A Multiple Risk Factors Model of the Development of Aggression among Early Adolescents from Urban Disadvantaged Neighborhoods

ERIC Educational Resources Information Center

Kim, Sangwon; Orpinas, Pamela; Kamphaus, Randy; Kelder, Steven H.

2011-01-01

This study empirically derived a multiple risk factors model of the development of aggression among middle school students in urban, low-income neighborhoods, using Hierarchical Linear Modeling (HLM). Results indicated that aggression increased from sixth to eighth grade. Additionally, the influences of four risk domains (individual, family,…

Complex Applications of HLM in Studies of Science and Mathematics Achievement: Cross-Classified Random Effects Models

ERIC Educational Resources Information Center

Moreno, Mario; Harwell, Michael; Guzey, S. Selcen; Phillips, Alison; Moore, Tamara J.

2016-01-01

Hierarchical linear models have become a familiar method for accounting for a hierarchical data structure in studies of science and mathematics achievement. This paper illustrates the use of cross-classified random effects models (CCREMs), which are likely less familiar. The defining characteristic of CCREMs is a hierarchical data structure…

Assessing exposure to violence using multiple informants: application of hierarchical linear model.

PubMed

Kuo, M; Mohler, B; Raudenbush, S L; Earls, F J

2000-11-01

The present study assesses the effects of demographic risk factors on children's exposure to violence (ETV) and how these effects vary by informants. Data on exposure to violence of 9-, 12-, and 15-year-olds were collected from both child participants (N = 1880) and parents (N = 1776), as part of the assessment of the Project on Human Development in Chicago Neighborhoods (PHDCN). A two-level hierarchical linear model (HLM) with multivariate outcomes was employed to analyze information obtained from these two different groups of informants. The findings indicate that parents generally report less ETV than do their children and that associations of age, gender, and parent education with ETV are stronger in the self-reports than in the parent reports. The findings support a multivariate approach when information obtained from different sources is being integrated. The application of HLM allows an assessment of interactions between risk factors and informants and uses all available data, including data from one informant when data from the other informant is missing.

Predictors of Burnout in Children's Residential Treatment Center Staff

ERIC Educational Resources Information Center

Lakin, Brittany L.; Leon, Scott C.; Miller, Steven A.

2008-01-01

This study explored burnout among frontline staff within a children's residential treatment center (RTC) population. Data were collected from 375 full-time, frontline, children's RTC staff employed at 21 RTCs in Illinois. Using hierarchical linear modeling (HLM), results indicated that frontline staff age, training, empathic concern, communicative…

School Health Promotion Policies and Adolescent Risk Behaviors in Israel: A Multilevel Analysis

ERIC Educational Resources Information Center

Tesler, Riki; Harel-Fisch, Yossi; Baron-Epel, Orna

2016-01-01

Background: Health promotion policies targeting risk-taking behaviors are being implemented across schools in Israel. This study identified the most effective components of these policies influencing cigarette smoking and alcohol consumption among adolescents. Methods: Logistic hierarchical linear model (HLM) analysis of data for 5279 students in…

What Is the Relationship between Teacher Quality and Student Achievement? An Exploratory Study

ERIC Educational Resources Information Center

Stronge, James H.; Ward, Thomas J.; Tucker, Pamela D.; Hindman, Jennifer L.

2007-01-01

The major purpose of the study was to examine what constitutes effective teaching as defined by measured increases in student learning with a focus on the instructional behaviors and practices. Ordinary least squares (OLS) regression analyses and hierarchical linear modeling (HLM) were used to identify teacher effectiveness levels while…

Testing the Intervention Effect in Single-Case Experiments: A Monte Carlo Simulation Study

ERIC Educational Resources Information Center

Heyvaert, Mieke; Moeyaert, Mariola; Verkempynck, Paul; Van den Noortgate, Wim; Vervloet, Marlies; Ugille, Maaike; Onghena, Patrick

2017-01-01

This article reports on a Monte Carlo simulation study, evaluating two approaches for testing the intervention effect in replicated randomized AB designs: two-level hierarchical linear modeling (HLM) and using the additive method to combine randomization test "p" values (RTcombiP). Four factors were manipulated: mean intervention effect,…

Factors Predicting Science Achievement of Immigrant and Non-Immigrant Students: A Multilevel Analysis

ERIC Educational Resources Information Center

Areepattamannil, Shaljan; Kaur, Berinderjeet

2013-01-01

This study, employing hierarchical linear modeling (HLM), sought to investigate the student-level and school-level factors associated with the science achievement of immigrant and non-immigrant students among a national sample of 22,646 students from 896 schools in Canada. While student background characteristics such as home language, family…

An International Meta-Analysis of Reading Recovery

ERIC Educational Resources Information Center

D'Agostino, Jerome V.; Harmey, Sinéad J.

2016-01-01

Reading Recovery is one of the most researched literacy programs worldwide. Although there have been at least 4 quantitative reviews of its effectiveness, none have considered all rigorous group-comparison studies from all implementing nations from the late 1970s to 2015. Using a hierarchical linear modeling (HLM) v-known analysis, we examined if…

Lab-based validation of different data processing methods for wrist-worn ActiGraph accelerometers in young adults.

PubMed

Ellingson, Laura D; Hibbing, Paul R; Kim, Youngwon; Frey-Law, Laura A; Saint-Maurice, Pedro F; Welk, Gregory J

2017-06-01

The wrist is increasingly being used as the preferred site for objectively assessing physical activity but the relative accuracy of processing methods for wrist data has not been determined. This study evaluates the validity of four processing methods for wrist-worn ActiGraph (AG) data against energy expenditure (EE) measured using a portable metabolic analyzer (OM; Oxycon mobile) and the Compendium of physical activity. Fifty-one adults (ages 18-40) completed 15 activities ranging from sedentary to vigorous in a laboratory setting while wearing an AG and the OM. Estimates of EE and categorization of activity intensity were obtained from the AG using a linear method based on Hildebrand cutpoints (HLM), a non-linear modification of this method (HNLM), and two methods developed by Staudenmayer based on a Linear Model (SLM) and using random forest (SRF). Estimated EE and classification accuracy were compared to the OM and Compendium using Bland-Altman plots, equivalence testing, mean absolute percent error (MAPE), and Kappa statistics. Overall, classification agreement with the Compendium was similar across methods ranging from a Kappa of 0.46 (HLM) to 0.54 (HNLM). However, specificity and sensitivity varied by method and intensity, ranging from a sensitivity of 0% (HLM for sedentary) to a specificity of ~99% for all methods for vigorous. None of the methods was significantly equivalent to the OM (p  >  0.05). Across activities, none of the methods evaluated had a high level of agreement with criterion measures. Additional research is needed to further refine the accuracy of processing wrist-worn accelerometer data.

STABILITY OF FMRI STRIATAL RESPONSE TO ALCOHOL CUES: A HIERARCHICAL LINEAR MODELING APPROACH

PubMed Central

Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh

2011-01-01

In functional magnetic resonance imaging (fMRI) studies of alcohol-dependent individuals, alcohol cues elicit activation of the ventral and dorsal aspects of the striatum (VS and DS), which are believed to underlie aspects of reward learning critical to the initiation and maintenance of alcohol dependence. Cue-elicited striatal activation may represent a biological substrate through which treatment efficacy may be measured. However, to be useful for this purpose, VS or DS activation must first demonstrate stability across time. Using hierarchical linear modeling (HLM), this study tested the stability of cue-elicited activation in anatomically and functionally defined regions of interest in bilateral VS and DS. Nine non-treatment-seeking alcohol-dependent participants twice completed an alcohol cue reactivity task during two fMRI scans separated by 14 days. HLM analyses demonstrated that, across all participants, alcohol cues elicited significant activation in each of the regions of interest. At the group level, these activations attenuated slightly between scans, but session-wise differences were not significant. Within-participants stability was best in the anatomically defined right VS and DS and in a functionally defined region that encompassed right caudate and putamen (intraclass correlation coefficients of .75, .81, and .76, respectively). Thus, within this small sample, alcohol cue-elicited fMRI activation had good reliability in the right striatum, though a larger sample is necessary to ensure generalizability and further evaluate stability. This study also demonstrates the utility of HLM analytic techniques for serial fMRI studies, in which separating within-participants variance (individual changes in activation) from between-participants factors (time or treatment) is critical. PMID:21316465

Equity in Educational Resources at the School Level in Korea

ERIC Educational Resources Information Center

Woo, Myung Suk

2010-01-01

This paper analyzed the equity of resources at the elementary school level in Korea using hierarchical linear modeling (HLM). The data included 2,327 Korean public elementary schools in 101 Local Governments within five Local Educational Offices (LEOs). This study found that schools in low property tax per resident areas receive fewer grants,…

High Achievers from Low Socioeconomic Backgrounds: The Critical Role of Disciplinary Climate and Grit

ERIC Educational Resources Information Center

Huang, Haigen; Zhu, Hao

2017-01-01

The purpose of this study was to examine whether school disciplinary climate and grit predicted low socioeconomic status (SES) students being high achievers in mathematics and science with a representative sample of 15-year-old students in the United States. Our analysis, using a two-level logistic hierarchical linear model (HLM), indicated both…

Does Access Matter? Time in General Education and Achievement for Students with Disabilities

ERIC Educational Resources Information Center

Cosier, Meghan; Causton-Theoharis, Julie; Theoharis, George

2013-01-01

This study examined the relationship between hours in general education and achievement in reading and mathematics for students with disabilities. The study population included more than 1,300 students between the ages of 6 and 9 years old within 180 school districts. Hierarchical linear modeling (HLM) was utilized with the Pre-Elementary…

Predicting Change in Parenting Stress across Early Childhood: Child and Maternal Factors

ERIC Educational Resources Information Center

Williford, Amanda P.; Calkins, Susan D.; Keane, Susan P.

2007-01-01

This study examined maternal parenting stress in a sample of 430 boys and girls including those at risk for externalizing behavior problems. Children and their mothers were assessed when the children were ages 2, 4, and 5. Hierarchical linear modeling (HLM) was used to examine stability of parenting stress across early childhood and to examine…

Relationships of Out-of-School-Time Mathematics Lessons to Mathematical Literacy in Singapore and Australia

ERIC Educational Resources Information Center

Kaur, Berinderjeet; Areepattamannil, Shaljan

2013-01-01

This study, drawing on date from the Programme for International Student Assessment (PISA) 2009, examined the relationships of out-of-school-time mathematics lessons to mathematical literacy in Singapore and Australia. Results of two-level hierarchical linear modelling (HLM) analyses revealed that out-of-school-time enrichment lessons in…

When Money Really Matters: Tying Resources of Specific Programmatic and Instructional Elements to Student Academic Growth

ERIC Educational Resources Information Center

Goetz, Michael Eric

2012-01-01

This study explores the cost-effectiveness ratios associated with individual tutoring, intensive reading/language arts instruction, and a focus on core subject areas. Using the Early Childhood Longitudinal Study (ECLS-K) database, this study analyzes these programs using a three-level hierarchical linear model (HLM) with a nationally…

The Challenge of Separating Effects of Simultaneous Education Projects on Student Achievement

ERIC Educational Resources Information Center

Ma, Xin; Ma, Lingling

2009-01-01

When multiple education projects operate in an overlapping or rear-ended manner, it is always a challenge to separate unique project effects on schooling outcomes. Our analysis represents a first attempt to address this challenge. A three-level hierarchical linear model (HLM) was presented as a general analytical framework to separate program…

A Longitudinal Study of Depressive Symptoms and Marijuana Use in a Sample of Inner-City African Americans

ERIC Educational Resources Information Center

Repetto, Paula B.; Zimmerman, Marc A.; Caldwell, Cleopatra H.

2008-01-01

The association between marijuana use and depressive symptoms was examined longitudinally in a sample of 622 African American youth, interviewed on six occasions, using hierarchical linear modeling (HLM). We considered whether depressive symptoms predicted changes in marijuana use and vice versa from high school through the transition into young…

Are Principal Background and School Processes Related to Teacher Job Satisfaction? A Multilevel Study Using Schools and Staffing Survey 2003-04

ERIC Educational Resources Information Center

Shen, Jianping; Leslie, Jeffrey M.; Spybrook, Jessaca K.; Ma, Xin

2012-01-01

Using nationally representative samples for public school teachers and principals, the authors inquired into whether principal background and school processes are related to teacher job satisfaction. Employing hierarchical linear modeling (HLM), the authors were able to control for background characteristics at both the teacher and school levels.…

School Effects on Educational Achievement in Mathematics and Science: 1985-86. National Assessment of Educational Progress. Research and Development Report.

ERIC Educational Resources Information Center

Arnold, Carolyn L.; Kaufman, Phillip D.

This report examines the effects of both student and school characteristics on mathematics and science achievement levels in the third, seventh, and eleventh grades using data from the 1985-86 National Assessment of Educational Progress (NAEP). Analyses feature hierarchical linear models (HLM), a regression-like statistical technique that…

Student Engagement in Two Countries: A Comparative Study Using National Survey of Student Engagement (NSSE) Data

ERIC Educational Resources Information Center

Kandiko, C. B.

2008-01-01

To compare college and university student engagement in two countries with different responses to global forces, Canada and the United States (US), a series of hierarchical linear regression (HLM) models were developed to analyse data from the 2006 administration of the National Survey of Student Engagement (NSSE). Overall, students in the U.S.…

The Impact of Salient Role Stress on Trajectories of Health in Late Life among Survivors of a Seven-Year Panel Study: Analyses of Individual Growth Curves

ERIC Educational Resources Information Center

Shaw, Benjamin A.; Krause, Neal

2002-01-01

The purpose of this study is twofold: 1) to model changes in health over time among older adults; and 2) to assess the degree to which stress arising in salient social roles accounts for individual variation in these changes. Individual growth curve analyses using Hierarchical Linear Modeling (HLM) software were employed with longitudinal data…

Transitioning to Middle School in the Sixth Grade: A Hierarchical Linear Modeling (HLM) Analysis of Substance Use, Violence, and Suicidal Thoughts

ERIC Educational Resources Information Center

Gunter, Whitney D.; Bakken, Nicholas W.

2010-01-01

In recent years, public schools have moved away from traditional grade configurations with junior high schools and have shifted toward integrating sixth-grade students into middle schools. It has been argued that the effect this will have on students is to allow for additional freedom and earlier social growth. However, the counterargument to this…

Gene-Environment Contributions to the Development of Infant Vagal Reactivity: The Interaction of Dopamine and Maternal Sensitivity

ERIC Educational Resources Information Center

Propper, Cathi; Moore, Ginger A.; Mills-Koonce, W. Roger; Halpern, Carolyn Tucker; Hill-Soderlund, Ashley L.; Calkins, Susan D.; Carbone, Mary Anna; Cox, Martha

2008-01-01

This study investigated dopamine receptor genes ("DRD2" and "DRD4") and maternal sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA reactivity, purported indices of vagal tone and vagal regulation, in a challenge task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear modeling (HLM) revealed that at…

Effects of Traditional and Nontraditional Forms of Parental Involvement on School-Level Achievement Outcome: An HLM Study Using SASS 2007-2008

ERIC Educational Resources Information Center

Shen, Jianping; Washington, Alandra L.; Bierlein Palmer, Louann; Xia, Jiangang

2014-01-01

The authors examined parental involvement's (PI) impact on school performance. The hierarchical linear modeling method was applied to national Schools and Staffing Survey 2007-2008 data. They found that PI variables explained significant variance for the outcomes of (a) meeting adequate yearly progress (AYP) and (b) being free from sanctions. The…

Evaluation for Water Conservation in Agriculture: Using a Multi-Method Econometric Approach

NASA Astrophysics Data System (ADS)

Ramirez, A.; Eaton, D. J.

2012-12-01

Since the 1960's, farmers have implemented new irrigation technology to increase crop production and planting acreage. At that time, technology responded to the increasing demand for food due to world population growth. Currently, the problem of decreased water supply threatens to limit agricultural production. Uncertain precipitation patterns, from prolonged droughts to irregular rains, will continue to hamper planting operations, and farmers are further limited by an increased competition for water from rapidly growing urban areas. Irrigation technology promises to reduce water usage while maintaining or increasing farm yields. The challenge for water managers and policy makers is to quantify and redistribute these efficiency gains as a source of 'new water.' Using conservation in farming as a source of 'new water' requires accurately quantifying the efficiency gains of irrigation technology under farmers' actual operations and practices. From a water resource management and policy perspective, the efficiency gains from conservation in farming can be redistributed to municipal, industrial and recreational uses. This paper presents a methodology that water resource managers can use to statistically verify the water savings attributable to conservation technology. The specific conservation technology examined in this study is precision leveling, and the study includes a mixed-methods approach using four different econometric models: Ordinary Least Squares, Fixed Effects, Propensity Score Matching, and Hierarchical Linear Models. These methods are used for ex-post program evaluation where random assignment is not possible, and they could be employed to evaluate agricultural conservation programs, where participation is often self-selected. The principal method taken in this approach is Hierarchical Linear Models (HLM), a useful model for agriculture because it incorporates the hierarchical nature of the data (fields, tenants, and landowners) as well as crop rotation (fields in and out of production). The other three methods provide verification of the accuracy of the HLM model and create a robust comparison of the water savings estimates. Seventeen factors were used to isolate the effect of precision leveling from variations in climate, investments in other irrigation improvements, and farmers' management skills. These statistical analyses yield accurate water savings estimates because they consider farmers' actual irrigation technology and practices. Results suggest that savings from water conservation technology under farmers' actual production systems and management are less than those reported by experimental field studies. These water savings measure the 'in situ' effect of the technology, considering farmers' actual irrigation practices and technology. In terms of the accuracy of the models, HLM provides the most precise estimate of the impact of precision leveling on a field's water usage. The HLM estimate was within the 95% confidence interval of the other three models, thus verifying the accuracy and robustness of the statistical findings and model.

Analysis of Student and School Level Variables Related to Mathematics Self-Efficacy Level Based on PISA 2012 Results for China-Shanghai, Turkey, and Greece

ERIC Educational Resources Information Center

Usta, H. Gonca

2016-01-01

This study aims to analyze the student and school level variables that affect students' self-efficacy levels in mathematics in China-Shanghai, Turkey, and Greece based on PISA 2012 results. In line with this purpose, the hierarchical linear regression model (HLM) was employed. The interschool variability is estimated at approximately 17% in…

Analyzing longitudinal data with the linear mixed models procedure in SPSS.

PubMed

West, Brady T

2009-09-01

Many applied researchers analyzing longitudinal data share a common misconception: that specialized statistical software is necessary to fit hierarchical linear models (also known as linear mixed models [LMMs], or multilevel models) to longitudinal data sets. Although several specialized statistical software programs of high quality are available that allow researchers to fit these models to longitudinal data sets (e.g., HLM), rapid advances in general purpose statistical software packages have recently enabled analysts to fit these same models when using preferred packages that also enable other more common analyses. One of these general purpose statistical packages is SPSS, which includes a very flexible and powerful procedure for fitting LMMs to longitudinal data sets with continuous outcomes. This article aims to present readers with a practical discussion of how to analyze longitudinal data using the LMMs procedure in the SPSS statistical software package.

Bayesian Hierarchical Random Intercept Model Based on Three Parameter Gamma Distribution

NASA Astrophysics Data System (ADS)

Wirawati, Ika; Iriawan, Nur; Irhamah

2017-06-01

Hierarchical data structures are common throughout many areas of research. Beforehand, the existence of this type of data was less noticed in the analysis. The appropriate statistical analysis to handle this type of data is the hierarchical linear model (HLM). This article will focus only on random intercept model (RIM), as a subclass of HLM. This model assumes that the intercept of models in the lowest level are varied among those models, and their slopes are fixed. The differences of intercepts were suspected affected by some variables in the upper level. These intercepts, therefore, are regressed against those upper level variables as predictors. The purpose of this paper would demonstrate a proven work of the proposed two level RIM of the modeling on per capita household expenditure in Maluku Utara, which has five characteristics in the first level and three characteristics of districts/cities in the second level. The per capita household expenditure data in the first level were captured by the three parameters Gamma distribution. The model, therefore, would be more complex due to interaction of many parameters for representing the hierarchical structure and distribution pattern of the data. To simplify the estimation processes of parameters, the computational Bayesian method couple with Markov Chain Monte Carlo (MCMC) algorithm and its Gibbs Sampling are employed.

Comparison of methods of extracting information for meta-analysis of observational studies in nutritional epidemiology.

PubMed

Bae, Jong-Myon

2016-01-01

A common method for conducting a quantitative systematic review (QSR) for observational studies related to nutritional epidemiology is the "highest versus lowest intake" method (HLM), in which only the information concerning the effect size (ES) of the highest category of a food item is collected on the basis of its lowest category. However, in the interval collapsing method (ICM), a method suggested to enable a maximum utilization of all available information, the ES information is collected by collapsing all categories into a single category. This study aimed to compare the ES and summary effect size (SES) between the HLM and ICM. A QSR for evaluating the citrus fruit intake and risk of pancreatic cancer and calculating the SES by using the HLM was selected. The ES and SES were estimated by performing a meta-analysis using the fixed-effect model. The directionality and statistical significance of the ES and SES were used as criteria for determining the concordance between the HLM and ICM outcomes. No significant differences were observed in the directionality of SES extracted by using the HLM or ICM. The application of the ICM, which uses a broader information base, yielded more-consistent ES and SES, and narrower confidence intervals than the HLM. The ICM is advantageous over the HLM owing to its higher statistical accuracy in extracting information for QSR on nutritional epidemiology. The application of the ICM should hence be recommended for future studies.

Prediction of percutaneous absorption in human using three-dimensional human cultured epidermis LabCyte EPI-MODEL.

PubMed

Hikima, Tomohiro; Kaneda, Noriaki; Matsuo, Kyouhei; Tojo, Kakuji

2012-01-01

The objective of this study is to establish a relationship of the skin penetration parameters between the three-dimensional cultured human epidermis LabCyte EPI-MODEL (LabCyte) and hairless mouse (HLM) skin penetration in vitro and to predict the skin penetration and plasma concentration profile in human. The skin penetration experiments through LabCyte and HLM skin were investigated using 19 drugs that have a different molecular weight and lipophilicity. The penetration flux for LabCyte reached 30 times larger at maximum than that for HLM skin. The human data can be estimated from the in silico approach with the diffusion coefficient (D), the partition coefficient (K) and the skin surface concentration (C) of drugs by assuming the bi-layer skin model for both LabCyte and HLM skin. The human skin penetration of β-estradiol, prednisolone, testosterone and ethynylestradiol was well agreed between the simulated profiles and in vitro experimental data. Plasma concentration profiles of β-estradiol in human were also simulated and well agreed with the clinical data. The present alternative method may decrease human or animal skin experiment for in vitro skin penetration.

Risk and resiliency processes in ethnically diverse families in poverty.

PubMed

Wadsworth, Martha E; Santiago, Catherine Decarlo

2008-06-01

Families living in poverty face numerous stressors that threaten the health and well-being of family members. This study examined the relationships among family-level poverty-related stress (PRS), individual-level coping with PRS, and a wide range of psychological symptoms in an ethnically diverse sample of 98 families (300 family members) living at or below 150% of the federal poverty line. Hierarchical linear model (HLM) analyses revealed that family PRS is robustly related to a wide range of psychological syndromes for family members of both genders, all ages, and all ethnic backgrounds. In addition, primary and secondary control coping were both found to serve as buffers of PRS for many syndromes. For several psychological syndromes, parents showed significantly higher levels of symptoms, but the link between PRS and symptoms was significantly stronger for children than for adults. Ethnicity was not a significant predictor in overall HLM models or follow-up analyses, suggesting that the broad construct of PRS and the theoretical model tested here apply across the 3 major ethnic groups included in this study. The findings suggest that family-based, coping-focused interventions have the potential to promote resiliency and break linkages in the pernicious cycle of family economic stress. (c) 2008 APA, all rights reserved

The Aachen miniaturized heart-lung machine--first results in a small animal model.

PubMed

Schnoering, Heike; Arens, Jutta; Sachweh, Joerg S; Veerman, Melanie; Tolba, Rene; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Vazquez-Jimenez, Jaime F

2009-11-01

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth-weight newborns. Taking these considerations into account, the Aachen miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross-clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O(2) and CO(2)) may reduce circuit-induced complications during heart surgery in neonates.

Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome.

PubMed

Lin, Meei-Hua; Miller, Joseph B; Kikkawa, Yamato; Suleiman, Hani Y; Tryggvason, Karl; Hodges, Bradley L; Miner, Jeffrey H

2018-05-01

Background Laminin α 5 β 2 γ 1 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity. Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2 -/- pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture. Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM. Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired. Copyright © 2018 by the American Society of Nephrology.

Impact of extended monitoring-guided intensive care on outcome after severe traumatic brain injury: A prospective multicentre cohort study (PariS-TBI study).

