

Correlation between radon level and confounders of cancer. A note on epidemiological inference at low doses

International Nuclear Information System (INIS)

Hajnal, M.A.; Toth, E.; Hamori, K.; Minda, M.; Koteles, Gy.J.

2007-01-01

Complete text of publication follows. Objective. The aim of this study was to examine and further clarify the extent of radon and progeny induced carcinogenesis, both separated from and combined with other confounders and health risk factors. This work was financed by National Development Agency, Hungary, with GVOP-3.1.1.-2004-05-0384/3.0. Methods. A case-control study was conducted in a Hungarian countryside region where the proportion of houses with yearly average radon level above 200 Bq.m -3 was estimated to be higher than 20% by our preceding regional surveys. Radon levels were measured with CR39 closed etched detectors for three seasons separately yielding yearly average by estimating the low summer level. The detectors were placed in the bedrooms, where people were expected to spend one third of a day. 520 patients with diagnosed cancers were included in these measurements, amongst which 77 developed lung or respiratory cancers. The control group consisted 6333 individuals, above 30 years of age. Lifestyle risk factors of cancers were collected by surveys including social status, pollution from indoor heating, smoking and alcohol history, nutrition, exercise and mental health index 5. Except smoking and alcohol habits, these cofactors were only available for the control group. Comparing disease occurrences the authors selected the multivariate generalised linear models. The case and control proportions along a given factor are binomially distributed, thus the logit link function was used. For radon both log and linear terms were probed for. Results. Many known health confounders of cancers correlated with radon levels, with an estimated total net increase of 50-150 Bq m -3 with increased risks. For lung cancers the model with the terms radon, age, gender and smoking was found to have the lowest Akaike Information Criterion (AIC). Heavy dependency on age, gender and smoking contribute largely to observed lung cancer incidence. However log linear relationship

Measuring collections effort improves cash performance.

Science.gov (United States)

Shutts, Joe

2009-09-01

Having a satisfied work force can lead to an improved collections effort. Hiring the right people and training them ensures employee engagement. Measuring collections effort and offering incentives is key to revenue cycle success.

Visual cues and listening effort: individual variability.

Science.gov (United States)

Picou, Erin M; Ricketts, Todd A; Hornsby, Benjamin W Y

2011-10-01

To investigate the effect of visual cues on listening effort as well as whether predictive variables such as working memory capacity (WMC) and lipreading ability affect the magnitude of listening effort. Twenty participants with normal hearing were tested using a paired-associates recall task in 2 conditions (quiet and noise) and 2 presentation modalities (audio only [AO] and auditory-visual [AV]). Signal-to-noise ratios were adjusted to provide matched speech recognition across audio-only and AV noise conditions. Also measured were subjective perceptions of listening effort and 2 predictive variables: (a) lipreading ability and (b) WMC. Objective and subjective results indicated that listening effort increased in the presence of noise, but on average the addition of visual cues did not significantly affect the magnitude of listening effort. Although there was substantial individual variability, on average participants who were better lipreaders or had larger WMCs demonstrated reduced listening effort in noise in AV conditions. Overall, the results support the hypothesis that integrating auditory and visual cues requires cognitive resources in some participants. The data indicate that low lipreading ability or low WMC is associated with relatively effortful integration of auditory and visual information in noise.

Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

Science.gov (United States)

Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

2017-06-01

In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

Science.gov (United States)

Ethier, C. R.; Best, L.; Gleason, R.; Mulugeta, L.; Myers, J. G.; Nelson, E. S.; Samuels, B. C.

2014-01-01

Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.

Science.gov (United States)

Suzuki, Masako; Maekawa, Ryo; Patterson, Nicole E; Reynolds, David M; Calder, Brent R; Reznik, Sandra E; Heo, Hye J; Einstein, Francine Hughes; Greally, John M

2016-01-01

Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8 % of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, using purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of the placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to proteinuria or hypertension and fetuses from normal pregnancies. We performed a genome-wide DNA methylation analysis, HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP)-tagging, on 62 amnion samples from the placentas of uncomplicated, normal pregnancies and from those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85, and 99 loci with high-confidence hypertension-associated, proteinuria-associated, and hypertension- and proteinuria-associated DNA methylation changes, respectively. A gene ontology analysis showed DNA methylation changes to be selecting genes with different biological processes in exposure status. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Our findings support prior observations that preeclampsia

Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage [version 2; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Darawan Rinchai

2016-10-01

Full Text Available Background: Members of the ADAM (a disintegrin and metalloprotease domain family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1 The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2 changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs. 3 Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes.

Culture Environment-Induced Pluripotency of SACK-Expanded Tissue Stem Cells

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Jean-François Paré

2011-01-01

Full Text Available Previous efforts to improve the efficiency of cellular reprogramming for the generation of induced pluripotent stem cells (iPSCs have focused mainly on transcription factors and small molecule combinations. Here, we report the results of our focus instead on the phenotype of the cells targeted for reprogramming. We find that adult mouse pancreatic tissue stem cells derived by the method of suppression of asymmetric cell kinetics (SACK acquire increased potency simply by culture under conditions for the production and maintenance of pluripotent stem cells. Moreover, supplementation with the SACK agent xanthine, which promotes symmetric self-renewal, significantly increases the efficiency and degree of acquisition of pluripotency properties. In transplantation analyses, clonal reprogrammed pancreatic stem cells produce slow-growing tumors with tissue derivative of all three embryonic germ layers. This acquisition of pluripotency, without transduction with exogenous transcription factors, supports the concept that tissue stem cells are predisposed to cellular reprogramming, particularly when symmetrically self-renewing.

Sociocultural perspective on organ and tissue donation among reservation-dwelling American Indian adults.

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Fahrenwald, Nancy L; Stabnow, Wendy

2005-11-01

To discover the sociocultural patterns that influence decisions about organ and tissue donation among American Indian (AI) adults. This qualitative ethnographic study used a social-ecological framework. A snowball sampling technique was used to recruit 21 Oglala Lakota Sioux participants (age >or= 19 years) living on the Pine Ridge Indian Reservation in South Dakota, USA. Face-to-face interviews were conducted using open-ended questions derived from the social-ecological perspective of Stokols (1992). Interviews were audiotaped and transcribed. Data were categorized into construct codes to identify concepts and to discover emerging themes. Personal and environmental themes regarding organ and tissue donation emerged. There were two personal themes: uncertain knowledge and the diabetes crisis. Participants knew very little about organ and tissue donation but there was a basic understanding of donor/recipient compatibility. The prevalence of diabetes in the community is contributing to a dire need for kidney donors. The diabetes crisis was acknowledged by every participant. There were three environmental themes: cultural transitions, healthcare system competence and outreach efforts. Traditional cultural beliefs such as entering the spirit world with an intact body were acknowledged. However, conversations reflected re-examination of traditional beliefs because of the need for kidney donors. The healthcare environmental context of organ and tissue donation emerged as a theme. Participants were not confident that the local health system was prepared to either address traditional beliefs about organ and tissue donation or implement a donation protocol. The final theme was the environmental context of outreach efforts. Participants desired relevant outreach targeted to the community and disseminated through local communication networks including the family, the media and tribal leaders. Sociocultural factors relevant to the personal and environmental context of the

Greater effort increases perceived value in an invertebrate.

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Czaczkes, Tomer J; Brandstetter, Birgit; di Stefano, Isabella; Heinze, Jürgen

2018-05-01

Expending effort is generally considered to be undesirable. However, both humans and vertebrates will work for a reward they could also get for free. Moreover, cues associated with high-effort rewards are preferred to low-effort associated cues. Many explanations for these counterintuitive findings have been suggested, including cognitive dissonance (self-justification) or a greater contrast in state (e.g., energy or frustration level) before and after an effort-linked reward. Here, we test whether effort expenditure also increases perceived value in ants, using both classical cue-association methods and pheromone deposition, which correlates with perceived value. In 2 separate experimental setups, we show that pheromone deposition is higher toward the reward that requires more effort: 47% more pheromone deposition was performed for rewards reached via a vertical runway (high effort) compared with ones reached via a horizontal runway (low effort), and deposition rates were 28% higher on rough (high effort) versus smooth (low effort) runways. Using traditional cue-association methods, 63% of ants trained on different surface roughness, and 70% of ants trained on different runway elevations, preferred the high-effort related cues on a Y maze. Finally, pheromone deposition to feeders requiring memorization of one path bifurcation was up to 29% higher than to an identical feeder requiring no learning. Our results suggest that effort affects value perception in ants. This effect may stem from a cognitive process, which monitors the change in a generalized hedonic state before and after reward. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

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Kuuranne, Tiia; Saugy, Martial; Baume, Norbert

2014-01-01

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module. PMID:24764553

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

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Atul A. Chaudhari

2016-11-01

Full Text Available Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL, and poly-ethylene-glycol (PEG, etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Is the association between general cognitive ability and violent crime caused by family-level confounders?

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Thomas Frisell

Full Text Available BACKGROUND: Research has consistently found lower cognitive ability to be related to increased risk for violent and other antisocial behaviour. Since this association has remained when adjusting for childhood socioeconomic position, ethnicity, and parental characteristics, it is often assumed to be causal, potentially mediated through school adjustment problems and conduct disorder. Socioeconomic differences are notoriously difficult to quantify, however, and it is possible that the association between intelligence and delinquency suffer substantial residual confounding. METHODS: We linked longitudinal Swedish total population registers to study the association of general cognitive ability (intelligence at age 18 (the Conscript Register, 1980-1993 with the incidence proportion of violent criminal convictions (the Crime Register, 1973-2009, among all men born in Sweden 1961-1975 (N = 700,514. Using probit regression, we controlled for measured childhood socioeconomic variables, and further employed sibling comparisons (family pedigree data from the Multi-Generation Register to adjust for shared familial characteristics. RESULTS: Cognitive ability in early adulthood was inversely associated to having been convicted of a violent crime (β = -0.19, 95% CI: -0.19; -0.18, the association remained when adjusting for childhood socioeconomic factors (β = -0.18, 95% CI: -0.18; -0.17. The association was somewhat lower within half-brothers raised apart (β = -0.16, 95% CI: -0.18; -0.14, within half-brothers raised together (β = -0.13, 95% CI: (-0.15; -0.11, and lower still in full-brother pairs (β = -0.10, 95% CI: -0.11; -0.09. The attenuation among half-brothers raised together and full brothers was too strong to be attributed solely to attenuation from measurement error. DISCUSSION: Our results suggest that the association between general cognitive ability and violent criminality is confounded partly by factors shared by

Desire thinking as a confounder in the relationship between mindfulness and craving: Evidence from a cross-cultural validation of the Desire Thinking Questionnaire.

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Chakroun-Baggioni, Nadia; Corman, Maya; Spada, Marcantonio M; Caselli, Gabriele; Gierski, Fabien

2017-10-01

Desire thinking and mindfulness have been associated with craving. The aim of the present study was to validate the French version of the Desire Thinking Questionnaire (DTQ) and to investigate the relationship between mindfulness, desire thinking and craving among a sample of university students. Four hundred and ninety six university students completed the DTQ and measures of mindfulness, craving and alcohol use. Results from confirmatory factor analyses showed that the two-factor structure proposed in the original DTQ exhibited suitable goodness-of-fit statistics. The DTQ also demonstrated good internal reliability, temporal stability and predictive validity. A set of linear regressions revealed that desire thinking had a confounding effect in the relationship between mindfulness and craving. The confounding role of desire thinking in the relationship between mindfulness and craving suggests that interrupting desire thinking may be a viable clinical option aimed at reducing craving. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of active brown adipose tissue in human metabolism

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Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

2016-02-15

The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

Listening Effort With Cochlear Implant Simulations

NARCIS (Netherlands)

Pals, Carina; Sarampalis, Anastasios; Başkent, Deniz

2013-01-01

Purpose: Fitting a cochlear implant (CI) for optimal speech perception does not necessarily optimize listening effort. This study aimed to show that listening effort may change between CI processing conditions for which speech intelligibility remains constant. Method: Nineteen normal-hearing

Dental Tissue — New Source for Stem Cells

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Vladimir Petrovic

2009-01-01

Full Text Available Stem cells have been isolated from many tissues and organs, including dental tissue. Five types of dental stem cells have been established: dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, and dental follicle progenitor cells. The main characteristics of dental stem cells are their potential for multilineage differentiation and self-renewal capacity. Dental stem cells can differentiate into odontoblasts, adipocytes, neuronal-like cells, glial cells, osteoblasts, chondrocytes, melanocytes, myotubes, and endothelial cells. Possible application of these cells in various fields of medicine makes them good candidates for future research as a new, powerful tool for therapy. Although the possible use of these cells in therapeutic purposes and tooth tissue engineering is still in the beginning stages, the results are promising. The efforts made in the research of dental stem cells have clarified many mechanisms underlying the biological processes in which these cells are involved. This review will focus on the new findings in the field of dental stem cell research and on their potential use in the therapy of various disorders.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

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Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.

Working conditions and effort-reward imbalance of German physicians in Sweden respective Germany: a comparative study.

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Ohlander, Johan; Weigl, Matthias; Petru, Raluca; Angerer, Peter; Radon, Katja

2015-05-01

Work stress among physicians is a growing concern in various countries and has led to migration. We compared the working conditions and the work stress between a migrated population of German physicians in Sweden and a population of physicians based in Germany. Additionally, specific risk factors for work stress were examined country wise. Using a cross-sectional design, 85 German physicians employed in Sweden were surveyed on working conditions and effort-reward imbalance and compared with corresponding data on 561 physicians working in Germany. Multiple linear regression analyses were applied on both populations separately to model the associations between working conditions and effort-reward ratio (ERR), adjusted for a priori confounders. German physicians in Sweden had a significantly lower ERR than physicians in Germany: mean (M) = 0.47, standard deviation (SD) = 0.24 vs. M = 0.80, SD = 0.35. Physicians in Sweden worked on average 8 h less per week and reported higher work support and responsibility. Multivariate analyses showed in both populations a negative association between work support and the ERR (β = -0.148, 95% CI -0.215 to (-0.081) for physicians in Sweden and β = -0.174, 95% CI -0.240 to (-0.106) for physicians in Germany). Further significant associations with the ERR were found among physicians in Sweden for daily breaks (β = -0.002, 95% CI -0.004 to (-0.001)) and among physicians in Germany for working hours per week (β = 0.006, 95% CI 0.002-0.009). Our findings show substantial differences in work stress and working conditions in favor of migrated German physicians in Sweden. To confirm our results and to explain demonstrated differences in physicians' work stress, longitudinal studies are recommended.

Accounting for the Confound of Meninges in Segmenting Entorhinal and Perirhinal Cortices in T1-Weighted MRI.

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Xie, Long; Wisse, Laura E M; Das, Sandhitsu R; Wang, Hongzhi; Wolk, David A; Manjón, Jose V; Yushkevich, Paul A

2016-10-01

Quantification of medial temporal lobe (MTL) cortices, including entorhinal cortex (ERC) and perirhinal cortex (PRC), from in vivo MRI is desirable for studying the human memory system as well as in early diagnosis and monitoring of Alzheimer's disease. However, ERC and PRC are commonly over-segmented in T1-weighted (T1w) MRI because of the adjacent meninges that have similar intensity to gray matter in T1 contrast. This introduces errors in the quantification and could potentially confound imaging studies of ERC/PRC. In this paper, we propose to segment MTL cortices along with the adjacent meninges in T1w MRI using an established multi-atlas segmentation framework together with super-resolution technique. Experimental results comparing the proposed pipeline with existing pipelines support the notion that a large portion of meninges is segmented as gray matter by existing algorithms but not by our algorithm. Cross-validation experiments demonstrate promising segmentation accuracy. Further, agreement between the volume and thickness measures from the proposed pipeline and those from the manual segmentations increase dramatically as a result of accounting for the confound of meninges. Evaluated in the context of group discrimination between patients with amnestic mild cognitive impairment and normal controls, the proposed pipeline generates more biologically plausible results and improves the statistical power in discriminating groups in absolute terms comparing to other techniques using T1w MRI. Although the performance of the proposed pipeline is inferior to that using T2-weighted MRI, which is optimized to image MTL sub-structures, the proposed pipeline could still provide important utilities in analyzing many existing large datasets that only have T1w MRI available.

Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.

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Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj

2011-07-01

In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-04-01

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

Interests, Effort, Achievement and Vocational Preference.

Science.gov (United States)

Sjoberg, L.

1984-01-01

Relationships between interest in natural sciences and technology and perceived ability, success, and invested effort were studied in Swedish secondary school students. Interests were accounted for by logical orientation and practical value. Interests and grades were strongly correlated, but correlations between interests and effort and vocational…

Has Malaysia's antidrug effort been effective?

Science.gov (United States)

Scorzelli, J F

1992-01-01

It is a common belief that a massive effort in law enforcement, preventive education and rehabilitation will result in the elimination of a country's drug problem. Based on this premise. Malaysia in 1983 implemented such a multifaceted anti-drug strategy, and the results of a 1987 study by the author suggested that Malaysia's effort had begun to contribute to a steady decrease in the number of identified drug abusers. Although the number of drug-addicted individuals declined, the country's recidivism rates were still high. Because of this high relapse rate, Malaysia expanded their rehabilitation effort and developed a community transition program. In order to determine the impact of these changes on the country's battle against drug abuse, a follow-up study was conducted in 1990. The results of this study did not clearly demonstrate that the Malaysian effort had been successful in eliminating the problem of drug abuse, and raised some questions concerning the effectiveness of the country's drug treatment programs.

Human tissue models in cancer research: looking beyond the mouse.

Science.gov (United States)

Jackson, Samuel J; Thomas, Gareth J

2017-08-01

Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

[Biofabrication: new approaches for tissue regeneration].

Science.gov (United States)

Horch, Raymund E; Weigand, Annika; Wajant, Harald; Groll, Jürgen; Boccaccini, Aldo R; Arkudas, Andreas

2018-04-01

The advent of Tissue Engineering (TE) in the early 1990ies was fostered by the increasing need for functional tissue and organ replacement. Classical TE was based on the combination of carrier matrices, cells and growth factors to reconstitute lost or damaged tissue and organs. Despite considerable results in vitro and in experimental settings the lack of early vascularization has hampered its translation into daily clinical practice so far. A new field of research, called "biofabrication" utilizing latest 3D printing technologies aims at hierarchically and spatially incorporating different cells, biomaterials and molecules into a matrix to alleviate a directed maturation of artificial tissue. A literature research of the relevant publications regarding biofabrication and bioprinting was performed using the PubMed data base. Relevant papers were selected and evaluated with secondary analysis of specific citations on the bioprinting techniques. 180 relevant papers containing the key words were identified and evaluated. Basic principles into the developing field of bioprinting technology could be discerned. Key elements comprise the high-throughput assembly of cells and the fabrication of complex and functional hierarchically organized tissue constructs. Five relevant technological principles for bioprinting were identified, such as stereolithography, extrusion-based printing, laser-assisted printing, inkjet-based printing and nano-bioprinting. The different technical methods of 3D printing were found to be associated with various positive but also negative effects on cells and proteins during the printing process. Research efforts in this field obviously aim towards the development of optimizing the so called bioinks and the printing technologies. This review details the evolution of the classical methods of TE in Regenerative Medicine into the evolving field of biofabrication by bioprinting. The advantages of 3D bioprinting over traditional tissue engineering

The interaction effect of effort-reward imbalance and overcommitment on hypertension among Chinese workers: findings from SHISO study.

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Xu, Weixian; Yu, Haiyi; Hang, Juan; Gao, Wei; Zhao, Yiming; Guo, Lijun

2013-12-01

No previous studies investigated the interaction of effort-reward imbalance (ERI) and overcommitment on blood pressure. Our aim was to investigate associations of ERI and overcommitment (and their interaction) with blood pressure and hypertension within a Chinese population. Seven hundred thirty-four participants from the Stress and Health in Shenzhen Workers study completed a demographics, job stressor and risk factor questionnaire, and their blood pressure was measured by mercury sphygmomanometers. Risk factors for blood pressure were analyzed by multiple linear regression and risk factors for hypertension by Poisson regression. Overcommitment was associated with diastolic blood pressure after adjustment for confounders and ERI among men (β = 0.17, P controlling for overcommitment, ERI remained significantly associated with hypertension risk (PR = 2.38, 95% CI 1.53-3.71). When high overcommitment and high ERI was combined, hypertension risk was highest (adjusted PR = 2.99, 95% CI 1.82-4.91, adjusted synergy index 5.85). The interaction was significant when it was tested by an interaction term in the regression (P < 0.001). The interaction effect of overcommitment and ERI on hypertension was independent and synergistic. © 2013 Wiley Periodicals, Inc.

Nanoparticle-enhanced spectral photoacoustic tomography: effect of oxygen saturation and tissue heterogeneity

Science.gov (United States)

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua

2016-03-01

Molecular imaging for breast cancer detection, infectious disease diagnostics and preclinical animal research may be achievable through combined use of targeted exogenous agents - such as nanoparticles - and spectral Photoacoustic Tomography (PAT). However, tissue heterogeneity can alter fluence distributions and acoustic propagation, corrupting measured PAT absorption spectra and complicating in vivo nanoparticle detection and quantitation. Highly absorptive vascular structures represent a common confounding factor, and variations in vessel hemoglobin saturation (SO2) may alter spectral content of signals from adjacent/deeper regions. To evaluate the impact of this effect on PAT nanoparticle detectability, we constructed heterogeneous phantoms with well-characterized channel-inclusion geometries and biologically relevant optical and acoustic properties. Phantoms contained an array of tubes at several depths filled with hemoglobin solutions doped with varying concentrations of gold nanorods with an absorption peak at 780 nm. Both overlying and target network SO2 was tuned using sodium dithionite. Phantoms were imaged from 700 to 900 nm using a custom PAT system comprised of a tunable pulsed laser and a research-grade ultrasound system. Recovered nanoparticle spectra were analyzed and compared with results from both spectrophotometry and PAT data from waterimmersed tubes containing blood and nanoparticle solutions. Results suggested that nanoparticle selection for a given PAT application should take into account expected oxygenation states of both target blood vessel and background tissue oxygenation to achieve optimal performance.

Effort Estimation in BPMS Migration

OpenAIRE

Drews, Christopher; Lantow, Birger

2018-01-01

Usually Business Process Management Systems (BPMS) are highly integrated in the IT of organizations and are at the core of their business. Thus, migrating from one BPMS solution to another is not a common task. However, there are forces that are pushing organizations to perform this step, e.g. maintenance costs of legacy BPMS or the need for additional functionality. Before the actual migration, the risk and the effort must be evaluated. This work provides a framework for effort estimation re...

Educational gains in cause-specific mortality: Accounting for cognitive ability and family-level confounders using propensity score weighting.

Science.gov (United States)

Bijwaard, Govert E; Myrskylä, Mikko; Tynelius, Per; Rasmussen, Finn

2017-07-01

A negative educational gradient has been found for many causes of death. This association may be partly explained by confounding factors that affect both educational attainment and mortality. We correct the cause-specific educational gradient for observed individual background and unobserved family factors using an innovative method based on months lost due to a specific cause of death re-weighted by the probability of attaining a higher educational level. We use data on men with brothers from the Swedish Military Conscription Registry (1951-1983), linked to administrative registers. This dataset of some 700,000 men allows us to distinguish between five education levels and many causes of death. The empirical results reveal that raising the educational level from primary to tertiary would result in an additional 20 months of survival between ages 18 and 63. This improvement in mortality is mainly attributable to fewer deaths from external causes. The highly educated gain more than nine months due to the reduction in deaths from external causes, but gain only two months due to the reduction in cancer mortality and four months due to the reduction in cardiovascular mortality. Ignoring confounding would lead to an underestimation of the gains by educational attainment, especially for the less educated. Our results imply that if the education distribution of 50,000 Swedish men from the 1951 cohort were replaced with that of the corresponding 1983 cohort, 22% of the person-years that were lost to death between ages 18 and 63 would have been saved for this cohort. Copyright © 2017 Elsevier Ltd. All rights reserved.

ASME Code Efforts Supporting HTGRs

Energy Technology Data Exchange (ETDEWEB)

D.K. Morton

2012-09-01

In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This report discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.

ASME Code Efforts Supporting HTGRs

Energy Technology Data Exchange (ETDEWEB)

D.K. Morton

2011-09-01

In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This report discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.

Biomaterials innovation for next generation ex vivo immune tissue engineering.

Science.gov (United States)

Singh, Ankur

2017-06-01

Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues. The complexity of such animal models limits our ability to modulate the parameters that control the process of immune cell development, differentiation, and immunomodulation. Engineering functional, living immune tissues using biomaterials can grant researchers the ability to reproduce immunological events with tunable parameters for more rapid development of immunotherapeutics, cell-based therapy, and enhancing our understanding of fundamental biology as well as improving efforts in regenerative medicine. Here the author provides his review and perspective on the bioengineering of primary and secondary lymphoid tissues, and biomaterials innovation needed for the construction of these immune organs in tissue culture plates and on-chip. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

International Nuclear Information System (INIS)

Travis, Elizabeth L.

1996-01-01

relationship of tissue architecture to radiation-induced damage and the available clinical and experimental data which demonstrate volume effects as well as those factors which complicate efforts to estimate normal tissue complication probabilities

Pocket money and child effort at school

OpenAIRE

François-Charles Wolff; Christine Barnet-Verzat

2008-01-01

In this paper, we study the relationship between the provision of parental pocket and the level of effort undertaken by the child at school. Under altruism, an increased amount of parental transfer should reduce the child's effort. Our empirical analysis is based on a French data set including about 1,400 parent-child pairs. We find that children do not undertake less effort when their parents are more generous.

Accounting for genetic and environmental confounds in associations between parent and child characteristics : a systematic review of children-of-twins studies

OpenAIRE

McAdams, Tom A; Neiderhiser, Jenae M; Rijsdijk, Fruhling V; Narusyte, Jurgita; Lichtenstein, Paul; Eley, Thalia C

2014-01-01

Parental psychopathology, parenting style, and the quality of intrafamilial relationships are all associated with child mental health outcomes. However, most research can say little about the causal pathways underlying these associations. This is because most studies are not genetically informative and are therefore not able to account for the possibility that associations are confounded by gene-environment correlation. That is, biological parents not only provide a rearing environment for th...

Trace elements determinations in cancerous and non-cancerous human tissues using instrumental neutron activation analysis

International Nuclear Information System (INIS)

Choi, Insup.

1989-01-01

Recent improvements in analyzing techniques when coupled to the growing knowledge of trace element biochemistry provide a powerful tool to investigate the relationship between trace elements and cancer. It is hoped that selective delivery or restriction of specific minerals may aid in cancer prevention or treatment. Tissues were collected at the time of surgery of various cancer patients including colon cancer and breast cancer. Three kinds of tissues were taken from a patient; cancerous, noncancerous, and transitional tissue obtained from a region located between the cancer and healthy tissues. A total of 57 tissues were obtained from 19 cancer patients. Seven of them were colon cancer patients, and 5 of them were breast cancer patients. Nine elements were determined using instrumental activation analysis. Cancerous colon tissue had significantly higher concentrations of selenium and iron than healthy tissues. Cancerous breast tissue had significantly higher concentrations of selenium, iron, manganese, and rubidium than healthy tissues. Iron can be enriched in cancer tissue because cancer tissue retains more blood vessels. Selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumors. The manganese enrichment can be explained in the same manner as selenium considering its suspected anticarcinogenicity. It is not certain why rubidium was enriched in cancer tissue. It could be that this is the result of alteration of cell membrane permeability, change in extracellular matrix, or increased metabolism in cancer tissue

Stretch-sensitive paresis and effort perception in hemiparesis.

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Vinti, Maria; Bayle, Nicolas; Hutin, Emilie; Burke, David; Gracies, Jean-Michel

2015-08-01

In spastic paresis, stretch applied to the antagonist increases its inappropriate recruitment during agonist command (spastic co-contraction). It is unknown whether antagonist stretch: (1) also affects agonist recruitment; (2) alters effort perception. We quantified voluntary activation of ankle dorsiflexors, effort perception, and plantar flexor co-contraction during graded dorsiflexion efforts at two gastrocnemius lengths. Eighteen healthy (age 41 ± 13) and 18 hemiparetic (age 54 ± 12) subjects performed light, medium and maximal isometric dorsiflexion efforts with the knee flexed or extended. We determined dorsiflexor torque, Root Mean Square EMG and Agonist Recruitment/Co-contraction Indices (ARI/CCI) from the 500 ms peak voluntary agonist recruitment in a 5-s maximal isometric effort in tibialis anterior, soleus and medial gastrocnemius. Subjects retrospectively reported effort perception on a 10-point visual analog scale. During gastrocnemius stretch in hemiparetic subjects, we observed: (1) a 25 ± 7 % reduction of tibialis anterior voluntary activation (maximum reduction 98 %; knee extended vs knee flexed; p = 0.007, ANOVA); (2) an increase in dorsiflexion effort perception (p = 0.03, ANCOVA). Such changes did not occur in healthy subjects. Effort perception depended on tibialis anterior recruitment only (βARI(TA) = 0.61, p hemiparesis, voluntary ability to recruit agonist motoneurones is impaired--sometimes abolished--by antagonist stretch, a phenomenon defined here as stretch-sensitive paresis. In addition, spastic co-contraction increases effort perception, an additional incentive to evaluate and treat this phenomenon.

Excess Mortality in Hyperthyroidism: The Influence of Preexisting Comorbidity and Genetic Confounding: A Danish Nationwide Register-Based Cohort Study of Twins and Singletons

Science.gov (United States)

Brandt, Frans; Almind, Dorthe; Christensen, Kaare; Green, Anders; Brix, Thomas Heiberg

2012-01-01

Context: Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding. Objective: The objective of the study was to investigate whether hyperthyroidism is associated with an increased mortality and, if so, whether the association is influenced by comorbidity and/or genetic confounding. Methods: This was an observational cohort study using record-linkage data from nationwide Danish health registers. We identified 4850 singletons and 926 twins from same-sex pairs diagnosed with hyperthyroidism. Each case was matched with four controls for age and gender. The Charlson score was calculated from discharge diagnoses on an individual level to measure comorbidity. Cases and controls were followed up for a mean of 10 yr (range 0–31 yr), and the hazard ratio (HR) for mortality was calculated using Cox regression analyses. Results: In singletons there was a significantly higher mortality in individuals diagnosed with hyperthyroidism than in controls [HR 1.37; 95% confidence interval (CI) 1.30–1.46]. This persisted after adjustment for preexisting comorbidity (HR 1,28; 95% CI 1.21–1.36). In twin pairs discordant for hyperthyroidism (625 pairs), the twin with hyperthyroidism had an increased mortality compared with the corresponding cotwin (HR 1.43; 95% CI 1.09–1.88). However, this was found only in dizygotic pairs (HR 1.80; 95% CI 1.27–2.55) but not in monozygotic pairs (HR 0.95; 95% CI 0.60–1.50). Conclusions: Hyperthyroidism is associated with an increased mortality independent of preexisting comorbidity. The study of twin pairs discordant for hyperthyroidism suggests that genetic confounding influences the association between hyperthyroidism and mortality. PMID:22930783

Effort-Based Career Opportunities and Working Time

OpenAIRE

Bratti, M.; Staffolani, S.

2005-01-01

The authors evaluate the economic effects of the hypothesis of effort-based career opportunities, described as a situation in which a firm creates incentives for employees to work longer hours than bargained (or desired), by making career prospects depend on relative working hours. Firms' personnel management policies may tend to increase working time (or workers' effort) in order to maximize profits. Effort-based career opportunities raise working time, production and output per worker, and ...

The influence of environmental factors on bone tissue engineering.

Science.gov (United States)

Szpalski, Caroline; Sagebin, Fabio; Barbaro, Marissa; Warren, Stephen M

2013-05-01

Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

Influence of potentially confounding factors on sea urchin porewater toxicity tests

Science.gov (United States)

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.

Current Concepts in Tissue Engineering: Skin and Wound.

Science.gov (United States)

Tenenhaus, Mayer; Rennekampff, Hans-Oliver

2016-09-01

Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

Trust and Reciprocity: Are Effort and Money Equivalent?

Science.gov (United States)

Vilares, Iris; Dam, Gregory; Kording, Konrad

2011-01-01

Trust and reciprocity facilitate cooperation and are relevant to virtually all human interactions. They are typically studied using trust games: one subject gives (entrusts) money to another subject, which may return some of the proceeds (reciprocate). Currently, however, it is unclear whether trust and reciprocity in monetary transactions are similar in other settings, such as physical effort. Trust and reciprocity of physical effort are important as many everyday decisions imply an exchange of physical effort, and such exchange is central to labor relations. Here we studied a trust game based on physical effort and compared the results with those of a computationally equivalent monetary trust game. We found no significant difference between effort and money conditions in both the amount trusted and the quantity reciprocated. Moreover, there is a high positive correlation in subjects' behavior across conditions. This suggests that trust and reciprocity may be character traits: subjects that are trustful/trustworthy in monetary settings behave similarly during exchanges of physical effort. Our results validate the use of trust games to study exchanges in physical effort and to characterize inter-subject differences in trust and reciprocity, and also suggest a new behavioral paradigm to study these differences. PMID:21364931

Real-time haptic cutting of high-resolution soft tissues.

Science.gov (United States)

Wu, Jun; Westermann, Rüdiger; Dick, Christian

2014-01-01

We present our systematic efforts in advancing the computational performance of physically accurate soft tissue cutting simulation, which is at the core of surgery simulators in general. We demonstrate a real-time performance of 15 simulation frames per second for haptic soft tissue cutting of a deformable body at an effective resolution of 170,000 finite elements. This is achieved by the following innovative components: (1) a linked octree discretization of the deformable body, which allows for fast and robust topological modifications of the simulation domain, (2) a composite finite element formulation, which thoroughly reduces the number of simulation degrees of freedom and thus enables to carefully balance simulation performance and accuracy, (3) a highly efficient geometric multigrid solver for solving the linear systems of equations arising from implicit time integration, (4) an efficient collision detection algorithm that effectively exploits the composition structure, and (5) a stable haptic rendering algorithm for computing the feedback forces. Considering that our method increases the finite element resolution for physically accurate real-time soft tissue cutting simulation by an order of magnitude, our technique has a high potential to significantly advance the realism of surgery simulators.

Perceived effort for motor control and decision-making.

Directory of Open Access Journals (Sweden)

Ignasi Cos

2017-08-01

Full Text Available How effort is internally quantified and how it influences both movement generation and decisions between potential movements are 2 difficult questions to answer. Physical costs are known to influence motor control and decision-making, yet we lack a general, principled characterization of how the perception of effort operates across tasks and conditions. Morel and colleagues introduce an insightful approach to that end, assessing effort indifference points and presenting a quadratic law between perceived effort and force production.

Handling stress may confound murine gut microbiota studies

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Cary R. Allen-Blevins

2017-01-01

Full Text Available 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

Reproductive performance and gestational effort in relation to dietary fatty acids in guinea pigs.

Science.gov (United States)

Nemeth, Matthias; Millesi, Eva; Siutz, Carina; Wagner, Karl-Heinz; Quint, Ruth; Wallner, Bernard

2017-01-01

Dietary saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can highly affect reproductive functions by providing additional energy, modulating the biochemical properties of tissues, and hormone secretions. In precocial mammals such as domestic guinea pigs the offspring is born highly developed. Gestation might be the most critical reproductive period in this species and dietary fatty acids may profoundly influence the gestational effort. We therefore determined the hormonal status at conception, the reproductive success, and body mass changes during gestation in guinea pigs maintained on diets high in PUFAs or SFAs, or a control diet. The diets significantly affected the females' plasma fatty acid status at conception, while cortisol and estrogen levels did not differ among groups. SFA females exhibited a significantly lower body mass and litter size, while the individual birth mass of pups did not differ among groups and a general higher pup mortality rate in larger litters was diminished by PUFAs and SFAs. The gestational effort, determined by a mother's body mass gain during gestation, increased with total litter mass, whereas this increase was lowest in SFA and highest in PUFA individuals. The mother's body mass after parturition did not differ among groups and was positively affected by the total litter mass in PUFA females. While SFAs reduce the litter size, but also the gestational effort as a consequence, PUFA supplementation may contribute to an adjustment of energy accumulations to the total litter mass, which may both favor a mother's body condition at parturition and perhaps increase the offspring survival at birth.

Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

Science.gov (United States)

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

Directory of Open Access Journals (Sweden)

Julien Barthes

2014-01-01

Full Text Available In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells’ behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Phase transitions in least-effort communications

International Nuclear Information System (INIS)

Prokopenko, Mikhail; Ay, Nihat; Obst, Oliver; Polani, Daniel

2010-01-01

We critically examine a model that attempts to explain the emergence of power laws (e.g., Zipf's law) in human language. The model is based on the principle of least effort in communications—specifically, the overall effort is balanced between the speaker effort and listener effort, with some trade-off. It has been shown that an information-theoretic interpretation of this principle is sufficiently rich to explain the emergence of Zipf's law in the vicinity of the transition between referentially useless systems (one signal for all referable objects) and indexical reference systems (one signal per object). The phase transition is defined in the space of communication accuracy (information content) expressed in terms of the trade-off parameter. Our study explicitly solves the continuous optimization problem, subsuming a recent, more specific result obtained within a discrete space. The obtained results contrast Zipf's law found by heuristic search (that attained only local minima) in the vicinity of the transition between referentially useless systems and indexical reference systems, with an inverse-factorial (sub-logarithmic) law found at the transition that corresponds to global minima. The inverse-factorial law is observed to be the most representative frequency distribution among optimal solutions

Men's Work Efforts and the Transition to Fatherhood.

Science.gov (United States)

Astone, Nan Marie; Dariotis, Jacinda; Sonenstein, Freya; Pleck, Joseph H; Hynes, Kathryn

2010-03-01

In this paper we tested three hypotheses: (a) the transition to fatherhood is associated with an increase in work effort; (b) the positive association (if any) between the transition to fatherhood and work effort is greater for fathers who are married at the time of the transition; and (c) the association (if any) is greater for men who make the transition at younger ages. The data are from the National Longitudinal Survey of Youth 1979 Cohort. The transition to fatherhood was associated with an increase in work effort among young unmarried men, but not for married men. Among married men who were on-time fathers, work effort decreased. Among childless men, the marriage transition was associated with increased work effort.

Dissociating variability and effort as determinants of coordination.

Directory of Open Access Journals (Sweden)

Ian O'Sullivan

2009-04-01

Full Text Available When coordinating movements, the nervous system often has to decide how to distribute work across a number of redundant effectors. Here, we show that humans solve this problem by trying to minimize both the variability of motor output and the effort involved. In previous studies that investigated the temporal shape of movements, these two selective pressures, despite having very different theoretical implications, could not be distinguished; because noise in the motor system increases with the motor commands, minimization of effort or variability leads to very similar predictions. When multiple effectors with different noise and effort characteristics have to be combined, however, these two cost terms can be dissociated. Here, we measure the importance of variability and effort in coordination by studying how humans share force production between two fingers. To capture variability, we identified the coefficient of variation of the index and little fingers. For effort, we used the sum of squared forces and the sum of squared forces normalized by the maximum strength of each effector. These terms were then used to predict the optimal force distribution for a task in which participants had to produce a target total force of 4-16 N, by pressing onto two isometric transducers using different combinations of fingers. By comparing the predicted distribution across fingers to the actual distribution chosen by participants, we were able to estimate the relative importance of variability and effort of 1:7, with the unnormalized effort being most important. Our results indicate that the nervous system uses multi-effector redundancy to minimize both the variability of the produced output and effort, although effort costs clearly outweighed variability costs.

Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations.

Science.gov (United States)

Newton, Adam J H; Wall, Mark J; Richardson, Magnus J E

2017-03-01

Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue

3D Printing of Scaffolds for Tissue Regeneration Applications

Science.gov (United States)

Do, Anh-Vu; Khorsand, Behnoush; Geary, Sean M.; Salem, Aliasger K.

2015-01-01

The current need for organ and tissue replacement, repair and regeneration for patients is continually growing such that supply is not meeting the high demand primarily due to a paucity of donors as well as biocompatibility issues that lead to immune rejection of the transplant. In an effort to overcome these drawbacks, scientists working in the field of tissue engineering and regenerative medicine have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired a growing interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity and precision, where fine details can be included at a micron level. In this review, we discuss the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering. A hybrid approach, employing both natural and synthetic materials, as well as multiple printing processes may be the key to yielding an ECM-like scaffold with high mechanical strength, porosity, interconnectivity, biocompatibility, biodegradability, and high processability. Creating such biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation. PMID:26097108

Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

Directory of Open Access Journals (Sweden)

Victoria eHolec

2014-01-01

Full Text Available The rat anterior cingulate cortex (ACC mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., courage. As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the high reward arm. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness.

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Sergios Gatidis

Full Text Available To evaluate the feasibility to detect activated brown adipose tissue (BAT using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT.120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data.Activated BAT was detected in 9 of 102 patients (8.8%. Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness.We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.

[Comparison between the risk of mobbing at work and conditions of job strain and effort-reward imbalance in relation to stress-related disorders: a study in the public administration].

Science.gov (United States)

Balducci, C; Fraccaroli, E

2013-01-01

A limitation of previous research on mobbing at work was that the individual consequences of the phenomenon were often assessed on 'clinical' samples of victims. Studies in organizations are less numerous and those available rarely evaluated the potential effect of mobbing over and above that of other psychosocial factors which provided robust evidence of adverse health effects. The relationship between exposure to mobbing and stress-related psychophysical conditions was investigated taking in consideration the possible concomitant exposure to job strain and effort-reward imbalance. Cross-sectional study on public administration administrative employees (No. = 538, 48% women). The psychosocial factors considered were assessed by means of well known and validated scales. The four health outcomes considered were psychological caseness (as operationalized by means of the general health questionnaire-12-item version), depression, gastritis and colitis/irritable colon syndrome as indicated by having reported a medical diagnosis of such conditions. Covariates: gender, age, body mass index, smoking habits and experience of a traumatic event in the last year. Analysis consisted of a series of logistic regressions. Exposure to mobbing was significantly associated with all the outcomes considered over and above the covariates. The inclusion in the models of job strain and effort-reward imbalance did not substantially alter the results. The relationship between mobbing at work and health outcomes is not confounded by concomitant exposure to job strain and effort-reward imbalance. These results offer further confirmation of the uniqueness of mobbing as a psychosocial risk factor.