PubMed

Mateo, Joaquim; Payen, Didier; Ghout, Idir; Vallée, Fabrice; Lescot, Thomas; Welschbillig, Stephane; Tazarourte, Karim; Azouvi, Philippe; Weiss, Jean-Jacques; Aegerter, Philippe; Vigué, Bernard

2017-01-01

We evaluated whether an integrated monitoring with systemic and specific monitoring affect mortality and disability in adults with severe traumatic brain injury (sTBI). Adults with severeTBI (Glasgow Coma Scale [GCS] ≤ 8) admitted alive in intensive care units (ICUs) were prospectively included. Primary endpoints were in-hospital 30-day mortality and extended Glasgow outcome score (GOSE) at 3 years. Association with the intensity of monitoring and outcome was studied by comparing a high level of monitoring (HLM) (systemic and ≥3 specific monitoring) and low level of monitoring (LLM) (systemic and 0-2 specific monitoring) and using inverse probability weighting procedure. 476 patients were included and IPW was used to improve the balance between the two groups of treatments (HLM/LMM). Overall hospital mortality (at 30 days) was 43%, being significantly lower in HLM than LLM group (27% vs. 53%: RR, 1.63: 95% CI: 1.23-2.15). The 14-day hospital mortality was also lower in the HLM group than expected, based upon the CRASH prediction model (35%). At 3 years, disability was not significantly different between the monitoring groups. After adjustment, HLM group improved short-term mortality but did not show any improvement in the 3-year outcome compared with LLM.

Right-Sizing Statistical Models for Longitudinal Data

PubMed Central

Wood, Phillip K.; Steinley, Douglas; Jackson, Kristina M.

2015-01-01

Arguments are proposed that researchers using longitudinal data should consider more and less complex statistical model alternatives to their initially chosen techniques in an effort to “right-size” the model to the data at hand. Such model comparisons may alert researchers who use poorly fitting overly parsimonious models to more complex better fitting alternatives, and, alternatively, may identify more parsimonious alternatives to overly complex (and perhaps empirically under-identified and/or less powerful) statistical models. A general framework is proposed for considering (often nested) relationships between a variety of psychometric and growth curve models. A three-step approach is proposed in which models are evaluated based on the number and patterning of variance components prior to selection of better-fitting growth models that explain both mean and variation/covariation patterns. The orthogonal, free-curve slope-intercept (FCSI) growth model is considered as a general model which includes, as special cases, many models including the Factor Mean model (FM, McArdle & Epstein, 1987), McDonald's (1967) linearly constrained factor model, Hierarchical Linear Models (HLM), Repeated Measures MANOVA, and the Linear Slope Intercept (LinearSI) Growth Model. The FCSI model, in turn, is nested within the Tuckerized factor model. The approach is illustrated by comparing alternative models in a longitudinal study of children's vocabulary and by comparison of several candidate parametric growth and chronometric models in a Monte Carlo study. PMID:26237507

The role of social networks in physical and relational aggression among young adolescents.

PubMed

Low, Sabina; Polanin, Joshua R; Espelage, Dorothy L

2013-07-01

Despite the veritable influence of the peer context on the elaboration of adolescent aggression, few studies of relational aggression have directly identified and measured peer groups, limiting our ability to draw formal conclusions about the level and nature of peer influence. The current study used a developmental framework to examine peer group influence on individual levels of physical and relational aggression over a year with 6th and 7th grade students (n = 346, 51 % female). A multilevel network approach was used in which peer groups were identified via social network analysis, and peer group influence was evaluated with hierarchical linear modeling (HLM). HLM analyses indicated that peer group aggression (physical and relational) at time 1 was predictive of individual aggression levels at time 2 after controlling for other peer group characteristics as well as other individual risk and protective factors. Although both forms of aggression were embedded in peer networks, findings suggest that physical aggression is relatively less endemic to peer networks, and is more likely to occur in smaller, predominantly male networks. The current study highlights the importance of understanding the influence of peer group membership on adolescent aggression and points to important implications for prevention.

School effects on non-verbal intelligence and nutritional status in rural Zambia

PubMed Central

Hein, Sascha; Tan, Mei; Reich, Jodi; Thuma, Philip E.; Grigorenko, Elena L.

2015-01-01

This study uses hierarchical linear modeling (HLM) to examine the school factors (i.e., related to school organization and teacher and student body) associated with non-verbal intelligence (NI) and nutritional status (i.e., body mass index; BMI) of 4204 3rd to 7th graders in rural areas of Southern Province, Zambia. Results showed that 23.5% and 7.7% of the NI and BMI variance, respectively, were conditioned by differences between schools. The set of 14 school factors accounted for 58.8% and 75.9% of the between-school differences in NI and BMI, respectively. Grade-specific HLM yielded higher between-school variation of NI (41%) and BMI (14.6%) for students in grade 3 compared to grades 4 to 7. School factors showed a differential pattern of associations with NI and BMI across grades. The distance to a health post and teacher’s teaching experience were the strongest predictors of NI (particularly in grades 4, 6 and 7); the presence of a preschool was linked to lower BMI in grades 4 to 6. Implications for improving access and quality of education in rural Zambia are discussed. PMID:27175053

An exploratory analysis of treatment completion and client and organizational factors using hierarchical linear modeling.

PubMed

Woodward, Albert; Das, Abhik; Raskin, Ira E; Morgan-Lopez, Antonio A

2006-11-01

Data from the Alcohol and Drug Services Study (ADSS) are used to analyze the structure and operation of the substance abuse treatment industry in the United States. Published literature contains little systematic empirical analysis of the interaction between organizational characteristics and treatment outcomes. This paper addresses that deficit. It develops and tests a hierarchical linear model (HLM) to address questions about the empirical relationship between treatment inputs (industry costs, types and use of counseling and medical personnel, diagnosis mix, patient demographics, and the nature and level of services used in substance abuse treatment), and patient outcomes (retention and treatment completion rates). The paper adds to the literature by demonstrating a direct and statistically significant link between treatment completion and the organizational and staffing structure of the treatment setting. Related reimbursement issues, questions for future analysis, and limitations of the ADSS for this analysis are discussed.

Effect of socioeconomic inequalities on cholecystectomy outcomes: a 10-year population-based analysis.

PubMed

Lu, Ping; Yang, Nan-Ping; Chang, Nien-Tzu; Lai, K Robert; Lin, Kai-Biao; Chan, Chien-Lung

2018-02-13

Although numerous epidemiological studies on cholecystectomy have been conducted worldwide, only a few have considered the effect of socioeconomic inequalities on cholecystectomy outcomes. Specifically, few studies have focused on the low-income population (LIP). A nationwide prospective study based on the Taiwan National Health Insurance dataset was conducted during 2003-2012. The International Classification of ICD-9-CM procedure codes 51.2 and 51.21-51.24 were identified as the inclusion criteria for cholecystectomy. Temporal trends were analyzed using a joinpoint regression, and the hierarchical linear modeling (HLM) method was used as an analytical strategy to evaluate the group-level and individual-level factors. Interactions between age, gender and SES were also tested in HLM model. Analyses were conducted on 225,558 patients. The incidence rates were 167.81 (95% CI: 159.78-175.83) per 100,000 individuals per year for the LIP and 123.24 (95% CI: 116.37-130.12) per 100,000 individuals per year for the general population (GP). After cholecystectomy, LIP patients showed higher rates of 30-day mortality, in-hospital complications, and readmission for complications, but a lower rate of routine discharge than GP patients. The hospital costs and length of stay for LIP patients were higher than those for GP patients. The multilevel analysis using HLM revealed that adverse socioeconomic status significantly negatively affects the outcomes of patients undergoing cholecystectomy. Additionally, male sex, advanced age, and high Charlson Comorbidity Index (CCI) scores were associated with higher rates of in-hospital complications and 30-day mortality. We also observed that the 30-day mortality rates for patients who underwent cholecystectomy in regional hospitals and district hospitals were significantly higher than those of patients receiving care in a medical center. Patients with a disadvantaged finance status appeared to be more vulnerable to cholecystectomy surgery. This result suggested that further interventions in the health care system are necessary to reduce this disparity.

In vitro characterization of sarizotan metabolism: hepatic clearance, identification and characterization of metabolites, drug-metabolizing enzyme identification, and evaluation of cytochrome p450 inhibition.

PubMed

Gallemann, Dieter; Wimmer, Elmar; Höfer, Constance C; Freisleben, Achim; Fluck, Markus; Ladstetter, Bernhard; Dolgos, Hugues

2010-06-01

In vitro biotransformation studies of sarizotan using human liver microsomes (HLM) showed aromatic and aliphatic monohydroxylation and dealkylation. Recombinant cytochromes P450 (P450) together with P450-selective inhibitors in HLM/hepatocyte cultures were used to evaluate the relative contribution of different P450s and revealed major involvement of CYP3A4, CYP2C9, CYP2C8, and CYP1A2 in sarizotan metabolism. The apparent K(m, u) and V(max) of sarizotan clearance, as investigated in HLM, were 9 microM and 3280 pmol/mg/min, predicting in vivo hepatic clearance of 0.94 l/h, which indicates that sarizotan is a low-clearance compound in humans and suggests nonsaturable metabolism at the targeted plasma concentration (< or =1 microM). This finding is confirmed by the reported human clearance (CL/F of 3.6-4.4 l/h) and by the dose-linear area under the curve increase observed with doses up to 25 mg. The inhibitory effect of sarizotan toward six major P450s was evaluated using P450-specific marker reactions in pooled HLM. K(i, u) values of sarizotan against CYP2C8, CYP2C19, and CYP3A4 were >10 microM, whereas those against CYP2D6 and CYP1A2 were 0.43 and 8.7 microM, respectively. Based on the estimates of sarizotan concentrations at the enzyme active sites, no clinically significant drug-drug interactions (DDIs) due to P450 inhibition are expected. This result has been confirmed in human DDI studies in which no inhibition of five major P450s was observed in terms of marker metabolite formation.

Influence of Leaders' Psychological Capital on Their Followers: Multilevel Mediation Effect of Organizational Identification

PubMed Central

Chen, Qishan; Wen, Zhonglin; Kong, Yurou; Niu, Jun; Hau, Kit-Tai

2017-01-01

We investigated the relationships between leaders' and their followers' psychological capital and organizational identification in a Chinese community. Participants included 423 followers on 34 work teams, each with its respective team leader. Hierarchical linear models (HLM) were used in the analyses to delineate the relationships among participants' demographic background (gender, age, marital status, and educational level), human capital, and tenure. The results revealed that leaders' psychological capital positively influenced their followers' psychological capital through the mediation effect of enhancing followers' organizational identification. The implications of these findings, the study's limitations, and directions for future research are discussed. PMID:29075218

Streptomyces clavuligerus HlmI is an intramolecular disulfide-forming dithiol oxidase in holomycin biosynthesis

PubMed Central

Li, Bo; Walsh, Christopher T.

2011-01-01

Holomycin and related dithiolopyrrolone antibiotics display broad-spectrum antimicrobial activities and contain a unique 5, 5-bicyclic ring structure with an N-acylated aminopyrrolone fused to a cyclic ene-disulfide. Here we show that the intramolecular disulfide bridge is constructed from the acyclic ene-dithiol at a late stage in the pathway by a thioredoxin oxidoreductase-like enzyme HlmI from the holomycin producer Streptomyces clavuligerus. Recombinant HlmI was purified from E. coli with bound flavin adenine dinucleotide (FAD), and converts reduced holomycin to holomycin utilizing O2 as cosubstrate. As a dithiol oxidase, HlmI is functionally homologous to GliT and DepH, which perform a similar dithiol to disulfide oxidation in the biosynthesis of fungal natural product gliotoxin and epigenetic regulator compound FK228 respectively. Deletion of the hlmI gene in the wild type S. clavuligerus and in a holomycin-overproducing mutant resulted in decreased level of holomycin production and increased sensitivity toward holomycin, suggesting a self-protection role of HlmI in the holomycin biosynthetic pathway. HlmI belongs to a new clade of uncharacterized thioredoxin oxidoreductase-like enzymes, distinctive from the GliT-like enzymes and the DepH-like enzymes, and represents a third example of oxidoreductases that catalyzes disulfide formation in the biosynthesis of small molecules. PMID:21504228

Association of area socioeconomic status with lung function in children.

PubMed

Wu, Yi-Fan; Wu, Cho-Kai; Chen, Duan-Rung; Chie, Wei-Chu; Lee, Yungling Leo

2012-12-01

The study investigates the association between area-level socioeconomic status (SES) and children's lung function. Participants were 3994 seventh grade students from the Taiwan Children Health Study living in 14 communities in Taiwan and were recruited in 2007. Area-level SES predictors were population size, occupation type, income and education level. Hierarchical linear models (HLM) were used to examine the effects of area-level SES on lung function, after accounting for area air pollution and individual SES (parental education and family income). Areas with high income were independently associated with lower child lung function. The coefficients for log transformation of area tax per person in HLM were -47.8 (95% confidence interval (CI): -80.9, -14.8) in FEV(1), -43.8 (95% CI: -75.2, -12.5) in FVC, -93.4 (95% CI: -179.3, -7.5) in FEF(25-75) and -203.2 (95% CI: -349.1, -57.2) in PEF. All SES predictors influenced in the same direction and affected males more. The interaction of area tax per person with parental educational level was significant on PEF, suggesting significant association of greater parental education with lower lung function in children. High area SES was inversely associated with lung function in Taiwanese children. Copyright © 2012 Elsevier Inc. All rights reserved.

Promoting mobility and reducing length of stay in hospitalized general medicine patients: A quality-improvement project.

PubMed

Hoyer, Erik H; Friedman, Michael; Lavezza, Annette; Wagner-Kosmakos, Kathleen; Lewis-Cherry, Robin; Skolnik, Judy L; Byers, Sherrie P; Atanelov, Levan; Colantuoni, Elizabeth; Brotman, Daniel J; Needham, Dale M

2016-05-01

To determine whether a multidisciplinary mobility promotion quality-improvement (QI) project would increase patient mobility and reduce hospital length of stay (LOS). Implemented using a structured QI model, the project took place between March 1, 2013 and March 1, 2014 on 2 general medicine units in a large academic medical center. There were 3352 patients admitted during the QI project period. The Johns Hopkins Highest Level of Mobility (JH-HLM) scale, an 8-point ordinal scale ranging from bed rest (score = 1) to ambulating ≥250 feet (score = 8), was used to quantify mobility. Changes in JH-HLM scores were compared for the first 4 months of the project (ramp-up phase) versus 4 months after project completion (post-QI phase) using generalized estimating equations. We compared the relative change in median LOS for the project months versus 12 months prior among the QI units, using multivariable linear regression analysis adjusting for 7 demographic and clinically relevant variables. Comparing the ramp-up versus post-QI phases, patients reaching JH-HLM's ambulation status increased from 43% to 70% (P < 0.001), and patients with improved JH-HLM mobility scores between admission and discharge increased from 32% to 45% (P < 0.001). For all patients, the QI project was associated with an adjusted median LOS reduction of 0.40 (95% confidence interval [CI]: -0.57 to -0.21, P < 0.001) days compared to 12 months prior. A subgroup of patients expected to have a longer LOS (expected LOS >7 days), were associated with a significantly greater adjusted median reduction in LOS of 1.11 (95% CI: -1.53 to -0.65, P < 0.001) days. Increased mobility was not associated with an increase in injurious falls compared to 12 months prior on the QI units (P = 0.73). Active prevention of a decline in physical function that commonly occurs during hospitalization may be achieved with a structured QI approach. In an adult medicine population, our QI project was associated with improved mobility, and this may have contributed to a reduction in LOS, particularly for more complex patients with longer expected hospital stay. Journal of Hospital Medicine 2016. © 2016 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

Growth trajectories of mathematics achievement: Longitudinal tracking of student academic progress.

PubMed

Mok, Magdalena M C; McInerney, Dennis M; Zhu, Jinxin; Or, Anthony

2015-06-01

A number of methods to investigate growth have been reported in the literature, including hierarchical linear modelling (HLM), latent growth modelling (LGM), and multidimensional scaling applied to longitudinal profile analysis (LPAMS). This study aimed at modelling the mathematics growth of students over a span of 6 years from Grade 3 to Grade 9. The sample comprised secondary longitudinal data collected in three waves from n = 866 Hong Kong students when they were in Grade 3, Grade 6, and Grade 9. Mathematics achievement was measured thrice on a vertical scale linked with anchor items. Linear and nonlinear latent growth models were used to assess students' growth. Gender differences were also examined. A nonlinear latent growth curve with a decelerated rate had a good fit to the data. Initial achievement and growth rate were negatively correlated. No gender difference was found. Mathematics growth from Grade 6 to Grade 9 was slower than that from Grade 3 to Grade 6. Students with lower initial achievement improved at a faster rate than those who started at a higher level. Gender did not affect growth rate. © 2014 The British Psychological Society.

Analytic methods for questions pertaining to a randomized pretest, posttest, follow-up design.

PubMed

Rausch, Joseph R; Maxwell, Scott E; Kelley, Ken

2003-09-01

Delineates 5 questions regarding group differences that are likely to be of interest to researchers within the framework of a randomized pretest, posttest, follow-up (PPF) design. These 5 questions are examined from a methodological perspective by comparing and discussing analysis of variance (ANOVA) and analysis of covariance (ANCOVA) methods and briefly discussing hierarchical linear modeling (HLM) for these questions. This article demonstrates that the pretest should be utilized as a covariate in the model rather than as a level of the time factor or as part of the dependent variable within the analysis of group differences. It is also demonstrated that how the posttest and the follow-up are utilized in the analysis of group differences is determined by the specific question asked by the researcher.

Impact of CYP2C8*3 polymorphism on in vitro metabolism of imatinib to N-desmethyl imatinib.

PubMed

Khan, Muhammad Suleman; Barratt, Daniel T; Somogyi, Andrew A

2016-01-01

1. Imatinib is metabolized to N-desmethyl imatinib by CYPs 3A4 and 2C8. The effect of CYP2C8*3 genotype on N-desmethyl imatinib formation was unknown. 2. We examined imatinib N-demethylation in human liver microsomes (HLMs) genotyped for CYP2C8*3, in CYP2C8*3/*3 pooled HLMs and in recombinant CYP2C8 and CYP3A4 enzymes. Effects of CYP-selective inhibitors on N-demethylation were also determined. 3. A single-enzyme Michaelis-Menten model with autoinhibition best fitted CYP2C8*1/*1 HLM (n = 5) and recombinant CYP2C8 kinetic data (median ± SD Ki = 139 ± 61 µM and 149 µM, respectively). Recombinant CYP3A4 showed two-site enzyme kinetics with no autoinhibition. Three of four CYP2C8*1/*3 HLMs showed single-enzyme kinetics with no autoinhibition. Binding affinity was higher in CYP2C8*1/*3 than CYP2C8*1/*1 HLM (median ± SD Km = 6 ± 2 versus 11 ± 2 µM, P=0.04). CYP2C8*3/*3 (pooled HLM) also showed high binding affinity (Km = 4 µM) and single-enzyme weak autoinhibition (Ki = 449 µM) kinetics. CYP2C8 inhibitors reduced HLM N-demethylation by 47-75%, compared to 0-30% for CYP3A4 inhibitors. 4. In conclusion, CYP2C8*3 is a gain-of-function polymorphism for imatinib N-demethylation, which appears to be mainly mediated by CYP2C8 and not CYP3A4 in vitro in HLM.

Relative contributions of the major human CYP450 to the metabolism of icotinib and its implication in prediction of drug-drug interaction between icotinib and CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.

PubMed

Chen, Jia; Liu, Dongyang; Zheng, Xin; Zhao, Qian; Jiang, Ji; Hu, Pei

2015-06-01

Icotinib is an anticancer drug, but relative contributions of CYP450 have not been identified. This study was carried out to identify the contribution percentage of CYP450 to icotinib and use the results to develop a physiologically based pharmacokinetic (PBPK) model, which can help to predict drug-drug interaction (DDI). Human liver microsome (HLM) and supersome using relative activity factor (RAF) were employed to determine the relative contributions of the major human P450 to the net hepatic metabolism of icotinib. These values were introduced to develop a PBPK model using SimCYP. The model was validated by the observed data in a Phase I clinical trial in Chinese healthy subjects. Finally, the model was used to simulate the DDI with ketoconazole or rifampin. Final contribution of CYP450 isoforms determined by HLM showed that CYP3A4 provided major contributions to the metabolism of icotinib. The percentage contributions of the P450 to the net hepatic metabolism of icotinib were determined by HLM inhibition assay and RAF. The AUC ratio under concomitant use of ketoconazole and rifampin was 3.22 and 0.55, respectively. Percentage of contribution of CYP450 to icotinib metabolism was calculated by RAF. The model has been proven to fit the observed data and is used in predicting icotinib-ketoconazole/rifampin interaction.

Investigating the connections between health lean management and clinical risk management.

PubMed

Crema, Maria; Verbano, Chiara

2015-01-01

The purpose of this paper is to investigate connections and overlaps between health lean management (HLM) and clinical risk management (CRM) understanding whether and how these two approaches can be combined together to pursue efficiency and patient safety improvements simultaneously. A systematic literature review has been carried out. Searching in academic databases, papers that focus not only on HLM, but also on clinical errors and risk reduction, were included. The general characteristics of the selected papers were analysed and a content analysis was conducted. In most of the papers, pursing objectives of HLM and CRM and adopting tools and practices of both approaches, results of quality and, particularly, of safety improvements were obtained. A two-way arrow between HLM and CRM emerged but so far, none of the studies has been focused on the relationship between HLM and CRM. Results highlight an emerging research stream, with many useful theoretical and practical implications and opportunities for further research.

Quantification of Flavin-containing Monooxygenases 1, 3, and 5 in Human Liver Microsomes by UPLC-MRM-Based Targeted Quantitative Proteomics and Its Application to the Study of Ontogeny.

PubMed

Chen, Yao; Zane, Nicole R; Thakker, Dhiren R; Wang, Michael Zhuo

2016-07-01

Flavin-containing monooxygenases (FMOs) have a significant role in the metabolism of small molecule pharmaceuticals. Among the five human FMOs, FMO1, FMO3, and FMO5 are the most relevant to hepatic drug metabolism. Although age-dependent hepatic protein expression, based on immunoquantification, has been reported previously for FMO1 and FMO3, there is very little information on hepatic FMO5 protein expression. To overcome the limitations of immunoquantification, an ultra-performance liquid chromatography (UPLC)-multiple reaction monitoring (MRM)-based targeted quantitative proteomic method was developed and optimized for the quantification of FMO1, FMO3, and FMO5 in human liver microsomes (HLM). A post-in silico product ion screening process was incorporated to verify LC-MRM detection of potential signature peptides before their synthesis. The developed method was validated by correlating marker substrate activity and protein expression in a panel of adult individual donor HLM (age 39-67 years). The mean (range) protein expression of FMO3 and FMO5 was 46 (26-65) pmol/mg HLM protein and 27 (11.5-49) pmol/mg HLM protein, respectively. To demonstrate quantification of FMO1, a panel of fetal individual donor HLM (gestational age 14-20 weeks) was analyzed. The mean (range) FMO1 protein expression was 7.0 (4.9-9.7) pmol/mg HLM protein. Furthermore, the ontogenetic protein expression of FMO5 was evaluated in fetal, pediatric, and adult HLM. The quantification of FMO proteins also was compared using two different calibration standards, recombinant proteins versus synthetic signature peptides, to assess the ratio between holoprotein versus total protein. In conclusion, a UPLC-MRM-based targeted quantitative proteomic method has been developed for the quantification of FMO enzymes in HLM. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Quantification of Flavin-containing Monooxygenases 1, 3, and 5 in Human Liver Microsomes by UPLC-MRM-Based Targeted Quantitative Proteomics and Its Application to the Study of Ontogeny

PubMed Central

Chen, Yao; Zane, Nicole R.; Thakker, Dhiren R.

2016-01-01

Flavin-containing monooxygenases (FMOs) have a significant role in the metabolism of small molecule pharmaceuticals. Among the five human FMOs, FMO1, FMO3, and FMO5 are the most relevant to hepatic drug metabolism. Although age-dependent hepatic protein expression, based on immunoquantification, has been reported previously for FMO1 and FMO3, there is very little information on hepatic FMO5 protein expression. To overcome the limitations of immunoquantification, an ultra-performance liquid chromatography (UPLC)-multiple reaction monitoring (MRM)-based targeted quantitative proteomic method was developed and optimized for the quantification of FMO1, FMO3, and FMO5 in human liver microsomes (HLM). A post-in silico product ion screening process was incorporated to verify LC-MRM detection of potential signature peptides before their synthesis. The developed method was validated by correlating marker substrate activity and protein expression in a panel of adult individual donor HLM (age 39–67 years). The mean (range) protein expression of FMO3 and FMO5 was 46 (26–65) pmol/mg HLM protein and 27 (11.5–49) pmol/mg HLM protein, respectively. To demonstrate quantification of FMO1, a panel of fetal individual donor HLM (gestational age 14–20 weeks) was analyzed. The mean (range) FMO1 protein expression was 7.0 (4.9–9.7) pmol/mg HLM protein. Furthermore, the ontogenetic protein expression of FMO5 was evaluated in fetal, pediatric, and adult HLM. The quantification of FMO proteins also was compared using two different calibration standards, recombinant proteins versus synthetic signature peptides, to assess the ratio between holoprotein versus total protein. In conclusion, a UPLC-MRM-based targeted quantitative proteomic method has been developed for the quantification of FMO enzymes in HLM. PMID:26839369

Model evaluation of the phytoextraction potential of heavy metal hyperaccumulators and non-hyperaccumulators.