Artificial light at night confounds broad-scale habitat use by migrating birds

NARCIS (Netherlands)

McLaren, J.D.; Buler, J.J.; Schreckengost, T.; Smolinsky, J.A.; Boone, M.; van Loon, E.E.; Dawson, D.K.; Walters, E.L.

With many of the world's migratory bird populations in alarming decline, broad-scale assessments of responses to migratory hazards may prove crucial to successful conservation efforts. Most birds migrate at night through increasingly light-polluted skies. Bright light sources can attract airborne

[Attitude towards organ and tissue donation in Europe : Prerequisite for osteochondral allograft treatment].

Science.gov (United States)

Schmidt, S; Schulte, A; Schwarz, S; Hofmann, N; Tietz, S; Boergel, M; Sixt, S U

2017-11-01

The biggest obstacle to overcome for routine treatment of various pathologies with fresh osteochondral allograft is the availability of tissue for transplantation. Large fresh osteochondral allografts are usually harvested from organ donors, but in contrast to organs, tissues can be procured after cardiac arrest. Medical staff as well the general public are much less aware of the possibilities and requirements of tissue donation compared to organ donation. This review aims to highlight the current situation of organ and tissue donation in Europe and to raise this much needed awareness. For this research, PubMed database was scanned using the terms "tissue/organ donation", "bone donation/transplantation", "cartilage transplantation/allografts" and "osteochrondral allografts". Relatives of potential donors are often not approached because physicians and nurses do not feel sufficiently prepared for this task and, thus, are reluctant to address this topic. Different options could alleviate the pressure medical staff is feeling. Furthermore, there are different factors influencing consent that can be addressed to increase donation rates. Currently, a lot of potential concerning musculoskeletal tissue grafts remains unused. Most importantly, families should be encouraged to speak about their potenzial will to donate and educational programs should be established to increase trust in organ and tissue donation and the allocation system and to increase knowledge about the importance of transplantation medicine. But joined efforts of different parts of the medical systems and different organizations involved in tissue transplantation should improve the situation for patients waiting for much needed transplants.

Human tissue models in cancer research: looking beyond the mouse

Directory of Open Access Journals (Sweden)

Samuel J. Jackson

2017-08-01

Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

Programming effort analysis of the ELLPACK language

Science.gov (United States)

Rice, J. R.

1978-01-01

ELLPACK is a problem statement language and system for elliptic partial differential equations which is implemented by a FORTRAN preprocessor. ELLPACK's principal purpose is as a tool for the performance evaluation of software. However, it is used here as an example with which to study the programming effort required for problem solving. It is obvious that problem statement languages can reduce programming effort tremendously; the goal is to quantify this somewhat. This is done by analyzing the lengths and effort (as measured by Halstead's software science technique) of various approaches to solving these problems.

Late effects of normal tissues (lent) scoring system: the soma scale

International Nuclear Information System (INIS)

Mornex, F.; Pavy, J.J.; Denekamp, J.

1997-01-01

Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

Science.gov (United States)

Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

2016-03-31

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

Motivation and effort in individuals with social anhedonia.

Science.gov (United States)

McCarthy, Julie M; Treadway, Michael T; Blanchard, Jack J

2015-06-01

It has been proposed that anhedonia may, in part, reflect difficulties in reward processing and effortful decision making. The current study aimed to replicate previous findings of effortful decision making deficits associated with elevated anhedonia and expand upon these findings by investigating whether these decision making deficits are specific to elevated social anhedonia or are also associated with elevated positive schizotypy characteristics. The current study compared controls (n=40) to individuals elevated on social anhedonia (n=30), and individuals elevated on perceptual aberration/magical ideation (n=30) on the Effort Expenditure for Rewards Task (EEfRT). Across groups, participants chose a higher proportion of hard tasks with increasing probability of reward and reward magnitude, demonstrating sensitivity to probability and reward values. Contrary to our expectations, when the probability of reward was most uncertain (50% probability), at low and medium reward values, the social anhedonia group demonstrated more effortful decision making than either individuals high in positive schizotypy or controls. The positive schizotypy group only differed from controls (making less effortful choices than controls) when reward probability was lowest (12%) and the magnitude of reward was the smallest. Our results suggest that social anhedonia is related to intact motivation and effort for monetary rewards, but that individuals with this characteristic display a unique and perhaps inefficient pattern of effort allocation when the probability of reward is most uncertain. Future research is needed to better understand effortful decision making and the processing of reward across a range of individual difference characteristics. Copyright © 2015 Elsevier B.V. All rights reserved.

[Tissue repositories for research at Sheba Medical Center(SMC].

Science.gov (United States)

Cohen, Yehudit; Barshack, Iris; Onn, Amir

2013-06-01

Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular

Manipulating substrate and pH in zymography protocols selectively distinguishes cathepsins K, L, S, and V activity in cells and tissues.

Science.gov (United States)

Wilder, Catera L; Park, Keon-Young; Keegan, Philip M; Platt, Manu O

2011-12-01

Cathepsins K, L, S, and V are cysteine proteases that have been implicated in tissue-destructive diseases such as atherosclerosis, tumor metastasis, and osteoporosis. Among these four cathepsins are the most powerful human collagenases and elastases, and they share 60% sequence homology. Proper quantification of mature, active cathepsins has been confounded by inhibitor and reporter substrate cross-reactivity, but is necessary to develop properly dosed therapeutic applications. Here, we detail a method of multiplex cathepsin zymography to detect and distinguish the activity of mature cathepsins K, L, S, and V by exploiting differences in individual cathepsin substrate preferences, pH effects, and electrophoretic mobility under non-reducing conditions. Specific identification of cathepsins K, L, S, and V in one cell/tissue extract was obtained with cathepsin K (37 kDa), V (35 kDa), S (25 kDa), and L (20 kDa) under non-reducing conditions. Cathepsin K activity disappeared and V remained when incubated at pH 4 instead of 6. Application of this antibody free, species independent, and medium-throughput method was demonstrated with primary human monocyte-derived macrophages and osteoclasts, endothelial cells stimulated with inflammatory cytokines, and normal and cancer lung tissues, which identified elevated cathepsin V in lung cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Time preferences, study effort, and academic performance

NARCIS (Netherlands)

Non, J.A.; Tempelaar, D.T.

2014-01-01

We analyze the relation between time preferences, study effort, and academic performance among first-year Business and Economics students. Time preferences are measured by stated preferences for an immediate payment over larger delayed payments. Data on study efforts are derived from an electronic

Effort problem of chemical pipelines

Energy Technology Data Exchange (ETDEWEB)

Okrajni, J.; Ciesla, M.; Mutwil, K. [Silesian Technical University, Katowice (Poland)

1998-12-31

The problem of the technical state assessment of the chemical pipelines working under mechanical and thermal loading has been shown in the paper. The pipelines effort after the long time operating period has been analysed. Material geometrical and loading conditions of the crack initiation and crack growth process in the chosen object has been discussed. Areas of the maximal effort have been determined. The material structure charges after the long time operating period have been described. Mechanisms of the crack initiation and crack growth in the pipeline elements have been analysed and mutual relations between the chemical and mechanical influences have been shown. (orig.) 16 refs.

Translational research: cells, tissues and organisms

International Nuclear Information System (INIS)

Chang, P.Y.

2003-01-01

Exposure to the complex space radiation environment poses an important health hazard for astronauts in long-term space missions. The central theme of NASA's space radiation health research effort is to acquire scientific knowledge to understand the mechanisms of particle radiation effects in biological systems and to use this knowledge to set exposure limits and to design countermeasures that will protect the astronauts. During the past few decades, a rich body of data has been developed to characterize HZE-induced biological responses both in vitro and in vivo using ground-based accelerator facilities available in a number of facilities around the world. Although much is known about particle-radiation-induced DNA damage and cell killing in cultured cell lines, recent evidence suggest that numerous other factors, such as membrane effects, altered gene expression, bystander effects and specific cell-type dependent features also play critical roles in cellular responses. Dose- and particle-dependent studies are also available for multicellular tissues and animal model systems where emerging information demonstrates complex interactions between cells including intercellular communications, activation of proteins, alterations in the microenvironment, tissue-specificity, and genetic status and these contribute in determining the consequences of HZE radiation. Due to the lack of human data, risk estimates depend on the extrapolation of experimental results in animals and cultured cell systems to man. In this presentation, selected topics reviewing particle radiation effects in cells, tissues and animal will be used to illustrate the importance of translational research and some of the limitations of such approaches

Tissue types (image)

Science.gov (United States)

... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders.

Science.gov (United States)

Frankenstein, Lutz; Zugck, Christian; Nelles, Manfred; Schellberg, Dieter; Katus, Hugo A; Remppis, B Andrew

2009-12-01

To verify whether controlling for indicators of disease severity and confounders represents a solution to the obesity paradox in chronic heart failure (CHF). From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m(2) (Group 3), BMI 20-24.9 k/m(2) (Group 1) and BMI 25-29.9 kg/m(2) (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78-1.05, chi(2): 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13-1.97, chi(2): 7.82) after multivariable adjustment. The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.

Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering.

Science.gov (United States)

Denry, Isabelle; Kuhn, Liisa T

2016-01-01

Our goal is to review design strategies for the fabrication of calcium phosphate ceramic scaffolds (CPS), in light of their transient role in bone tissue engineering and associated requirements for effective bone regeneration. We examine the various design options available to meet mechanical and biological requirements of CPS and later focus on the importance of proper characterization of CPS in terms of architecture, mechanical properties and time-sensitive properties such as biodegradability. Finally, relationships between in vitro versus in vivo testing are addressed, with an attempt to highlight reliable performance predictors. A combinatory design strategy should be used with CPS, taking into consideration 3D architecture, adequate surface chemistry and topography, all of which are needed to promote bone formation. CPS represent the media of choice for delivery of osteogenic factors and anti-infectives. Non-osteoblast mediated mineral deposition can confound in vitro osteogenesis testing of CPS and therefore the expression of a variety of proteins or genes including collagen type I, bone sialoprotein and osteocalcin should be confirmed in addition to increased mineral content. CPS are a superior scaffold material for bone regeneration because they actively promote osteogenesis. Biodegradability of CPS via calcium and phosphate release represents a unique asset. Structural control of CPS at the macro, micro and nanoscale and their combination with cells and polymeric materials is likely to lead to significant developments in bone tissue engineering. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Image-guided urologic surgery: intraoperative optical imaging and tissue interrogation (Conference Presentation)

Science.gov (United States)

Liao, Joseph C.

2017-02-01

Emerging optical imaging technologies can be integrated in the operating room environment during minimally invasive and open urologic surgery, including oncologic surgery of the bladder, prostate, and kidney. These technologies include macroscopic fluorescence imaging that provides contrast enhancement between normal and diseased tissue and microscopic imaging that provides tissue characterization. Optical imaging technologies that have reached the clinical arena in urologic surgery are reviewed, including photodynamic diagnosis, near infrared fluorescence imaging, optical coherence tomography, and confocal laser endomicroscopy. Molecular imaging represents an exciting future arena in conjugating cancer-specific contrast agents to fluorophores to improve the specificity of disease detection. Ongoing efforts are underway to translate optimal targeting agents and imaging modalities, with the goal to improve cancer-specific and functional outcomes.

Is social isolation/alienation confounded with, and non-independent of, emotional distress in its association with early onset of coronary artery disease?

Science.gov (United States)

Ketterer, Mark; Rose, Benjamin; Knysz, Walter; Farha, Amjad; Deveshwar, Sangita; Schairer, John; Keteyian, Steven J

2011-03-01

Both emotional distress (ED) and social isolation/alienation (SI/A) have been found to prospectively predict adverse cardiac events, but few studies have tested the confounding/redundancy of these measures as correlates/predictors of outcomes. In this study, 163 patients with documented coronary artery disease (CAD) were interviewed for multiple indices of SI/A and administered the Symptom Checklist 90 - Revised (SCL90R). A spouse or friend provided an independent rating of ED using the spouse/friend version of the Ketterer Stress Symptom Frequency Checklist (KSSFC). The measures of ED and SI/A covaried. All three scales from the KSSFC (depression, anxiety, and "AIAI" - aggravation, irritation, anger, and impatience), and three scales from the SCL90R (anxiety, depression, and psychoticism), were associated with early Age at Initial Diagnosis (AAID) of CAD. Neither three scales derived from the SCL90R (shyness, feeling abused, and feeling lonely) nor the interview indices of SI/A (married, living alone, having a confidant, self description as a lone wolf, and self-description as lonely) were associated with early AAID. Thus, it is concluded that the present results indicate that ED and SI/A are confounded and that, even when tested head-to-head in a multivariate analysis, only ED is associated with AAID.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

Science.gov (United States)

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

15 CFR 930.114 - Secretarial mediation efforts.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Secretarial mediation efforts. 930.114... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.114 Secretarial mediation efforts. (a) Following the close of the hearing, the hearing officer shall transmit the...

Effort and Selection Effects of Incentive Contracts

NARCIS (Netherlands)

Bouwens, J.F.M.G.; van Lent, L.A.G.M.

2003-01-01

We show that the improved effort of employees associated with incentive contracts depends on the properties of the performance measures used in the contract.We also find that the power of incentives in the contract is only indirectly related to any improved employee effort.High powered incentive

Characterisation of a bystander effect induced in human tissue explant cultures by low LET radiation

International Nuclear Information System (INIS)

Motersill, C.; O'Malley, K.; Seymour, C.B.

2002-01-01

The existence of a bystander effect following both alpha and gamma irradiation of many cell lines is not now in dispute. The significance of this effect for cancer risk assessment and radiotherapy treatment planning requires demonstration of its relevance in vivo. The problem in demonstrating the existence of the effect in vivo is that other systemic effects may mask or confound the effect being investigated and it is practically impossible to attribute an effect in a particular cell to a signal produced in another irradiated cell. To approach this problem, an assay has been developed where fragments of human tissue can be irradiated ex vivo and the media harvested and added to unirradiated, clonogenic cells which have a well characterised and stable response to the bystander signal. The variation in the production of a signal from patient to patient can thus be assessed. The results of a study using tissue from over 100 patients attending Beaumont and St Vincent's Hospitals in Dublin for investigation of urological disorders including follow-up after treatment for transitional cell carcinoma (TCC) and resection of suspect prostatic lesions, are now available. Blood samples from the prostate group were also obtained. The results show that there is variation in the effect of the signal produced by irradiated tissue from different patients. This holds for bladder, prostate and blood. Gender, smoking status and the existence of a malignancy influence the expression of the signal by normal tissue. Male gender, smoking and a pre-existing malignancy all reduce the amount or effect of the signal produced into medium when the tissue is exposed. The effects of exposure to medium containing the signal are transmitted to distant progeny of the exposed cell population. The results may be important not only for understanding radiation risk mechanisms for protection but also for radiotherapy treatment planning where they may open new avenues for development of drugs for combined

Stochastic evolutionary dynamics in minimum-effort coordination games

Science.gov (United States)

Li, Kun; Cong, Rui; Wang, Long

2016-08-01

The minimum-effort coordination game draws recently more attention for the fact that human behavior in this social dilemma is often inconsistent with the predictions of classical game theory. Here, we combine evolutionary game theory and coalescence theory to investigate this game in finite populations. Both analytic results and individual-based simulations show that effort costs play a key role in the evolution of contribution levels, which is in good agreement with those observed experimentally. Besides well-mixed populations, set structured populations have also been taken into consideration. Therein we find that large number of sets and moderate migration rate greatly promote effort levels, especially for high effort costs.

High SNR Acquisitions Improve the Repeatability of Liver Fat Quantification Using Confounder-corrected Chemical Shift-encoded MR Imaging

Science.gov (United States)

Motosugi, Utaroh; Hernando, Diego; Wiens, Curtis; Bannas, Peter; Reeder, Scott. B

2017-01-01

Purpose: To determine whether high signal-to-noise ratio (SNR) acquisitions improve the repeatability of liver proton density fat fraction (PDFF) measurements using confounder-corrected chemical shift-encoded magnetic resonance (MR) imaging (CSE-MRI). Materials and Methods: Eleven fat-water phantoms were scanned with 8 different protocols with varying SNR. After repositioning the phantoms, the same scans were repeated to evaluate the test-retest repeatability. Next, an in vivo study was performed with 20 volunteers and 28 patients scheduled for liver magnetic resonance imaging (MRI). Two CSE-MRI protocols with standard- and high-SNR were repeated to assess test-retest repeatability. MR spectroscopy (MRS)-based PDFF was acquired as a standard of reference. The standard deviation (SD) of the difference (Δ) of PDFF measured in the two repeated scans was defined to ascertain repeatability. The correlation between PDFF of CSE-MRI and MRS was calculated to assess accuracy. The SD of Δ and correlation coefficients of the two protocols (standard- and high-SNR) were compared using F-test and t-test, respectively. Two reconstruction algorithms (complex-based and magnitude-based) were used for both the phantom and in vivo experiments. Results: The phantom study demonstrated that higher SNR improved the repeatability for both complex- and magnitude-based reconstruction. Similarly, the in vivo study demonstrated that the repeatability of the high-SNR protocol (SD of Δ = 0.53 for complex- and = 0.85 for magnitude-based fit) was significantly higher than using the standard-SNR protocol (0.77 for complex, P magnitude-based fit, P = 0.003). No significant difference was observed in the accuracy between standard- and high-SNR protocols. Conclusion: Higher SNR improves the repeatability of fat quantification using confounder-corrected CSE-MRI. PMID:28190853

Animal models for bone tissue engineering and modelling disease

Science.gov (United States)

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Detailing the relation between renal T2* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements.

Science.gov (United States)

Pohlmann, Andreas; Arakelyan, Karen; Hentschel, Jan; Cantow, Kathleen; Flemming, Bert; Ladwig, Mechthild; Waiczies, Sonia; Seeliger, Erdmann; Niendorf, Thoralf

2014-08-01

, as did renal vascular conductance with T2*. Our findings indicate that changes in T2* qualitatively mirror changes in renal tissue pO2 but are also associated with confounding factors including vascular volume fraction and tubular volume fraction. Our results demonstrate that MR-PHYSIOL is instrumental to detail the link between renal tissue pO2 and T2* in vivo. Unravelling the link between regional renal T2* and tissue pO2, including the role of the T2* confounding parameters vascular and tubular volume fraction and oxy-hemoglobin dissociation curve, requires further research. These explorations are essential before the quantitative capabilities of parametric MRI can be translated from experimental research to improved clinical understanding of hemodynamics/oxygenation in kidney disorders.

Multi-scale, multi-modal analysis uncovers complex relationship at the brain tissue-implant neural interface: new emphasis on the biological interface

Science.gov (United States)

Michelson, Nicholas J.; Vazquez, Alberto L.; Eles, James R.; Salatino, Joseph W.; Purcell, Erin K.; Williams, Jordan J.; Cui, X. Tracy; Kozai, Takashi D. Y.

2018-06-01

Objective. Implantable neural electrode devices are important tools for neuroscience research and have an increasing range of clinical applications. However, the intricacies of the biological response after implantation, and their ultimate impact on recording performance, remain challenging to elucidate. Establishing a relationship between the neurobiology and chronic recording performance is confounded by technical challenges related to traditional electrophysiological, material, and histological limitations. This can greatly impact the interpretations of results pertaining to device performance and tissue health surrounding the implant. Approach. In this work, electrophysiological activity and immunohistological analysis are compared after controlling for motion artifacts, quiescent neuronal activity, and material failure of devices in order to better understand the relationship between histology and electrophysiological outcomes. Main results. Even after carefully accounting for these factors, the presence of viable neurons and lack of glial scarring does not convey single unit recording performance. Significance. To better understand the biological factors influencing neural activity, detailed cellular and molecular tissue responses were examined. Decreases in neural activity and blood oxygenation in the tissue surrounding the implant, shift in expression levels of vesicular transporter proteins and ion channels, axon and myelin injury, and interrupted blood flow in nearby capillaries can impact neural activity around implanted neural interfaces. Combined, these tissue changes highlight the need for more comprehensive, basic science research to elucidate the relationship between biology and chronic electrophysiology performance in order to advance neural technologies.

Tissue bionics: examples in biomimetic tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

2008-09-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

Tissue bionics: examples in biomimetic tissue engineering

International Nuclear Information System (INIS)

Green, David W

2008-01-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

Repair and tissue engineering techniques for articular cartilage.

Science.gov (United States)

Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.

Directory of Open Access Journals (Sweden)

Alexandra C Nica

2011-02-01

Full Text Available While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL, skin, and fat. The samples (156 LCL, 160 skin, 166 fat were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes. In addition, we apply factor analysis (FA to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes. The unique study design (Matched Co-Twin Analysis--MCTA permits immediate replication of eQTLs using co-twins (93%-98% and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20% have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.

New Therapeutic Targets in Soft Tissue Sarcoma

Science.gov (United States)

Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

2012-01-01

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues [v2; ref status: indexed, http://f1000r.es/2dl

Directory of Open Access Journals (Sweden)

Liliana Florea

2013-11-01

Full Text Available Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads.  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60% were novel, involving new exons (~3000, new introns (~16000, or both. When tracing these events across the sixteen tissues, only a small number (4-7% appeared to be differentially expressed (‘switched’ between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository (http://zenodo.org/record/7068; doi:10.5281/zenodo.7068 and from our web site http://ccb.jhu.edu/software/ASprofile.

Neuroticism explains unwanted variance in Implicit Association Tests of personality: Possible evidence for an affective valence confound

Directory of Open Access Journals (Sweden)

Monika eFleischhauer

2013-09-01

Full Text Available Meta-analytic data highlight the value of the Implicit Association Test (IAT as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling, latent Big-Five personality factors (based on self- and peer-report were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign, biases that might result, for example, from the IAT’s stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis. However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis, a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to

Adjusting for the Confounding Effects of Treatment Switching—The BREAK-3 Trial: Dabrafenib Versus Dacarbazine

Science.gov (United States)

Abrams, Keith R.; Amonkar, Mayur M.; Stapelkamp, Ceilidh; Swann, R. Suzanne

2015-01-01

Background. Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48–1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Materials and Methods. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, “treatment group” (assumes treatment effect could continue until death) and “on-treatment observed” (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. Results. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE “treatment group” and “on-treatment observed” analyses performed similarly well. Conclusion. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching—a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Implications for Practice: Treatment switching is common in oncology trials, and the implications of this for the interpretation of the

Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine.

Science.gov (United States)

Latimer, Nicholas R; Abrams, Keith R; Amonkar, Mayur M; Stapelkamp, Ceilidh; Swann, R Suzanne

2015-07-01

Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48-1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, "treatment group" (assumes treatment effect could continue until death) and "on-treatment observed" (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE "treatment group" and "on-treatment observed" analyses performed similarly well. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching-a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Treatment switching is common in oncology trials, and the implications of this for the interpretation of the clinical effectiveness and cost-effectiveness of the novel treatment are important to consider. If

Heuristics Made Easy: An Effort-Reduction Framework

Science.gov (United States)

Shah, Anuj K.; Oppenheimer, Daniel M.

2008-01-01

In this article, the authors propose a new framework for understanding and studying heuristics. The authors posit that heuristics primarily serve the purpose of reducing the effort associated with a task. As such, the authors propose that heuristics can be classified according to a small set of effort-reduction principles. The authors use this…

Mildly elevated serum total bilirubin is negatively associated with hemoglobin A1c independently of confounding factors among community-dwelling middle-aged and elderly persons

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Ryuichi Kawamoto

2017-08-01

Full Text Available Abnormally high glycated hemoglobin (Hb (HbA1c is significantly associated with oxidative stress and an increased risk of cardiovascular disease (CVD. Serum total bilirubin (T-B may have a beneficial role in preventing oxidative changes and be a negative risk factor of CVD. Limited information is available on whether serum T-B is an independent confounding factor of HbA1c. The study subjects were 633 men aged 70 ± 9 (mean ± standard deviation (SD years and 878 women aged 70 ± 8 years who were enrolled consecutively from among patients aged ≥40 years through a community-based annual check-up process. We evaluated the relationship between various confounding factors including serum T-B and HbA1c in each gender. Multiple linear regression analysis pertaining to HbA1c showed that in men, serum T-B ( β = −0.139 as well as waist circumference ( β = 0.099, exercise habit ( β = 0.137, systolic blood pressure (SBP ( β = 0.076, triglycerides ( β = 0.087, and uric acid ( β = −0.123 were significantly and independently associated with HbA1c, and in women, serum T-B ( β = −0.084 as well as body mass index ( β = 0.090, smoking status ( β = −0.077, SBP ( β = 0.117, diastolic blood pressure (DBP ( β = −0.155, low-density lipoprotein cholesterol ( β = 0.074, prevalence of antidyslipidemic medication ( β = 0.174, and uric acid ( β = 0.090 were also significantly and independently associated with HbA1c. Multivariate-adjusted serum HbA1c levels were significantly high in subjects with the lowest serum T-B levels in both genders. Serum T-B is an independent confounding factor for HbA1c among community-dwelling middle-aged and elderly persons.

High-throughput simultaneous analysis of RNA, protein, and lipid biomarkers in heterogeneous tissue samples.

Science.gov (United States)

Reiser, Vladimír; Smith, Ryan C; Xue, Jiyan; Kurtz, Marc M; Liu, Rong; Legrand, Cheryl; He, Xuanmin; Yu, Xiang; Wong, Peggy; Hinchcliffe, John S; Tanen, Michael R; Lazar, Gloria; Zieba, Renata; Ichetovkin, Marina; Chen, Zhu; O'Neill, Edward A; Tanaka, Wesley K; Marton, Matthew J; Liao, Jason; Morris, Mark; Hailman, Eric; Tokiwa, George Y; Plump, Andrew S

2011-11-01

With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD). We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured. The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting. The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.

An Effort to Improve Teacher Perceptions and Knowledge of Cyberbullying: A Pre-Post Assessment

Science.gov (United States)

Nesshengel-Hopp, Marleny T.

2017-01-01

Cyberbullying is a growing concern, confounded by the limited training resources available for teachers. The problem undertaken in this study was determining the most effective way to teach teachers about cyberbullying given the limited 1-hour time constraint of a typical school in-service activity. Using a pre-test, post-test experimental…

Tissue engineering

CERN Document Server

Fisher, John P; Bronzino, Joseph D

2007-01-01

Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

The Effect of Age on Listening Effort

Science.gov (United States)

Degeest, Sofie; Keppler, Hannah; Corthals, Paul

2015-01-01

Purpose: The objective of this study was to investigate the effect of age on listening effort. Method: A dual-task paradigm was used to evaluate listening effort in different conditions of background noise. Sixty adults ranging in age from 20 to 77 years were included. A primary speech-recognition task and a secondary memory task were performed…

Toward a Rational and Mechanistic Account of Mental Effort.

Science.gov (United States)

Shenhav, Amitai; Musslick, Sebastian; Lieder, Falk; Kool, Wouter; Griffiths, Thomas L; Cohen, Jonathan D; Botvinick, Matthew M

2017-07-25

In spite of its familiar phenomenology, the mechanistic basis for mental effort remains poorly understood. Although most researchers agree that mental effort is aversive and stems from limitations in our capacity to exercise cognitive control, it is unclear what gives rise to those limitations and why they result in an experience of control as costly. The presence of these control costs also raises further questions regarding how best to allocate mental effort to minimize those costs and maximize the attendant benefits. This review explores recent advances in computational modeling and empirical research aimed at addressing these questions at the level of psychological process and neural mechanism, examining both the limitations to mental effort exertion and how we manage those limited cognitive resources. We conclude by identifying remaining challenges for theoretical accounts of mental effort as well as possible applications of the available findings to understanding the causes of and potential solutions for apparent failures to exert the mental effort required of us.

Comorbidity and confounding factors in attention-deficit/hyperactivity disorder and sleep disorders in children

Directory of Open Access Journals (Sweden)

Huang YS

2011-09-01

Full Text Available Ya-Wen Jan1,2, Chien-Ming Yang1,3, Yu-Shu Huang4,51Department of Psychology, National Cheng-Chi University, Taipei; 2Sleep Center of Taipei Medical University Hospital, Taipei; 3The Research Center for Mind Brain and Learning, National Cheng-Chi University, Taipei; 4Department of Child Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan; 5College of Medicine, Chang Gung University, Taoyuan, TaiwanAbstract: Sleep problems are commonly reported in children with attention-deficit/hyperactivity disorder (ADHD symptoms. Research data regarding the complex and reciprocal relationship between ADHD and sleep disturbances has now accumulated. This paper is focused on the types of sleep problems that are associated with ADHD symptomatology, and attempts to untangle confounding factors and overlapping symptoms. The goal is also to present an updated overview of the pathophysiology of and treatment strategies for sleep problems in children with ADHD. The review also points out that future research will be needed to clarify further the other psychiatric comorbidities and side effects of medication in order to improve treatment outcomes and prevent misdiagnosis in clinical practice.Keywords: attention-deficit/hyperactivity disorder, sleep, children 

Inclusion of residual tissue in biobanks: opt-in or opt-out?

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Noor A A Giesbertz

Full Text Available Residual samples are an important source of tissue for biobanks. They refer to leftover tissue that is obtained in the course of clinical care. Residual samples can be included through an opt-in method--that is, a person explicitly expresses consent to include residual tissue--or an opt-out method--that is, the tissue is stored unless a person explicitly refuses. At the moment there is a renewed interest in the appropriate method for the inclusion of residual samples in biobanks. The expansion of biobanks and rapid developments in biomedical research underscore the need to evaluate the proper procedure. In this article we revisit the arguments in favor and against opt-in and opt-out methods for residual tissue research. We conclude firstly that an opt-out method is only justifiable when certain conditions are met: (1 awareness has to be raised, (2 sufficient information has to be provided, and (3 a genuine possibility to object has to be offered. An opt-out procedure that fulfills these conditions can be called a "thick" opt-out method. As a consequence, the dichotomy between opt-in and opt-out is less stark than usually suggested, as both methods require a certain amount of effort. Secondly, we conclude that because of the diversity of tissue and research, not every situation can be treated alike. There are at least four situations that require opt-in procedures: (1 research with higher risks or increased burdens, (2 the use of controversial or high-impact techniques, (3 research on sensitive tissue types, and (4 research involving vulnerable patients. We suggest that further interdisciplinary debate should answer the question when to opt-in or when to opt-out.

Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues [v1; ref status: indexed, http://f1000r.es/1p0

Directory of Open Access Journals (Sweden)

Liliana Florea

2013-09-01

Full Text Available Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads.  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60% were novel, involving new exons (~3000, new introns (~16000, or both. When tracing these events across the sixteen tissues, only a small number (4-7% appeared to be differentially expressed (‘switched’ between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository (http://zenodo.org/record/7068; doi:10.5281/zenodo.7068 and from our web site http://ccb.jhu.edu/software/ASprofile.

The Role of Cognitive Effort in Framing Effects

OpenAIRE

Krzysztof Przybyszewski; Dorota Rutkowska

2013-01-01

Framing effects are a common bias in people making risky decisions. The account for this bias is found in the loss aversion derived from Prospect Theory. Most often in the decision making literature this is the effortful processes that are claimed to reduce framing effects in risky choice tasks i.e. investing of mental effort should de-bias the decision makers. However, in goal framing studies, effortful mental processes may produce those effects. In our experiment participants were primed wi...

Dopamine does double duty in motivating cognitive effort

Science.gov (United States)

Westbrook, Andrew; Braver, Todd S.

2015-01-01

Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: 1) modulating the functional parameters of working memory circuits subserving effortful cognition, and 2) mediating value-learning and decision-making about effortful cognitive action. Here we tie together these two lines of research, proposing how dopamine serves “double duty”, translating incentive information into cognitive motivation. PMID:26889810

Cognitive Load and Listening Effort: Concepts and Age-Related Considerations.

Science.gov (United States)

Lemke, Ulrike; Besser, Jana

2016-01-01

Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

Science.gov (United States)

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of

Target gene expression levels and competition between transfected and endogenous microRNAs are strong confounding factors in microRNA high-throughput experiments

Science.gov (United States)

2012-01-01

Background MicroRNA (miRNA) target genes tend to have relatively long and conserved 3' untranslated regions (UTRs), but to what degree these characteristics contribute to miRNA targeting is poorly understood. Different high-throughput experiments have, for example, shown that miRNAs preferentially regulate genes with both short and long 3' UTRs and that target site conservation is both important and irrelevant for miRNA targeting. Results We have analyzed several gene context-dependent features, including 3' UTR length, 3' UTR conservation, and messenger RNA (mRNA) expression levels, reported to have conflicting influence on miRNA regulation. By taking into account confounding factors such as technology-dependent experimental bias and competition between transfected and endogenous miRNAs, we show that two factors - target gene expression and competition - could explain most of the previously reported experimental differences. Moreover, we find that these and other target site-independent features explain about the same amount of variation in target gene expression as the target site-dependent features included in the TargetScan model. Conclusions Our results show that it is important to consider confounding factors when interpreting miRNA high throughput experiments and urge special caution when using microarray data to compare average regulatory effects between groups of genes that have different average gene expression levels. PMID:22325809

Bodily Effort Enhances Learning and Metacognition: Investigating the Relation Between Physical Effort and Cognition Using Dual-Process Models of Embodiment.

Science.gov (United States)

Skulmowski, Alexander; Rey, Günter Daniel

2017-01-01

Recent embodiment research revealed that cognitive processes can be influenced by bodily cues. Some of these cues were found to elicit disparate effects on cognition. For instance, weight sensations can inhibit problem-solving performance, but were shown to increase judgments regarding recall probability (judgments of learning; JOLs) in memory tasks. We investigated the effects of physical effort on learning and metacognition by conducting two studies in which we varied whether a backpack was worn or not while 20 nouns were to be learned. Participants entered a JOL for each word and completed a recall test. Experiment 1 ( N = 18) revealed that exerting physical effort by wearing a backpack led to higher JOLs for easy nouns, without a notable effect on difficult nouns. Participants who wore a backpack reached higher recall scores. Therefore, physical effort may act as a form of desirable difficulty during learning. In Experiment 2 ( N = 30), the influence of physical effort on JOL s and learning disappeared when more difficult nouns were to be learned, implying that a high cognitive load may diminish bodily effects. These findings suggest that physical effort mainly influences superficial modes of thought and raise doubts concerning the explanatory power of metaphor-centered accounts of embodiment for higher-level cognition.

Optical imaging of oral pathological tissue using optical coherence tomography and synchrotron radiation computed microtomography

Science.gov (United States)

Cânjǎu, Silvana; Todea, Carmen; Sinescu, Cosmin; Negrutiu, Meda L.; Duma, Virgil; Mǎnescu, Adrian; Topalǎ, Florin I.; Podoleanu, Adrian Gh.

2013-06-01

The efforts aimed at early diagnosis of oral cancer should be prioritized towards developing a new screening instrument, based on optical coherence tomography (OCT), to be used directly intraorally, able to perform a fast, real time, 3D and non-invasive diagnosis of oral malignancies. The first step in this direction would be to optimize the OCT image interpretation of oral tissues. Therefore we propose plastination as a tissue preparation method that better preserves three-dimensional structure for study by new optical imaging techniques. The OCT and the synchrotron radiation computed microtomography (micro-CT) were employed for tissue sample analyze. For validating the OCT results we used the gold standard diagnostic procedure for any suspicious lesion - histopathology. This is a preliminary study of comparing features provided by OCT and Micro-CT. In the conditions of the present study, OCT proves to be a highly promising imaging modality. The use of x-ray based topographic imaging of small biological samples has been limited by the low intrinsic x-ray absorption of non-mineralized tissue and the lack of established contrast agents. Plastination can be used to enhance optical imagies of oral soft tissue samples.

Pandemic Influenza: Domestic Preparedness Efforts

National Research Council Canada - National Science Library

Lister, Sarah A

2005-01-01

.... Though influenza pandemics occur with some regularity, and the United States has been involved in specific planning efforts since the early 1990s, the H5N1 situation has created a sense of urgency...

The promise of organ and tissue preservation to transform medicine.

Science.gov (United States)

Giwa, Sebastian; Lewis, Jedediah K; Alvarez, Luis; Langer, Robert; Roth, Alvin E; Church, George M; Markmann, James F; Sachs, David H; Chandraker, Anil; Wertheim, Jason A; Rothblatt, Martine; Boyden, Edward S; Eidbo, Elling; Lee, W P Andrew; Pomahac, Bohdan; Brandacher, Gerald; Weinstock, David M; Elliott, Gloria; Nelson, David; Acker, Jason P; Uygun, Korkut; Schmalz, Boris; Weegman, Brad P; Tocchio, Alessandro; Fahy, Greg M; Storey, Kenneth B; Rubinsky, Boris; Bischof, John; Elliott, Janet A W; Woodruff, Teresa K; Morris, G John; Demirci, Utkan; Brockbank, Kelvin G M; Woods, Erik J; Ben, Robert N; Baust, John G; Gao, Dayong; Fuller, Barry; Rabin, Yoed; Kravitz, David C; Taylor, Michael J; Toner, Mehmet

2017-06-07

The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

Science.gov (United States)

Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

2018-01-01

It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

Job Satisfaction, Effort, and Performance: A Reasoned Action Perspective

Directory of Open Access Journals (Sweden)

Icek Ajzen

2011-12-01

Full Text Available In this article the author takes issue with the recurrent reliance on job satisfaction to explain job-related effort and performance.  The disappointing findings in this tradition are explained by lack of compatibility between job satisfaction–-a very broad attitude–-and the more specific effort and performance criteria.  Moreover, attempts to apply the expectancy-value model of attitude to explore the determinants of effort and performance suffer from reliance on unrepresentative sets of beliefs about the likely consequences of these behaviors.  The theory of planned behavior (Ajzen, 1991, 2012, with its emphasis on the proximal antecedents of job effort and performance, is offered as an alternative.  According to the theory, intentions to exert effort and to attain a certain performance level are determined by attitudes, subjective norms, and perceptions of control in relation to these behaviors; and these variables, in turn, are a function of readily accessible beliefs about the likely outcomes of effort and performance, about the normative expectations of important others, and about factors that facilitate or hinder effective performance.

The use of aquatic bioconcentration factors in ecological risk assessments: Confounding issues, laboratory v/s modeled results

International Nuclear Information System (INIS)

Brandt, C.; Blanton, M.L.; Dirkes, R.

1995-01-01

Bioconcentration in aquatic systems is generally taken to refer to contaminant uptake through non-ingestion pathways (i.e., dermal and respiration uptake). Ecological risk assessments performed on aquatic systems often rely on published data on bioconcentration factors to calibrate models of exposure. However, many published BCFs, especially those from in situ studies, are confounded by uptake from ingestion of prey. As part of exposure assessment and risk analysis of the Columbia River's Hanford Reach, the authors tested a methodology to estimate radionuclide BCFs for several aquatic species in the Hanford Reach of the Columbia River. The iterative methodology solves for BCFs from known body burdens and environmental media concentrations. This paper provides BCF methodology description comparisons of BCF from literature and modeled values and how they were used in the exposure assessment and risk analysis of the Columbia River's Hanford Reach

Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.

Science.gov (United States)

Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

2012-03-01

Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular Markers for Prostate Cancer in Formalin-Fixed Paraffin-Embedded Tissues

Directory of Open Access Journals (Sweden)

Tamara Sequeiros

2013-01-01

Full Text Available Prostate cancer (PCa is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE tissues, due to their stability over long periods of time. In the last few years, a concerted effort has been made to develop the necessary tools for their reliable measurement in these types of samples. Furthermore, the use of these kinds of markers may also help in establishing tumor grade and aggressiveness, as well as predicting the possible outcomes in each particular case for the different treatments available. This would aid clinicians in the decision-making process. In this review, we attempt to summarize and discuss the potential use of microRNA and protein profiles in FFPE tissue samples as markers to better predict PCa diagnosis, progression, and response to therapy.

Best-effort Support for a Virtual Seminar Room

DEFF Research Database (Denmark)

Sharp, Robin; Todirica, Edward Alexandru

2002-01-01

This paper describes the RTMM Virtual Seminar Room, an interactive distributed multimedia application based on a platform with a simple middleware architecture, using best effort scheduling and a best effort network service. Emphasis has been placed on achieving low latency in all parts...

Experimental and computational laser tissue welding using a protein patch.

Science.gov (United States)

Small, W; Heredia, N J; Maitland, D J; Eder, D C; Celliers, P M; Da Silva, L B; London, R A; Matthews, D L

1998-01-01

An in vitro study of laser tissue welding mediated with a dye-enhanced protein patch was conducted. Fresh sections of porcine aorta were used for the experiments. Arteriotomies were treated using an indocyanine green dye-enhanced collagen patch activated by an 805-nm continuous-wave fiber-delivered diode laser. Temperature histories of the surface of the weld site were obtained using a hollow glass optical fiber-based two-color infrared thermometer. The experimental effort was complemented by simulations with the LATIS (LAser-TISsue) computer code, which uses coupled Monte Carlo, thermal transport, and mass transport models. Comparison of simulated and experimental thermal data indicated that evaporative cooling clamped the surface temperature of the weld site below 100 °C. For fluences of approximately 200 J/cm2, peak surface temperatures averaged 74°C and acute burst strengths consistently exceeded 0.14×106 dyn/cm (hoop tension). The combination of experimental and simulation results showed that the inclusion of water transport and evaporative losses in the computer code has a significant impact on the thermal distributions and hydration levels throughout the tissue volume. The solid-matrix protein patch provided a means of controllable energy delivery and yielded consistently strong welds. © 1998 Society of Photo-Optical Instrumentation Engineers.

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

Science.gov (United States)

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.

Enhanced bioactive scaffolds for bone tissue regeneration

Science.gov (United States)

Karnik, Sonali

Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37

Inpo/industry job and task analysis efforts

International Nuclear Information System (INIS)

Wigley, W.W.