PubMed

Liang, Hong-Ming; Lin, Ting-Hsiang; Chiou, Jeng-Min; Yeh, Kuo-Chen

2009-06-01

Evaluation of the remediation ability of zinc/cadmium in hyper- and non-hyperaccumulator plant species through greenhouse studies is limited. To bridge the gap between greenhouse studies and field applications for phytoextraction, we used published data to examine the partitioning of heavy metals between plants and soil (defined as the bioconcentration factor). We compared the remediation ability of the Zn/Cd hyperaccumulators Thlaspi caerulescens and Arabidopsis halleri and the non-hyperaccumulators Nicotiana tabacum and Brassica juncea using a hierarchical linear model (HLM). A recursive algorithm was then used to evaluate how many harvest cycles were required to clean a contaminated site to meet Taiwan Environmental Protection Agency regulations. Despite the high bioconcentration factor of both hyperaccumulators, metal removal was still limited because of the plants' small biomass. Simulation with N. tabacum and the Cadmium model suggests further study and development of plants with high biomass and improved phytoextraction potential for use in environmental cleanup.

How Team-Level and Individual-Level Conflict Influences Team Commitment: A Multilevel Investigation.

PubMed

Lee, Sanghyun; Kwon, Seungwoo; Shin, Shung J; Kim, MinSoo; Park, In-Jo

2017-01-01

We investigate how two different types of conflict (task conflict and relationship conflict) at two different levels (individual-level and team-level) influence individual team commitment. The analysis was conducted using data we collected from 193 employees in 31 branch offices of a Korean commercial bank. The relationships at multiple levels were tested using hierarchical linear modeling (HLM). The results showed that individual-level relationship conflict was negatively related to team commitment while individual-level task conflict was not. In addition, both team-level task and relationship conflict were negatively associated with team commitment. Finally, only team-level relationship conflict significantly moderated the relationship between individual-level relationship conflict and team commitment. We further derive theoretical implications of these findings.

How Team-Level and Individual-Level Conflict Influences Team Commitment: A Multilevel Investigation

PubMed Central

Lee, Sanghyun; Kwon, Seungwoo; Shin, Shung J.; Kim, MinSoo; Park, In-Jo

2018-01-01

We investigate how two different types of conflict (task conflict and relationship conflict) at two different levels (individual-level and team-level) influence individual team commitment. The analysis was conducted using data we collected from 193 employees in 31 branch offices of a Korean commercial bank. The relationships at multiple levels were tested using hierarchical linear modeling (HLM). The results showed that individual-level relationship conflict was negatively related to team commitment while individual-level task conflict was not. In addition, both team-level task and relationship conflict were negatively associated with team commitment. Finally, only team-level relationship conflict significantly moderated the relationship between individual-level relationship conflict and team commitment. We further derive theoretical implications of these findings. PMID:29387033

A fast exact simulation method for a class of Markov jump processes.

PubMed

Li, Yao; Hu, Lili

2015-11-14

A new method of the stochastic simulation algorithm (SSA), named the Hashing-Leaping method (HLM), for exact simulations of a class of Markov jump processes, is presented in this paper. The HLM has a conditional constant computational cost per event, which is independent of the number of exponential clocks in the Markov process. The main idea of the HLM is to repeatedly implement a hash-table-like bucket sort algorithm for all times of occurrence covered by a time step with length τ. This paper serves as an introduction to this new SSA method. We introduce the method, demonstrate its implementation, analyze its properties, and compare its performance with three other commonly used SSA methods in four examples. Our performance tests and CPU operation statistics show certain advantages of the HLM for large scale problems.

Poverty and involuntary engagement stress responses: examining the link to anxiety and aggression within low-income families.

PubMed

Wolff, Brian C; Santiago, Catherine DeCarlo; Wadsworth, Martha E

2009-05-01

Families living with the burdens of poverty-related stress are at risk for developing a range of psychopathology. The present study examines the year-long prospective relationships among poverty-related stress, involuntary engagement stress response (IESR) levels, and anxiety symptoms and aggression in an ethnically diverse sample of 98 families (300 individual family members) living at or below 150% of the US federal poverty line. Hierarchical Linear Modeling (HLM) moderator model analyses provided strong evidence that IESR levels moderated the influence of poverty-related stress on anxiety symptoms and provided mixed evidence for the same interaction effect on aggression. Higher IESR levels, a proxy for physiological stress reactivity, worsened the impact of stress on symptoms. Understanding how poverty-related stress and involuntary stress responses affect psychological functioning has implications for efforts to prevent or reduce psychopathology, particularly anxiety, among individuals and families living in poverty.

Office manager and nurse perspectives on facilitators of adult immunization.

PubMed

Nowalk, Mary Patricia; Tabbarah, Melissa; Hart, Jonathan A; Fox, Dwight E; Raymund, Mahlon; Wilson, Stephen A; Zimmerman, Richard K

2009-10-01

To assess which characteristics of primary care practices serving low- to middle-income white and minority patients relate to pneumococcal polysaccharide vaccine (PPV) and influenza vaccination rates. In an intentional sample of 18 primary care practices, PPV and influenza vaccination rates were determined for a sample of 2289 patients >or=65 years old using medical record review. Office managers and lead nurses were surveyed about their office systems for providing adult immunizations, beliefs about PPV and influenza vaccines, and their own vaccination status. Hierarchical linear modeling (HLM) analyses were used to account for the clustered nature of the data. Sampled patients were most frequently female (61%) and white (83%), and averaged 76 years of age. Weighted vaccination rates were 61.1% for PPV and 52.5% for influenza; rates varied by practice. Using HLM, with patient age and race entered as level 1 variables and office factors entered as level 2 variables, time allotted for an annual well visit was associated with a higher likelihood of influenza vaccination (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 1.02, 1.07; P = .003). Nurse influenza vaccination status was associated with a higher likelihood of PPV vaccination (OR = 3.81; 95% CI = 1.49, 9.78; P = .009). In addition to race and age, visit length and the nurses' vaccination status were associated with adult vaccination rates. Quality improvement initiatives for adult vaccination might include strengthening social influence of providers and/or ensuring that adequate time is scheduled for preventive care.

Daily occupational stressors and marital behavior.

PubMed

Story, Lisa B; Repetti, Rena

2006-12-01

This study examined daily fluctuations in marital behavior (anger and withdrawal) as a function of same-day job stressors, using hierarchical linear modeling (HLM). Forty-three couples provided daily diary reports of their workload and negative social interactions at work on 5 consecutive days. Within-subject analyses demonstrate that husbands and wives reported greater marital anger and withdrawal following negative social interactions at work, and wives reported greater marital anger and withdrawal following days of heavy workload. Mediation analyses provide support for the negative mood spillover hypothesis (e.g., workload no longer predicted wives' marital anger when controlling for negative mood). Between-subjects analyses suggest that spouses in high-conflict families may be especially vulnerable to the effects of job stressors on marital interaction. (c) 2006 APA, all rights reserved.

The Development of Coordinated Communication in Infants at Heightened Risk for Autism Spectrum Disorder

PubMed Central

Parladé, Meaghan V.; Iverson, Jana M.

2015-01-01

This study evaluated the extent to which developmental change in coordination of social communication in early infancy differentiates children eventually diagnosed with ASD from those not likely to develop the disorder. A prospective longitudinal design was used to compare 9 infants at heightened risk for ASD (HR) later diagnosed with ASD, to 13 HR infants with language delay, 28 HR infants with no diagnosis, and 30 low risk infants. Hierarchical Linear Modeling (HLM) analyses revealed that ASD infants exhibited significantly slower growth in coordinations overall and in gestures coordinated with vocalizations, even relative to HR infants with language delay. Disruption in the development of gesture-vocalization coordinations may result in negative cascading effects that negatively impact later social and linguistic development. PMID:25689930

CORRELATES OF INTERORGANIZATIONAL SERVICE COORDINATION IN COMMUNITY CORRECTIONS

PubMed Central

Welsh, Wayne N.; Prendergast, Michael; Knight, Kevin; Knudsen, Hannah; Monico, Laura; Gray, Julie; Abdel-Salam, Sami; Redden, Shawna Malvini; Link, Nathan; Hamilton, Leah; Shafer, Michael S.; Friedmann, Peter D.

2016-01-01

Because weak interagency coordination between community correctional agencies (e.g., probation and parole) and community-based treatment providers has been identified as a major barrier to the use of evidence-based practices (EBPs) for treating druginvolved offenders, this study sought to examine how key organizational (e.g., leadership, support, staffing) and individual (e.g., burnout, satisfaction) factors influence interagency relationships between these agencies. At each of 20 sites, probation/parole officials (n = 366) and community treatment providers (n = 204) were surveyed about characteristics of their agencies, themselves, and interorganizational relationships with each other. Key organizational and individual correlates of interagency relationships were examined using hierarchical linear models (HLM) analyses, supplemented by interview data. The strongest correlates included Adaptability, Efficacy, and Burnout. Implications for policy and practice are discussed. PMID:27546925

A fast exact simulation method for a class of Markov jump processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yao, E-mail: yaoli@math.umass.edu; Hu, Lili, E-mail: lilyhu86@gmail.com

2015-11-14

A new method of the stochastic simulation algorithm (SSA), named the Hashing-Leaping method (HLM), for exact simulations of a class of Markov jump processes, is presented in this paper. The HLM has a conditional constant computational cost per event, which is independent of the number of exponential clocks in the Markov process. The main idea of the HLM is to repeatedly implement a hash-table-like bucket sort algorithm for all times of occurrence covered by a time step with length τ. This paper serves as an introduction to this new SSA method. We introduce the method, demonstrate its implementation, analyze itsmore » properties, and compare its performance with three other commonly used SSA methods in four examples. Our performance tests and CPU operation statistics show certain advantages of the HLM for large scale problems.« less

Epilepsy and its Impact on psychosocial outcomes in Canadian children: Data from the National Longitudinal Study of Children and Youth (NLSCY).

PubMed

Prasad, A N; Corbett, B

2016-12-01

The purpose of this study was to use data from a population-based survey to evaluate the association between childhood epilepsy and social outcomes through tests of mathematics skills, and sense of general self-esteem (GSS). Using data from Cycles 1 to 8 of the National Longitudinal Survey of Children and Youth (NLSCY), Hierarchical linear modeling (HLM) was used to compare baseline math scores and changes in math scores and sense of general self esteem (GSS) over time in children with and without epilepsy. Scores of Health Utility Index (HUI) were factored into the analysis. Children with epilepsy do not significantly differ in their scaled math scores in comparison to their peers without epilepsy, at age 12; however, in the two level HLM model the children with epilepsy lagged behind the healthy comparison group in terms of their growth in acquiring knowledge in mathematics. Additionally, when children with epilepsy carry an added health impairment as measured by an imperfect health utility (HUI) score the group shows a slower rate of growth in their math scores over time. Self-esteem measures show variable effects in children with epilepsy alone, and those with added health impairments. The interaction with HUI scores shows a significant negative effect on self-esteem, when epilepsy is associated with added health impairment. The findings suggest that the population of Canadian children surveyed with epilepsy are vulnerable to poorer academic outcomes in mathematics in later years, and this problem is compounded further with the presence of other additional health impairments. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative assessment of coagulation changes induced by two different types of heart-lung machine.

PubMed

Rahe-Meyer, Niels; Solomon, Cristina; Tokuno, Marie-Louise; Winterhalter, Michael; Shrestha, Malakh; Hahn, Andreas; Tanaka, Kenichi

2010-01-01

The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart-lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB (P < 0.05, Mann-Whitney U-test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group (P < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM.

Identification of an unusual type II thioesterase in the dithiolopyrrolone antibiotics biosynthetic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Ying; Bai, Silei; Liu, Jingjing

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-framemore » gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. - Highlights: • Cloning of the aureothricin biosynthetic gene cluster from Streptomyces thioluteus DSM 40027. • Identification of the aureothricin gene cluster by heterologous expression and in-frame gene deletion. • The heterogenetic thioesterase HlmK significantly improved dithiolopyrrolones production of the aureothricin gene cluster. • Identification of HlmK as an unusual type II thioesterase.« less

Identification and characterization of human UDP-glucuronosyltransferases responsible for the in-vitro glucuronidation of arctigenin.

PubMed

Xin, Hong; Xia, Yang-Liu; Hou, Jie; Wang, Ping; He, Wei; Yang, Ling; Ge, Guang-Bo; Xu, Wei

2015-12-01

This study aimed to characterize the glucuronidation pathway of arctigenin (AR) in human liver microsomes (HLM) and human intestine microsomes (HIM). HLM and HIM incubation systems were employed to catalyse the formation of AR glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards AR was screened. A combination of chemical inhibition assay and kinetic analysis was used to determine the UGT isoforms involved in the glucuronidation of AR in HLM and HIM. AR could be extensively metabolized to one mono-glucuronide in HLM and HIM. The mono-glucuronide was biosynthesized and characterized as 4'-O-glucuronide. UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7 and 2B17 participated in the formation of 4'-O-G, while UGT2B17 demonstrated the highest catalytic activity in this biotransformation. Both kinetic analysis and chemical inhibition assays demonstrated that UGT1A9, UGT2B7 and UGT2B17 played important roles in AR-4'-O-glucuronidation in HLM. Furthermore, HIM demonstrated moderate efficiency for AR-4'-O-glucuronidation, implying that AR may undergo a first-pass metabolism during the absorption process. UGT1A9, UGT2B7 and UGT2B17 were the major isoforms responsible for the 4'-O-glucuronidation of AR in HLM, while UGT2B7 and UGT2B17 were the major contributors to this biotransformation in HIM. © 2015 Royal Pharmaceutical Society.

Economic Evaluation of Manitoba Health Lines in the Management of Congestive Heart Failure

PubMed Central

Cui, Yang; Doupe, Malcolm; Katz, Alan; Nyhof, Paul; Forget, Evelyn L.

2013-01-01

Objective: This one-year study investigated whether the Manitoba Provincial Health Contact program for congestive heart failure (CHF) is a cost-effective intervention relative to the standard treatment. Design: Individual patient-level, randomized clinical trial of cost-effective model using data from the Health Research Data Repository at the Manitoba Centre for Health Policy, University of Manitoba. Methods: A total of 179 patients aged 40 and over with a diagnosis of CHF levels II to IV were recruited from Winnipeg and Central Manitoba and randomized into three treatment groups: one receiving standard care, a second receiving Health Lines (HL) intervention and a third receiving Health Lines intervention plus in-house monitoring (HLM). A cost-effectiveness study was conducted in which outcomes were measured in terms of QALYs derived from the SF-36 and costs using 2005 Canadian dollars. Costs included intervention and healthcare utilization. Bootstrap-resampled incremental cost-effectiveness ratios were computed to take into account the uncertainty related to small sample size. Results: The total per-patient mean costs (including intervention cost) were not significantly different between study groups. Both interventions (HL and HLM) cost less and are more effective than standard care, with HL able to produce an additional QALY relative to HLM for $2,975. The sensitivity analysis revealed that there is an 85.8% probability that HL is cost-effective if decision-makers are willing to pay $50,000. Conclusion: Findings demonstrate that the HL intervention from the Manitoba Provincial Health Contact program for CHF is an optimal intervention strategy for CHF management compared to standard care and HLM. PMID:24359716

Toward a Common Language for Measuring Patient Mobility in the Hospital: Reliability and Construct Validity of Interprofessional Mobility Measures.

PubMed

Hoyer, Erik H; Young, Daniel L; Klein, Lisa M; Kreif, Julie; Shumock, Kara; Hiser, Stephanie; Friedman, Michael; Lavezza, Annette; Jette, Alan; Chan, Kitty S; Needham, Dale M

2018-02-01

The lack of common language among interprofessional inpatient clinical teams is an important barrier to achieving inpatient mobilization. In The Johns Hopkins Hospital, the Activity Measure for Post-Acute Care (AM-PAC) Inpatient Mobility Short Form (IMSF), also called "6-Clicks," and the Johns Hopkins Highest Level of Mobility (JH-HLM) are part of routine clinical practice. The measurement characteristics of these tools when used by both nurses and physical therapists for interprofessional communication or assessment are unknown. The purposes of this study were to evaluate the reliability and minimal detectable change of AM-PAC IMSF and JH-HLM when completed by nurses and physical therapists and to evaluate the construct validity of both measures when used by nurses. A prospective evaluation of a convenience sample was used. The test-retest reliability and the interrater reliability of AM-PAC IMSF and JH-HLM for inpatients in the neuroscience department (n = 118) of an academic medical center were evaluated. Each participant was independently scored twice by a team of 2 nurses and 1 physical therapist; a total of 4 physical therapists and 8 nurses participated in reliability testing. In a separate inpatient study protocol (n = 69), construct validity was evaluated via an assessment of convergent validity with other measures of function (grip strength, Katz Activities of Daily Living Scale, 2-minute walk test, 5-times sit-to-stand test) used by 5 nurses. The test-retest reliability values (intraclass correlation coefficients) for physical therapists and nurses were 0.91 and 0.97, respectively, for AM-PAC IMSF and 0.94 and 0.95, respectively, for JH-HLM. The interrater reliability values (intraclass correlation coefficients) between physical therapists and nurses were 0.96 for AM-PAC IMSF and 0.99 for JH-HLM. Construct validity (Spearman correlations) ranged from 0.25 between JH-HLM and right-hand grip strength to 0.80 between AM-PAC IMSF and the Katz Activities of Daily Living Scale. The results were obtained from inpatients in the neuroscience department of a single hospital. The AM-PAC IMSF and JH-HLM had excellent interrater reliability and test-retest reliability for both physical therapists and nurses. The evaluation of convergent validity suggested that AM-PAC IMSF and JH-HLM measured constructs of patient mobility and physical functioning. © 2017 American Physical Therapy Association

Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Liangliang; Xiao, Ling; Xia, Yangliu

This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1 ± 0.3 μM, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In themore » presence of DES (0–6.25 μM), K{sub m} values for E2-17-O-glucuronidation are located in the range of 7.2–7.4 μM, while V{sub max} values range from 0.38 to 1.54 nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2 μM) can elevate V{sub max} from 0.016 to 0.81 nmol/min/mg, while lifting K{sub m} in a much lesser extent from 4.4 to 11 μM. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with K{sub A}, α, and β values of 0.077 ± 0.18 μM, 3.3 ± 1.1 and 104 ± 56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. - Highlights: • E2-3-O-glucuronidation in HLM is inhibited when co-incubated with DES. • E2-17-O-glucuronidation in HLM is stimulated when co-incubated with DES. • Acceleration of E2-17-O-glucuronidationin in HLM by DES is via activating the activity of UGT1A4.« less

Science-Technology-Society literacy in college non-majors biology: Comparing problem/case studies based learning and traditional expository methods of instruction

NASA Astrophysics Data System (ADS)

Peters, John S.

This study used a multiple response model (MRM) on selected items from the Views on Science-Technology-Society (VOSTS) survey to examine science-technology-society (STS) literacy among college non-science majors' taught using Problem/Case Studies Based Learning (PBL/CSBL) and traditional expository methods of instruction. An initial pilot investigation of 15 VOSTS items produced a valid and reliable scoring model which can be used to quantitatively assess student literacy on a variety of STS topics deemed important for informed civic engagement in science related social and environmental issues. The new scoring model allows for the use of parametric inferential statistics to test hypotheses about factors influencing STS literacy. The follow-up cross-institutional study comparing teaching methods employed Hierarchical Linear Modeling (HLM) to model the efficiency and equitability of instructional methods on STS literacy. A cluster analysis was also used to compare pre and post course patterns of student views on the set of positions expressed within VOSTS items. HLM analysis revealed significantly higher instructional efficiency in the PBL/CSBL study group for 4 of the 35 STS attitude indices (characterization of media vs. school science; tentativeness of scientific models; cultural influences on scientific research), and more equitable effects of traditional instruction on one attitude index (interdependence of science and technology). Cluster analysis revealed generally stable patterns of pre to post course views across study groups, but also revealed possible teaching method effects on the relationship between the views expressed within VOSTS items with respect to (1) interdependency of science and technology; (2) anti-technology; (3) socioscientific decision-making; (4) scientific/technological solutions to environmental problems; (5) usefulness of school vs. media characterizations of science; (6) social constructivist vs. objectivist views of theories; (7) impact of cultural religious/ethical views on science; (8) tentativeness of scientific models, evidence and predictions; (9) civic control of technological developments. This analysis also revealed common relationships between student views which would not have been revealed under the original unique response model (URM) of VOSTS and also common viewpoint patterns that warrant further qualitative exploration.

A Strategy for Teaching Students Interpersonal Skills

ERIC Educational Resources Information Center

Sanchez-Craig, Martha

1977-01-01

Using the Lazarus model, the author presents a reappraisal strategy to help students cope with inadequate, stressful social interactions. Identification of the unsatisfactory situation, generation of alternative interpretations and behaviors, cognitive rehearsal, and new response implementation are described. (Author/HLM)

Effect of housing relocation and neighborhood environment on adolescent mental and behavioral health.

PubMed

Byck, Gayle R; Bolland, John; Dick, Danielle; Swann, Gregory; Henry, David; Mustanski, Brian

2015-11-01

This study examined whether relocating from a high-poverty neighborhood to a lower poverty neighborhood as part of a federal housing relocation program (HOPE VI; Housing Opportunities for People Everywhere) had effects on adolescent mental and behavioral health compared to adolescents consistently living in lower poverty neighborhoods. Sociodemographic, risk behavior, and neighborhood data were collected from 592 low-income, primarily African-American adolescents and their primary caregivers. Structured psychiatric interviews were conducted with adolescents. Prerelocation neighborhood, demographic, and risk behavior data were also included. Hierarchical Linear Modeling (HLM) was used to test associations between neighborhood variables and risk outcomes. HLM was used to test whether the effect of neighborhood relocation and neighborhood characteristics might explain differences in sexual risk taking, substance use, and mental health outcomes. Adolescents who relocated of HOPE VI neighborhoods (n = 158) fared worse than control group participants (n = 429) on most self-reported mental health outcomes. The addition of subjective neighborhood measures generally did not substantively change these results. Our findings suggest that moving from a high-poverty neighborhood to a somewhat lower poverty neighborhood is not associated with better mental health and risk behavior outcomes in adolescents. The continued effects of having grown up in a high-poverty neighborhood, the small improvements in their new neighborhoods, the comparatively short length of time they lived in their new neighborhood, and/or the stress of moving appears to worsen most of the mental health outcomes of HOPE VI compared to control group participants who consistently lived in the lower poverty neighborhoods. © 2015 Association for Child and Adolescent Mental Health.

A multilevel model of organizational health culture and the effectiveness of health promotion.

PubMed

Lin, Yea-Wen; Lin, Yueh-Ysen

2014-01-01

Organizational health culture is a health-oriented core characteristic of the organization that is shared by all members. It is effective in regulating health-related behavior for employees and could therefore influence the effectiveness of health promotion efforts among organizations and employees. This study applied a multilevel analysis to verify the effects of organizational health culture on the organizational and individual effectiveness of health promotion. At the organizational level, we investigated the effect of organizational health culture on the organizational effectiveness of health promotion. At the individual level, we adopted a cross-level analysis to determine if organizational health culture affects employee effectiveness through the mediating effect of employee health behavior. The study setting consisted of the workplaces of various enterprises. We selected 54 enterprises in Taiwan and surveyed 20 full-time employees from each organization, for a total sample of 1011 employees. We developed the Organizational Health Culture Scale to measure employee perceptions and aggregated the individual data to formulate organization-level data. Organizational effectiveness of health promotion included four dimensions: planning effectiveness, production, outcome, and quality, which were measured by scale or objective indicators. The Health Promotion Lifestyle Scale was adopted for the measurement of health behavior. Employee effectiveness was measured subjectively in three dimensions: self-evaluated performance, altruism, and happiness. Following the calculation of descriptive statistics, hierarchical linear modeling (HLM) was used to test the multilevel hypotheses. Organizational health culture had a significant effect on the planning effectiveness (β = .356, p < .05) and production (β = .359, p < .05) of health promotion. In addition, results of cross-level moderating effect analysis by HLM demonstrated that the effects of organizational health culture on three dimensions of employee effectiveness were completely mediated by health behavior. The construct connections established in this multilevel model will help in the construction of health promotion theories. The findings remind business executives that organizational health culture and employee health behavior help improve employee effectiveness.

Prilocaine- and lidocaine-induced methemoglobinemia is caused by human carboxylesterase-, CYP2E1-, and CYP3A4-mediated metabolic activation.