1985-01-01

One of the goals of INPO is to develop and coordinate industrywide programs to improve the education, training and qualification of nuclear utility personnel. To accomplish this goal, INPO's Training and Education Division: conducts periodic evaluations of industry training programs; provides assistance to the industry in developing training programs; manages the accreditation of utility training programs. These efforts are aimed at satisfying the need for training programs for nuclear utility personnel to be performance-based. Performance-based means that training programs provide an incumbent with the skills and knowledge required to safely perform the job. One of the ways that INPO has provided assistance to the industry is through the industrywide job and task analysis effort. I will discuss the job analysis and task analysis processes, the current status of JTA efforts, JTA products and JTA lessons learned

An imaging colorimeter for noncontact tissue color mapping.

Science.gov (United States)

Balas, C

1997-06-01

There has been a considerable effort in several medical fields, for objective color analysis and characterization of biological tissues. Conventional colorimeters have proved inadequate for this purpose, since they do not provide spatial color information and because the measuring procedure randomly affects the color of the tissue. In this paper an imaging colorimeter is presented, where the nonimaging optical photodetector of colorimeters is replaced with the charge-coupled device (CCD) sensor of a color video camera, enabling the independent capturing of the color information for any spatial point within its field-of-view. Combining imaging and colorimetry methods, the acquired image is calibrated and corrected, under several ambient light conditions, providing noncontact reproducible color measurements and mapping, free of the errors and the limitations present in conventional colorimeters. This system was used for monitoring of blood supply changes of psoriatic plaques, that have undergone Psoralens and ultraviolet-A radiation (PUVA) therapy, where reproducible and reliable measurements were demonstrated. These features highlight the potential of the imaging colorimeters as clinical and research tools for the standardization of clinical diagnosis and for the objective evaluation of treatment effectiveness.

Money Laundering and International Efforts to Fight It

OpenAIRE

David Scott

1996-01-01

According to one estimate, US$300 billion to US$500 billion in proceeds from serious crime is laundered each year. Left unchecked, money laundering could criminalize the financial system and undermine development efforts in emerging markets. The author reviews efforts by international bodies to fight it.

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

Directory of Open Access Journals (Sweden)

Michaela Thomas

2017-11-01

Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

Economic effort management in multispecies fisheries: the FcubEcon model

DEFF Research Database (Denmark)

Hoff, Ayoe; Frost, Hans; Ulrich, Clara

2010-01-01

in the development of management tools based on fleets, fisheries, and areas, rather than on unit fish stocks. A natural consequence of this has been to consider effort rather than quota management, a final effort decision being based on fleet-harvest potential and fish-stock-preservation considerations. Effort...... allocation between fleets should not be based on biological considerations alone, but also on the economic behaviour of fishers, because fisheries management has a significant impact on human behaviour as well as on ecosystem development. The FcubEcon management framework for effort allocation between fleets...... the past decade, increased focus on this issue has resulted in the development of management tools based on fleets, fisheries, and areas, rather than on unit fish stocks. A natural consequence of this has been to consider effort rather than quota management, a final effort decision being based on fleet...

The ad-libitum alcohol 'taste test': secondary analyses of potential confounds and construct validity.

Science.gov (United States)

Jones, Andrew; Button, Emily; Rose, Abigail K; Robinson, Eric; Christiansen, Paul; Di Lemma, Lisa; Field, Matt

2016-03-01

Motivation to drink alcohol can be measured in the laboratory using an ad-libitum 'taste test', in which participants rate the taste of alcoholic drinks whilst their intake is covertly monitored. Little is known about the construct validity of this paradigm. The objective of this study was to investigate variables that may compromise the validity of this paradigm and its construct validity. We re-analysed data from 12 studies from our laboratory that incorporated an ad-libitum taste test. We considered time of day and participants' awareness of the purpose of the taste test as potential confounding variables. We examined whether gender, typical alcohol consumption, subjective craving, scores on the Alcohol Use Disorders Identification Test and perceived pleasantness of the drinks predicted ad-libitum consumption (construct validity). We included 762 participants (462 female). Participant awareness and time of day were not related to ad-libitum alcohol consumption. Males drank significantly more alcohol than females (p alcohol consumption (p = 0.04), craving (p alcohol consumption. The construct validity of the taste test was supported by relationships between ad-libitum consumption and typical alcohol consumption, craving and pleasantness ratings of the drinks. The ad-libitum taste test is a valid method for the assessment of alcohol intake in the laboratory.

Localization of IAA transporting tissue by tissue printing and autoradiography

International Nuclear Information System (INIS)

Mee-Rye Cha; Evans, M.L.; Hangarter, R.P.

1991-01-01

Tissue printing on nitrocellulose membranes provides a useful technique for visualizing anatomical details of tissue morphology of cut ends of stem segments. Basal ends of Coleus stem and corn coleoptile segments that were transporting 14 C-IAA were gently blotted onto DEAE-nitrocellulose for several minutes to allow 14 C-IAA to efflux from the tissue. Because of the anion exchange properties of DEAE-nitrocellulose the 14 C-IAA remains on the membrane at the point it leaves the transporting tissue. Autoradiography of the DEAE membrane allowed indirect visualization of the tissues preferentially involved in auxin transport. The authors observed that polar transport through the stem segments occurred primarily through or in association with vascular tissues. However, in Coleus stems, substantial amounts of the label appeared to move through the tissue by diffusion as well as by active transport

Modelling cardiac signal as a confound in EEG-fMRI and its application in focal epilepsy studies

DEFF Research Database (Denmark)

Liston, A. D.; Ellegaard Lund, Torben; Salek-Haddadi, A

2006-01-01

effects to be modelled, as effects of no interest. Our model is based on an over-complete basis set covering a linear relationship between cardiac-related MR signal and the phase of the cardiac cycle or time after pulse (TAP). This method showed that, on average, 24.6 +/- 10.9% of grey matter voxels......Cardiac noise has been shown to reduce the sensitivity of functional Magnetic Resonance Imaging (fMRI) to an experimental effect due to its confounding presence in the blood oxygenation level-dependent (BOLD) signal. Its effect is most severe in particular regions of the brain and a method is yet...... to take it into account in routine fMRI analysis. This paper reports the development of a general and robust technique to improve the reliability of EEG-fMRI studies to BOLD signal correlated with interictal epileptiform discharges (IEDs). In these studies, ECG is routinely recorded, enabling cardiac...

Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding.

Science.gov (United States)

Fukagawa, Masafumi; Kido, Ryo; Komaba, Hirotaka; Onishi, Yoshihiro; Yamaguchi, Takuhiro; Hasegawa, Takeshi; Kurita, Noriaki; Fukuma, Shingo; Akizawa, Tadao; Fukuhara, Shunichi

2014-06-01

Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers. Multicenter, 3-year, prospective, case-cohort study. 8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan. Serum phosphorus, calcium, and parathyroid hormone levels. All-cause mortality. Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding. The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (secondary hyperparathyroidism. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Reproductive effort in viscous populations

NARCIS (Netherlands)

Pen, Ido

Here I study a kin selection model of reproductive effort, the allocation of resources to fecundity versus survival, in a patch-structured population. Breeding females remain in the same patch for life. Offspring have costly, partial long-distance dispersal and compete for breeding sites, which

Engineering Complex Tissues

Science.gov (United States)

MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

Quantifying commercial catch and effort of monkfish Lophius ...

African Journals Online (AJOL)

Catch-per-unit-effort (cpue) data of vessels targeting monkfish and sole (the two ... analysed using two different methods to construct indices of abundance. ... in Namibia to all tail-weight classes is not appropriate for the current fishery and needs ... Keywords: catch per unit effort, Generalized Linear Model, Lophius vaillanti, ...

Viscoelastic Properties of Dental Pulp Tissue and Ramifications on Biomaterial Development for Pulp Regeneration.

Science.gov (United States)

Erisken, Cevat; Kalyon, Dilhan M; Zhou, Jian; Kim, Sahng G; Mao, Jeremy J

2015-10-01

A critical step in biomaterial selection effort is the determination of material as well as the biological properties of the target tissue. Previously, the selection of biomaterials and carriers for dental pulp regeneration has been solely based on empirical experience. In this study, first, the linear viscoelastic material functions and compressive properties of miniature pig dental pulp were characterized using small-amplitude oscillatory shear and uniaxial compression at a constant rate. They were then compared with the properties of hydrogels (ie, agarose, alginate, and collagen) that are widely used in tissue regeneration. The comparisons of the linear viscoelastic material functions of the native pulp tissue with those of the 3 hydrogels revealed the gel-like behavior of the pulp tissue over a relatively large range of time scales (ie, over the frequency range of 0.1-100 rps). At the constant gelation agent concentration of 2%, the dynamic properties (ie, storage and loss moduli and the tanδ) of the collagen-based gel approached those of the native tissue. Under uniaxial compression, the peak normal stresses and compressive moduli of the agarose gel were similar to those of the native tissue, whereas alginate and collagen exhibited significantly lower compressive properties. The linear viscoelastic and uniaxial compressive properties of the dental pulp tissue reported here should enable the more appropriate selection of biogels for dental pulp regeneration via the better tailoring of gelation agents and their concentrations to better mimic the dynamic and compressive properties of native pulp tissue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Acoustic correlate of vocal effort in spasmodic dysphonia.

Science.gov (United States)

Eadie, Tanya L; Stepp, Cara E

2013-03-01

This study characterized the relationship between relative fundamental frequency (RFF) and listeners' perceptions of vocal effort and overall spasmodic dysphonia severity in the voices of 19 individuals with adductor spasmodic dysphonia. Twenty inexperienced listeners evaluated the vocal effort and overall severity of voices using visual analog scales. The squared correlation coefficients (R2) between average vocal effort and overall severity and RFF measures were calculated as a function of the number of acoustic instances used for the RFF estimate (from 1 to 9, of a total of 9 voiced-voiceless-voiced instances). Increases in the number of acoustic instances used for the RFF average led to increases in the variance predicted by the RFF at the first cycle of voicing onset (onset RFF) in the perceptual measures; the use of 6 or more instances resulted in a stable estimate. The variance predicted by the onset RFF for vocal effort (R2 range, 0.06 to 0.43) was higher than that for overall severity (R2 range, 0.06 to 0.35). The offset RFF was not related to the perceptual measures, irrespective of the sample size. This study indicates that onset RFF measures are related to perceived vocal effort in patients with adductor spasmodic dysphonia. These results have implications for measuring outcomes in this population.

Tissue

Directory of Open Access Journals (Sweden)

David Morrissey

2012-01-01

Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

Stress-sensitive tissue regeneration in viscoelastic biomaterials subjected to modulated tensile strain.

Science.gov (United States)

Belfiore, Laurence A; Floren, Michael L; Paulino, Alexandre T; Belfiore, Carol J

2011-09-01

This research contribution addresses the mechanochemistry of intra-tissue mass transfer for nutrients, oxygen, growth factors, and other essential ingredients that anchorage-dependent cells require for successful proliferation on biocompatible surfaces. The unsteady state reaction-diffusion equation (i.e., modified diffusion equation) is solved according to the von Kármán-Pohlhausen integral method of boundary layer analysis when nutrient consumption and tissue regeneration are stimulated by harmonically imposed stress. The mass balance with diffusion and stress-sensitive kinetics represents a rare example where the Damköhler and Deborah numbers appear together in an effort to simulate the development of mass transfer boundary layers in porous viscoelastic biomaterials. The Boltzmann superposition integral is employed to calculate time-dependent strain in terms of the real and imaginary components of dynamic compliance for viscoelastic solids that transmit harmonic excitation to anchorage-dependent cells. Rates of nutrient consumption under stress-free conditions are described by third-order kinetics which include local mass densities of nutrients, oxygen, and attached cells that maintain dynamic equilibrium with active protein sites in the porous matrix. Thinner nutrient mass transfer boundary layers are stabilized at shorter dimensionless diffusion times when the stress-free intra-tissue Damköhler number increases above its initial-condition-sensitive critical value. The critical stress-sensitive intra-tissue Damköhler number, above which it is necessary to consider the effect of harmonic strain on nutrient consumption and tissue regeneration, is proportional to the Deborah number and corresponds to a larger fraction of the stress-free intra-tissue Damköhler number in rigid biomaterials. Copyright © 2011 Elsevier B.V. All rights reserved.

Porous magnesium-based scaffolds for tissue engineering

International Nuclear Information System (INIS)

Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Moharamzadeh, Keyvan; Boccaccini, Aldo R.; Tayebi, Lobat

2017-01-01

Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

Porous magnesium-based scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Yazdimamaghani, Mostafa [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Razavi, Mehdi [Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304 (United States); Vashaee, Daryoosh [Electrical and Computer Engineering Department, North Carolina State University, Raleigh, NC 27606 (United States); Moharamzadeh, Keyvan [School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield (United Kingdom); Marquette University School of Dentistry, Milwaukee, WI 53233 (United States); Boccaccini, Aldo R. [Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen (Germany); Tayebi, Lobat, E-mail: lobat.tayebi@marquette.edu [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States)

2017-02-01

Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

Effortful semantic decision-making boosts memory performance in older adults.

Science.gov (United States)

Fu, Li; Maes, Joseph H R; Varma, Samarth; Kessels, Roy P C; Daselaar, Sander M

2017-04-01

A major concern in age-related cognitive decline is episodic memory (EM). Previous studies indicate that both resource and binding deficits contribute to EM decline. Environmental support by task manipulations encouraging stronger cognitive effort and deeper levels of processing may facilitate compensation for these two deficits. To clarify factors that can counteract age-related EM decline, we assessed effects of cognitive effort (four levels) and level of processing (LoP, shallow/deep) during encoding on subsequent retrieval. Young (YAs, N = 23) and older (OAs, N = 23) adults performed two incidental encoding tasks, deep/semantic and shallow/perceptual. Cognitive effort was manipulated by varying decision-making demands. EM performance, indexed by d-prime, was later tested using a recognition task. Results showed that regardless of LoP, increased cognitive effort caused higher d-primes in both age groups. Compared to YAs, OAs showed a lower d-prime after shallow encoding across all cognitive effort levels, and after deep encoding with low cognitive effort. Deep encoding with higher levels of cognitive effort completely eliminated these age differences. Our findings support an environmental-compensatory account of cognitive ageing and can have important therapeutic implications.

Brain and effort: brain activation and effort-related working memory in healthy participants and patients with working memory deficits

Directory of Open Access Journals (Sweden)

Maria eEngstrom

2013-04-01

Full Text Available Despite the interest in the neuroimaging of working memory, little is still known about the neurobiology of complex working memory in tasks that require simultaneous manipulation and storage of information. In addition to the central executive network, we assumed that the recently described salience network (involving the anterior insular cortex and the anterior cingulate cortex might be of particular importance to working memory tasks that require complex, effortful processing. Method: Healthy participants (n=26 and participants suffering from working memory problems related to the Kleine-Levin syndrome (a specific form of periodic idiopathic hypersomnia; n=18 participated in the study. Participants were further divided into a high and low capacity group, according to performance on a working memory task (listening span. In a functional Magnetic Resonance Imaging (fMRI study, participants were administered the reading span complex working memory task tapping cognitive effort. Principal findings: The fMRI-derived blood oxygen level dependent (BOLD signal was modulated by 1 effort in both the central executive and the salience network and 2 capacity in the salience network in that high performers evidenced a weaker BOLD signal than low performers. In the salience network there was a dichotomy between the left and the right hemisphere; the right hemisphere elicited a steeper increase of the BOLD signal as a function of increasing effort. There was also a stronger functional connectivity within the central executive network because of increased task difficulty. Conclusion: The ability to allocate cognitive effort in complex working memory is contingent upon focused resources in the executive and in particular the salience network. Individual capacity during the complex working memory task is related to activity in the salience (but not the executive network so that high-capacity participants evidence a lower signal and possibly hence a larger

Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders.

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Mosner, Maya G; Kinard, Jessica L; McWeeny, Sean; Shah, Jasmine S; Markiewitz, Nathan D; Damiano-Goodwin, Cara R; Burchinal, Margaret R; Rutherford, Helena J V; Greene, Rachel K; Treadway, Michael T; Dichter, Gabriel S

2017-10-01

This study investigated vicarious effort-based decision-making in 50 adolescents with autism spectrum disorders (ASD) compared to 32 controls using the Effort Expenditure for Rewards Task. Participants made choices to win money for themselves or for another person. When choosing for themselves, the ASD group exhibited relatively similar patterns of effort-based decision-making across reward parameters. However, when choosing for another person, the ASD group demonstrated relatively decreased sensitivity to reward magnitude, particularly in the high magnitude condition. Finally, patterns of responding in the ASD group were related to individual differences in consummatory pleasure capacity. These findings indicate atypical vicarious effort-based decision-making in ASD and more broadly add to the growing body of literature addressing social reward processing deficits in ASD.

Dopamine, Effort-Based Choice, and Behavioral Economics: Basic and Translational Research.

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Salamone, John D; Correa, Merce; Yang, Jen-Hau; Rotolo, Renee; Presby, Rose

2018-01-01

Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA) system and other brain circuits, are involved in regulating effort-related aspects of motivation. Considerable evidence indicates that mesolimbic DA transmission exerts a bi-directional control over exertion of effort on instrumental behavior tasks. Interference with DA transmission produces a low-effort bias in animals tested on effort-based choice tasks, while increasing DA transmission with drugs such as DA transport blockers tends to enhance selection of high-effort options. The results from these pharmacology studies are corroborated by the findings from recent articles using optogenetic, chemogenetic and physiological techniques. In addition to providing important information about the neural regulation of motivated behavior, effort-based choice tasks are useful for developing animal models of some of the motivational symptoms that are seen in people with various psychiatric and neurological disorders (e.g., depression, schizophrenia, Parkinson's disease). Studies of effort-based decision making may ultimately contribute to the development of novel drug treatments for motivational dysfunction.

Dopamine, Effort-Based Choice, and Behavioral Economics: Basic and Translational Research

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John D. Salamone

2018-03-01

Full Text Available Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA system and other brain circuits, are involved in regulating effort-related aspects of motivation. Considerable evidence indicates that mesolimbic DA transmission exerts a bi-directional control over exertion of effort on instrumental behavior tasks. Interference with DA transmission produces a low-effort bias in animals tested on effort-based choice tasks, while increasing DA transmission with drugs such as DA transport blockers tends to enhance selection of high-effort options. The results from these pharmacology studies are corroborated by the findings from recent articles using optogenetic, chemogenetic and physiological techniques. In addition to providing important information about the neural regulation of motivated behavior, effort-based choice tasks are useful for developing animal models of some of the motivational symptoms that are seen in people with various psychiatric and neurological disorders (e.g., depression, schizophrenia, Parkinson’s disease. Studies of effort-based decision making may ultimately contribute to the development of novel drug treatments for motivational dysfunction.

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

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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.

Effect of social influence on effort-allocation for monetary rewards.

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Gilman, Jodi M; Treadway, Michael T; Curran, Max T; Calderon, Vanessa; Evins, A Eden

2015-01-01

Though decades of research have shown that people are highly influenced by peers, few studies have directly assessed how the value of social conformity is weighed against other types of costs and benefits. Using an effort-based decision-making paradigm with a novel social influence manipulation, we measured how social influence affected individuals' decisions to allocate effort for monetary rewards during trials with either high or low probability of receiving a reward. We found that information about the effort-allocation of peers modulated participant choices, specifically during conditions of low probability of obtaining a reward. This suggests that peer influence affects effort-based choices to obtain rewards especially under conditions of risk. This study provides evidence that people value social conformity in addition to other costs and benefits when allocating effort, and suggests that neuroeconomic studies that assess trade-offs between effort and reward should consider social environment as a factor that can influence decision-making.

Effect of social influence on effort-allocation for monetary rewards.

Directory of Open Access Journals (Sweden)

Jodi M Gilman

Full Text Available Though decades of research have shown that people are highly influenced by peers, few studies have directly assessed how the value of social conformity is weighed against other types of costs and benefits. Using an effort-based decision-making paradigm with a novel social influence manipulation, we measured how social influence affected individuals' decisions to allocate effort for monetary rewards during trials with either high or low probability of receiving a reward. We found that information about the effort-allocation of peers modulated participant choices, specifically during conditions of low probability of obtaining a reward. This suggests that peer influence affects effort-based choices to obtain rewards especially under conditions of risk. This study provides evidence that people value social conformity in addition to other costs and benefits when allocating effort, and suggests that neuroeconomic studies that assess trade-offs between effort and reward should consider social environment as a factor that can influence decision-making.

Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity

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Tuomo T Tompuri

2015-08-01

Full Text Available Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor.

Comorbidity of intellectual disability confounds ascertainment of autism: implications for genetic diagnosis.

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Polyak, Andrew; Kubina, Richard M; Girirajan, Santhosh

2015-10-01

While recent studies suggest a converging role for genetic factors towards risk for nosologically distinct disorders including autism, intellectual disability (ID), and epilepsy, current estimates of autism prevalence fail to take into account the impact of comorbidity of these disorders on autism diagnosis. We aimed to assess the effect of comorbidity on the diagnosis and prevalence of autism by analyzing 11 years (2000-2010) of special education enrollment data on approximately 6.2 million children per year. We found a 331% increase in the prevalence of autism from 2000 to 2010 within special education, potentially due to a diagnostic recategorization from frequently comorbid features such as ID. The decrease in ID prevalence equaled an average of 64.2% of the increase of autism prevalence for children aged 3-18 years. The proportion of ID cases potentially undergoing recategorization to autism was higher (P = 0.007) among older children (75%) than younger children (48%). Some US states showed significant negative correlations between the prevalence of autism compared to that of ID while others did not, suggesting state-specific health policy to be a major factor in categorizing autism. Further, a high frequency of autistic features was observed when individuals with classically defined genetic syndromes were evaluated for autism using standardized instruments. Our results suggest that current ascertainment practices are based on a single facet of autism-specific clinical features and do not consider associated comorbidities that may confound diagnosis. Longitudinal studies with detailed phenotyping and deep molecular genetic analyses are necessary to completely understand the cause of this complex disorder. © 2015 Wiley Periodicals, Inc.

Vascular smooth muscle cells for use in vascular tissue engineering obtained by endothelial-to-mesenchymal transdifferentiation (EnMT) on collagen matrices

NARCIS (Netherlands)

Krenning, Guido; Moonen, Jan-Renier A. J.; van Luyn, Marja J. A.; Harmsen, Martin C.

The discovery of the endothelial progenitor cell (EPC) has led to an intensive research effort into progenitor cell-based tissue engineering of (small-diameter) blood vessels. Herein, EPC are differentiated to vascular endothelial cells and serve as the inner lining of bioartificial vessels. As yet,

Breaking the Double-Edged Sword of Effort/Trying Hard: Developmental Equilibrium and Longitudinal Relations among Effort, Achievement, and Academic Self-Concept

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Marsh, Herbert W.; Pekrun, Reinhard; Lichtenfeld, Stephanie; Guo, Jiesi; Arens, A. Katrin; Murayama, Kou

2016-01-01

Ever since the classic research of Nicholls (1976) and others, effort has been recognized as a double-edged sword: while it might enhance achievement, it undermines academic self-concept (ASC). However, there has not been a thorough evaluation of the longitudinal reciprocal effects of effort, ASC, and achievement, in the context of modern…

Men’s Work Efforts and the Transition to Fatherhood1

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Astone, Nan Marie; Dariotis, Jacinda; Sonenstein, Freya; Pleck, Joseph H.; Hynes, Kathryn

2010-01-01

In this paper we tested three hypotheses: (a) the transition to fatherhood is associated with an increase in work effort; (b) the positive association (if any) between the transition to fatherhood and work effort is greater for fathers who are married at the time of the transition; and (c) the association (if any) is greater for men who make the transition at younger ages. The data are from the National Longitudinal Survey of Youth 1979 Cohort. The transition to fatherhood was associated with an increase in work effort among young unmarried men, but not for married men. Among married men who were on-time fathers, work effort decreased. Among childless men, the marriage transition was associated with increased work effort. PMID:20221306

Perception of effort in Exercise Science: Definition, measurement and perspectives.

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Pageaux, Benjamin

2016-11-01

Perception of effort, also known as perceived exertion or sense of effort, can be described as a cognitive feeling of work associated with voluntary actions. The aim of the present review is to provide an overview of what is perception of effort in Exercise Science. Due to the addition of sensations other than effort in its definition, the neurophysiology of perceived exertion remains poorly understood. As humans have the ability to dissociate effort from other sensations related to physical exercise, the need to use a narrower definition is emphasised. Consequently, a definition and some brief guidelines for its measurement are provided. Finally, an overview of the models present in the literature aiming to explain its neurophysiology, and some perspectives for future research are offered.

The RBANS Effort Index: base rates in geriatric samples.

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Duff, Kevin; Spering, Cynthia C; O'Bryant, Sid E; Beglinger, Leigh J; Moser, David J; Bayless, John D; Culp, Kennith R; Mold, James W; Adams, Russell L; Scott, James G

2011-01-01

The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer's disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cutoff scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer's disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in three of the four clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia.

Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

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Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

2014-01-01

Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

Policies and Programmatic Efforts Pertaining to Fatherhood: Commentary

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Raikes, Helen; Bellotti, Jeanne

2007-01-01

The articles in this section focus attention on (1) the historical shift in policies that affect the young men of this nation (2) how fatherhood policies and programmatic efforts are expanding and (3) how fatherhood practices and policies could and perhaps should be expanded and elaborated further. These efforts are linked to a growing body of…

Goal Setting and Expectancy Theory Predictions of Effort and Performance.

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Dossett, Dennis L.; Luce, Helen E.

Neither expectancy (VIE) theory nor goal setting alone are effective determinants of individual effort and task performance. To test the combined ability of VIE and goal setting to predict effort and performance, 44 real estate agents and their managers completed questionnaires. Quarterly income goals predicted managers' ratings of agents' effort,…

Strain modulations as a mechanism to reduce stress relaxation in laryngeal tissues.

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Hunter, Eric J; Siegmund, Thomas; Chan, Roger W

2014-01-01

Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1-10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude), as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation) and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored.

Strain modulations as a mechanism to reduce stress relaxation in laryngeal tissues.

Directory of Open Access Journals (Sweden)

Eric J Hunter

Full Text Available Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so, cyclic and faster posturing often found in speech tasks or vocal embellishment (1-10 Hz, and shear strain associated with vocal fold vibration during phonation (100 Hz and higher. Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude, as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored.

Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis.

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Konstantonis, Dimitrios; Vasileiou, Dimitrios; Papageorgiou, Spyridon N; Eliades, Theodore

2018-02-26

The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convexity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made. © 2018 Eur J Oral Sci.

Is the co-occurrence of smoking and poor consumption of fruits and vegetables confounded by socioeconomic conditions?

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Muff, Christine; Dragano, N; Jöckel, K-H; Moebus, S; Möhlenkamp, S; Erbel, R; Mann, K; Siegrist, J

2010-08-01

As smoking and unhealthy diet are more prevalent in lower socioeconomic groups, this study aims at exploring whether associations between smoking and fruit and vegetable consumption are confounded by socioeconomic conditions or if smoking is independently associated with consumption. Cross-sectional analyses of 4,814 middle-aged participants from the Heinz Nixdorf recall study, a population-based cohort study in Germany. Fruit and vegetable consumption was assessed by a food frequency questionnaire. Education and income were used as indicators for socioeconomic groups. Logistic regression models were run to estimate odds ratios for consumption by smoking status. Smoking is associated with poor consumption of fruits and raw vegetables/salad in both genders, and with poor consumption of boiled vegetables and fruit/vegetable juice in men. Importantly, poor consumption is related to smoking independently of people's socioeconomic conditions. The findings imply that smokers in all socioeconomic groups are at higher risk for unhealthy intake of fruits and vegetables. Public health interventions targeted to smokers should include dietary instructions.

Testosterone and reproductive effort in male primates.

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Muller, Martin N

2017-05-01

Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the "Challenge Hypothesis," which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition. Copyright © 2016 Elsevier Inc. All rights reserved.

Student Effort, Consistency and Online Performance

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Hilde Patron

2011-07-01

Full Text Available This paper examines how student effort, consistency, motivation, and marginal learning, influence student grades in an online course. We use data from eleven Microeconomics courses taught online for a total of 212 students. Our findings show that consistency, or less time variation, is a statistically significant explanatory variable, whereas effort, or total minutes spent online, is not. Other independent variables include GPA and the difference between a pre-test and a post-test. The GPA is used as a measure of motivation, and the difference between a post-test and pre-test as marginal learning. As expected, the level of motivation is found statistically significant at a 99% confidence level, and marginal learning is also significant at a 95% level.

Effects of tissue susceptibility on brain temperature mapping.

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Maudsley, Andrew A; Goryawala, Mohammed Z; Sheriff, Sulaiman

2017-02-01

A method for mapping of temperature over a large volume of the brain using volumetric proton MR spectroscopic imaging has been implemented and applied to 150 normal subjects. Magnetic susceptibility-induced frequency shifts in gray- and white-matter regions were measured and included as a correction in the temperature mapping calculation. Additional sources of magnetic susceptibility variations of the individual metabolite resonance frequencies were also observed that reflect the cellular-level organization of the brain metabolites, with the most notable differences being attributed to changes of the N-Acetylaspartate resonance frequency that reflect the intra-axonal distribution and orientation of the white-matter tracts with respect to the applied magnetic field. These metabolite-specific susceptibility effects are also shown to change with age. Results indicate no change of apparent brain temperature with age from 18 to 84 years old, with a trend for increased brain temperature throughout the cerebrum in females relative for males on the order of 0.1°C; slightly increased temperatures in the left hemisphere relative to the right; and a lower temperature of 0.3°C in the cerebellum relative to that of cerebral white-matter. This study presents a novel acquisition method for noninvasive measurement of brain temperature that is of potential value for diagnostic purposes and treatment monitoring, while also demonstrating limitations of the measurement due to the confounding effects of tissue susceptibility variations. Copyright © 2016 Elsevier Inc. All rights reserved.

Accounting for Time-Varying Confounding in the Relationship Between Obesity and Coronary Heart Disease: Analysis With G-Estimation: The ARIC Study.

Science.gov (United States)

Shakiba, Maryam; Mansournia, Mohammad Ali; Salari, Arsalan; Soori, Hamid; Mansournia, Nasrin; Kaufman, Jay S

2018-06-01

In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study was performed in a subset of participants from the Atherosclerosis Risk in Communities (ARIC) Study (1987-2010), a US study designed to investigate risk factors for atherosclerosis. General obesity was defined as body mass index (weight (kg)/height (m)2) ≥30, and abdominal obesity (AOB) was defined according to either waist circumference (≥102 cm in men and ≥88 cm in women) or waist:hip ratio (≥0.9 in men and ≥0.85 in women). The association of obesity with CHD was estimated by G-estimation and compared with results from accelerated failure-time models using 3 specifications. The first model, which adjusted for baseline covariates, excluding metabolic mediators of obesity, showed increased risk of CHD for all obesity measures. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model produced negligible changes in the hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95% confidence interval (CI): 0.83, 1.47) for general obesity, 1.65 (95% CI: 1.35, 1.92) for AOB based on waist circumference, and 1.38 (95% CI: 1.13, 1.99) for AOB based on waist:hip ratio, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratios for both measures were further from the null than those derived from standard models.

Accounting for genetic and environmental confounds in associations between parent and child characteristics: a systematic review of children-of-twins studies.

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McAdams, Tom A; Neiderhiser, Jenae M; Rijsdijk, Fruhling V; Narusyte, Jurgita; Lichtenstein, Paul; Eley, Thalia C

2014-07-01

Parental psychopathology, parenting style, and the quality of intrafamilial relationships are all associated with child mental health outcomes. However, most research can say little about the causal pathways underlying these associations. This is because most studies are not genetically informative and are therefore not able to account for the possibility that associations are confounded by gene-environment correlation. That is, biological parents not only provide a rearing environment for their child, but also contribute 50% of their genes. Any associations between parental phenotype and child phenotype are therefore potentially confounded. One technique for disentangling genetic from environmental effects is the children-of-twins (COT) method. This involves using data sets comprising twin parents and their children to distinguish genetic from environmental associations between parent and child phenotypes. The COT technique has grown in popularity in the last decade, and we predict that this surge in popularity will continue. In the present article we explain the COT method for those unfamiliar with its use. We present the logic underlying this approach, discuss strengths and weaknesses, and highlight important methodological considerations for researchers interested in the COT method. We also cover variations on basic COT approaches, including the extended-COT method, capable of distinguishing forms of gene-environment correlation. We then present a systematic review of all the behavioral COT studies published to date. These studies cover such diverse phenotypes as psychosis, substance abuse, internalizing, externalizing, parenting, and marital difficulties. In reviewing this literature, we highlight past applications, identify emergent patterns, and suggest avenues for future research. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

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Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

2013-09-01

Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.

The promise of organ and tissue preservation to transform medicine

Science.gov (United States)

Giwa, Sebastian; Lewis, Jedediah K; Alvarez, Luis; Langer, Robert; Roth, Alvin E; Church, George M; Markmann, James F; Sachs, David H; Chandraker, Anil; Wertheim, Jason A; Rothblatt, Martine; Boyden, Edward S; Eidbo, Elling; Lee, W P Andrew; Pomahac, Bohdan; Brandacher, Gerald; Weinstock, David M; Elliott, Gloria; Nelson, David; Acker, Jason P; Uygun, Korkut; Schmalz, Boris; Weegman, Brad P; Tocchio, Alessandro; Fahy, Greg M; Storey, Kenneth B; Rubinsky, Boris; Bischof, John; Elliott, Janet A W; Woodruff, Teresa K; Morris, G John; Demirci, Utkan; Brockbank, Kelvin G M; Woods, Erik J; Ben, Robert N; Baust, John G; Gao, Dayong; Fuller, Barry; Rabin, Yoed; Kravitz, David C; Taylor, Michael J; Toner, Mehmet

2017-01-01

The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science. PMID:28591112

Effortful control and school adjustment: The moderating role of classroom chaos.

Science.gov (United States)

Berger, Rebecca H; Valiente, Carlos; Eisenberg, Nancy; Hernandez, Maciel M; Thompson, Marilyn; Spinrad, Tracy; VanSchyndel, Sarah; Silva, Kassondra; Southworth, Jody

2017-11-01

Guided by the person by environment framework, the primary goal of this study was to determine whether classroom chaos moderated the relation between effortful control and kindergarteners' school adjustment. Classroom observers reported on children's ( N = 301) effortful control in the fall. In the spring, teachers reported on classroom chaos and school adjustment outcomes (teacher-student relationship closeness and conflict, and school liking and avoidance). Cross-level interactions between effortful control and classroom chaos predicting school adjustment outcomes were assessed. A consistent pattern of interactions between effortful control and classroom chaos indicated that the relations between effortful control and the school adjustment outcomes were strongest in high chaos classrooms. Post-hoc analyses indicated that classroom chaos was associated with poor school adjustment when effortful control was low, suggesting that the combination of high chaos and low effortful control was associated with the poorest school outcomes.

Tissue-specific mRNA expression profiling in grape berry tissues

Science.gov (United States)

Grimplet, Jerome; Deluc, Laurent G; Tillett, Richard L; Wheatley, Matthew D; Schlauch, Karen A; Cramer, Grant R; Cushman, John C

2007-01-01

Background Berries of grape (Vitis vinifera) contain three major tissue types (skin, pulp and seed) all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin) and mesocarp (pulp), not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Results Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater) differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell wall function and

Tissue-specific mRNA expression profiling in grape berry tissues

Directory of Open Access Journals (Sweden)

Cramer Grant R

2007-06-01

Full Text Available Abstract Background Berries of grape (Vitis vinifera contain three major tissue types (skin, pulp and seed all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin and mesocarp (pulp, not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Results Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell

Monitoring of tissue optical properties during thermal coagulation of ex vivo tissues.

Science.gov (United States)

Nagarajan, Vivek Krishna; Yu, Bing

2016-09-01

Real-time monitoring of tissue status during thermal ablation of tumors is critical to ensure complete destruction of tumor mass, while avoiding tissue charring and excessive damage to normal tissues. Currently, magnetic resonance thermometry (MRT), along with magnetic resonance imaging (MRI), is the most commonly used technique for monitoring and assessing thermal ablation process in soft tissues. MRT/MRI is very expensive, bulky, and often subject to motion artifacts. On the other hand, light propagation within tissue is sensitive to changes in tissue microstructure and physiology which could be used to directly quantify the extent of tissue damage. Furthermore, optical monitoring can be a portable, and cost-effective alternative for monitoring a thermal ablation process. The main objective of this study, is to establish a correlation between changes in tissue optical properties and the status of tissue coagulation/damage during heating of ex vivo tissues. A portable diffuse reflectance spectroscopy system and a side-firing fiber-optic probe were developed to study the absorption (μa (λ)), and reduced scattering coefficients (μ's (λ)) of native and coagulated ex vivo porcine, and chicken breast tissues. In the first experiment, both porcine and chicken breast tissues were heated at discrete temperature points between 24 and 140°C for 2 minutes. Diffuse reflectance spectra (430-630 nm) of native and coagulated tissues were recorded prior to, and post heating. In a second experiment, porcine tissue samples were heated at 70°C and diffuse reflectance spectra were recorded continuously during heating. The μa (λ) and μ's (λ) of the tissues were extracted from the measured diffuse reflectance spectra using an inverse Monte-Carlo model of diffuse reflectance. Tissue heating was stopped when the wavelength-averaged scattering plateaued. The wavelength-averaged optical properties, and , for native porcine tissues (n = 66) at room temperature, were 5.4�

Quantification of the impact of a confounding variable on functional connectivity confirms anti-correlated networks in the resting-state.

Science.gov (United States)

Carbonell, F; Bellec, P; Shmuel, A

2014-02-01

The effect of regressing out the global average signal (GAS) in resting state fMRI data has become a concern for interpreting functional connectivity analyses. It is not clear whether the reported anti-correlations between the Default Mode and the Dorsal Attention Networks are intrinsic to the brain, or are artificially created by regressing out the GAS. Here we introduce a concept, Impact of the Global Average on Functional Connectivity (IGAFC), for quantifying the sensitivity of seed-based correlation analyses to the regression of the GAS. This voxel-wise IGAFC index is defined as the product of two correlation coefficients: the correlation between the GAS and the fMRI time course of a voxel, times the correlation between the GAS and the seed time course. This definition enables the calculation of a threshold at which the impact of regressing-out the GAS would be large enough to introduce spurious negative correlations. It also yields a post-hoc impact correction procedure via thresholding, which eliminates spurious correlations introduced by regressing out the GAS. In addition, we introduce an Artificial Negative Correlation Index (ANCI), defined as the absolute difference between the IGAFC index and the impact threshold. The ANCI allows a graded confidence scale for ranking voxels according to their likelihood of showing artificial correlations. By applying this method, we observed regions in the Default Mode and Dorsal Attention Networks that were anti-correlated. These findings confirm that the previously reported negative correlations between the Dorsal Attention and Default Mode Networks are intrinsic to the brain and not the result of statistical manipulations. Our proposed quantification of the impact that a confound may have on functional connectivity can be generalized to global effect estimators other than the GAS. It can be readily applied to other confounds, such as systemic physiological or head movement interferences, in order to quantify their

Automatic estimation of elasticity parameters in breast tissue

Science.gov (United States)

Skerl, Katrin; Cochran, Sandy; Evans, Andrew

2014-03-01

Shear wave elastography (SWE), a novel ultrasound imaging technique, can provide unique information about cancerous tissue. To estimate elasticity parameters, a region of interest (ROI) is manually positioned over the stiffest part of the shear wave image (SWI). The aim of this work is to estimate the elasticity parameters i.e. mean elasticity, maximal elasticity and standard deviation, fully automatically. Ultrasonic SWI of a breast elastography phantom and breast tissue in vivo were acquired using the Aixplorer system (SuperSonic Imagine, Aix-en-Provence, France). First, the SWI within the ultrasonic B-mode image was detected using MATLAB then the elasticity values were extracted. The ROI was automatically positioned over the stiffest part of the SWI and the elasticity parameters were calculated. Finally all values were saved in a spreadsheet which also contains the patient's study ID. This spreadsheet is easily available for physicians and clinical staff for further evaluation and so increase efficiency. Therewith the efficiency is increased. This algorithm simplifies the handling, especially for the performance and evaluation of clinical trials. The SWE processing method allows physicians easy access to the elasticity parameters of the examinations from their own and other institutions. This reduces clinical time and effort and simplifies evaluation of data in clinical trials. Furthermore, reproducibility will be improved.

Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing.

Science.gov (United States)

Moreira, Andre L; Thornton, Raymond H

2012-09-01

In light of recent advances in individualized therapy for non-small-cell lung cancer (NSCLC), molecular and histologic profiling is essential for guiding therapeutic decisions. Results of these analyses may have implications for both response (eg, molecular testing for EGFR [epidermal growth factor receptor] mutations) and safety (eg, contraindications for squamous histology) in NSCLC. Most patients with NSCLC present with unresectable advanced disease; therefore, greater emphasis is being placed on minimally invasive tissue acquisition techniques, such as small biopsy and cytology specimens. Due to the need for increasing histologic and molecular information and increasingly smaller tissue sample sizes, efforts must be focused on optimizing tissue acquisition and the development of more sensitive molecular assays. Recent advances in tissue acquisition techniques and specimen preservation may help to address this challenge and lead to enhanced personalized treatment in NSCLC. Copyright © 2012 Elsevier Inc. All rights reserved.

The Galileo Teacher Training Program Global Efforts

Science.gov (United States)

Doran, R.; Pennypacker, C.; Ferlet, R.

2012-08-01

The Galileo Teacher Training Program (GTTP) successfully named representatives in nearly 100 nations in 2009, the International Year of Astronomy (IYA2009). The challenge had just begun. The steps ahead are how to reach educators that might benefit from our program and how to help build a more fair and science literate society, a society in which good tools and resources for science education are not the privilege of a few. From 2010 on our efforts have been to strengthen the newly formed network and learn how to equally help educators and students around the globe. New partnerships with other strong programs and institutions are being formed, sponsorship schemes being outlined, new tools and resources being publicized, and on-site and video conference training conducted all over the world. Efforts to officially accredit a GTTP curriculum are on the march and a stronger certification process being outlined. New science topics are being integrated in our effort and we now seek to discuss the path ahead with experts in this field and the community of users, opening the network to all corners of our beautiful blue dot. The main aim of this article is to open the discussion regarding the urgent issue of how to reawaken student interest in science, how to solve the gender inequality in science careers, and how to reach the underprivileged students and open to them the same possibilities. Efforts are in strengthening the newly formed network and learning how to equally help educators and students around the globe.

Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.

Science.gov (United States)

van de Ven, Stephanie M W Y; Bemis, Kyle D; Lau, Kenneth; Adusumilli, Ravali; Kota, Uma; Stolowitz, Mark; Vitek, Olga; Mallick, Parag; Gambhir, Sanjiv S

2016-06-01

MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI-MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI-MSI workflows. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control and Effort Costs Influence the Motivational Consequences of Choice

Directory of Open Access Journals (Sweden)

Holly Sullivan-Toole

2017-05-01

Full Text Available The act of making a choice, apart from any outcomes the choice may yield, has, paradoxically, been linked to both the enhancement and the detriment of intrinsic motivation. Research has implicated two factors in potentially mediating these contradictory effects: the personal control conferred by a choice and the costs associated with a choice. Across four experiments, utilizing a physical effort task disguised as a simple video game, we systematically varied costs across two levels of physical effort requirements (Low-Requirement, High-Requirement and control over effort costs across three levels of choice (Free-Choice, Restricted-Choice, and No-Choice to disambiguate how these factors affect the motivational consequences of choosing within an effortful task. Together, our results indicated that, in the face of effort requirements, illusory control alone may not sufficiently enhance perceptions of personal control to boost intrinsic motivation; rather, the experience of actual control may be necessary to overcome effort costs and elevate performance. Additionally, we demonstrated that conditions of illusory control, while otherwise unmotivating, can through association with the experience of free-choice, be transformed to have a positive effect on motivation.

Soft Tissue Sarcoma

Science.gov (United States)

... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

A Web-based database for pathology faculty effort reporting.

Science.gov (United States)

Dee, Fred R; Haugen, Thomas H; Wynn, Philip A; Leaven, Timothy C; Kemp, John D; Cohen, Michael B

2008-04-01

To ensure appropriate mission-based budgeting and equitable distribution of funds for faculty salaries, our compensation committee developed a pathology-specific effort reporting database. Principles included the following: (1) measurement should be done by web-based databases; (2) most entry should be done by departmental administration or be relational to other databases; (3) data entry categories should be aligned with funding streams; and (4) units of effort should be equal across categories of effort (service, teaching, research). MySQL was used for all data transactions (http://dev.mysql.com/downloads), and scripts were constructed using PERL (http://www.perl.org). Data are accessed with forms that correspond to fields in the database. The committee's work resulted in a novel database using pathology value units (PVUs) as a standard quantitative measure of effort for activities in an academic pathology department. The most common calculation was to estimate the number of hours required for a specific task, divide by 2080 hours (a Medicare year) and then multiply by 100. Other methods included assigning a baseline PVU for program, laboratory, or course directorship with an increment for each student or staff in that unit. With these methods, a faculty member should acquire approximately 100 PVUs. Some outcomes include (1) plotting PVUs versus salary to identify outliers for salary correction, (2) quantifying effort in activities outside the department, (3) documenting salary expenditure for unfunded research, (4) evaluating salary equity by plotting PVUs versus salary by sex, and (5) aggregating data by category of effort for mission-based budgeting and long-term planning.

Communication Breakdown: Unraveling the Islamic States Media Efforts

Science.gov (United States)

2016-10-01

Communication Breakdown: Unraveling the Islamic State’s Media Efforts Daniel Milton Communication Breakdown: Unraveling the Islamic State’s Media ...production arm of central media office).28 The high level of communication between the central media office and the satellite offices illustrates the tension...and discussed by the mass media . Those products are likely important to the group’s recruitment efforts, but clearly it is trying to portray itself

Automated MALDI Matrix Coating System for Multiple Tissue Samples for Imaging Mass Spectrometry

Science.gov (United States)

Mounfield, William P.; Garrett, Timothy J.

2012-03-01

Uniform matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is key for reproducible analyte ion signals. Current methods often result in nonhomogenous matrix deposition, and take time and effort to produce acceptable ion signals. Here we describe a fully-automated method for matrix deposition using an enclosed spray chamber and spray nozzle for matrix solution delivery. A commercial air-atomizing spray nozzle was modified and combined with solenoid controlled valves and a Programmable Logic Controller (PLC) to control and deliver the matrix solution. A spray chamber was employed to contain the nozzle, sample, and atomized matrix solution stream, and to prevent any interference from outside conditions as well as allow complete control of the sample environment. A gravity cup was filled with MALDI matrix solutions, including DHB in chloroform/methanol (50:50) at concentrations up to 60 mg/mL. Various samples (including rat brain tissue sections) were prepared using two deposition methods (spray chamber, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed a uniform coating of matrix crystals across the sample. Overall, the mass spectral images gathered from tissues coated using the spray chamber system were of better quality and more reproducible than from tissue specimens prepared by the inkjet deposition method.

Mapping telemedicine efforts

DEFF Research Database (Denmark)

Kierkegaard, Patrick

2015-01-01

are being utilized? What medical disciplines are being addressed using telemedicine systems? Methods: All data was surveyed from the "Telemedicinsk Landkort", a newly created database designed to provide a comprehensive and systematic overview of all telemedicine technologies in Denmark. Results......Objectives: The aim of this study is to survey telemedicine services currently in operation across Denmark. The study specifically seeks to answer the following questions: What initiatives are deployed within the different regions? What are the motivations behind the projects? What technologies......: The results of this study suggest that a growing number of telemedicine initiatives are currently in operation across Denmark but that considerable variations existed in terms of regional efforts as the number of operational telemedicine projects varied from region to region. Conclusions: The results...

In-shoe plantar tri-axial stress profiles during maximum-effort cutting maneuvers.

Science.gov (United States)

Cong, Yan; Lam, Wing Kai; Cheung, Jason Tak-Man; Zhang, Ming

2014-12-18

Soft tissue injuries, such as anterior cruciate ligament rupture, ankle sprain and foot skin problems, frequently occur during cutting maneuvers. These injuries are often regarded as associated with abnormal joint torque and interfacial friction caused by excessive external and in-shoe shear forces. This study simultaneously investigated the dynamic in-shoe localized plantar pressure and shear stress during lateral shuffling and 45° sidestep cutting maneuvers. Tri-axial force transducers were affixed at the first and second metatarsal heads, lateral forefoot, and heel regions in the midsole of a basketball shoe. Seventeen basketball players executed both cutting maneuvers with maximum efforts. Lateral shuffling cutting had a larger mediolateral braking force than 45° sidestep cutting. This large braking force was concentrated at the first metatarsal head, as indicated by its maximum medial shear stress (312.2 ± 157.0 kPa). During propulsion phase, peak shear stress occurred at the second metatarsal head (271.3 ± 124.3 kPa). Compared with lateral shuffling cutting, 45° sidestep cutting produced larger peak propulsion shear stress (463.0 ± 272.6 kPa) but smaller peak braking shear stress (184.8 ± 181.7 kPa), of which both were found at the first metatarsal head. During both cutting maneuvers, maximum medial and posterior shear stress occurred at the first metatarsal head, whereas maximum pressure occurred at the second metatarsal head. The first and second metatarsal heads sustained relatively high pressure and shear stress and were expected to be susceptible to plantar tissue discomfort or injury. Due to different stress distribution, distinct pressure and shear cushioning mechanisms in basketball footwear might be considered over different foot regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effort sharing in ambitious, global climate change mitigation scenarios

International Nuclear Information System (INIS)

Ekholm, Tommi; Soimakallio, Sampo; Moltmann, Sara; Hoehne, Niklas; Syri, Sanna; Savolainen, Ilkka

2010-01-01

The post-2012 climate policy framework needs a global commitment to deep greenhouse gas emission cuts. This paper analyzes reaching ambitious emission targets up to 2050, either -10% or -50% from 1990 levels, and how the economic burden from mitigation efforts could be equitably shared between countries. The scenarios indicate a large low-cost mitigation potential in electricity and industry, while reaching low emission levels in international transportation and agricultural emissions might prove difficult. The two effort sharing approaches, Triptych and Multistage, were compared in terms of equitability and coherence. Both approaches produced an equitable cost distribution between countries, with least developed countries having negative or low costs and more developed countries having higher costs. There is, however, no definitive solution on how the costs should be balanced equitably between countries. Triptych seems to be yet more coherent than other approaches, as it can better accommodate national circumstances. Last, challenges and possible hindrances to effective mitigation and equitable effort sharing are presented. The findings underline the significance of assumptions behind effort sharing on mitigation potentials and current emissions, the challenge of sharing the effort with uncertain future allowance prices and how inefficient markets might undermine the efficiency of a cap-and-trade system.

Effort sharing in ambitious, global climate change mitigation scenarios

Energy Technology Data Exchange (ETDEWEB)

Ekholm, Tommi [TKK Helsinki University of Technology, Espoo (Finland); Soimakallio, Sampo; Syri, Sanna; Savolainen, Ilkka [VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Finland); Moltmann, Sara; Hoehne, Niklas [Ecofys Germany GmbH, Cologne (Germany)

2010-04-15

The post-2012 climate policy framework needs a global commitment to deep greenhouse gas emission cuts. This paper analyzes reaching ambitious emission targets up to 2050, either or from 1990 levels, and how the economic burden from mitigation efforts could be equitably shared between countries. The scenarios indicate a large low-cost mitigation potential in electricity and industry, while reaching low emission levels in international transportation and agricultural emissions might prove difficult. The two effort sharing approaches, Triptych and Multistage, were compared in terms of equitability and coherence. Both approaches produced an equitable cost distribution between countries, with least developed countries having negative or low costs and more developed countries having higher costs. There is, however, no definitive solution on how the costs should be balanced equitably between countries. Triptych seems to be yet more coherent than other approaches, as it can better accommodate national circumstances. Last, challenges and possible hindrances to effective mitigation and equitable effort sharing are presented. The findings underline the significance of assumptions behind effort sharing on mitigation potentials and current emissions, the challenge of sharing the effort with uncertain future allowance prices and how inefficient markets might undermine the efficiency of a cap-and-trade system. (author)

Ontology-based, Tissue MicroArray oriented, image centered tissue bank

Directory of Open Access Journals (Sweden)

Viti Federica

2008-04-01

Full Text Available Abstract Background Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information. Results In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data. Conclusions Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.

A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

Directory of Open Access Journals (Sweden)

Christina Marie Gutierrez

2015-11-01

Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

Children as donors: a national study to assess procurement of organs and tissues in pediatric intensive care units.

Science.gov (United States)

Siebelink, Marion J; Albers, Marcel J I J; Roodbol, Petrie F; Van de Wiel, Harry B M

2012-12-01

A shortage of size-matched organs and tissues is the key factor limiting transplantation in children. Empirical data on procurement from pediatric donors is sparse. This study investigated donor identification, parental consent, and effectuation rates, as well as adherence to the national protocol. A national retrospective cohort study was conducted in all eight Dutch pediatric intensive care units. Records of deceased children were analyzed by an independent donation officer. Seventy-four (11%) of 683 deceased children were found to be suitable for organ donation and 132 (19%) for tissue donation. Sixty-two (84%) potential organ donors had been correctly identified; the parental consent and effectuation rate was 42%. Sixty-three (48%) potential tissue donors had been correctly identified; the parental consent and effectuation rate was 27%. Correct identification increased with age (logistic regression, organs: P = .024; tissues: P = .011). Although an overall identification rate of 84% of potential organ donors may seem acceptable, the variation observed suggests room for improvement, as does the overall low rate of identification of pediatric tissue donors. Efforts to address the shortage of organs and tissues for transplantation in children should focus on identifying potential donors and on the reasons why parents do not consent. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Modeling collagen remodeling in tissue engineered cardiovascular tissues

NARCIS (Netherlands)

Soares, A.L.F.

2012-01-01

Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

Science.gov (United States)

McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.

2011-01-01

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.

Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors.

Science.gov (United States)

Miles, George; Rae, James; Ramalingam, Suresh S; Pfeifer, John

2015-10-01

Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient's cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups' clinical research efforts. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of tissue bank

Directory of Open Access Journals (Sweden)

R P Narayan

2012-01-01

Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

Development Efforts Of Oil Companies As Perceived By Rural ...

African Journals Online (AJOL)

... that the host communities are highly satisfied with companies' efforts (projects and services) to them. Based on these findings, recommendations were made. Key words: Oil producing communities; oil exploration/production; company's development efforts; Journal of Agriculture and Social Research Vol.4(1) 2004: 60-71 ...

Ethical tissue: a not-for-profit model for human tissue supply.

Science.gov (United States)

Adams, Kevin; Martin, Sandie

2011-02-01

Following legislative changes in 2004 and the establishment of the Human Tissue Authority, access to human tissues for biomedical research became a more onerous and tightly regulated process. Ethical Tissue was established to meet the growing demand for human tissues, using a process that provided ease of access by researchers whilst maintaining the highest ethical and regulatory standards. The establishment of a licensed research tissue bank entailed several key criteria covering ethical, legal, financial and logistical issues being met. A wide range of stakeholders, including the HTA, University of Bradford, flagged LREC, hospital trusts and clinical groups were also integral to the process.

Cognitive dissonance in children: justification of effort or contrast?

Science.gov (United States)

Alessandri, Jérôme; Darcheville, Jean-Claude; Zentall, Thomas R

2008-06-01

Justification of effort is a form of cognitive dissonance in which the subjective value of an outcome is directly related to the effort that went into obtaining it. However, it is likely that in social contexts (such as the requirements for joining a group) an inference can be made (perhaps incorrectly) that an outcome that requires greater effort to obtain in fact has greater value. Here we present evidence that a cognitive dissonance effect can be found in children under conditions that offer better control for the social value of the outcome. This effect is quite similar to contrast effects that recently have been studied in animals. We suggest that contrast between the effort required to obtain the outcome and the outcome itself provides a more parsimonious account of this phenomenon and perhaps other related cognitive dissonance phenomena as well. Research will be needed to identify cognitive dissonance processes that are different from contrast effects of this kind.

The role of cognitive effort in subjective reward devaluation and risky decision-making.

Science.gov (United States)

Apps, Matthew A J; Grima, Laura L; Manohar, Sanjay; Husain, Masud

2015-11-20

Motivation is underpinned by cost-benefit valuations where costs-such as physical effort or outcome risk-are subjectively weighed against available rewards. However, in many environments risks pertain not to the variance of outcomes, but to variance in the possible levels of effort required to obtain rewards (effort risks). Moreover, motivation is often guided by the extent to which cognitive-not physical-effort devalues rewards (effort discounting). Yet, very little is known about the mechanisms that underpin the influence of cognitive effort risks or discounting on motivation. We used two cost-benefit decision-making tasks to probe subjective sensitivity to cognitive effort (number of shifts of spatial attention) and to effort risks. Our results show that shifts of spatial attention when monitoring rapidly presented visual stimuli are perceived as effortful and devalue rewards. Additionally, most people are risk-averse, preferring safe, known amounts of effort over risky offers. However, there was no correlation between their effort and risk sensitivity. We show for the first time that people are averse to variance in the possible amount of cognitive effort to be exerted. These results suggest that cognitive effort sensitivity and risk sensitivity are underpinned by distinct psychological and neurobiological mechanisms.

Tissue Classification

DEFF Research Database (Denmark)

Van Leemput, Koen; Puonti, Oula

2015-01-01

Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

Analyzing and Predicting Effort Associated with Finding and Fixing Software Faults

Science.gov (United States)

Hamill, Maggie; Goseva-Popstojanova, Katerina

2016-01-01

Context: Software developers spend a significant amount of time fixing faults. However, not many papers have addressed the actual effort needed to fix software faults. Objective: The objective of this paper is twofold: (1) analysis of the effort needed to fix software faults and how it was affected by several factors and (2) prediction of the level of fix implementation effort based on the information provided in software change requests. Method: The work is based on data related to 1200 failures, extracted from the change tracking system of a large NASA mission. The analysis includes descriptive and inferential statistics. Predictions are made using three supervised machine learning algorithms and three sampling techniques aimed at addressing the imbalanced data problem. Results: Our results show that (1) 83% of the total fix implementation effort was associated with only 20% of failures. (2) Both safety critical failures and post-release failures required three times more effort to fix compared to non-critical and pre-release counterparts, respectively. (3) Failures with fixes spread across multiple components or across multiple types of software artifacts required more effort. The spread across artifacts was more costly than spread across components. (4) Surprisingly, some types of faults associated with later life-cycle activities did not require significant effort. (5) The level of fix implementation effort was predicted with 73% overall accuracy using the original, imbalanced data. Using oversampling techniques improved the overall accuracy up to 77%. More importantly, oversampling significantly improved the prediction of the high level effort, from 31% to around 85%. Conclusions: This paper shows the importance of tying software failures to changes made to fix all associated faults, in one or more software components and/or in one or more software artifacts, and the benefit of studying how the spread of faults and other factors affect the fix implementation

Determinants of Tourists Information Search Effort: The Case of ...

African Journals Online (AJOL)

The paper examines tourist information search effort prior to the visit to a selected destination. The focus was on identifying the key variables that influence the information search effort of Ghana's international visitors from the United States of America, the United Kingdom and Germany. The Dummy Multiple Regression ...

Effort reward imbalance, and salivary cortisol in the morning

DEFF Research Database (Denmark)

Eller, Nanna Hurwitz; Nielsen, Søren Feodor; Blønd, Morten

2012-01-01

Effort reward imbalance (ERI) is suggested to increase risk for stress and is hypothesized to increase cortisol levels, especially the awakening cortisol response, ACR.......Effort reward imbalance (ERI) is suggested to increase risk for stress and is hypothesized to increase cortisol levels, especially the awakening cortisol response, ACR....

Distance to High-Voltage Power Lines and Risk of Childhood Leukemia – an Analysis of Confounding by and Interaction with Other Potential Risk Factors

DEFF Research Database (Denmark)

Pedersen, Camilla; Bräuner, Elvira V; Rod, Naja Hulvej

2014-01-01

. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically......We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters...

Duke Power's liquid radwaste processing improvement efforts

International Nuclear Information System (INIS)

Baker, R.E. Jr.; Bramblett, J.W.

1995-01-01

The rising cost of processing liquid radwaste and industry efforts to reduce offsite isotopic contributions has drawn greater attention to the liquid radwaste area. Because of economic pressures to reduce cost and simultaneously improve performance, Duke Power has undertaken a wide ranging effort to cost effectively achieve improvements in the liquid radwaste processing area. Duke Power has achieved significant reductions over recent years in the release of curies to the environment from the Liquid Radwaste Treatmentt systems at its Catawba, McGuire, and Oconee stations. System wide site curie reductions of 78% have been achieved in a 3 year period. These curie reductions have been achieved while simultaneously reducing the amount of media used to accomplish treatment. The curie and media usage reductions have been achieved at low capital cost expenditures. A large number of approaches and projects have been used to achieve these curie and media usage reductions. This paper will describe the various projects and the associated results for Duke Power's processing improvement efforts. The subjects/projects which will be described include: (1) Cooperative philosophy between stations (2) Source Control (3) Processing Improvements (4) Technology Testing

Connective Tissue Disorders

Science.gov (United States)

... of connective tissue. Over 200 disorders that impact connective tissue. There are different types: Genetic disorders, such as Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta Autoimmune disorders, such as lupus and scleroderma Cancers, like some types of soft tissue sarcoma Each ...

Pitfalls in Designing Zero-Effort Deauthentication: Opportunistic Human Observation Attacks

OpenAIRE

Huhta, O.; Shrestha, P.; Udar, S.; Juuti, M.; Saxena, N.; Asokan, N.

2015-01-01

VK: Asokan, N. Deauthentication is an important component of any authentication system. The widespread use of computing devices in daily life has underscored the need for zero-effort deauthentication schemes. However, the quest for eliminating user effort may lead to hidden security flaws in the authentication schemes. As a case in point, we investigate a prominent zero-effort deauthentication scheme, called ZEBRA, which provides an interesting and a useful solution to a difficult problem ...

Analysis Efforts Supporting NSTX Upgrades

International Nuclear Information System (INIS)

Zhang, H.; Titus, P.; Rogoff, P.; Zolfaghari, A.; Mangra, D.; Smith, M.

2010-01-01

The National Spherical Torus Experiment (NSTX) is a low aspect ratio, spherical torus (ST) configuration device which is located at Princeton Plasma Physics Laboratory (PPPL) This device is presently being updated to enhance its physics by doubling the TF field to 1 Tesla and increasing the plasma current to 2 Mega-amperes. The upgrades include a replacement of the centerstack and addition of a second neutral beam. The upgrade analyses have two missions. The first is to support design of new components, principally the centerstack, the second is to qualify existing NSTX components for higher loads, which will increase by a factor of four. Cost efficiency was a design goal for new equipment qualification, and reanalysis of the existing components. Showing that older components can sustain the increased loads has been a challenging effort in which designs had to be developed that would limit loading on weaker components, and would minimize the extent of modifications needed. Two areas representing this effort have been chosen to describe in more details: analysis of the current distribution in the new TF inner legs, and, second, analysis of the out-of-plane support of the existing TF outer legs.

Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

Science.gov (United States)

Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

2017-01-01

Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

Investigating the Nature of Relationship between Software Size and Development Effort

OpenAIRE

Bajwa, Sohaib-Shahid

2008-01-01

Software effort estimation still remains a challenging and debatable research area. Most of the software effort estimation models take software size as the base input. Among the others, Constructive Cost Model (COCOMO II) is a widely known effort estimation model. It uses Source Lines of Code (SLOC) as the software size to estimate effort. However, many problems arise while using SLOC as a size measure due to its late availability in the software life cycle. Therefore, a lot of research has b...

Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders

Science.gov (United States)

Mosner, Maya G.; Kinard, Jessica L.; McWeeny, Sean; Shah, Jasmine S.; Markiewitz, Nathan D.; Damiano-Goodwin, Cara R.; Burchinal, Margaret R.; Rutherford, Helena J. V.; Greene, Rachel K.; Treadway, Michael T.; Dichter, Gabriel S.

2017-01-01

This study investigated vicarious effort-based decision-making in 50 adolescents with autism spectrum disorders (ASD) compared to 32 controls using the Effort Expenditure for Rewards Task. Participants made choices to win money for themselves or for another person. When choosing for themselves, the ASD group exhibited relatively similar patterns…

Anticipated emotions and effort allocation in weight goal striving.

Science.gov (United States)

Nelissen, Rob M A; de Vet, Emely; Zeelenberg, Marcel

2011-02-01

This study aimed to investigate the influence of anticipated emotions on preventive health behaviour if specified at the level of behavioural outcomes. Consistent with predictions from a recently developed model of goal pursuit, we hypothesized that the impact of emotions on effort levels depended on the perceived proximity to the goal. Participants with weight-loss intentions were randomly selected from an Internet panel and completed questionnaires at three points in time, baseline (T1; N= 725), 2 weeks later at T2 (N= 582) and again 2 months later at T3 (N= 528). Questionnaires assessed anticipated emotions (at T1) and experienced emotions (at T2) towards goal attainment and non-attainment. Goal proximity, goal desirability, and effort levels in striving for weight loss were assessed at both T1 and T2. Current and target weights were reported at all three assessments. In line with predictions, we found that negative anticipated emotions towards goal non-attainment resulted in increased effort but only if people perceived themselves in close proximity to their goal. Effort, in turn, predicted weight loss and goal achievement. The current data bear important practical implications as they identify anticipated emotions as targets of behaviour change interventions aimed to stimulate effort in striving for broad, health-related goals like weight loss. ©2010 The British Psychological Society.

The effect of sleep loss on next day effort.

Science.gov (United States)

Engle-Friedman, Mindy; Riela, Suzanne; Golan, Rama; Ventuneac, Ana M; Davis, Christine M; Jefferson, Angela D; Major, Donna

2003-06-01

The study had two primary objectives. The first was to determine whether sleep loss results in a preference for tasks demanding minimal effort. The second was to evaluate the quality of performance when participants, under conditions of sleep loss, have control over task demands. In experiment 1, using a repeated-measures design, 50 undergraduate college students were evaluated, following one night of no sleep loss and one night of sleep loss. The Math Effort Task (MET) presented addition problems via computer. Participants were able to select additions at one of five levels of difficulty. Less-demanding problems were selected and more additions were solved correctly when the participants were subject to sleep loss. In experiment 2, 58 undergraduate college students were randomly assigned to a no sleep deprivation or a sleep deprivation condition. Sleep-deprived participants selected less-demanding problems on the MET. Percentage correct on the MET was equivalent for both the non-sleep-deprived and sleep-deprived groups. On a task selection question, the sleep-deprived participants also selected significantly less-demanding non-academic tasks. Increased sleepiness, fatigue, and reaction time were associated with the selection of less difficult tasks. Both groups of participants reported equivalent effort expenditures; sleep-deprived participants did not perceive a reduction in effort. These studies demonstrate that sleep loss results in the choice of low-effort behavior that helps maintain accurate responding.

Efek Keadilan Remunerasi, Kompetensi Atasan dan Kohesivitas Kelompok terhadap Withholding Effort

Directory of Open Access Journals (Sweden)

Ida Ayu Kartika Maharani

2016-12-01

Full Text Available Withholding effort is a tendency employee to reduce work contribution as the possibility of an individual in giving less than maximum effort on tasks associated with the job. The purpose of this study is to analyze the remuneration fairness influences, supervisor competencies and group cohesiveness on withholding effort. The population in this study was all administrative employees with the status of civil servants and probationary civil servants who were actively working in the Institute Hindu Dharma Negeri Denpasar. The number of respondents were 80 people. The research data was primary data obtained from questionnaires. This study used confirmatory factor analysis and multiple linear regression analysis as analytic technique. The results show that fairness of remuneration has a negative and significant effect on the withholding effort, supervisor competencies has a negative and significant effect on the withholding effort, group cohesiveness  has a negative and significant effect on the withholding effort

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

Science.gov (United States)

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M; Jiang, Tao; Wirtel, Anthony J; Deng, Meng; Lv, Qing; Nair, Lakshmi S; Doty, Steven B; Laurencin, Cato T

2008-08-12

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: A combined gene therapy–cell transplantation approach

Science.gov (United States)

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M.; Jiang, Tao; Wirtel, Anthony J.; Deng, Meng; Lv, Qing; Nair, Lakshmi S.; Doty, Steven B.; Laurencin, Cato T.

2008-01-01

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials. PMID:18678895

Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion

DEFF Research Database (Denmark)

Otvos, Balint; Silver, Daniel J; Mulkearns-Hubert, Erin E

2016-01-01

Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cel...

Summary of process research analysis efforts

Science.gov (United States)

Burger, D. R.

1985-01-01

A summary of solar-cell process research analysis efforts was presented. Process design and cell design are interactive efforts where technology from integrated circuit processes and other processes are blended. The primary factors that control cell efficiency are: (1) the bulk parameters of the available sheet material, (2) the retention and enhancement of these bulk parameters, and (3) the cell design and the cost to produce versus the finished cells performance. The process sequences need to be tailored to be compatible with the sheet form, the cell shape form, and the processing equipment. New process options that require further evaluation and utilization are lasers, robotics, thermal pulse techniques, and new materials. There are numerous process control techniques that can be adapted and used that will improve product uniformity and reduced costs. Two factors that can lead to longer life modules are the use of solar cell diffusion barriers and improved encapsulation.

Engineering Musculoskeletal Tissue Interfaces

Directory of Open Access Journals (Sweden)

Ece Bayrak

2018-04-01

Full Text Available Tissue engineering aims to bring together biomaterials, cells, and signaling molecules within properly designed microenvironments in order to create viable treatment options for the lost or malfunctioning tissues. Design and production of scaffolds and cell-laden grafts that mimic the complex structural and functional features of tissues are among the most important elements of tissue engineering strategy. Although all tissues have their own complex structure, an even more complex case in terms of engineering a proper carrier material is encountered at the tissue interfaces, where two distinct tissues come together. The interfaces in the body can be examined in four categories; cartilage-bone and ligament-bone interfaces at the knee and the spine, tendon-bone interfaces at the shoulder and the feet, and muscle-tendon interface at the skeletal system. These interfaces are seen mainly at the soft-to-hard tissue transitions and they are especially susceptible to injury and tear due to the biomechanical inconsistency between these tissues where high strain fields are present. Therefore, engineering the musculoskeletal tissue interfaces remain a challenge. This review focuses on recent advancements in strategies for musculoskeletal interface engineering using different biomaterial-based platforms and surface modification techniques.

Measuring listening effort: driving simulator versus simple dual-task paradigm.

Science.gov (United States)

Wu, Yu-Hsiang; Aksan, Nazan; Rizzo, Matthew; Stangl, Elizabeth; Zhang, Xuyang; Bentler, Ruth

2014-01-01

The dual-task paradigm has been widely used to measure listening effort. The primary objectives of the study were to (1) investigate the effect of hearing aid amplification and a hearing aid directional technology on listening effort measured by a complicated, more real world dual-task paradigm and (2) compare the results obtained with this paradigm to a simpler laboratory-style dual-task paradigm. The listening effort of adults with hearing impairment was measured using two dual-task paradigms, wherein participants performed a speech recognition task simultaneously with either a driving task in a simulator or a visual reaction-time task in a sound-treated booth. The speech materials and road noises for the speech recognition task were recorded in a van traveling on the highway in three hearing aid conditions: unaided, aided with omnidirectional processing (OMNI), and aided with directional processing (DIR). The change in the driving task or the visual reaction-time task performance across the conditions quantified the change in listening effort. Compared to the driving-only condition, driving performance declined significantly with the addition of the speech recognition task. Although the speech recognition score was higher in the OMNI and DIR conditions than in the unaided condition, driving performance was similar across these three conditions, suggesting that listening effort was not affected by amplification and directional processing. Results from the simple dual-task paradigm showed a similar trend: hearing aid technologies improved speech recognition performance, but did not affect performance in the visual reaction-time task (i.e., reduce listening effort). The correlation between listening effort measured using the driving paradigm and the visual reaction-time task paradigm was significant. The finding showing that our older (56 to 85 years old) participants' better speech recognition performance did not result in reduced listening effort was not

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

Science.gov (United States)

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

2013-12-01

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

Pattern classification of brain activation during emotional processing in subclinical depression: psychosis proneness as potential confounding factor.

Science.gov (United States)

Modinos, Gemma; Mechelli, Andrea; Pettersson-Yeo, William; Allen, Paul; McGuire, Philip; Aleman, Andre

2013-01-01

We used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in healthy participants with subclinical depressive symptoms. Six-hundred undergraduate students completed the Beck Depression Inventory II (BDI-II). Two groups were subsequently formed: (i) subclinical (mild) mood disturbance (n = 17) and (ii) no mood disturbance (n = 17). Participants also completed a self-report questionnaire on subclinical psychotic symptoms, the Community Assessment of Psychic Experiences Questionnaire (CAPE) positive subscale. The functional magnetic resonance imaging (fMRI) paradigm entailed passive viewing of negative emotional and neutral scenes. The pattern of brain activity during emotional processing allowed correct group classification with an overall accuracy of 77% (p = 0.002), within a network of regions including the amygdala, insula, anterior cingulate cortex and medial prefrontal cortex. However, further analysis suggested that the classification accuracy could also be explained by subclinical psychotic symptom scores (correlation with SVM weights r = 0.459, p = 0.006). Psychosis proneness may thus be a confounding factor for neuroimaging studies in subclinical depression.

The Index of Asia-Pacific Regional Integration Effort

Directory of Open Access Journals (Sweden)

Victor Yifan Ye

2016-06-01

Full Text Available The Asia-Pacific region is not typically seen as one geographic or socio-economic space. Yet, 58 regional economies occupying the space of 28 million square kilometers from Turkey in the West, Russian Federation in the North, French Polynesia in the East and New Zealand in the South belong to the Economic and Social Commission of Asia and the Pacific (ESCAP. This commission provides a forum for member states that "promotes regional cooperation and collective action, assisting countries in building and sustaining shared economic growth and social equity". In 2013, ESCAP's members adopted the Bangkok Declaration to enhance efforts towards deeper regional economic integration. Yet this document neither proposes a concrete modality or modalities of achieving deeper integration, nor provides a sense of distance of individual countries to a "perceived" integrated Asia-Pacific.This paper aims to comprehensively quantify recent integration efforts of economies in the Asia-Pacific region. We provide an "index of integration effort" based on twelve metrics that measure the relative distance of a given economy to the region as an economic entity. Generally, we find that while the region has trended towards becoming integrated in general, both the level of integration and integration effort are inconsistent among Asia-Pacific economies. We discuss potential applications and extensions of the index in developing our perspective of the region's economic and social dynamics.

Dynamic impact indentation of hydrated biological tissues and tissue surrogate gels

Science.gov (United States)

Ilke Kalcioglu, Z.; Qu, Meng; Strawhecker, Kenneth E.; Shazly, Tarek; Edelman, Elazer; VanLandingham, Mark R.; Smith, James F.; Van Vliet, Krystyn J.

2011-03-01

For both materials engineering research and applied biomedicine, a growing need exists to quantify mechanical behaviour of tissues under defined hydration and loading conditions. In particular, characterisation under dynamic contact-loading conditions can enable quantitative predictions of deformation due to high rate 'impact' events typical of industrial accidents and ballistic insults. The impact indentation responses were examined of both hydrated tissues and candidate tissue surrogate materials. The goals of this work were to determine the mechanical response of fully hydrated soft tissues under defined dynamic loading conditions, and to identify design principles by which synthetic, air-stable polymers could mimic those responses. Soft tissues from two organs (liver and heart), a commercially available tissue surrogate gel (Perma-Gel™) and three styrenic block copolymer gels were investigated. Impact indentation enabled quantification of resistance to penetration and energy dissipative constants under the rates and energy densities of interest for tissue surrogate applications. These analyses indicated that the energy dissipation capacity under dynamic impact increased with increasing diblock concentration in the styrenic gels. Under the impact rates employed (2 mm/s to 20 mm/s, corresponding to approximate strain energy densities from 0.4 kJ/m3 to 20 kJ/m3), the energy dissipation capacities of fully hydrated soft tissues were ultimately well matched by a 50/50 triblock/diblock composition that is stable in ambient environments. More generally, the methodologies detailed here facilitate further optimisation of impact energy dissipation capacity of polymer-based tissue surrogate materials, either in air or in fluids.

Anticipating cognitive effort: roles of perceived error-likelihood and time demands.

Science.gov (United States)

Dunn, Timothy L; Inzlicht, Michael; Risko, Evan F

2017-11-13

Why are some actions evaluated as effortful? In the present set of experiments we address this question by examining individuals' perception of effort when faced with a trade-off between two putative cognitive costs: how much time a task takes vs. how error-prone it is. Specifically, we were interested in whether individuals anticipate engaging in a small amount of hard work (i.e., low time requirement, but high error-likelihood) vs. a large amount of easy work (i.e., high time requirement, but low error-likelihood) as being more effortful. In between-subject designs, Experiments 1 through 3 demonstrated that individuals anticipate options that are high in perceived error-likelihood (yet less time consuming) as more effortful than options that are perceived to be more time consuming (yet low in error-likelihood). Further, when asked to evaluate which of the two tasks was (a) more effortful, (b) more error-prone, and (c) more time consuming, effort-based and error-based choices closely tracked one another, but this was not the case for time-based choices. Utilizing a within-subject design, Experiment 4 demonstrated overall similar pattern of judgments as Experiments 1 through 3. However, both judgments of error-likelihood and time demand similarly predicted effort judgments. Results are discussed within the context of extant accounts of cognitive control, with considerations of how error-likelihood and time demands may independently and conjunctively factor into judgments of cognitive effort.

Automated classification of immunostaining patterns in breast tissue from the human protein atlas.

Science.gov (United States)

Swamidoss, Issac Niwas; Kårsnäs, Andreas; Uhlmann, Virginie; Ponnusamy, Palanisamy; Kampf, Caroline; Simonsson, Martin; Wählby, Carolina; Strand, Robin

2013-01-01

The Human Protein Atlas (HPA) is an effort to map the location of all human proteins (http://www.proteinatlas.org/). It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA) are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples. The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM)-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM) and linear discriminant analysis (LDA) classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue. We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert. Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification of staining patterns in histopathology have many

Automated classification of immunostaining patterns in breast tissue from the human protein Atlas

Directory of Open Access Journals (Sweden)

Issac Niwas Swamidoss

2013-01-01

Full Text Available Background: The Human Protein Atlas (HPA is an effort to map the location of all human proteins (http://www.proteinatlas.org/. It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples. Materials and Methods: The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM features, complex wavelet co-occurrence matrix (CWCM features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM and linear discriminant analysis (LDA classifier. Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue. Results: We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert. Conclusions: Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for

Rapid tissue regeneration induced by intracellular ATP delivery-A preliminary mechanistic study.

Directory of Open Access Journals (Sweden)

Harshini Sarojini

Full Text Available We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery-extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Science.gov (United States)

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

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Bellera, Carine; Proust-Lima, Cécile; Joseph, Lawrence; Richaud, Pierre; Taylor, Jeremy; Sandler, Howard; Hanley, James; Mathoulin-Pélissier, Simone

2018-04-01

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was

Shell Inspection History and Current CMM Inspection Efforts

Energy Technology Data Exchange (ETDEWEB)

Montano, Joshua Daniel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-01-26

The following report provides a review of past and current CMM Shell Inspection efforts. Calibration of the Sheffield rotary contour gauge has expired and the primary inspector, Matthew Naranjo, has retired. Efforts within the Inspection team are transitioning from maintaining and training new inspectors on Sheffield to off-the-shelf CMM technology. Although inspection of a shell has many requirements, the scope of the data presented in this report focuses on the inner contour, outer contour, radial wall thickness and mass comparisons.

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Peru.

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Gamero, Emma Castro; Morales Pedraza, Jorge

2009-05-01

The tissue bank "Rosa Guerzoni Chambergo" (RGCTB) located at the Child's Health Institute was inaugurated in 1996, with the financial and technical support of the IAEA program on radiation and tissue banking. Since 1998, the biological bandage of fresh and lyophilised pigskin, amnion and bone tissue is processed routinely in this bank. In all cases, the tissue is sterilised with the use of Cobalt-60 radiation, process carried out at the Laboratories of Irradiation of the Peruvian Institute of Nuclear Energy (IPEN). The tissue bank in the Child's Health Institute helped to save lives in an accident occurred in Lima, when a New Year's fireworks celebration ran out of control in January 2002. Nearly 300 people died in the tragic blaze and hundreds more were seriously burned and injured. Eight Lima hospitals and clinics suddenly were faced with saving the lives of severely burned men, women and children. Fortunately, authorities were ready to respond to the emergency. More than 1,600 dressings were sterilised and supplied to Lima surgeons. The efforts helped save the lives of patients who otherwise might not have survived the Lima fire. Between 1998 and September 2007, 35,012 tissue grafts were produced and irradiated. Radiation sterilised tissues are used by 20 national medical institutions as well as 17 private health institutions. The tissue bank established in Peru with the support of the IAEA is now producing the following tissues: pigskin dressings, fresh and freeze-dried; bone allografts, chips, wedges and powdered, and amnion dressings air-dried. It is also now leading the elaboration of national standards, assignment being entrusted by ONDT (Organización Nacional de Donación y Transplantes; National Organisation on Donation and Transplant). This among other will permit the accreditation of the tissue bank. In this task is also participating IPEN.

Study of relationship of selenium concentration in blood components and tumor tissues of breast and GI tract cancers using neutron activation analysis technique

International Nuclear Information System (INIS)

Othman, I.; Bakir, M. A.; Yassine, T.; Sarhel, A.

2001-12-01

The purpose of this study was to investigate the relationship between selenium (Se) concentration in blood components and tumour tissues of breast and GI tract cancers using neutron activation analysis. red blood cell (RBC) and serum Se concentrations were determined in 50 healthy volunteers aged 25-84 years, 70 breast cancer patients aged 25-70 years and 34 GI tract cancer patients aged 31-85 years, Se levels were also determined in malignant and adjacent normal tissues from breast cancer and GI tract cancer patients. The results showed that Se concentrations in serum and RBC were significantly lower among breast and GI cancer compared to healthy volunteers. The results also showed that Se concentrations were significantly higher in the cancer tissues compared to adjacent normal tissues. These data have shown a relationship between selenium status in blood components and both cancer. selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumours. (author)

How hearing aids, background noise, and visual cues influence objective listening effort.

Science.gov (United States)

Picou, Erin M; Ricketts, Todd A; Hornsby, Benjamin W Y

2013-09-01

The purpose of this article was to evaluate factors that influence the listening effort experienced when processing speech for people with hearing loss. Specifically, the change in listening effort resulting from introducing hearing aids, visual cues, and background noise was evaluated. An additional exploratory aim was to investigate the possible relationships between the magnitude of listening effort change and individual listeners' working memory capacity, verbal processing speed, or lipreading skill. Twenty-seven participants with bilateral sensorineural hearing loss were fitted with linear behind-the-ear hearing aids and tested using a dual-task paradigm designed to evaluate listening effort. The primary task was monosyllable word recognition and the secondary task was a visual reaction time task. The test conditions varied by hearing aids (unaided, aided), visual cues (auditory-only, auditory-visual), and background noise (present, absent). For all participants, the signal to noise ratio was set individually so that speech recognition performance in noise was approximately 60% in both the auditory-only and auditory-visual conditions. In addition to measures of listening effort, working memory capacity, verbal processing speed, and lipreading ability were measured using the Automated Operational Span Task, a Lexical Decision Task, and the Revised Shortened Utley Lipreading Test, respectively. In general, the effects measured using the objective measure of listening effort were small (~10 msec). Results indicated that background noise increased listening effort, and hearing aids reduced listening effort, while visual cues did not influence listening effort. With regard to the individual variables, verbal processing speed was negatively correlated with hearing aid benefit for listening effort; faster processors were less likely to derive benefit. Working memory capacity, verbal processing speed, and lipreading ability were related to benefit from visual cues. No