PubMed

Higuchi, Ryota; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

2013-06-01

Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzymes that are responsible for prilocaine- and lidocaine-induced methemoglobinemia. Our experiments revealed that prilocaine was hydrolyzed by recombinant human carboxylesterase (CES) 1A and CES2, whereas lidocaine was hydrolyzed by only human CES1A. When the parent compounds (prilocaine and lidocaine) were incubated with human liver microsomes (HLM), methemoglobin (Met-Hb) formation was lower than when the hydrolyzed metabolites were incubated with HLM. In addition, Met-Hb formation when prilocaine and o-toluidine were incubated with HLM was higher than that when lidocaine and 2,6-xylidine were incubated with HLM. Incubation with diisopropyl fluorophosphate and bis-(4-nitrophenyl) phosphate, which are general inhibitors of CES, significantly decreased Met-Hb formation when prilocaine and lidocaine were incubated with HLM. An anti-CYP3A4 antibody further decreased the residual formation of Met-Hb. Met-Hb formation after the incubation of o-toluidine and 2,6-xylidine with HLM was only markedly decreased by incubation with an anti-CYP2E1 antibody. o-Toluidine and 2,6-xylidine were further metabolized by CYP2E1 to 4- and 6-hydroxy-o-toluidine and 4-hydroxy-2,6-xylidine, respectively, and these metabolites were shown to more efficiently induce Met-Hb formation than the parent compounds. Collectively, we found that the metabolites produced by human CES-, CYP2E1-, and CYP3A4-mediated metabolism were involved in prilocaine- and lidocaine-induced methemoglobinemia.

Socio-dramatic affective-relational intervention for adolescents with asperger syndrome & high functioning autism: pilot study.

PubMed

Lerner, Matthew D; Mikami, Amori Yee; Levine, Karen

2011-01-01

This study examined the effectiveness of a novel intervention called 'socio-dramatic affective-relational intervention' (SDARI), intended to improve social skills among adolescents with Asperger syndrome and high functioning autism diagnoses. SDARI adapts dramatic training activities to focus on in vivo practice of areas of social skill deficit among this population. SDARI was administered as a six-week summer program in a community human service agency. Nine SDARI participants and eight age- and diagnosis-group matched adolescents not receiving SDARI were compared on child- and parent-report of social functioning at three week intervals beginning six weeks prior to intervention and ending six weeks post-intervention. Hierarchical Linear Modeling (HLM) was used to estimate growth trends between groups to assess treatment outcomes and post-treatment maintenance. Results indicated significant improvement and post-treatment maintenance among SDARI participants on several measures of child social functioning. Implications for practice and research are discussed.

Leadership, Burnout, and Job Satisfaction in Outpatient Drug-Free Treatment Programs

PubMed Central

Broome, Kirk M.; Knight, Danica K.; Edwards, Jennifer R.; Flynn, Patrick M.

2009-01-01

Counselors are a critical component of substance abuse treatment programming, but their working experiences are not yet well understood. As treatment-improvement efforts focus increasingly on these individuals, their perceptions of program leadership, emotional burnout, and job satisfaction and related attitudes take on greater significance. This study explores counselor views and the impact of organizational context using data from a nationwide set of 94 outpatient drug-free (ODF) treatment programs in a hierarchical linear model (HLM) analysis. Results show counselors hold generally positive opinions of program director leadership and job satisfaction, and have low levels of burnout, but they also have important variations in their ratings. Higher counselor caseloads were related to poorer ratings, and leadership behaviors predicted both satisfaction and burnout. These findings add further evidence that treatment providers should also address the workplace environment for staff as part of quality-improvement efforts. PMID:19339143

Mediating effect of cooperative norm in predicting organizational citizenship behaviors from procedural justice climate.

PubMed

Lin, Shang-Ping; Tang, Ta-Wei; Li, Chao-Hua; Wu, Chien-Ming; Lin, Hsiu-Hsia

2007-08-01

Although the relationships between procedural justice climate and organizational citizenship behaviors have been examined in recent years, little research has explored the mechanism by which procedural justice climate shapes individual employee prosocial behaviors in the workplace. The purpose of this study was to examine the mediating role of a group-level cooperative norm on the relationships between the group-level procedural justice climate and individual-level organizational citizenship behaviors. The survey involved 45 work groups in four different industry fields in Taiwan, including manufacturing, technology, banking, and insurance, and each of the groups was composed of one supervisor and three subordinates. Cross-level analyses using hierarchical linear modeling (HLM) indicated that the cooperative norm fully mediated the relationship between procedural justice climate and individual helping behaviors. Procedural justice climate indirectly affects individual helping behaviors through their effects on the cooperative norm.

Cross-National Moral Beliefs: The Influence of National Religious Context

PubMed Central

Finke, Roger; Adamczyk, Amy

2014-01-01

International surveys have documented wide variation in religious beliefs and practices across nations, but does this variation in the national religious context make a difference? Building on existing theory we explain why religion should have both micro and macro-level effects on morality not sanctioned by the state and why the effects of religion differ from other forms of culture. Using two international surveys and Hierarchical Linear Modeling Techniques (HLM) we sort out the effects of national context and personal beliefs on morality with and without legal underpinnings. We find that national religious context, the respondent’s age, and religious beliefs and practices are the most consistent predictors of the sexual morality index. For morality sanctioned by the state, however, the effects for personal beliefs and practices are attenuated and the effects of the national religious context are no longer significant. PMID:25097270

Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

PubMed

Rosen, Lisa H; Principe, Connor P; Langlois, Judith H

2013-02-13

The authors examined whether early adolescents ( N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived themselves as having both strengths and weaknesses were more likely to seek negative feedback regarding a self-perceived weakness compared to a self-perceived strength. The authors found similar support for self-verification processes when they considered the entire sample regardless of perceived strengths and weaknesses; hierarchical linear modeling (HLM) examined the predictive power of ratings of self-perceived ability, certainty, and importance on feedback seeking for all participants and provided additional evidence of self-verification strivings in adolescence.

Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

PubMed Central

Rosen, Lisa H.; Principe, Connor P.; Langlois, Judith H.

2012-01-01

The authors examined whether early adolescents (N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived themselves as having both strengths and weaknesses were more likely to seek negative feedback regarding a self-perceived weakness compared to a self-perceived strength. The authors found similar support for self-verification processes when they considered the entire sample regardless of perceived strengths and weaknesses; hierarchical linear modeling (HLM) examined the predictive power of ratings of self-perceived ability, certainty, and importance on feedback seeking for all participants and provided additional evidence of self-verification strivings in adolescence. PMID:23543746

Young Athletes program: impact on motor development.

PubMed

Favazza, Paddy C; Siperstein, Gary N; Zeisel, Susan A; Odom, Samuel L; Sideris, John H; Moskowitz, Andrew L

2013-07-01

This study examined the effectiveness of the Young Athletes program to promote motor development in preschool-aged children with disabilities. In the study, 233 children were randomly assigned to a control group or the Young Athletes (YA) intervention group which consisted of 24 motor skill lessons delivered 3 times per week for 8 weeks. Hierarchical Linear Modeling (HLM) showed that children who participated in the YA intervention exhibited mean gains of 7-9 months on the Peabody Developmental Motor Subscales (PDMS) compared with mean gains of 3-5 months for the control group. Children in the YA intervention also exhibited significant gains on the gross motor subscale of the Vineland Teacher Rating Form (VTRF). Teachers and parents reported benefits for children not only in specific motor skills, but also kindergarten readiness skills and social/play skills. The necessity for direct and intentional instruction of motor skills, as well as the challenges of involving families in the YA program, are discussed.

Understanding neighbourhoods, communities and environments: new approaches for social work research.

PubMed

Holland, Sally; Burgess, Stephen; Grogan-Kaylor, Andy; Delva, Jorge

2010-06-01

This article discusses some new ways in which social work research can explore the interaction between neighbourhoods and child and adult wellbeing. The authors note that social work practices are often criticised for taking an individualistic approach and paying too little attention to the service user's environment. The article uses examples of research projects from Chile, the United States of America and Wales, to discuss the use of spatially oriented research methods for understanding neighbourhood factors. Quantitative, qualitative and mixed methods approaches that are particularly appropriate for investigating social work relevant topics are discussed in turn, including quantitative and qualitative uses for geographical information systems (GIS), hierarchical linear modelling (HLM) for analysing spatially clustered data and qualitative mobile interviews. The article continues with a discussion of the strengths and limitations of using spatially orientated research designs in social work research settings and concludes optimistically with suggestions for future directions in this area.

School-Level Contextual Effects of Parent Involvement on Children's Achievement during Elementary Grades

ERIC Educational Resources Information Center

Oh, Yoonkyung

2012-01-01

This study used the ECLS-K to examine the contextual influences of parent involvement on children's achievement growth in reading and math during elementary grades. The study used Rasch models and HLM measurement models to develop reliable and valid constructs of parent involvement both at the student and at the school level. Piecewise linear…

Counselor Attitudes toward the Use of Buprenorphine in Substance Abuse Treatment: A Multi-level Modeling Approach

PubMed Central

Kovas, Anne E.; McFarland, Bentson H.; Abraham, Amanda J.

2012-01-01

In spite of evidence that buprenorphine is effective, safe, and offers greater access as compared with methadone, implementation for treatment of opiate dependence continues to be weak. Research indicates that legal and regulatory factors, state policies, and organizational and provider variables affect adoption of buprenorphine. This study uses hierarchical linear modeling (HLM) to examine National Treatment Center Study (NTCS) data to identify counselor characteristics (attitudes, training, beliefs) and organizational factors (accreditation, caseload, access to buprenorphine and other evidence-based practices) that influence implementation of buprenorphine for treatment of opiate dependence. Analyses showed that provider training about buprenorphine, higher prevalence of opiate dependent clients, and less treatment program emphasis on a 12-step model predicted greater counselor acceptance and perceived effectiveness of buprenorphine. Results also indicate that program use of buprenorphine for any treatment purpose (detoxification, maintenance, and/or pain management) and time (calendar year in data collection) were associated with increased diffusion of knowledge about buprenorphine among counselors and with more favorable counselor attitudes toward buprenorphine. PMID:21821379

Social comparison, competition and teacher-student relationships in junior high school classrooms predicts bullying and victimization.

PubMed

Di Stasio, Maria Rosaria; Savage, Robert; Burgos, Giovani

2016-12-01

This cross-sectional research examines how social comparison, competition and teacher-student relationships as classroom characteristics are associated with bullying and victimization among junior high school students in grades 7 and 8 in Canada. The study tests a conceptual model of youth outcomes that highlights the importance of modeling the effects of teaching practices as proximal structural conditions at the classroom level (N = 38) that affect bullying outcomes at the individual level (N = 687). Results of Hierarchal linear modeling (HLM) revealed significant classroom-level effects in that increased social comparison, competition and teacher-student relationships were related to bullying and victimization. An interaction for teacher-student relationships and gender also emerged. These findings may guide future intervention programs for junior high schools that focus on enhancing cooperation and pro-social behavior in classrooms. The findings could also inform programs that focus on building strong relationships between students and teachers to help prevent bullying and victimization, particularly among boys. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. All rights reserved.

Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples.

PubMed

Behnia, Behnoush; Heinrichs, Markus; Bergmann, Wiebke; Jung, Stefanie; Germann, Janine; Schedlowski, Manfred; Hartmann, Uwe; Kruger, Tillmann H C

2014-03-01

Knowledge about the effects of the neuropeptide oxytocin (OXT) on human sexual behaviors and partner interactions remains limited. Based on our previous studies, we hypothesize that OXT should be able to positively influence parameters of sexual function and couple interactions. Employing a naturalistic setting involving 29 healthy heterosexual couples (n=58 participants), we analyzed the acute effects of intranasally administered OXT (24IU) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior together with partner interactions. Data were assessed by psychometric instruments (Acute Sexual Experiences Scale, Arizona Sexual Experience Scale) as well as biomarkers, such as cortisol, α-amylase and heart rate. Intranasal OXT administration did not alter "classical" parameters of sexual function, such as sexual drive, arousal or penile erection and lubrication. However, analysis of variance and a hierarchical linear model (HLM) revealed specific effects related to the orgasmic/post-orgasmic interval as well as parameters of partner interactions. According to HLM analysis, OXT increased the intensity of orgasm, contentment after sexual intercourse and the effect of study participation. According to ANOVA analysis, these effects were more pronounced in men. Men additionally indicated higher levels of sexual satiety after sexual intercourse with OXT administration. Women felt more relaxed and subgroups indicated better abilities to share sexual desires or to empathize with their partners. The effect sizes were small to moderate. Biomarkers indicated moderate psychophysiological activation but were not affected by OXT, gender or method of contraception. Using a naturalistic setting, intranasal OXT administration in couples exerted differential effects on parameters of sexual function and partner interactions. These results warrant further investigations, including subjects with sexual and relationship problems. Copyright © 2014 Elsevier Inc. All rights reserved.

Randomized trial of the Availability, Responsiveness and Continuity (ARC) organizational intervention for improving youth outcomes in community mental health programs.

PubMed

Glisson, Charles; Hemmelgarn, Anthony; Green, Philip; Williams, Nathaniel J

2013-05-01

The primary objective of the study was to assess whether the Availability, Responsiveness and Continuity (ARC) organizational intervention improved youth outcomes in community based mental health programs. The second objective was to assess whether programs with more improved organizational social contexts following the 18-month ARC intervention had better youth outcomes than programs with less improved social contexts. Eighteen community mental health programs that serve youth between the ages of 5 and 18 were randomly assigned to ARC or control conditions. Clinicians (n = 154) in the participating programs completed the Organizational Social Context (OSC) measure at baseline and following the 18-month ARC organizational intervention. Caregivers of 393 youth who were served by the 18 programs (9 in ARC and 9 in control) completed the Shortform Assessment for Children (SAC) once a month for six months beginning at intake. Hierarchical linear models (HLM) analyses indicated that youth outcomes were significantly better in the programs that completed the 18 month ARC intervention. HLM analyses also showed that youth outcomes were best in the programs with the most improved organizational social contexts following the 18 month ARC intervention. Youth outcomes in community mental health programs can be improved with the ARC organizational intervention and outcomes are best in programs that make the most improvements in organizational social context. The relationships linking ARC, organizational social context, and youth outcomes suggest that service improvement efforts will be more successful if those efforts include strategies to improve the organizational social contexts in which the services are embedded. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

The effects of a mass media HIV-risk reduction strategy on HIV-related stigma and knowledge among African American adolescents.

PubMed

Kerr, Jelani C; Valois, Robert F; DiClemente, Ralph J; Carey, Michael P; Stanton, Bonita; Romer, Daniel; Fletcher, Faith; Farber, Naomi; Brown, Larry K; Vanable, Peter A; Salazar, Laura F; Juzang, Ivan; Fortune, Thierry

2015-03-01

HIV-related stigma undermines HIV prevention, testing, and treatment. Multipronged risk-reduction strategies may reduce stigma among African American adolescents. To test the effectiveness of a risk-reduction strategy in addressing stigma, 1613 African American adolescents from four mid-sized cities participated in a randomized control trial. Participants received a sexual-risk reduction [Focus on Youth (FOY)] or general health curriculum [Promoting Health Among Teens (PHAT)]. Two cities received a culturally-tailored media intervention. Participants completed baseline, 3-, 6-, and 12-month surveys to measure HIV-related stigma and knowledge. Analysis of covariance tested for stigma and knowledge differences by media city status and curriculum/media city status (PHAT media vs. PHAT non-media, FOY media vs. FOY non-media; FOY media vs. PHAT media; FOY non-media vs. PHAT non-media) at each measurement. Hierarchical linear modeling (HLM) determined stigma and knowledge differences over time. Media participants demonstrated greater HIV-related knowledge (p<0.10) at 6 months and lower stigma at 3 months (p<0.10). FOY media participants had lower 3-month (p<0.05) and 12-month (p<0.10) stigma scores than non-media FOY participants. FOY media and non-media participants had greater knowledge than PHAT for all intervals after baseline. FOY media had lower stigma than PHAT media after baseline for all intervals after baseline. HLM indicated greater knowledge slopes for the media group (p<0.05). FOY media participants had greater knowledge slopes (p<0.05) relative to non-media FOY participants and media PHAT participants (p<0.01). A combination of a HIV risk-reduction curriculum and culturally-tailored media demonstrated some effectiveness in reducing stigma. Future use of media in HIV-prevention should include and evaluate effects on stigma.

Caregiver Life Satisfaction: Relationship to Youth Symptom Severity through Treatment

PubMed Central

Athay, M. Michele

2013-01-01

Objective This study utilized the Satisfaction with Life Scale (SWLS) to investigate the life satisfaction of caregivers for youth receiving mental health services (N = 383), specifically how it relates to youth symptom severity throughout treatment. Method Hierarchical linear modeling (HLM) with a time-varying covariate was used to estimate the linear trajectory of caregiver life satisfaction and how it relates to youth symptom severity as rated by caregivers, youth, and clinicians. Results Initial caregiver life satisfaction was inversely related to caregiver and clinician rated youth symptom severity. Additionally, subsequent caregiver life satisfaction demonstrated a small but significant relationship to changes in youth symptom severity during treatment where a decrease in youth symptoms corresponded to an increase in caregiver life satisfaction, and vice versa. Caregiver background characteristics related to higher life satisfaction include being: married, a birth-parent, under 40 years old and having the absence of previous diagnoses of an emotional, behavioral or substance use disorder. Conclusion Caregivers of clinically-referred youth report low levels of life satisfaction throughout youth treatment. Given the bi-directional influences on one another, tending to the well-being of caregivers may positively influence both caregivers and youths. PMID:22571285

Identification of an unusual type II thioesterase in the dithiolopyrrolone antibiotics biosynthetic pathway.

PubMed

Zhai, Ying; Bai, Silei; Liu, Jingjing; Yang, Liyuan; Han, Li; Huang, Xueshi; He, Jing

2016-04-22

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-frame gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Climatic interpretation of tree-ring methoxyl d2H time-series from a central alpine larch forest

NASA Astrophysics Data System (ADS)

Riechelmann, Dana F. C.; Greule, Markus; Siegwolf, Rolf T. W.; Esper, Jan; Keppler, Frank

2017-04-01

We measured stable hydrogen isotope ratios of lignin methoxyl groups (d2HLM) in high elevation larch trees (Larix decidua Mill.) from the Simplon Valley in southern Switzerland. Thirty-seven larch trees were sampled and five individuals analysed for their d2HLM values at annual (1971-2009) and pentadal resolution (1746-2009). Testing the climate response of the d2HLM series, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation and weaker but negative correlation with June/July temperature. In addition, a negative correlation with June-August d2H in precipitation of the nearby GNIP station in Locarno is observed. The pentadally resolved d2HLM series show no significant correlation to climate parameters. The positive correlation of the annually resolved data to summer precipitation is uncommon to d2H measurements from tree-rings (Feakins et al., 2013; Helle and Schleser, 2004; McCarroll and Loader, 2004; Mischel et al., 2015; White et al., 1994). However, we explain the positive association with warm season hydroclimate as follows: methoxyl groups of lignin are directly formed from tissues in the xylem water. More precipitation during June and July, which are on average relatively dry month, results in higher d2H values of the xylem water and therefore, higher d2H value in the lignin methoxyl groups. Therefore, we suggest that d2HLM values of high elevation larch trees might likely serve as a summer precipitation proxy. References: Feakins, S.J., Ellsworth, P.V., Sternberg, L.d.S.L., 2013. Lignin methoxyl hydrogen isotope rations in a coastal ecosystem. Geochimica et Cosmochimica Acta, 121: 54-66. Helle, G., Schleser, G.H., 2004. Interpreting Climate Proxies from Tree-rings. In: Fischer, H., Floeser, G., Kumke, T., Lohmann, G., Miller, H., Negendank, J.F.W., et al., editors. The Climate in Historical Times. Springer Berlin Heidelberg, pp. 129-148. McCarroll, D., Loader, N.J., 2004. Stable isotopes in tree rings. Quaternary Science Reviews, 23: 771-801. Mischel, M., Esper, J., Keppler, F., Greule, M., Werner, W., 2015. d2H, d13C and d18O from whole wood, a-cellulose and lignin methoxyl groups in Pinus sylvestris: a multi-parameter approach. Isotopes in Environmental and Health Studies, 1-16. White, J.W.C., Lawrence, J.R., Broecker, W.S., 1994. Modeling and interpreting D/H ratios in tree rings: A test case of white pine in the northeastern United States. Geochimica et Cosmochimica Acta, 58: 851-862.

Student Background Factors Influencing Student Achievement in Serbia

ERIC Educational Resources Information Center

Teodorovic, Jelena

2012-01-01

This paper describes student-level findings of the first large-scale comprehensive school effectiveness study of the primary education in Serbia. Twenty-five student-level variables were examined in a three-level HLM model using a study sample of almost 5000 students, over 250 classrooms and over 100 schools. Differences between the students were…

Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations

PubMed Central

Quinto-Sánchez, Mirsha; Cintas, Celia; Silva de Cerqueira, Caio Cesar; Ramallo, Virginia; Acuña-Alonzo, Victor; Adhikari, Kaustubh; Castillo, Lucía; Gomez-Valdés, Jorge; Everardo, Paola; De Avila, Francisco; Hünemeier, Tábita; Jaramillo, Claudia; Arias, Williams; Fuentes, Macarena; Gallo, Carla; Poletti, Giovani; Schuler-Faccini, Lavinia; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Rosique, Javier; Ruiz-Linares, Andrés; González-José, Rolando

2017-01-01

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries. PMID:28060876

The Impact of Individual and Institutional Factors on Turnover Intent Among Taiwanese Correctional Staff.

PubMed

Lai, Yung-Lien

2017-01-01

The existing literature on turnover intent among correctional staff conducted in Western societies focuses on the impact of individual-level factors; the possible effects of institutional contexts have been largely overlooked. Moreover, the relationships of various multidimensional conceptualizations of both job satisfaction and organizational commitment to turnover intent are still largely unknown. Using data collected by a self-reported survey of 676 custody staff employed in 22 Taiwanese correctional facilities during April of 2011, the present study expands upon theoretical models developed in Western societies and examines the effects of both individual and institutional factors on turnover intent simultaneously. Results from the use of the hierarchical linear modeling (HLM) statistical method indicate that, at the individual-level, supervisory versus non-supervisory status, job stress, job dangerousness, job satisfaction, and organizational commitment consistently produce a significant association with turnover intent after controlling for personal characteristics. Specifically, three distinct forms of organizational commitment demonstrated an inverse impact on turnover intent. Among institutional-level variables, custody staff who came from a larger facility reported higher likelihood of thinking about quitting their job. © The Author(s) 2015.

Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations.

PubMed

Quinto-Sánchez, Mirsha; Cintas, Celia; Silva de Cerqueira, Caio Cesar; Ramallo, Virginia; Acuña-Alonzo, Victor; Adhikari, Kaustubh; Castillo, Lucía; Gomez-Valdés, Jorge; Everardo, Paola; De Avila, Francisco; Hünemeier, Tábita; Jaramillo, Claudia; Arias, Williams; Fuentes, Macarena; Gallo, Carla; Poletti, Giovani; Schuler-Faccini, Lavinia; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Rosique, Javier; Ruiz-Linares, Andrés; González-José, Rolando

2017-01-01

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.

Inhibition of fipronil and nonane metabolism in human liver microsomes and human cytochrome P450 isoforms by chlorpyrifos.

PubMed

Joo, Hyun; Choi, Kyoungju; Rose, Randy L; Hodgson, Ernest

2007-01-01

Previous studies have established that chlorpyrifos (CPS), fipronil, and nonane can all be metabolized by human liver microsomes (HLM) and a number of cytochrome P450 (CYP) isoforms. However, metabolic interactions between these three substrates have not been described. In this study the effect of either coincubation or preincubation of CPS with HLM or CYP isoforms with either fipronil or nonane as substrate was investigated. In both co- and preincubation experiments, CPS significantly inhibited the metabolism of fipronil or nonane by HLM although CPS inhibited the metabolism of fipronil more effectively than that of nonane. CPS significantly inhibited the metabolism of fipronil by CYP3A4 as well as the metabolism of nonane by CYP2B6. In both cases, preincubation with CPS caused greater inhibition than coincubation, suggesting that the inhibition is mechanism based.

Utility of Squeeze Flow in the Food Industry

NASA Astrophysics Data System (ADS)

Huang, T. A.

2008-07-01

Squeeze flow for obtaining shear viscosity on Newtonian and non-Newtonian fluids has long been established in the literature. Rotational shear flow using cone/plate, a set of parallel plates, or concentric cylinders all develop wall slip, shear fracture, or instability on food related materials such as peanut butter or mayonnaise. Viscosity data obtained using any one of the above mentioned set-ups is suspect or potentially results in significant error. They are unreliable to support or predict the textural differences perceived by consumer evaluation. RMS-800, from Rheometrics Inc., was employed to conduct the squeezing flow under constant speeds on a set of parallel plates. Viscosity data, over a broad range of shear rates, is compared between Hellmann's real (HRM) and light mayonnaise (HLM). The Consistency and shear-thinning indices, as defined in the Power-Law Model, were determined. HRM exhibits a more pronounced shear-thinning when compared to HLM yet the Consistency of HRM is significantly higher. Sensory evaluation by a trained expert panel ranked that adhesiveness and cohesiveness of HLM are significantly higher. It appears that the degree of shear thinning is one of the key rheological parameters in predicting the above mentioned difference in textural attributes. Error involved in determining viscosity from non-parallelism between two plates can be significant to affect the accuracy of the viscosity, in particular, shear-thinning index. Details are a subject for the next presentation. Nevertheless, the method is proven to be fast, rugged, simple, and reliable. It can be developed as a QC tool.

Factors influencing the occupational injuries of physical therapists in Taiwan: A hierarchical linear model approach.

PubMed

Tao, Yu-Hui; Wu, Yu-Lung; Huang, Wan-Yun

2017-01-01

The evidence literature suggests that physical therapy practitioners are subjected to a high probability of acquiring work-related injuries, but only a few studies have specifically investigated Taiwanese physical therapy practitioners. This study was conducted to determine the relationships among individual and group hospital-level factors that contribute to the medical expenses for the occupational injuries of physical therapy practitioners in Taiwan. Physical therapy practitioners in Taiwan with occupational injuries were selected from the 2013 National Health Insurance Research Databases (NHIRD). The age, gender, job title, hospitals attributes, and outpatient data of physical therapy practitioners who sustained an occupational injury in 2013 were obtained with SAS 9.3. SPSS 20.0 and HLM 7.01 were used to conduct descriptive and hierarchical linear model analyses, respectively. The job title of physical therapy practitioners at the individual level and the hospital type at the group level exert positive effects on per person medical expenses. Hospital hierarchy moderates the individual-level relationships of age and job title with the per person medical expenses. Considering that age, job title, and hospital hierarchy affect medical expenses for the occupational injuries of physical therapy practitioners, we suggest strengthening related safety education and training and elevating the self-awareness of the risk of occupational injuries of physical therapy practitioners to reduce and prevent the occurrence of such injuries.

Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes

PubMed Central

2011-01-01

Background Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp., Lepidium meyenii and L-Leucine on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants. Methods Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucine mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits. Results HLM tested in these in vitro studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β. Conclusion Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery. PMID:21854562

Cross (Unit)-Level Effects of Cohesion on Relationships of Suicide Thoughts to Combat Exposure, Postdeployment Stressors, and Postdeployment Social Support.

PubMed

Griffith, James

2015-01-01

A behavioral health concern for the US military has been suicide, largely due to its increased prevalence in the last several years during US involvement in the Iraq and Afghanistan wars. Using hierarchical linear modeling (HLM), the present study examined relationships among combat exposure, postdeployment stressors, social support, and unit cohesion. Survey data were obtained from 4,567 soldiers who were members of 50 company-sized units. At the individual level, combat exposure and postdeployment stressors were associated with suicidal thoughts. Postdeployment social support was associated with fewer suicidal thoughts. There was no evidence of the stress-buffering effect of social support. At the group level, reduced risk for suicidal thoughts was associated with units having higher than average cohesion. Reduced risk for suicidal thoughts in conjunction with combat experiences was observed in units having higher than average cohesion, though not reaching a traditional level of statistical significance.

Malaysian and Singaporean students' affective characteristics and mathematics performance: evidence from PISA 2012.

PubMed

Thien, Lei Mee; Ong, Mei Yean

2015-01-01

This paper attempts to identify the extent to which the affective characteristics of Malaysian and Singaporean students' attainment compared to the OECD average in Programme for International Student Assessment (PISA) 2012, and examine the influence of students' affective characteristics, gender, and their socioeconomic status on mathematics performance at both student and school levels. Sample consisted of 5197 and 5546 15-year-old Malaysian and Singaporean students. Data were analysed using hierarchical linear modelling approach with HLM 7.0 software. Results showed that the Index of economic, social, and cultural status (ESCS), mathematics self-efficacy, and mathematics anxiety have significant effects on mathematics performance in Malaysia and Singapore at the student level. Proportion of boys at the school level has no significant effects on mathematics performance for both Malaysian and Singaporean students. ESCS mean at the school level has positive and significant effects on mathematics performance in Malaysia, but not in Singapore. Limitations, implications, and future studies were discussed.

Less invasive coronary artery revascularization with a minimized extracorporeal circulation system: preliminary results of a comparative study with off-pump-procedures

PubMed Central

2013-01-01

Background Coronary-artery-bypass-grafting (CABG) with conventional extracorporeal circulation (CECC) is associated with adverse effects such as systemic inflammatory response leading to a decrease in systemic vascular resistance and hemodynamic instability. Modern "less invasive" procedures have been established recently which potentially avoid negative side effects of CECC. The aim of this study was to compare perioperative outcome following coronary revascularization using either a minimized extracorporeal circuit (Mini-HLM) or off-pump technique (OPCAB). Methods In this prospective ethics-approved trial, 120 patients referred for CABG were randomly assigned either to off-pump coronary artery bypass (OPCAB) or to a Mini-HLM procedure. Patient demographics, preoperative characteristics and extensive postoperative outcome were analyzed for both groups. Hemodynamic data were measured at seven time points perioperatively. Results Operation-time was longer in the Mini-HLM group (178,3 ± 32,9 min) compared to OPCAB (133,2 ± 32,7 min, p < 0,001) with higher graft numbers in Mini-HLM group (3,11 ± 0,7 vs. 1,78 ± 0,7, p < 0.001). There were no significant differences in perioperative hemodynamic criteria, catecholaminergic support, hospital (p = 0,534) and intensive care unit stay (p = 0,880), ventilation time (p = 0,113), blood loss (p = 0,570), transfusion requirements, postoperative atrial fibrillation rate (p = 0,706) and neurocognitive disturbance (p = 0,297). No deaths and no myocardial infarctions were observed. Conclusions Coronary revascularisation with Mini-HLM represents a suitable and "less invasive" procedure which achieves all benefits of OPCAB but may allow for less demanding revascularisation than OPCAB in special patients with complex coronary anatomy and can therefore be used both on a routine basis and in all "conversion" cases of OPCAB. PMID:23577663

Consumer Health Informatics: Empowering Healthy-Living-Seekers Through mHealth.

PubMed

Faiola, Anthony; Holden, Richard J

People are at risk from noncommunicable diseases (NCD) and poor health habits, with interventions like medications and surgery carrying further risk of adverse effects. This paper addresses ways people are increasingly moving to healthy living medicine (HLM) to mitigate such health threats. HLM-seekers increasingly leverage mobile technologies that enable control of personal health information, collaboration with clinicians/other agents to establish healthy living practices. For example, outcomes from consumer health informatics research include empowering users to take charge of their health through active participation in decision-making about healthcare delivery. Because the success of health technology depends on its alignment/integration with a person's sociotechnical system, we introduce SEIPS 2.0 as a useful conceptual model and analytic tool. SEIPS 2.0 approaches human work (i.e., life's effortful activities) within the complexity of the design and implementation of mHealth technologies and their potential to emerge as consumer-facing NLM products that support NCDs like diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.

PubMed

Albuquerque, Kevin; Tell, Dina; Lobo, Philip; Millbrandt, Linda; Mathews, Herbert L; Janusek, Linda Witek

2012-06-18

This pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery. Women (N = 30) with early-stage breast cancer received either PBRT, Mammosite brachytherapy at dose of 34 Gy 10 fractions/5 days, (N = 15) or WBRT, 3-D conformal techniques at dose of 50 Gy +10 Gy Boost/30 fractions, (N = 15). Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need. Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy. At each assessment, blood was obtained for determination of NKCA and the following instruments were administered: Perceived Stress Scale (PSS), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Functional Assessment of Cancer Therapy-General (FACT-G). Hierarchical linear modeling (HLM) was used to evaluate group differences in initial outcomes and change in outcomes over time. Fatigue (FACT-F) levels, which were similar prior to radiation therapy, demonstrated a significant difference in trajectory. Women who received PBRT reported progressively lower fatigue; conversely fatigue worsened over time for women who received WBRT. No difference in perceived stress was observed between women who received PBRT or WBRT. Both groups of women reported similar levels of quality of life (FACT-G) prior to initiation of radiation therapy. However, HLM analysis revealed significant group differences in the trajectory of quality of life, such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy; whereas women receiving WBRT showed a decreasing trajectory. NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy. Compared to WBRT, PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy. Additionally, better quality of life predicts higher NKCA against tumor targets, emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy.

Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems.

PubMed

Pu, Qiang-Hong; Shi, Liang; Yu, Chao

2015-03-01

1.Gallic acid is a main polyphenol in various fruits and plants. Inhibitory characteristics of gallic acid on CYP3A4 were still unclear. The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. 2.Gallic acid caused concentration-dependent loss of CYP3A4 activity with IC50 values of 615.2 μM and 669.5 μM in HLM and rCYP3A4 systems, respectively. IC50-shift experiments showed that pre-incubation with gallic acid in the absence of NADPH contributed to 12- or 14-fold reduction of IC50 in HLM and rCYP3A4 systems, respectively, supporting a time-dependent inhibition. In HLM, time-dependent inactivation variables KI and Kinact were 485.8 μM and 0.05 min(-1), respectively. 3.Compared with the presence of NADPH, pre-incubation of gallic acid in the absence of NADPH markedly increased its inhibitory effects in HLM and rCYP3A4 systems. Those results indicate that CYP3A4 inactivation by gallic acid was independent on NADPH and was mainly mediated its oxidative products. 4.In conclusion, we showed that gallic acid weakly and time-dependently inactivated CYP3A4 via its oxidative products.

Strategies for Determining Correct Cytochrome P450 Contributions in Hepatic Clearance Predictions: In Vitro-In Vivo Extrapolation as Modelling Approach and Tramadol as Proof-of Concept Compound.

PubMed

T'jollyn, Huybrecht; Snoeys, Jan; Van Bocxlaer, Jan; De Bock, Lies; Annaert, Pieter; Van Peer, Achiel; Allegaert, Karel; Mannens, Geert; Vermeulen, An; Boussery, Koen

2017-06-01

Although the measurement of cytochrome P450 (CYP) contributions in metabolism assays is straightforward, determination of actual in vivo contributions might be challenging. How representative are in vitro for in vivo CYP contributions? This article proposes an improved strategy for the determination of in vivo CYP enzyme-specific metabolic contributions, based on in vitro data, using an in vitro-in vivo extrapolation (IVIVE) approach. Approaches are exemplified using tramadol as model compound, and CYP2D6 and CYP3A4 as involved enzymes. Metabolism data for tramadol and for the probe substrates midazolam (CYP3A4) and dextromethorphan (CYP2D6) were gathered in human liver microsomes (HLM) and recombinant human enzyme systems (rhCYP). From these probe substrates, an activity-adjustment factor (AAF) was calculated per CYP enzyme, for the determination of correct hepatic clearance contributions. As a reference, tramadol CYP contributions were scaled-back from in vivo data (retrograde approach) and were compared with the ones derived in vitro. In this view, the AAF is an enzyme-specific factor, calculated from reference probe activity measurements in vitro and in vivo, that allows appropriate scaling of a test drug's in vitro activity to the 'healthy volunteer' population level. Calculation of an AAF, thus accounts for any 'experimental' or 'batch-specific' activity difference between in vitro HLM and in vivo derived activity. In this specific HLM batch, for CYP3A4 and CYP2D6, an AAF of 0.91 and 1.97 was calculated, respectively. This implies that, in this batch, the in vitro CYP3A4 activity is 1.10-fold higher and the CYP2D6 activity 1.97-fold lower, compared to in vivo derived CYP activities. This study shows that, in cases where the HLM pool does not represent the typical mean population CYP activities, AAF correction of in vitro metabolism data, optimizes CYP contributions in the prediction of hepatic clearance. Therefore, in vitro parameters for any test compound, obtained in a particular batch, should be corrected with the AAF for the respective enzymes. In the current study, especially the CYP2D6 contribution was found, to better reflect the average in vivo situation. It is recommended that this novel approach is further evaluated using a broader range of compounds.

Relationships Among Teacher Preparedness and Instructional Approaches to Secondary Student Achievement in STEM: A Secondary Analysis of TIMSS Data

NASA Astrophysics Data System (ADS)

Miller-Ricks, Karen A.

Educational reform efforts in Science, Technology, Engineering, Math (STEM) place emphasis on teachers as conduits for student achievement. The purpose of this study was to use TIMSS 2011 data to examine relationships between Science-Technology-Society (STS) instructional practices (student-centered instruction established to promote learning through real-world applications) teacher preparedness, and student achievement and identify variations of achievement between and among eighth-grade science and math classes. The research was framed by both Harper's Anti-Deficit Achievement Theory and Bronfenbrenner's Ecological Systems Theory (BEST). 501 U.S. schools contributed to the TIMSS 2011 data from both the teacher questionnaires and student booklets. Chi-Square, Spearman Correlation, and 2-level hierarchical linear modeling (HLM) were used to analyze data about teachers' preparedness to teach science and math, frequency of using STS instructional practices, and student achievement. The chi-square null hypothesis for math teachers was rejected, providing the assumption that there was an association between the frequency of using STS instruction in math and teacher preparedness. However, the chi-square null hypothesis for science teachers failed to be rejected, providing the assumption that there was no significant association between the frequency of using STS instruction in science and science teacher preparedness. The Spearman Correlation revealed statistically positively significant differences between STS instruction and science achievement, as well as between teacher preparedness and science achievement. The HLM results suggested that 33% of the variance of mathematics achievement was at the individual level and 66% was at the group level. The results for science teachers suggested that 54% of the variance of science achievement was at the individual level and 46% of the variance was at the group level. The data findings support the conclusion that secondary STEM teachers who are more prepared to teach within the STEM content domains and implement STS instructional practices into lessons have higher achievement scores.

The Effects of a Mass Media HIV-Risk Reduction Strategy on HIV-Related Stigma and Knowledge Among African American Adolescents

PubMed Central

Valois, Robert F.; DiClemente, Ralph J.; Carey, Michael P.; Stanton, Bonita; Romer, Daniel; Fletcher, Faith; Farber, Naomi; Brown, Larry K.; Vanable, Peter A.; Salazar, Laura F.; Juzang, Ivan; Fortune, Thierry

2015-01-01

Abstract HIV-related stigma undermines HIV prevention, testing, and treatment. Multipronged risk-reduction strategies may reduce stigma among African American adolescents. To test the effectiveness of a risk-reduction strategy in addressing stigma, 1613 African American adolescents from four mid-sized cities participated in a randomized control trial. Participants received a sexual-risk reduction [Focus on Youth (FOY)] or general health curriculum [Promoting Health Among Teens (PHAT)]. Two cities received a culturally-tailored media intervention. Participants completed baseline, 3-, 6-, and 12-month surveys to measure HIV-related stigma and knowledge. Analysis of covariance tested for stigma and knowledge differences by media city status and curriculum/media city status (PHAT media vs. PHAT non-media, FOY media vs. FOY non-media; FOY media vs. PHAT media; FOY non-media vs. PHAT non-media) at each measurement. Hierarchical linear modeling (HLM) determined stigma and knowledge differences over time. Media participants demonstrated greater HIV-related knowledge (p<0.10) at 6 months and lower stigma at 3 months (p<0.10). FOY media participants had lower 3-month (p<0.05) and 12-month (p<0.10) stigma scores than non-media FOY participants. FOY media and non-media participants had greater knowledge than PHAT for all intervals after baseline. FOY media had lower stigma than PHAT media after baseline for all intervals after baseline. HLM indicated greater knowledge slopes for the media group (p<0.05). FOY media participants had greater knowledge slopes (p<0.05) relative to non-media FOY participants and media PHAT participants (p<0.01). A combination of a HIV risk-reduction curriculum and culturally-tailored media demonstrated some effectiveness in reducing stigma. Future use of media in HIV-prevention should include and evaluate effects on stigma. PMID:25738952

Improving influenza vaccination rates in the workplace: a randomized trial.

PubMed

Nowalk, Mary Patricia; Lin, Chyongchiou J; Toback, Seth L; Rousculp, Matthew D; Eby, Charles; Raymund, Mahlon; Zimmerman, Richard K

2010-03-01

To minimize absenteeism resulting from influenza, employers frequently offer on-site influenza vaccination to employees. Yet the level of uptake of vaccine is low among working adults. This study was designed to increase workplace influenza vaccination rates by offering both a choice of intranasal (LAIV) and injectable (TIV) influenza vaccines to eligible employees, and an incentive for being vaccinated, and by increasing awareness of the vaccine clinic. This study used a stratified randomized cluster trial. A total of 12,222 employees in 53 U.S. companies with previous influenza vaccine clinics were examined. Control sites advertised and offered vaccine clinics as previously done. Choice sites offered LAIV or TIV and maintained their previous advertising level but promoted the choice of vaccines. Choice Plus sites increased advertising and promoted and offered a choice of vaccines and a nominal incentive. These included vaccination rates among eligible employees. Hierarchic linear modeling (HLM) was used to determine factors associated with vaccination. The overall vaccination rate increased from 39% in 2007-2008 to 46% in 2008-2009 (p<0.001). The difference in vaccination rates for LAIV was 6.5% for Choice versus Control and 9.9% for Choice Plus versus Control (both p<0.001). Rates of TIV increased by 15.9 percentage points in the Choice Plus arm versus Control for workers aged > or =50 years (p=0.024). Rates of TIV did not change in workers aged 18-49 years in either intervention arm or in workers aged > or =50 years in the Choice arm. In HLM analyses, factors significantly associated with increased vaccination were older age, female gender, previous company vaccination rate, and the Choice Plus intervention. An incentive for vaccination, an intensified advertising campaign, and offering a choice of influenza vaccines improved vaccination rates in the workplace. Copyright (c) 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Implications of a Cognitive Science Model Integrating Literacy in Science on Achievement in Science and Reading: Direct Effects in Grades 3-5 with Transfer to Grades 6-7

ERIC Educational Resources Information Center

Romance, Nancy; Vitale, Michael

2017-01-01

Reported are the results of a multiyear study in which reading comprehension and writing were integrated within an in-depth science instructional model (Science IDEAS) in daily 1.5 to 2 h daily lessons on a schoolwide basis in grades 3-4-5. Multilevel (HLM7) achievement findings showed the experimental intervention resulted in significant and…

Metabolism of methylstenbolone studied with human liver microsomes and the uPA⁺/⁺-SCID chimeric mouse model.

PubMed

Geldof, Lore; Lootens, Leen; Polet, Michael; Eichner, Daniel; Campbell, Thane; Nair, Vinod; Botrè, Francesco; Meuleman, Philip; Leroux-Roels, Geert; Deventer, Koen; Eenoo, Peter Van

2014-07-01

Anti-doping laboratories need to be aware of evolutions on the steroid market and elucidate steroid metabolism to identify markers of misuse. Owing to ethical considerations, in vivo and in vitro models are preferred to human excretion for nonpharmaceutical grade substances. In this study the chimeric mouse model and human liver microsomes (HLM) were used to elucidate the phase I metabolism of a new steroid product containing, according to the label, methylstenbolone. Analysis revealed the presence of both methylstenbolone and methasterone, a structurally closely related steroid. Via HPLC fraction collection, methylstenbolone was isolated and studied with both models. Using HLM, 10 mono-hydroxylated derivatives (U1-U10) and a still unidentified derivative of methylstenbolone (U13) were detected. In chimeric mouse urine only di-hydroxylated metabolites (U11-U12) were identified. Although closely related, neither methasterone nor its metabolites were detected after administration of isolated methylstenbolone. Administration of the steroid product resulted mainly in the detection of methasterone metabolites, which were similar to those already described in the literature. Methylstenbolone metabolites previously described were not detected. A GC-MS/MS multiple reaction monitoring method was developed to detect methylstenbolone misuse. In one out of three samples, previously tested positive for methasterone, methylstenbolone and U13 were additionally detected, indicating the applicability of the method. Copyright © 2014 John Wiley & Sons, Ltd.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

PubMed

Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N

2015-08-01

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals.

PubMed

Usmani, Khawja A; Cho, Taehyeon M; Rose, Randy L; Hodgson, Ernest

2006-09-01

Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and endogenous substrates such as estradiol (E2). It has previously been shown that E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2-hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of deployment-related and other chemicals on E2 metabolism by human liver microsomes (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2 showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein; those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450. Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4 have the greatest potential to metabolize E2. Preincubation of HLM with a variety of chemicals, including those used in military deployments, resulted in varying levels of inhibition of E2 metabolism. The greatest inhibition was observed with organophosphorus compounds, including chlorpyrifos and fonofos, with up to 80% inhibition for 2-OHE2 production. Carbaryl, a carbamate pesticide, and naphthalene, a jet fuel component, inhibited ca. 40% of E2 metabolism. Preincubation of CYP1A2 with chlorpyrifos, fonofos, carbaryl, or naphthalene resulted in 96, 59, 84, and 87% inhibition of E2 metabolism, respectively. Preincubation of CYP3A4 with chlorpyrifos, fonofos, deltamethrin, or permethrin resulted in 94, 87, 58, and 37% inhibition of E2 metabolism. Chlorpyrifos inhibition of E2 metabolism is shown to be irreversible.

Teachers' Mastery Goals: Using a Self-Report Survey to Study the Relations between Teaching Practices and Students' Motivation for Science Learning

NASA Astrophysics Data System (ADS)

Vedder-Weiss, Dana; Fortus, David

2018-02-01

Employing achievement goal theory (Ames Journal of Educational psychology, 84(3), 261-271, 1992), we explored science teachers' instruction and its relation to students' motivation for science learning and school culture. Based on the TARGETS framework (Patrick et al. The Elementary School Journal, 102(1), 35-58, 2001) and using data from 95 teachers, we developed a self-report survey assessing science teachers' usage of practices that emphasize mastery goals. We then used this survey and hierarchical linear modeling (HLM) analyses to study the relations between 35 science teachers' mastery goals in each of the TARGETS dimensions, the decline in their grade-level 5-8 students' ( N = 1.356) classroom and continuing motivation for science learning, and their schools' mastery goal structure. The findings suggest that adolescents' declining motivation for science learning results in part from a decreasing emphasis on mastery goals by schools and science teachers. Practices that relate to the nature of tasks and to student autonomy emerged as most strongly associated with adolescents' motivation and its decline with age.

Racioethnicity, community makeup, and potential employees' reactions to organizational diversity management approaches.

PubMed

Olsen, Jesse E; Martins, Luis L

2016-05-01

We draw on the values literature from social psychology and the acculturation literature from cross-cultural psychology to develop and test a theory of how signals about an organization's diversity management (DM) approach affect perceptions of organizational attractiveness among potential employees. We examine the mediating effects of individuals' merit-based attributions about hiring decisions at the organization, as well as the moderating effects of their racioethnicity and the racioethnic composition of their home communities. We test our theory using a within-subject policy-capturing experimental design that simulates organizational DM approaches, supplemented with census data for the participants' home communities. Results of hierarchical linear modeling (HLM) analyses suggest that the manipulated instrumental value for diversity leads to higher perceptions of organizational attractiveness, in part through heightened expectations of merit-based hiring decisions. Further, the manipulated assimilative and integrative DM approach signals are positively related to organizational attractiveness and the effect of integrative DM is strongest for racioethnic minorities from communities with especially high proportions of Whites and Whites from communities with especially low proportions of Whites. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data

PubMed Central

Yau, Estelle; Petersson, Carl; Dolgos, Hugues

2017-01-01

Abstract Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter‐mediated secretion (F g) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models – the ADAM, Q gut and Competing Rates – was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under‐predict human F g. Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. PMID:28152562

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data.

PubMed

Yau, Estelle; Petersson, Carl; Dolgos, Hugues; Peters, Sheila Annie

2017-04-01

Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter-mediated secretion (F g ) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models - the ADAM, Q gut and Competing Rates - was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under-predict human F g . Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g . © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd.

CYP3A4 and CYP3A5 catalyse the conversion of the N-methyl-D-aspartate (NMDA) antagonist CJ-036878 to two novel dimers.

PubMed

Emoto, C; Nishida, H; Hirai, H; Iwasaki, K

2007-12-01

CJ-036878, N-(3-phenethoxybenzyl)-4-hydroxybenzamide, was developed as an antagonist of the N-methyl-D-aspartate receptor NR2B subunit. Two dimeric metabolites, CJ-047710 and CJ-047713, were identified from the incubation mixture with CJ-036878 in human liver microsomes (HLM). The identification of the enzymes involved in the formation of these dimeric metabolites was investigated in the current study. Inhibition of the formation of CJ-047710 and CJ-047713 in pooled HLM by 1-aminobenztriazole, SKF-525A, and ketoconazole were observed. Ketoconazole played a significant role in inhibiting formation of these two metabolites in a concentration-dependent manner. Recombinant CYP3A4 and CYP3A5 exhibited a markedly high activity toward the formation of CJ-047710 and CJ-047713 from CJ-036878, but the contribution of other CYP enzymes to these formations was at a very low level or negligible. The formation of CJ-047710 and CJ-047713 in pooled HLM, CYP3A4, and CYP3A5 showed sigmoid characteristics. S50 values for CJ-047710 and CJ-047713 formation in HLM were almost equivalent with those for CYP3A4 and CYP3A5. For the CYP3A enzymes, maximal clearance due to auto-activation values for CJ-047710 and CJ-047713 formation catalysed by CYP3A5 were 3.6- and 3.1-fold higher than those catalysed by CYP3A4. This is the first report that shows both CYP3A4 and CYP3A5 simultaneously contribute to dimerization through oxidative C-C and C-O coupling reactions.

An Investigation into the Prediction of in Vivo Clearance for a Range of Flavin-containing Monooxygenase Substrates.

PubMed

Jones, Barry C; Srivastava, Abhishek; Colclough, Nicola; Wilson, Joanne; Reddy, Venkatesh Pilla; Amberntsson, Sara; Li, Danxi

2017-10-01

Flavin-containing monooxygenases (FMO) are metabolic enzymes mediating the oxygenation of nucleophilic atoms such as nitrogen, sulfur, phosphorus, and selenium. These enzymes share similar properties to the cytochrome P450 system but can be differentiated through heat inactivation and selective substrate inhibition by methimazole. This study investigated 10 compounds with varying degrees of FMO involvement to determine the nature of the correlation between human in vitro and in vivo unbound intrinsic clearance. To confirm and quantify the extent of FMO involvement six of the compounds were investigated in human liver microsomal (HLM) in vitro assays using heat inactivation and methimazole substrate inhibition. Under these conditions FMO contribution varied from 21% (imipramine) to 96% (itopride). Human hepatocyte and HLM intrinsic clearance (CL int ) data were scaled using standard methods to determine the predicted unbound intrinsic clearance (predicted CL int u ) for each compound. This was compared with observed unbound intrinsic clearance (observed CL int u ) values back calculated from human pharmacokinetic studies. A good correlation was observed between the predicted and observed CL int u using hepatocytes ( R 2 = 0.69), with 8 of the 10 compounds investigated within or close to a factor of 2. For HLM the in vitro-in vivo correlation was maintained ( R 2 = 0.84) but the accuracy was reduced with only 3 out of 10 compounds falling within, or close to, twofold. This study demonstrates that human hepatocytes and HLM can be used with standard scaling approaches to predict the human in vivo clearance for FMO substrates. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Ancestry of a human endogenous retrovirus family.

PubMed Central

Mariani-Costantini, R; Horn, T M; Callahan, R

1989-01-01

The human endogenous retrovirus type II (HERVII) family of HERV genomes has been found by Southern blot analysis to be characteristic of humans, apes, and Old World monkeys. New World monkeys and prosimians lack HERVII proviral genomes. Cellular DNAs of humans, common chimpanzees, gorillas, and orangutans, but not lesser ape lar gibbons, appear to contain the HERVII-related HLM-2 proviral genome integrated at the same site (HLM-2 maps to human chromosome 1). This suggests that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids. Images PMID:2507793

Tracking chemistry self-efficacy and achievement in a preparatory chemistry course

NASA Astrophysics Data System (ADS)

Garcia, Carmen Alicia

Self-efficacy is a person's own perception about performing a task with a certain level of proficiency (Bandura, 1986). An important affective aspect of learning chemistry is chemistry self-efficacy (CSE). Several researchers have found chemistry self-efficacy to be a fair predictor of achievement in chemistry. This study was done in a college preparatory chemistry class for science majors exploring chemistry self-efficacy and its change as it relates to achievement. A subscale of CAEQ, Chemistry Attitudes and Experiences Questionnaire (developed by Dalgety et al, 2003) as well as student interviews were used to determine student chemistry self-efficacy as it changed during the course. The questionnaire was given to the students five times during the semester: in the first class and the class before each the four tests taken through the semester. Twenty-six students, both men and women, of the four major races/ethnicities were interviewed three times during the semester and events that triggered changes in CSE were followed through the interviews. HLM (hierarchical linear modeling) was used to model the results of the CSE surveys. Among the findings, women who started at significantly lower CSE than men accomplished a significant gain by the end of the semester. Blacks' CSE trends through the semester were found to be significantly different from the rest of the ethnicities.

Changing Community Readiness To Prevent The Abuse Of Inhalants And Other Harmful Legal Products In Alaska1

PubMed Central

Ogilvie, Kristen A.; Moore, Roland S.; Ogilvie, Diane C.; Johnson, Knowlton W.; Collins, David A.; Shamblen, Stephen R.

2008-01-01

This paper presents results from an application of the Community Readiness Model (CRM) as part of a multi-stage community mobilization strategy to engage community leaders, retailers, parents, and school personnel in preventing youth use of inhalants and other harmful legal products in rural Alaska. The CRM is designed to assess readiness to address a single social problem, based on a limited set of key informant interviews. In this study, researchers conducted 32 baseline and 34 post-intervention community readiness assessment interviews in four rural Alaskan communities. These interviews with key informants from the communities were coded and analyzed using CRM methods to yield readiness scores for each community. The aggregate results were analyzed using hierarchical linear modeling (HLM), and the individual community scores were analyzed in the context of the overall study. Significant positive changes in community readiness were found across six readiness dimensions as well as for the overall readiness score. Variation in the degree of changes in readiness across the four communities is attributed to differences in the intervention’s implementation. The implications of these results include the potential for CRM assessments to serve as an integral component of a community mobilization strategy and also to offer meaningful feedback to communities participating in prevention research. PMID:18392927

Inflammatory Pathway Genes Associated with Inter-Individual Variability in the Trajectories of Morning and Evening Fatigue in Patients Receiving Chemotherapy

PubMed Central

Wright, Fay; Hammer, Marilyn; Paul, Steven M.; Aouizerat, Bradley E.; Kober, Kord M.; Conley, Yvette P.; Cooper, Bruce A.; Dunn, Laura B.; Levine, Jon D.; Melkus, Gail DEramo; Miaskowski, Christine

2017-01-01

Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue. Patients completed the Lee Fatigue Scale to determine morning and evening fatigue severity a total of six times over two cycles of CTX. Using a whole exome array, 309 single nucleotide polymorphisms among the 64 candidate genes that passed all quality control filters were evaluated using hierarchical linear modeling (HLM). Based on the results of the HLM analyses, the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/signal transducers and activators of transcription (JAK/STAT, 10 genes); mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms in six genes from the cytokine (2 genes); inflammasome (2 genes); and NFkB (2 genes) pathways were associated with both morning and evening fatigue. Polymorphisms in six genes from the inflammasome (1 gene); JAK/STAT (1 gene); and NFkB (4 genes) pathways were associated with only morning fatigue. Polymorphisms in three genes from the inflammasome (2 genes) and the NFkB (1 gene) pathways were associated with only evening fatigue. Taken together, these findings add to the growing body of evidence that suggests that morning and evening fatigue are distinct symptoms. PMID:28110208

Binge eating frequency and regular eating adherence: the role of eating pattern in cognitive behavioral guided self-help.

PubMed

Zendegui, Elaina A; West, Julia A; Zandberg, Laurie J

2014-04-01

Cognitive behavioral guided self-help (CBTgsh) is an evidence-based, brief, and cost-effective treatment for eating disorders characterized by recurrent binge eating. However, more research is needed to improve patient outcomes and clarify treatment components most associated with symptom change. A main component of CBTgsh is establishing a regular pattern of eating to disrupt dietary restriction, which prior research has implicated in the maintenance of binge eating. The present study used session-by-session assessments of regular eating adherence and weekly binge totals to examine the association between binge frequency and regular eating in a sample of participants (n = 38) receiving 10 sessions of CBTgsh for recurrent binge eating. Analyses were conducted using Hierarchical Linear Modeling (HLM) to allow for data nesting, and a likelihood ratio test determined which out of three regression models best fit the data. Results demonstrated that higher regular eating adherence (3 meals and 2-3 planned snacks daily) was associated with lower weekly binge frequency in this sample, and both the magnitude and direction of the association were maintained after accounting for individual participant differences in binge and adherent day totals. Findings provide additional empirical support for the cognitive behavioral model informing CBTgsh. Possible clinical implications for treatment emphasis and sequencing in CBTgsh are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Impact of Sustainable Development Technology on a Small Economy-The Case of Energy-Saving Technology.

PubMed

Chen, Xiding; Huang, Qinghua; Huang, Weilun; Li, Xue

2018-02-08

We investigated the impact of a sustainable development technology on the macroeconomic variables in a small economy utilizing a case study with a stochastically improving energy saving technology and a stochastically increasing energy price. The results show the technological displacement effects of energy saving technology are stronger, but there are more ambiguous instantaneous returns to physical capital. However, the energy saving technology's displacement effects might not affect the conditions under which the Harberger-Laursen-Metzler (HLM) effect holds. The effects of rising energy prices on bonds are stronger, and there are more ambiguous instantaneous returns, but the conditions under which the HLM effect holds are different.

The Impact of Sustainable Development Technology on a Small Economy—The Case of Energy-Saving Technology

PubMed Central

Huang, Qinghua; Huang, Weilun; Li, Xue

2018-01-01

We investigated the impact of a sustainable development technology on the macroeconomic variables in a small economy utilizing a case study with a stochastically improving energy saving technology and a stochastically increasing energy price. The results show the technological displacement effects of energy saving technology are stronger, but there are more ambiguous instantaneous returns to physical capital. However, the energy saving technology’s displacement effects might not affect the conditions under which the Harberger-Laursen-Metzler (HLM) effect holds. The effects of rising energy prices on bonds are stronger, and there are more ambiguous instantaneous returns, but the conditions under which the HLM effect holds are different. PMID:29419788

Characterization of moclobemide N-oxidation in human liver microsomes.

PubMed

Hoskins, J; Shenfield, G; Murray, M; Gross, A

2001-07-01

1. Moclobemide underdergoes morpholine ring N-oxidation to form a major metabolite in plasma Rol2-5637. 2. The kinetics of moclobemide N-oxidation in human liver microsomes (HLM) (n = 6) have been investigated and the mixed-function oxidase enzymes catalysing this reaction have been identified using inhibition, enzyme correlation, altered pH and heat pretreatment experiments. 3. N-oxidation followed single enzyme Michealis-Menten kinetics (0.02-4.0 mm). Km app and Vmax ranged from 0.48 to 1.35 mM (mean +/- SD) 0.77 +/- 0.34 mM) and 0.22 to 2.15 nmol mg(-1) min(-1) (1.39 +/- 0.80 nmol mg(-1) respectively. 4. The N-oxidation of moclobemide strongly correlated with benzydamine N-oxidation a probe reaction for flavin-containing monoxygenase (FMO) activity (0.1 mM moclobemide, rs = 0.81, p < 0.005; 4 mM moclobemide, rs = 0.94, p = 0.0001). Correlations were observed between moclobemide N-oxidation and specific cytochromre P450 (CYP) activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 0.66, p < 0.05; 4 mM moclobemide, CYP2E1 rs = 0.56, p < 0.05). 5. The general P450 inhibitor, N-benzylimidazole, did not affect the rate of Rol2-5637 formation (0% inhibition versus control) (at 1.3 mM moclobemide. Furthermore, the rate of Ro12-5637 formation in HLM was unaffected by inhibitors Or substrates of specific P450s (< 10% inhibition versus control). 6. Heat pretreatment of HLM in the absence of NADPH (inactivating FMOs) resulted in 97% inhibition of Ro12-5637 formation. N-oxidation activity was greatest when incubated at pH 8.5. These results ilre consistent with the reaction being FMO medialtetd . 7. In conclusion, moclobemide N-oxidation activity has been observed in HLM in vitro and the reaction is predominantly catalysed by FMOs with a potentially small contribution from cytochrome P450 isoforms.

Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole.

PubMed

Zhuang, XiaoMei; Zhang, TianHong; Yue, SiJia; Wang, Juan; Luo, Huan; Zhang, YunXia; Li, Zheng; Che, JinJing; Yang, HaiYing; Li, Hua; Zhu, MingShe; Lu, Chuang

2016-12-01

Icotinib (ICO), a novel small molecule and a tyrosine kinase inhibitor, was developed and approved recently in China for non-small cell lung cancer. During screening for CYP inhibition potential in human liver microsomes (HLM), heterotropic activation toward CYP3A5 was revealed. Activation by icotinib was observed with CYP3A-mediated midazolam hydroxylase activity in HLM (∼40% over the baseline) or recombinant human CYP3A5 (rhCYP3A5) (∼70% over the baseline), but not in the other major CYPs including rhCYP3A4. When co-incubated with selective CYP3A4 inhibitor CYP3cide or monoclonal human CYP3A4 inhibitory antibody in HLM, the activation was extended to ∼60%, suggesting CYP3A5 might be the isozyme involved. Further, the relative activation was enhanced to ∼270% in rhCYP3A5 in the presence of ketoconazole. The activation was substrate and pathway dependent and observed only in the formation of 1'-OH-midazolam, and not 4-OH-midazolam, 6β-OH-testosterone, or oxidized nifedipine. The activation requires the presence of cytochrome b5 and it is only observed in the liver microsomes of dogs, monkeys, and humans, but not in rats and mice. Kinetic analyses of 1'-OH-midazolam formation showed that ICO increased the V max values in HLM and rhCYP3A5 with no significant changes in K m values. By adding CYP3cide with ICO to the incubation, the V max values increased 2-fold over the CYP3cide control. Addition of ketoconazole with ICO alone or ICO plus CYP3cide resulted in an increase in V max values and decrease in K m values compared to their controls. This phenomenon may be attributed to a new mechanism of CYP3A5 heterotropic activation, which warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

When goals diverge: Staff consensus and the organizational climate.

PubMed

Melnick, Gerald; Ulaszek, Wendy R; Lin, Hsiu-Ju; Wexler, Harry K

2009-08-01

A sample of correctional officers and prison substance abuse treatment staff collected by the National Criminal Justice Treatment Practices Survey is used to provide an exploratory study of an aspect of organizational culture consisting of consensus (agreement) among prison personnel regarding their beliefs about rehabilitation in the presence of conflicting organizational goals and aspects of the organizational climate important to change. Findings show that among those staff members responding to the survey, the belief in rehabilitation scale mean score was associated with higher levels of organizational commitment, and interdepartmental coordination. However, an hierarchical linear modeling (HLM) analysis that used an index score derived from the standard deviation for staff consensus regarding these same beliefs about rehabilitation produced a different pattern of results, showing that high levels of consensus were associated with job frustration, cynicism towards the ability of the institution to change, and lower levels of organizational commitment. The authors conclude that, although the sample may not express the beliefs of corrections officers or prison-based treatment staff at large, within the sample, consensus appeared to play a unique role in evaluating the effect of divergent goals on organizational climate as it relates to change, and warrants consideration when considering the effects of organizational climate.

The Limited Effects of Obstetrical and Neonatal Complications on Conduct and ADHD Symptoms in Middle Childhood

PubMed Central

Wagner, Anna I.; Schmidt, Nicole L.; Lemery-Chalfant, Kathryn; Leavitt, Lewis A.; Goldsmith, H. Hill

2016-01-01

Objective The purpose of this study was to examine the effects of a wide range of obstetrical and neonatal complications as well as socioeconomic variables on the behaviors characterized by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Method Data were collected on 7–8 year old twins, using multiple instruments assessing many areas of individual and family functioning. The influence of several aspects of prenatal care, labor and delivery, and early life were considered as well as indicators of socioeconomic status such as family income and maternal education. Results The observed associations were stronger for ADHD than CD symptoms and stronger for females than males. Family income and gender significantly predicted both behavioral outcomes, while birthweight predicted ADHD symptoms only. However, the presence of ADHD and conduct symptom behaviors were not associated with an occurrence of more obstetrical or neonatal complications as indicated by hierarchical linear modeling (HLM) analyses. Conclusions By school age, behavioral problems related to inattention, impulsivity, hyperactivity, defiance, and conduct are relatively unaffected by general adversity in the neonatal and perinatal periods. PMID:19433988

Psychosocial safety climate, emotional demands, burnout, and depression: a longitudinal multilevel study in the Malaysian private sector.

PubMed

Idris, Mohd Awang; Dollard, Maureen F; Yulita

2014-07-01

This multilevel longitudinal study investigates a newly identified climate construct, psychosocial safety climate (PSC), as a precursor to job characteristics (e.g., emotional demands), and psychological outcomes (i.e., emotional exhaustion and depression). We argued that PSC, as an organizational climate construct, has cross-level effects on individually perceived job design and psychological outcomes. We hypothesized a mediation process between PSC and emotional exhaustion particularly through emotional demands. In sequence, we predicted that emotional exhaustion would predict depression. At Time 1, data were collected from employees in 36 Malaysian private sector organizations (80% responses rate), n = 253 (56%), and at Time 2 from 27 organizations (60%) and n = 117 (46%). Using hierarchical linear modeling (HLM), we found that there were cross-level effects of PSC Time 1 on emotional demands Time 2 and emotional exhaustion Time 2, but not on depression Time 2, across a 3-month time lag. We found evidence for a lagged mediated effect; emotional demands mediated the relationship between PSC and emotional exhaustion. Emotional exhaustion did not predict depression. Finally, our results suggest that PSC is an important organizational climate construct, and acts to reduce employee psychological problems in the workplace, via working conditions.

The association between workers' employability and burnout in a reorganization context: longitudinal evidence building upon the conservation of resources theory.

PubMed

De Cuyper, Nele; Raeder, Sabine; Van der Heijden, Beatrice I J M; Wittekind, Anette

2012-04-01

This longitudinal study probes the relationship between employability and burnout among employees from a company undergoing reorganization. We advanced employability as a personal resource that relates negatively to burnout. We expected that this hypothesis would hold for different operationalizations of employability, including (1) job-related and (2) transferable skills, (3) willingness to change jobs and (4) to develop competences, (5) opportunity awareness, (6) self-esteem, and (7) self-perceived employability (i.e., perceived employment opportunities). In a similar vein, we expected that the hypothesis would hold for the different dimensions of burnout; namely emotional exhaustion, depersonalization, and reduced personal accomplishment. We used longitudinal Hierarchical Linear Modeling (HLM) to test our hypotheses. Employees from a Swiss company undergoing a major reorganization were surveyed at three times with a total time lag of 19 months (Time 1: N = 287; Time 2: N = 128; Time 3: N = 107). Our results indicate that particularly self-esteem, but also job-related and transferable skills as indicators of one's employability were important predictors of burnout, with all relationships being negative. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Schooling effects on preschoolers’ self-regulation, early literacy, and language growth

PubMed Central

Skibbe, Lori E.; Connor, Carol McDonald; Morrison, Frederick J.; Jewkes, Abigail M.

2010-01-01

The present study examined the influence of schooling during children’s first and second years of preschool for children who experienced different amounts of preschool (i.e., one or two years), but who were essentially the same chronological age. Children (n = 76) were tested in the fall and spring of the school year using measures of self-regulation, decoding, letter knowledge, and vocabulary. Using hierarchical linear modeling (HLM), preschool was not associated with children’s development of self-regulation in either year. For decoding and letter knowledge, children finishing their second year of preschool had higher scores, although both groups of children grew similarly during the school year. Thus, our results suggest that the first and second years of preschool are both systematically associated with decoding and letter knowledge gains, and the effects are cumulative (two years predicted greater gains overall than did one year of preschool). Finally, children’s chronological age, and not whether they experienced one versus two years of preschool, predicted children’s vocabulary and self-regulation outcomes. Implications for preschool curricula and instruction are discussed, including the increasing emphasis on literacy learning prior to kindergarten entry and the need to address self-regulation development along with academic learning. PMID:24068856

The trajectories of overall disability in the first 5 years after moderate and severe traumatic brain injury.

PubMed

Forslund, Marit V; Roe, Cecilie; Perrin, Paul B; Sigurdardottir, Solrun; Lu, Juan; Berntsen, Svein; Andelic, Nada

2017-01-01

To assess longitudinal trajectories of overall disability after moderate-to-severe traumatic brain injury (TBI) and to examine whether those trajectories could be predicted by socio-demographic and injury characteristics. Demographics and injury characteristics of 105 individuals with moderate-to-severe TBI were extracted from medical records. At the 1-, 2-, and 5-year follow-ups, TBI-related disability was assessed by the GOSE. A hierarchical linear model (HLM) was used to examine functional outcomes up to 5 years following injury and whether those outcomes could be predicted by: time, gender, age, relationship, education, employment pre-injury, occupation, GCS, cause of injury, length of post-traumatic amnesia (PTA), CT findings and injury severity score, as well as the interactions between each of these predictors and time. Higher GOSE trajectories (lower disability) were predicted by younger age at injury and shorter PTA, as well as by the interaction terms of time*PTA and time*employment. Those who had been employed at injury decreased in disability over time, while those who had been unemployed increased in disability. The study results support the view that individual factors generally outweigh injury-related factors as predictors of disability after TBI, except for PTA.

Mass spectrometry-based proteomic analysis of human liver cytochrome(s) P450

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shrivas, Kamlesh; Mindaye, Samuel T.; Getie-Kebtie, Melkamu

2013-02-15

The major objective of personalized medicine is to select optimized drug therapies and to a large degree such mission is determined by the expression profiles of cytochrome(s) P450 (CYP). Accordingly, a proteomic case study in personalized medicine is provided by the superfamily of cytochromes P450. Our knowledge about CYP isozyme expression on a protein level is very limited and based exclusively on DNA/mRNA derived data. Such information is not sufficient because transcription and translation events do not lead to correlated levels of expressed proteins. Here we report expression profiles of CYPs in human liver obtained by mass spectrometry (MS)-based proteomicmore » approach. We analyzed 32 samples of human liver microsomes (HLM) of different sexes, ages and ethnicity along with samples of recombinant human CYPs. We have experimentally confirmed that each CYP isozyme can be effectively differentiated by their unique isozyme-specific tryptic peptide(s). Trypsin digestion patterns for almost 30 human CYP isozymes were established. Those findings should assist in selecting tryptic peptides suitable for MS-based quantitation. The data obtained demonstrate remarkable differences in CYP expression profiles. CYP2E1, CYP2C8 and CYP4A11 were the only isozymes found in all HLM samples. Female and pediatric HLM samples revealed much more diverse spectrum of expressed CYPs isozymes compared to male HLM. We have confirmed expression of a number of “rare” CYP (CYP2J2, CYP4B1, CYP4V2, CYP4F3, CYP4F11, CYP8B1, CYP19A1, CYP24A1 and CYP27A1) and obtained first direct experimental data showing expression of such CYPs as CYP2F1, CYP2S1, CYP2W1, CYP4A22, CYP4X1, and CYP26A1 on a protein level. - Highlights: ► First detailed proteomic analysis of CYP isozymes expression in human liver ► Trypsin digestion patterns for almost 30 human CYP isozymes established ► The data obtained demonstrate remarkable differences in CYP expression profiles. ► Female HLM samples revealed more diverse spectrum of CYP isozymes than male. ► First data showing expression of 2F1, 2S1, 2W1, 4A22, 4X1, 26A1 on a protein level.« less

Assessment of variation in the alberta context tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings

PubMed Central

2011-01-01

Background There are few validated measures of organizational context and none that we located are parsimonious and address modifiable characteristics of context. The Alberta Context Tool (ACT) was developed to meet this need. The instrument assesses 8 dimensions of context, which comprise 10 concepts. The purpose of this paper is to report evidence to further the validity argument for ACT. The specific objectives of this paper are to: (1) examine the extent to which the 10 ACT concepts discriminate between patient care units and (2) identify variables that significantly contribute to between-unit variation for each of the 10 concepts. Methods 859 professional nurses (844 valid responses) working in medical, surgical and critical care units of 8 Canadian pediatric hospitals completed the ACT. A random intercept, fixed effects hierarchical linear modeling (HLM) strategy was used to quantify and explain variance in the 10 ACT concepts to establish the ACT's ability to discriminate between units. We ran 40 models (a series of 4 models for each of the 10 concepts) in which we systematically assessed the unique contribution (i.e., error variance reduction) of different variables to between-unit variation. First, we constructed a null model in which we quantified the variance overall, in each of the concepts. Then we controlled for the contribution of individual level variables (Model 1). In Model 2, we assessed the contribution of practice specialty (medical, surgical, critical care) to variation since it was central to construction of the sampling frame for the study. Finally, we assessed the contribution of additional unit level variables (Model 3). Results The null model (unadjusted baseline HLM model) established that there was significant variation between units in each of the 10 ACT concepts (i.e., discrimination between units). When we controlled for individual characteristics, significant variation in the 10 concepts remained. Assessment of the contribution of specialty to between-unit variation enabled us to explain more variance (1.19% to 16.73%) in 6 of the 10 ACT concepts. Finally, when we assessed the unique contribution of the unit level variables available to us, we were able to explain additional variance (15.91% to 73.25%) in 7 of the 10 ACT concepts. Conclusion The findings reported here represent the third published argument for validity of the ACT and adds to the evidence supporting its use to discriminate patient care units by all 10 contextual factors. We found evidence of relationships between a variety of individual and unit-level variables that explained much of this between-unit variation for each of the 10 ACT concepts. Future research will include examination of the relationships between the ACT's contextual factors and research utilization by nurses and ultimately the relationships between context, research utilization, and outcomes for patients. PMID:21970404

The developmental association of relationship quality, hormonal contraceptive choice and condom non-use among adolescent women.

PubMed

Sayegh, M Aaron; Fortenberry, J Dennis; Shew, Marcia; Orr, Donald P

2006-09-01

Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.

Emotional insecurity in the family and community and youth delinquency in Northern Ireland: a person-oriented analysis across five waves

PubMed Central

Cummings, E. Mark; Taylor, Laura K.; Merrilees, Christine E.; Goeke-Morey, Marcie C.; Shirlow, Peter

2015-01-01

Background Over one billion children are exposed worldwide to political violence and armed conflict. Currently, conclusions about bases for adjustment problems are qualified by limited longitudinal research from a process-oriented, social-ecological perspective. In this study, we examined a theoretically-based model for the impact of multiple levels of the social ecology (family, community) on adolescent delinquency. Specifically, this study explored the impact of children's emotional insecurity about both the family and community on youth delinquency in Northern Ireland. Methods In the context of a five-wave longitudinal research design, participants included 999 mother–child dyads in Belfast (482 boys, 517 girls), drawn from socially-deprived, ethnically-homogenous areas that had experienced political violence. Youth ranged in age from 10 to 20 and were 12.18 (SD = 1.82) years old on average at Time 1. Findings The longitudinal analyses were conducted in hierarchical linear modeling (HLM), allowing for the modeling of interindividual differences in intraindividual change. Intraindividual trajectories of emotional insecurity about the family related to children's delinquency. Greater insecurity about the community worsened the impact of family conflict on youth's insecurity about the family, consistent with the notion that youth's insecurity about the community sensitizes them to exposure to family conflict in the home. Conclusions The results suggest that ameliorating children's insecurity about family and community in contexts of political violence is an important goal toward improving adolescents' well-being, including reduced risk for delinquency. PMID:25981614

Children, Death, and the Media

ERIC Educational Resources Information Center

Dobson, Joanne

1977-01-01

The author asserts that children's literature, such as books, fairy tales, and contemporary classics, has contributed more to the development of healthy attitudes toward aging and dying than has television. (Author/HLM)

Validation of Reported Whole-Grain Intake from a Web-Based Dietary Record against Plasma Alkylresorcinol Concentrations in 8- to 11-Year-Olds Participating in a Randomized Controlled Trial.

PubMed

Biltoft-Jensen, Anja; Damsgaard, Camilla T; Andersen, Elisabeth W; Ygil, Karin H; Andersen, Rikke; Ege, Majken; Christensen, Tue; Thorsen, Anne-Vibeke; Tetens, Inge; Wu, Huaxing; Landberg, Rikard

2016-02-01

Whole-grain (WG) intake is important for human health, but accurate intake estimation is challenging. Use of a biomarker for WG intake provides a possible way to validate dietary assessment methods. Our aim was to validate WG intake from 2 diets reported by children, using plasma alkylresorcinol (AR) concentrations, and to investigate the 3-mo reproducibility of AR concentrations and reported WG intake. AR concentrations were analyzed in fasting blood plasma samples, and WG intake was estimated in a 7-d web-based diary by 750 participants aged 8-11 y in a 2 school meal × 3 mo crossover trial. Reported WG intake and plasma AR concentrations were compared when children ate their usual bread-based lunch (UBL) and when served a hot lunch meal (HLM). Correlations and cross-classification were used to rank subjects according to intake. The intraclass correlation coefficients (ICCs) between subjects' measurements at baseline and after the UBL were used to assess reproducibility. Correlations between reported WG wheat + rye intake and plasma AR were 0.40 and 0.37 (P < 0.001) for the UBL and the HLM diets, and 78% and 77% were classified in the same or adjacent quartiles for the UBL and HLM diets, respectively. The ICC over 3 mo was 0.47 (95% CI: 0.38, 0.55) for plasma total ARs and 0.64 (95% CI: 0.58, 0.70) for reported WG intake. Correlations were higher when using the AR C17:0 homolog as a biomarker, reflecting rye intake instead of plasma total ARs [UBL: r = 0.47; HLM: r = 0.43, P < 0.001; ICC = 0.51 (95% CI: 0.43, 0.59)]. Self-reported WG wheat + rye intake among children showed moderate correlations with plasma AR concentrations. Substantial intraindividual variation was found in WG intake and plasma AR concentrations. The AR homolog C17:0 may be used as a biomarker for WG intake when the WG intake primarily comes from rye as in the present study. This trial was registered at clinicaltrials.gov as NCT01457794. © 2016 American Society for Nutrition.

Human Cytochrome P450 Enzyme Modulation by Gymnema sylvestre: A Predictive Safety Evaluation by LC-MS/MS.

PubMed

Rammohan, Bera; Samit, Karmakar; Chinmoy, Das; Arup, Saha; Amit, Kundu; Ratul, Sarkar; Sanmoy, Karmakar; Dipan, Adhikari; Tuhinadri, Sen

2016-07-01

Traditionally GS is used to treat diabetes mellitus. Drug-herb interaction of GS via cytochrome P450 enzyme system by substrate cocktail method using HLM has not been reported. To evaluate the in-vitro modulatory effects of GS extracts (aqueous, methanol, ethyl acetate, chloroform and n -hexane) and deacylgymnemic acid (DGA) on human CYP1A2, 2C8, 2C9, 2D6 and 3A4 activities in HLM. Probe substrate-based LCMS/MS method was established for all CYPs. The metabolite formations were examined after incubation of probe substrates with HLM in the presence or absence of extracts and DGA. The inhibitory effects of GS extracts and DGA were characterized with kinetic parameters IC50 and Ki values. GS extracts showed differential effect on CYP activities in the following order of inhibitory potency: ethyl acetate > Chloroform > methanol > n -hexane > aqueous > DGA. This differential effect was observed against CYP1A2, 2C9 and less on CYP3A4 and 2C8 but all CYPs were unaffected by aqueous extract and DGA. The ethyl acetate and chloroform extract exhibited moderate inhibition towards CYP1A2 and 3A4. The aqueous extract and DGA however showed negligible inhibition towards all five major human CYPs with very high IC50 values (>90μg/ml). The results of our study revealed that phytoconstituents contained in GS, particularly in ethyl acetate and chloroform extracts, were able to inhibit CYP1A2, 3A4 and 2C9. The presence of relatively small, lipophillic yet slightly polar compounds within the GS extracts may be attributed for inhibition activities. These suggest that the herb or its extracts should be examined for potential pharmacokinetic drug interactions in vivo . Abbreviations used: GS: Gymnema sylvestre , GSE: Gymnema sylvestre extract, DGA: deacyl gymnemic acid, CYP: cytochrome P450, DMSO: dimethylsulphoxide, HLM: human liver microsomes, LC-MS/MS: liquid chromatography tandem mass spectroscopy, NADPH: reduced nicotinamide adeninedinucleotide phosphate, NRS: nicotinamide adeninedinucleotide phosphate regenerating system, CHE: chloroform extract, EAE: ethyl acetate extract, NHE- n -hexane extract, AE: aqueous extract, ME: methanol extract.

Address By Frances "Sissy" Farenthold

ERIC Educational Resources Information Center

Farenthold, Frances

1978-01-01

Discusses the need for child advocates in the schools and the issues presented in two books entitled "The Plug-In Drug" and "All Our Children". Presented at the IAPPW Convention, Houston, Texas, 1977. (Author/HLM)

Strengthening STEM performance and persistence: Influence of undergraduate teaching assistants on entry-level STEM students

NASA Astrophysics Data System (ADS)

Philipp, Stephanie B.

Increasing retention of students in science, technology, engineering, or mathematics (STEM) programs of study is a priority for many colleges and universities. This study examines an undergraduate teaching assistant (UTA) program implemented in a general chemistry course for STEM majors to provide peer learning assistance to entrylevel students. This study measured the content knowledge growth of UTAs compared to traditional graduate teaching assistants (GTAs) over the semester, and described the development of peer learning assistance skills of the UTAs as an outcome of semesterlong training and support from both science education and STEM faculty. Impact of the UTA program on final exam grades, persistence of students to enroll in the next chemistry course required by their intended major, and STEM identity of students were estimated. The study sample comprised 284 students in 14 general chemistry recitation sections led by six UTAs and 310 students in 15 general chemistry recitation sections led by three traditional GTAs for comparison. Results suggested that both UTAs and GTAs made significant learning gains in general chemistry content knowledge, and there was no significant difference in content knowledge between UTA and GTA groups. Student evaluations, researcher observations, and chemistry faculty comments confirm UTAs were using the learning strategies discussed in the semester-long training program. UTA-led students rated their TAs significantly higher in teaching quality and student care and encouragement, which correlated with stronger STEM recognition by those students. The results of hierarchical linear model (HLM) analysis showed little variance in final exam grades explained by section-level variables; most variance was explained by student-level variables: mathematics ACT score, college GPA, and intention to enroll in the next general chemistry course. Students having higher college GPAs were helped more by having a UTA. Results from logistic regression of persistence outcome variable showed that students are three times more likely to persist to CHEM 202 if they had a UTA in CHEM 201. Other positive predictors of retention included having strong college grades, and having strong ACT math scores. Coupled with HLM analysis result that UTAs were more effective at helping students with higher college GPAs achieve higher grades, the stronger persistence of UTA-led students showed that the UTA program is an effective program for retention of introductory-level students in STEM majors.

A multilevel study of the impact of project manager's leadership on extra-role performance of project team members

NASA Astrophysics Data System (ADS)

Shokory, Suzyanty Mohd; Suradi, Nur Riza Mohd

2018-04-01

The current study examines the impact of transformational and transactional leadership of project manager on the extra-role performance of project team members. In addition, this study also identifies factor dominant to extra-role performance of project team members when the transformational and transactional leadership of project managers are analyzed simultaneously. The study involved 175 of project team members from 35 project teams (each project team consists of different contracting companies registered in the Selangor (N = 175 from 35 contractors company). A multilevel analysis with hierarchical linear modeling (HLM) approach was used in this study. The analysis showed that transformational and transactional leadership of the project manager is a positive significant with extra-role performance project team members when analyzed separately. However when the two constructs (transformational leadership and transactional leadership of project manager) were analyzed simultaneously, transformational leadership was found to have more impact on extra-role performance project team members compared to transactional leadership. These findings explained that although transformational and transactional leadership of project managers can improve extra-role performance project team members, but this study has proved that transformational leadership of project managers affect extra-role performance project team members more as compared to transactional leadership.

The effects of the ARC organizational intervention on caseworker turnover, climate, and culture in children's service systems.

PubMed

Glisson, Charles; Dukes, Denzel; Green, Philip

2006-08-01

This study examines the effects of the Availability, Responsiveness, and Continuity (ARC) organizational intervention strategy on caseworker turnover, climate, and culture in a child welfare and juvenile justice system. Using a pre-post, randomized blocks, true experimental design, 10 urban and 16 rural case management teams were randomly assigned to either the ARC organizational intervention condition or to a control condition. The culture and climate of each case management team were assessed at baseline and again after the one-year organizational intervention was completed. In addition, caseworker turnover was assessed by identifying caseworkers on the sampled teams who quit their jobs during the year. Hierarchical Linear Models (HLM) analyses indicate that the ARC organizational intervention reduced the probability of caseworker turnover by two-thirds and improved organizational climate by reducing role conflict, role overload, emotional exhaustion, and depersonalization in both urban and rural case management teams. Organizational intervention strategies can be used to reduce staff turnover and improve organizational climates in urban and rural child welfare and juvenile justice systems. This is important because child welfare and juvenile justice systems in the U.S.A. are plagued by high turnover rates, and there is evidence that high staff turnover and poor organizational climates negatively affect service quality and outcomes in these systems.

Mammography screening trends: the perspective of African American women born pre/post World War II.

PubMed

Williams, Karen Patricia; Mabiso, Athur; Lo, Yun-Jia; Penner, Louis A

2010-06-01

Researchers have traditionally combined aging women (aged > or =50 years) when reporting their mammography use. This may inadvertently mask important cohort effects in mammography use, which are likely to result from distinct personal life experiences and generational differences. Using the Health and Retirement Study samples of 1998, 2000, and 2004, we examined cohort differences in mammography use between African American women born before 1946 (non-baby boomers) and those born in 1946 to 1953 (baby boomers). Between 1998 and 2004, screening rates for non-baby boomers declined, while those for baby boomers remained relatively steady. Hierarchical linear modeling (HLM) analyses suggest that while screening rates decreased with age (OR, 0.957; 95% CI, 0.947-0.968) cohort effects may have partially reversed the age effect, with non-baby boomers having an increased likelihood of receiving a mammogram compared to baby boomers (OR, 1.697; 95% CI, 1.278-2.254). Because African American women are diagnosed at later stages of breast cancer, documentation of cohort differences in mammography use among older African American women is important as health care professionals design intervention programs that are maximally effective for women from different cohorts. This is particularly critical as more African American women in the baby boomer cohort become part of the aging population.

The organizational social context of mental health services and clinician attitudes toward evidence-based practice: a United States national study

PubMed Central

2012-01-01

Background Evidence-based practices have not been routinely adopted in community mental health organizations despite the support of scientific evidence and in some cases even legislative or regulatory action. We examined the association of clinician attitudes toward evidence-based practice with organizational culture, climate, and other characteristics in a nationally representative sample of mental health organizations in the United States. Methods In-person, group-administered surveys were conducted with a sample of 1,112 mental health service providers in a nationwide sample of 100 mental health service institutions in 26 states in the United States. The study examines these associations with a two-level Hierarchical Linear Modeling (HLM) analysis of responses to the Evidence-Based Practice Attitude Scale (EBPAS) at the individual clinician level as a function of the Organizational Social Context (OSC) measure at the organizational level, controlling for other organization and clinician characteristics. Results We found that more proficient organizational cultures and more engaged and less stressful organizational climates were associated with positive clinician attitudes toward adopting evidence-based practice. Conclusions The findings suggest that organizational intervention strategies for improving the organizational social context of mental health services may contribute to the success of evidence-based practice dissemination and implementation efforts by influencing clinician attitudes. PMID:22726759

Daily diary study of personality disorder traits: Momentary affect and cognitive appraisals in response to stressful events.

PubMed

Jarnecke, Amber M; Miller, Michelle L; South, Susan C

2017-01-01

Difficulties in emotional expression and emotion regulation are core features of many personality disorders (PDs); yet, we know relatively little about how individuals with PDs affectively respond to stressful situations. The present study seeks to fill this gap in the literature by examining how PD traits are associated with emotional responses to subjective daily stressors, while accounting for cognition and type of stressor experienced (interpersonal vs. noninterpersonal). PD features were measured with the Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2) diagnostic scores. Participants (N = 77) completed a 1-week experience sampling procedure that measured affect and cognition related to a current stressor 5 times per day. Hierarchical linear modeling (HLM) was used to examine whether and how baseline PD features, momentary cognitions, and type of stressor predicted level of affect. Results demonstrated that paranoid, borderline, and avoidant PD traits predicted negative affect beyond what could be accounted for by cognitions and type of stressor. No PD traits predicted positive affect after accounting for the effects of cognitive appraisals and type of stressor. Findings have implications for validating the role of affect in PDs and understanding how individuals with PDs react in the presence of daily hassles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

School Health Promotion Policies and Adolescent Risk Behaviors in Israel: A Multilevel Analysis.

PubMed

Tesler, Riki; Harel-Fisch, Yossi; Baron-Epel, Orna

2016-06-01

Health promotion policies targeting risk-taking behaviors are being implemented across schools in Israel. This study identified the most effective components of these policies influencing cigarette smoking and alcohol consumption among adolescents. Logistic hierarchical linear model (HLM) analysis of data for 5279 students in 95 Jewish public schools from the Health Behavior in School-Aged Children (HBSC) 2010-2011 survey in Israel enabled simultaneous estimation of the relationship between student- and school-level variables (health promotion policy) to alcohol consumption and smoking behavior. Principals of participating schools also were interviewed to ascertain their degree of adoption and implementation of a health promotion policy. Most of the variance in adolescent risk behaviors is explained by student-level variables: negative perceptions of school, lack of parental support for school issues, and more time spent with friends. Among the school-level policy measures, parental participation in health promotion intervention programs was repeatedly associated with lower rates of risk behaviors, over and above student characteristics. School health promotion policies should focus on parents' involvement in intervention programs and should seek to improve students' perceptions of school and their sense of well-being to promote resilience. Further research is needed to identify additional factors that may increase the effectiveness of school health promotion policies. © 2016, American School Health Association.

In-School Military Recruiting: An Appraisal

ERIC Educational Resources Information Center

Conrad, Tom; And Others

1977-01-01

The authors feel that military recruiting should not be permitted in schools. Counselors should help students who consider enlisting look at the positive and negative aspects of military life as well as legal contractual obligations. (Author/HLM)

Identification of AKB-48 and 5F-AKB-48 Metabolites in Authentic Human Urine Samples Using Human Liver Microsomes and Time of Flight Mass Spectrometry.

PubMed

Vikingsson, Svante; Josefsson, Martin; Gréen, Henrik

2015-01-01

The occurrence of structurally related synthetic cannabinoids makes the identification of unique markers of drug intake particularly challenging. The aim of this study was to identify unique and abundant metabolites of AKB-48 and 5F-AKB-48 for toxicological screening in urine. Investigations of authentic urine samples from forensic cases in combination with human liver microsome (HLM) experiments were used for identification of metabolites. HLM incubations of AKB-48 and 5F-AKB-48 along with 35 urine samples from authentic cases were analyzed with liquid chromatography quadrupole tandem time of flight mass spectrometry. Using HLMs 41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 were identified, principally represented by hydroxylation but also ketone formation and dealkylation. Monohydroxylated metabolites were replaced by di- and trihydroxylated metabolites within 30 min. The metabolites from the HLM incubations accounted for on average 84% (range, 67-100) and 91% (range, 71-100) of the combined area in the case samples for AKB-48 and 5F-AKB-48, respectively. While defluorinated metabolites accounted for on average 74% of the combined area after a 5F-AKB-48 intake only a few identified metabolites were shared between AKB-48 and 5F-AKB-48, illustrating the need for a systematic approach to identify unique metabolites. HLMs in combination with case samples seem suitable for this purpose. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Particularized trust, generalized trust, and immigrant self-rated health: cross-national analysis of World Values Survey.

PubMed

Kim, H H-S

2018-05-01

This research examined the associations between two types of trust, generalized and particularized, and self-rated health among immigrants. Data were drawn from the World Values Survey (WVS6), the latest wave of cross-sectional surveys based on face-to-face interviews. The immigrant subsample analyzed herein contains 3108 foreign-born individuals clustered from 51 countries. Given the hierarchically nested data, two-level logistic regressions models were estimated using HLM (Hierarchical Linear Modeling) 7.1. At the individual level, net of socio-economic and demographic factors (age, gender, marital status, education, income, neighborhood security, and subjective well-being), particularized trust was positively related to physical health (odds ratio [OR] = 1.11, P < .001). Generalized trust, however, was not a significant predictor. At the country level, based on alternative models, the aggregate measure of particularized trust was negatively associated with subjective health. The odds of being healthy were on average about 30% lower. The interdisciplinary literature on social determinants of health has largely focused on the salubrious impact of trust and other forms of social capital on physical well-being. Many previous studies based on general, not immigrant, populations also did not differentiate between generalized and particularized types of trust. Results from this study suggest that this conceptual distinction is critical in understanding how and to what extent the two are differentially related to immigrant well-being across multiple levels of analysis. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Emotional insecurity in the family and community and youth delinquency in Northern Ireland: a person-oriented analysis across five waves.

PubMed

Cummings, E Mark; Taylor, Laura K; Merrilees, Christine E; Goeke-Morey, Marcie C; Shirlow, Peter

2016-01-01

Over one billion children are exposed worldwide to political violence and armed conflict. Currently, conclusions about bases for adjustment problems are qualified by limited longitudinal research from a process-oriented, social-ecological perspective. In this study, we examined a theoretically-based model for the impact of multiple levels of the social ecology (family, community) on adolescent delinquency. Specifically, this study explored the impact of children's emotional insecurity about both the family and community on youth delinquency in Northern Ireland. In the context of a five-wave longitudinal research design, participants included 999 mother-child dyads in Belfast (482 boys, 517 girls), drawn from socially-deprived, ethnically-homogenous areas that had experienced political violence. Youth ranged in age from 10 to 20 and were 12.18 (SD = 1.82) years old on average at Time 1. The longitudinal analyses were conducted in hierarchical linear modeling (HLM), allowing for the modeling of interindividual differences in intraindividual change. Intraindividual trajectories of emotional insecurity about the family related to children's delinquency. Greater insecurity about the community worsened the impact of family conflict on youth's insecurity about the family, consistent with the notion that youth's insecurity about the community sensitizes them to exposure to family conflict in the home. The results suggest that ameliorating children's insecurity about family and community in contexts of political violence is an important goal toward improving adolescents' well-being, including reduced risk for delinquency. © 2015 Association for Child and Adolescent Mental Health.

Size- and time-dependent alteration in metabolic activities of human hepatic cytochrome P450 isozymes by gold nanoparticles via microsomal coincubations

NASA Astrophysics Data System (ADS)

Ye, Meiling; Tang, Ling; Luo, Mengjun; Zhou, Jing; Guo, Bin; Liu, Yangyuan; Chen, Bo

2014-11-01

Nano-sized particles are known to interfere with drug-metabolizing cytochrome P450 (CYP) enzymes, which can be anticipated to be a potential source of unintended adverse reactions, but the mechanisms underlying the inhibition are still not well understood. Herein we report a systematic investigation of the impacts of gold nanoparticles (AuNPs) on five major CYP isozymes under in vitro incubations of human liver microsomes (HLMs) with tannic acid (TA)-stabilized AuNPs in the size range of 5 to 100 nm. It is found that smaller AuNPs show more pronounced inhibitory effects on CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in a dose-dependent manner, while 1A2 is the least susceptible to the AuNP inhibition. The size- and dose-dependent CYP-specific inhibition and the nonspecific drug-nanogold binding in the coincubation media can be significantly reduced by increasing the concentration ratio of microsomal proteins to AuNPs, probably via a noncompetitive mode. Remarkably, AuNPs are also found to exhibit a slow time-dependent inactivation of 2D6 and 3A4 in a β-nicotinamide adenine dinucleotide 2'-phosphate reduced tetrasodium salt hydrate (NADPH)-independent manner. During microsomal incubations, UV-vis spectroscopy, dynamic light scattering, and zeta-potential measurements were used to monitor the changes in particle properties under the miscellaneous AuNP/HLM/CYP dispersion system. An improved stability of AuNPs by mixing HLM with the gold nanocolloid reveals that the stabilization via AuNP-HLM interactions may occur on a faster time scale than the salt-induced nanoaggregation by incubation in phosphate buffer. The results suggest that the AuNP induced CYP inhibition can be partially attributed to its adhesion onto the enzymes to alter their structural conformations or onto the HLM membrane therefore impairing the integral membrane proteins. Additionally, AuNPs likely block the substrate pocket on the CYP surface, depending on both the particle characteristics and the structural diversity of the isozymes. These findings may represent additional mechanisms for the differential inhibitory effects arising from the coincubated AuNPs on the metabolic activities of the hepatic CYP isozymes.

Reductive Detoxication of Arylhydroxylamine Carcinogens by Human NADH Cytochrome b5 Reductase and Cytochrome b5

PubMed Central

Kurian, Joseph R.; Chin, Nathaniel A.; Longlais, Brett J.; Hayes, Kristie L.; Trepanier, Lauren A.

2008-01-01

Heterocyclic and aromatic amine carcinogens are thought to lead to tumor initiation via the formation of DNA adducts, and bioactivation to arylhydroxylamine metabolites is necessary for reactivity with DNA. Carcinogenic arylhydroxylamine metabolites are cleared by a microsomal, NADH-dependent, oxygen-insensitive reduction pathway in humans, which may be a source of inter-individual variability in response to aromatic amine carcinogens. The purpose of this study was to characterize the identity of this reduction pathway in human liver. Based on our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxication of arylhydroxylamine carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and cytochrome b5 (cyt b5). We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2- amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and cyt b5. Specific activities were 56 to 346-fold higher in the purified system compared to human liver microsomes (HLM), with similar Michaelis-Menten constants (Km values) in both systems. The stoichiometry for b5R and cyt b5 that yielded the highest activity in the purified system was also similar to that found in native HLM (∼1:8 to 1:10). Polyclonal antisera to either b5R or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). Finally, titration of HLM into the purified b5R/cyt b5 system did not enhance the efficiency of reduction activity. We conclude that b5R and cyt b5 are together solely capable of the reduction of arylhydroxylamine carcinogens, and we further hypothesize that this pathway may be a source of individual variability with respect to cancer susceptibility following 4-ABP or PhIP exposure. PMID:17040106

Human Cytochrome P450 Enzyme Modulation by Gymnema sylvestre: A Predictive Safety Evaluation by LC-MS/MS

PubMed Central

Rammohan, Bera; Samit, Karmakar; Chinmoy, Das; Arup, Saha; Amit, Kundu; Ratul, Sarkar; Sanmoy, Karmakar; Dipan, Adhikari; Tuhinadri, Sen

2016-01-01

Background: Traditionally GS is used to treat diabetes mellitus. Drug-herb interaction of GS via cytochrome P450 enzyme system by substrate cocktail method using HLM has not been reported. Objective: To evaluate the in-vitro modulatory effects of GS extracts (aqueous, methanol, ethyl acetate, chloroform and n-hexane) and deacylgymnemic acid (DGA) on human CYP1A2, 2C8, 2C9, 2D6 and 3A4 activities in HLM. Material and Methods: Probe substrate-based LCMS/MS method was established for all CYPs. The metabolite formations were examined after incubation of probe substrates with HLM in the presence or absence of extracts and DGA. The inhibitory effects of GS extracts and DGA were characterized with kinetic parameters IC50 and Ki values. Results: GS extracts showed differential effect on CYP activities in the following order of inhibitory potency: ethyl acetate > Chloroform > methanol > n-hexane > aqueous > DGA. This differential effect was observed against CYP1A2, 2C9 and less on CYP3A4 and 2C8 but all CYPs were unaffected by aqueous extract and DGA. The ethyl acetate and chloroform extract exhibited moderate inhibition towards CYP1A2 and 3A4. The aqueous extract and DGA however showed negligible inhibition towards all five major human CYPs with very high IC50 values (>90μg/ml). Conclusion: The results of our study revealed that phytoconstituents contained in GS, particularly in ethyl acetate and chloroform extracts, were able to inhibit CYP1A2, 3A4 and 2C9. The presence of relatively small, lipophillic yet slightly polar compounds within the GS extracts may be attributed for inhibition activities. These suggest that the herb or its extracts should be examined for potential pharmacokinetic drug interactions in vivo. Abbreviations used: GS: Gymnema sylvestre, GSE: Gymnema sylvestre extract, DGA: deacyl gymnemic acid, CYP: cytochrome P450, DMSO: dimethylsulphoxide, HLM: human liver microsomes, LC-MS/MS: liquid chromatography tandem mass spectroscopy, NADPH: reduced nicotinamide adeninedinucleotide phosphate, NRS: nicotinamide adeninedinucleotide phosphate regenerating system, CHE: chloroform extract, EAE: ethyl acetate extract, NHE- n-hexane extract, AE: aqueous extract, ME: methanol extract PMID:27761064

Longitudinal associations between case management and supportive services use among black and Latina HIV-positive women in New York City.

PubMed

Halkitis, Perry N; Kupprat, Sandra A; Mukherjee, Preetika Pandey

2010-01-01

The literature analyzing the relationship between case management and supportive service use longitudinally among African American and Latina HIV-positive women is limited. This retrospective analysis of participant case management, supportive service, and medical charts sought to examine both descriptive and relational data on use of case management and supportive services over a 2-year period from 2002 to 2005 and to analyze moderating person- level or institution-level factors. The analyzed case management, supportive service, and medical charts revealed that participants interacted with their case manager four times and received 3.6 supportive services per month. Transportation, primary healthcare/medical specialists, and support groups were the services most used, with rates ranging from 70% to 80%. Using hierarchical linear modeling (HLM), the unconditional growth models showed that case management and supportive service use patterns remained constant over the 24-month period. Additionally, the multivariate unconditional model suggests a significant positive relationship between case management and supportive services. No moderation was indicated in the association between case management and supportive service use by person-level (e.g., mental illness, substance use) and institution-level (i.e., service delivery model) factors. Participants use supportive and case management services in a similar manner based on individual need. This synergistic relationship suggests that increases in either may result in retaining women in care. Implications for service delivery point to the need for skills building training for case managers, outreach workers, or system navigators to assist with short-term goals of establishing rapport and maintaining the client relationship, as this may lead to HIV-positive women accessing services. Additionally, outreach and engagement strategies need to be developed for those who typically underuse these services.

The effect of organisational context variables on employer attitudes toward employability of ex-offenders.

PubMed

Lukies, John; Graffam, Joseph; Shinkfield, Alison J

2011-05-01

The authors tested the premise that organisational context variables (i.e., size of organisation, industry type, location, and respondent's position in organisation) had significant effects on employer (N = 596) attitudes toward employability of ex-offenders. They also examined whether organisational context variables had an equivalent effect on employer attitudes to that of job-seeker criminal history and employer personal characteristics (e.g., respondent age and gender). Using linear regression (HLM 6.02a), organisational context variables were shown to have a significant effect on employer attitudes. In addition, organisational context variables had a significantly greater effect on employer attitudes than did employer personal characteristics. However, job-seeker criminal history contributed more to respondent ratings of ex-offender employability than did organisational context variables. The finding that judgements of employability are influenced by organisational context variables has implications for future research relevant to reintegration. Stakeholder attitudes toward the reintegration success of ex-offenders may be generally influenced by context variables.

An extensive cocktail approach for rapid risk assessment of in vitro CYP450 direct reversible inhibition by xenobiotic exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spaggiari, Dany, E-mail: dany.spaggiari@unige.ch

Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6,more » 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5 min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC{sub 50} values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC{sub 50} values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. - Highlights: • Ten P450 isoforms activities assessed simultaneously with only one incubation. • P450 activity levels measured using the metabolic ratio approach. • IC{sub 50} values generated 10-fold faster and cheaper compared to individual assays. • P450 2B6 was the most affected by pesticides with IC{sub 50} in the nanomolar range. • Cumulative inhibition of P450 2B6 by mixtures of four low-dosed insecticides.« less

CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide

PubMed Central

Bidstrup, Tanja Busk; Bjørnsdottir, Inga; Sidelmann, Ulla Grove; Thomsen, Mikael Søndergård; Hansen, Kristian Tage

2003-01-01

Aims To identify the principal human cytochrome P450 (CYP) enzyme(s) responsible for the human in vitro biotransformation of repaglinide. Previous experiments have identified CYP3A4 as being mainly responsible for the in vitro metabolism of repaglinide, but the results of clinical investigations have suggested that more than one enzyme may be involved in repaglinide biotransformation. Methods [14C]-Repaglinide was incubated with recombinant CYP and with human liver microsomes (HLM) from individual donors in the presence of inhibitory antibodies specific for individual CYP enzymes. Metabolites, measured by high-performance liquid chromatography (HPLC) with on-line radiochemical detection, were identified by liquid chromatography-mass spectrophotometry (LC-MS) and LC-MS coupled on-line to a nuclear magnetic resonance spectrometer (LC-MS-NMR). Results CYP3A4 and CYP2C8 were found to be responsible for the conversion of repaglinide into its two primary metabolites, M4 (resulting from hydroxylation on the piperidine ring system) and M1 (an aromatic amine). Specific inhibitory monoclonal antibodies against CYP3A4 and CYP2C8 significantly inhibited (> 71%) formation of M4 and M1 in HLM. In a panel of HLM from 12 individual donors formation of M4 and M1 varied from approximately 160–880 pmol min−1 mg−1 protein and from 100–1110 pmol min−1 mg−1 protein, respectively. The major metabolite generated by CYP2C8 was found to be M4. The rate of formation of this metabolite in HLM correlated significantly with paclitaxel 6α-hydroxylation (rs = 0.80; P = 0.0029). Two other minor metabolites were also detected. One of them was M1 and the other was repaglinide hydroxylated on the isopropyl moiety (M0-OH). The rate of formation of M4 in CYP2C8 Supersomes™ was 2.5 pmol min−1 pmol−1 CYP enzyme and only about 0.1 pmol min−1 pmol−1 CYP enzyme in CYP3A4 Supersomes™. The major metabolite generated by CYP3A4 was M1. The rate of formation of this metabolite in HLM correlated significantly with testosterone 6β-hydroxylation (rs = 0.90; P = 0.0002). Three other metabolites were identified, namely, M0-OH, M2 (a dicarboxylic acid formed by oxidative opening of the piperidine ring) and M5. The rate of M1 formation in CYP3A4 Supersomes™ was 1.6 pmol min−1 pmol−1 CYP enzyme but in CYP2C8 Super-somes™ it was only approximately 0.4 pmol min−1 pmol−1 CYP enzyme. Conclusions The results confirm an important role for both CYP3A4 and CYP2C8 in the human in vitro biotransformation of repaglinide. This dual CYP biotransformation may have consequences for the clinical pharmacokinetics and drug-drug interactions involving repaglinide if one CYP pathway has sufficient capacity to compensate if the other is inhibited. PMID:12919179

Dying and the Conspiracy of Denial

ERIC Educational Resources Information Center

Doherty, Gillian; Doherty, Joseph

1976-01-01

The first author presents her reviews on death based on her experiences as a nurse and a wife whose husband had a terminal illness. The second author presents a poem expressing his views on death while he was dying of a terminal illness. (HLM)

Organophosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Consiglio, Emma; Meneguz, Annarita; Testai, Emanuela

2005-06-15

The drug-toxicant interaction between the antidepressant imipramine (IMI) and three organophosphorothionate pesticides (OPTs), to which humans may be chronically and simultaneously exposed, has been investigated in vitro. Concentrations of IMI (2-400 {mu}M) and OPTs ({<=}10 {mu}M) representative of actual human exposure have been tested with recombinant human CYPs and human liver microsomes (HLM). The different CYPs involved in IMI demethylation to the pharmacologically active metabolite desipramine (DES) were CYP2C19 > CYP1A2 > CYP3A4. The OPTs significantly inhibited (up to >80%) IMI bioactivation catalyzed by the recombinant CYPs tested, except CYP2D6, and by HLM; the inhibition was dose-dependent and started atmore » low pesticide concentrations (0.25-2.5 {mu}M). The OPTs, having lower K {sub m} values, efficiently competed with IMI for the enzyme active site, as in the case of CYP2C19. However, with CYP1A2 and CYP3A4, a time- and NADPH-dependent mechanism-based inactivation also occurred, consistently with irreversible inhibition due to the release of the sulfur atom, binding to the active CYP during OPT desulfuration. At low IMI and OPT concentrations, lower IC50 values have been obtained with recombinant CYP1A2 (0.7-1.1 {mu}M) or with HLM rich in 1A2-related activity (2-10.8 {mu}M). The K {sub i} values (2-14 {mu}M), independent on substrate concentrations, were quite low and similar for the three pesticides. Exposure to OPTs during IMI therapeutic treatments may lead to decreased DES formation, resulting in high plasma levels of the parent drug, eventual impairment of its pharmacological action and possible onset of adverse drug reactions (ADRs)« less

Orally available stilbene derivatives as potent HDAC inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts.

PubMed

Kachhadia, Virendra; Rajagopal, Sridharan; Ponpandian, Thanasekaran; Vignesh, Radhakrishnan; Anandhan, Karnambaram; Prabhu, Daivasigamani; Rajendran, Praveen; Nidhyanandan, Saranya; Roy, Anshu Mittal; Ahamed, Fakrudeen Ali; Surendran, Narayanan; Rajagopal, Sriram; Narayanan, Shridhar; Gopalan, Balasubramanian

2016-01-27

Herein we report the synthesis and activity of a novel class of HDAC inhibitors based on 2, 3-diphenyl acrylic acid derivatives. The compounds in this series have shown to be potent HDAC inhibitors possessing significant antiproliferative activity. Further compounds in this series were subjected to metabolic stability in human liver microsomes (HLM), mouse liver microsomes (MLM), and exhibits promising stability in both. These efforts culminated with the identification of a developmental candidate (5a), which displayed desirable PK/PD relationships, significant efficacy in the xenograft models and attractive ADME profiles. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Making a Place for Space: Spatial Thinking in Social Science

PubMed Central

Logan, John R.

2013-01-01

New technologies and multilevel data sets that include geographic identifiers have heightened sociologists’ interest in spatial analysis. I review several of the key concepts, measures, and methods that are brought into play in this work, and offer examples of their application in a variety of substantive fields. I argue that the most effective use of the new tools requires greater emphasis on spatial thinking. A device as simple as an illustrative map requires some understanding of how people respond to visual cues; models as complex as HLM with spatial lags require thoughtful measurement decisions and raise questions about what a spatial effect represents. PMID:24273374

Mammography Screening Trends: The Perspective of African American Women Born Pre/Post World War II

PubMed Central

Williams, Karen Patricia; Mabiso, Athur; Lo, Yun-Jia; Penner, Louis A.

2013-01-01

Researchers have traditionally combined aging women (aged ≥50 years) when reporting their mammography use. This may inadvertently mask important cohort effects in mammography use, which are likely to result from distinct personal life experiences and generational differences. Using the Health and Retirement Study samples of 1998, 2000, and 2004, we examined cohort differences in mammography use between African American women born before 1946 (non–baby boomers) and those born in 1946 to 1953 (baby boomers). Between 1998 and 2004, screening rates for non–baby boomers declined, while those for baby boomers remained relatively steady. Hierarchical linear modeling (HLM) analyses suggest that while screening rates decreased with age (OR, 0.957; 95% CI, 0.947–0.968) cohort effects may have partially reversed the age effect, with non–baby boomers having an increased likelihood of receiving a mammogram compared to baby boomers (OR, 1.697; 95% CI, 1.278–2.254). Because African American women are diagnosed at later stages of breast cancer, documentation of cohort differences in mammography use among older African American women is important as health care professionals design intervention programs that are maximally effective for women from different cohorts. This is particularly critical as more African American women in the baby boomer cohort become part of the aging population. PMID:20575209

Cross-cultural differences in item and background memory: examining the influence of emotional intensity and scene congruency.

PubMed

Mickley Steinmetz, Katherine R; Sturkie, Charlee M; Rochester, Nina M; Liu, Xiaodong; Gutchess, Angela H

2018-07-01

After viewing a scene, individuals differ in what they prioritise and remember. Culture may be one factor that influences scene memory, as Westerners have been shown to be more item-focused than Easterners (see Masuda, T., & Nisbett, R. E. (2001). Attending holistically versus analytically: Comparing the context sensitivity of Japanese and Americans. Journal of Personality and Social Psychology, 81, 922-934). However, cultures may differ in their sensitivity to scene incongruences and emotion processing, which may account for cross-cultural differences in scene memory. The current study uses hierarchical linear modeling (HLM) to examine scene memory while controlling for scene congruency and the perceived emotional intensity of the images. American and East Asian participants encoded pictures that included a positive, negative, or neutral item placed on a neutral background. After a 20-min delay, participants were shown the item and background separately along with similar and new items and backgrounds to assess memory specificity. Results indicated that even when congruency and emotional intensity were controlled, there was evidence that Americans had better item memory than East Asians. Incongruent scenes were better remembered than congruent scenes. However, this effect did not differ by culture. This suggests that Americans' item focus may result in memory changes that are robust despite variations in scene congruency and perceived emotion.

The effects of professional development related to classroom assessment on student achievement in science

NASA Astrophysics Data System (ADS)

Mazzie, Dawn Danielle

This study investigated the relationship between students' standardized test scores in science and (a) increases in teacher assessment literacy and (b) teacher participation in a Teacher Quality Research (TQR) project on classroom assessment. The samples for these studies were teachers from underperforming schools who volunteered to take part in a professional development program in classroom assessment. School groups were randomly assigned to the treatment group. For Study 1, teachers in the treatment received professional development in classroom assessment from a trained assessment coach. Teachers in the control received no professional development. For Study 2, teachers in Treatment 1 received professional development in classroom assessment from a trained assessment coach and teachers in Treatment 2 received professional development in classroom assessment from a facilitator with one day of training. Teachers in both groups completed a measure of assessment literacy, the Teacher Quality Research Test of Assessment Literacy Skills (TQR_TALS), prior to the beginning and then again at the conclusion of the four month professional development program. A hierarchical linear model (HLM) analysis was conducted to determine the relationship between students' standardized test scores in science and (a) increases in teacher assessment literacy and (b) teacher TQR status. Based upon these analyses, the professional development program increased teachers' assessment literacy skills; however, the professional development had no significant impact on students' achievement.

An Investigation of International Science Achievement Using the OECD's PISA 2006 Data Set

NASA Astrophysics Data System (ADS)

Milford, Todd

School Effectiveness Research (SER) is concerned with efforts to better understand the effectiveness enhancing relationship between student and school variables and how these variables primarily influence academic achievement (Scheerens, 2004). However, one identified methodological shortcoming in SER is the absence of cross-cultural perspectives (Kyriakides, 2006). This is a concern as what may prove effective in one nation does not necessarily mean that it can be easily and seamlessly imported into another with the same results. This study looked at the relationships between science self-beliefs and academic achievement in science across all nations who participated in the Programme for International Student Assessment (PISA) in 2006. It further explored the variance accounted for by cultural, social and economic capital (the elements of the PISA socioeconomic status variable) for each country in PISA 2006 when predicting scientific literacy. Lastly, it used hierarchical linear modeling (HLM) to analyze data from PISA 2006 for nations experiencing high rates of immigration (i.e., Germany, Spain, Canada, the United States, Australia and New Zealand). The outcome measures used for these countries were achievement scores in science, mathematics and reading. The variables examined at the student level were science self-efficacy, science self-concept, immigrant status and socioeconomic status. The variables examined at the school level were student level aggregates of school proportion of immigrants and school socioeconomic status. In the correlation analysis between science literacy and either science self-concept of science self-efficacy, findings suggest that at the student level, students with both higher science self-concept and higher science self-efficacy tend to achieve higher academically. However, at the country level the relationship was negative between self-concept and academic achievement in science (i.e., countries with higher science self-concept tend to achieve lower on scientific literacy). When the variables that comprised each of the cultural, social, and economic components of SES were regressed on scientific literacy for the PISA sample, cultural capital accounted for 16% of the variance in scientific literacy scores compared to 14% for social capital, 13% for the composite Economic Social and Cultural Status (ESCS), and 12% for economic capital. In the HLM null models, the intraclass correlations for the all countries except for Germany ranged from .16 to .29 (Germany's was between .57 and .68). In the final models, at level-1 country, immigrant status tended to negatively influence achievement (i.e., non-native students are predicted to have lower performance), while science self-efficacy and science self-concept positively influenced achievement The student level ESCS variable also impacted achievement positively. At the school level, level-2, school mean ESCS or school proportion of immigrants were found to significantly influence the level-1 predictors; however, a good deal of variability across nations was observed. The findings from this study demonstrate that there are some distinct national differences in the relationships between science self-beliefs, immigrant status and academic achievement.

Sex, Love, and the Committed Relationship

ERIC Educational Resources Information Center

Whitaker, Carl A.; And Others

1976-01-01

Six responses are presented to the question of relationship of love, sex, and commitment as revised by Sager in the Spring 1976 issue of this journal. Theoretical and historical perspectives as well as issues of coupling, eroticism, sexual dysfunction and therapy, and psychosexual development are discussed. (HLM)

Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist.

PubMed

Usmani, Khawja A; Chen, Weichao G; Sadeque, Abu J M

2012-04-01

Lorcaserin, a selective serotonin 5-hydroxytryptamine 2C receptor agonist, is being developed for weight management. The oxidative metabolism of lorcaserin, mediated by recombinant human cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes, was examined in vitro to identify the enzymes involved in the generation of its primary oxidative metabolites, N-hydroxylorcaserin, 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin. Human CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, and FMO1 are major enzymes involved in N-hydroxylorcaserin; CYP2D6 and CYP3A4 are enzymes involved in 7-hydroxylorcaserin; CYP1A1, CYP1A2, CYP2D6, and CYP3A4 are enzymes involved in 5-hydroxylorcaserin; and CYP3A4 is an enzyme involved in 1-hydroxylorcaserin formation. In 16 individual human liver microsomal preparations (HLM), formation of N-hydroxylorcaserin was correlated with CYP2B6, 7-hydroxylorcaserin was correlated with CYP2D6, 5-hydroxylorcaserin was correlated with CYP1A2 and CYP3A4, and 1-hydroxylorcaserin was correlated with CYP3A4 activity at 10.0 μM lorcaserin. No correlation was observed for N-hydroxylorcaserin with any P450 marker substrate activity at 1.0 μM lorcaserin. N-Hydroxylorcaserin formation was not inhibited by CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 inhibitors at the highest concentration tested. Furafylline, quinidine, and ketoconazole, selective inhibitors of CYP1A2, CYP2D6, and CYP3A4, respectively, inhibited 5-hydroxylorcaserin (IC(50) = 1.914 μM), 7-hydroxylorcaserin (IC(50) = 0.213 μM), and 1-hydroxylorcaserin formation (IC(50) = 0.281 μM), respectively. N-Hydroxylorcaserin showed low and high K(m) components in HLM and 7-hydroxylorcaserin showed lower K(m) than 5-hydroxylorcaserin and 1-hydroxylorcaserin in HLM. The highest intrinsic clearance was observed for N-hydroxylorcaserin, followed by 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin in HLM. Multiple human P450 and FMO enzymes catalyze the formation of four primary oxidative metabolites of lorcaserin, suggesting that lorcaserin has a low probability of drug-drug interactions by concomitant medications.

The importance of age composition of 12-step meetings as a moderating factor in the relation between young adults' 12-step participation and abstinence.

PubMed

Labbe, Allison K; Greene, Claire; Bergman, Brandon G; Hoeppner, Bettina; Kelly, John F

2013-12-01

Participation in 12-step mutual help organizations (MHO) is a common continuing care recommendation for adults; however, little is known about the effects of MHO participation among young adults (i.e., ages 18-25 years) for whom the typically older age composition at meetings may serve as a barrier to engagement and benefits. This study examined whether the age composition of 12-step meetings moderated the recovery benefits derived from attending MHOs. Young adults (n=302; 18-24 years; 26% female; 94% White) enrolled in a naturalistic study of residential treatment effectiveness were assessed at intake, and 3, 6, and 12 months later on 12-step attendance, age composition of attended 12-step groups, and treatment outcome (Percent Days Abstinent [PDA]). Hierarchical linear models (HLM) tested the moderating effect of age composition on PDA concurrently and in lagged models controlling for confounds. A significant three-way interaction between attendance, age composition, and time was detected in the concurrent (p=0.002), but not lagged, model (b=0.38, p=0.46). Specifically, a similar age composition was helpful early post-treatment among low 12-step attendees, but became detrimental over time. Treatment and other referral agencies might enhance the likelihood of successful remission and recovery among young adults by locating and initially linking such individuals to age appropriate groups. Once engaged, however, it may be prudent to encourage gradual integration into the broader mixed-age range of 12-step meetings, wherein it is possible that older members may provide the depth and length of sober experience needed to carry young adults forward into long-term recovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Assessing the Organizational Social Context (OSC) of child welfare systems: implications for research and practice.

PubMed

Glisson, Charles; Green, Philip; Williams, Nathaniel J

2012-09-01

The study: (1) provides the first assessment of the a priori measurement model and psychometric properties of the Organizational Social Context (OSC) measurement system in a US nationwide probability sample of child welfare systems; (2) illustrates the use of the OSC in constructing norm-based organizational culture and climate profiles for child welfare systems; and (3) estimates the association of child welfare system-level organizational culture and climate profiles with individual caseworker-level job satisfaction and organizational commitment. The study applies confirmatory factor analysis (CFA) and hierarchical linear models (HLM) analysis to a US nationwide sample of 1,740 caseworkers from 81 child welfare systems participating in the second National Survey of Child and Adolescent Wellbeing (NSCAW II). The participating child welfare systems were selected using a national probability procedure reflecting the number of children served by child welfare systems nationwide. The a priori OSC measurement model is confirmed in this nationwide sample of child welfare systems. In addition, caseworker responses to the OSC scales generate acceptable to high scale reliabilities, moderate to high within-system agreement, and significant between-system differences. Caseworkers in the child welfare systems with the best organizational culture and climate profiles report higher levels of job satisfaction and organizational commitment. Organizational climates characterized by high engagement and functionality, and organizational cultures characterized by low rigidity are associated with the most positive work attitudes. The OSC is the first valid and reliable measure of organizational culture and climate with US national norms for child welfare systems. The OSC provides a useful measure of Organizational Social Context for child welfare service improvement and implementation research efforts which include a focus on child welfare system culture and climate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Do individuals higher in impulsivity drink more impulsively? A pilot study within a high risk sample of young adults.

PubMed

Stevens, Angela K; Littlefield, Andrew K; Talley, Amelia E; Brown, Jennifer L

2017-02-01

Extant literature has established a strong relation between individual differences in "impulsivity" and alcohol consumption. However, the relation between "impulsivity," intentions-to-drink, and alcohol consumption has remained understudied. As a part of a larger study, 77 participants (60.5% female, 76.3% White, M age=20.8) completed 10days of daily diary reports regarding their intention to use alcohol and alcohol consumption. Hierarchical linear modeling (HLM) was used to estimate within-person relations between intentions-to-drink and subsequent alcohol use. All models were adjusted for participant age, biological sex, and day of the week. Results showed a strong positive association between daily intention to consume alcohol and self-reported alcohol use (β=0.50, p<0.01). Importantly, tests of interactions indicated that individuals higher in impulsivity were not significantly more likely to engage in unplanned drinking. Multilevel mediation analyses indicated significant indirect effects between impulsivity-like constructs, including positive urgency, lack-of-planning, and self-report delay discounting, and reported daily alcohol consumption via higher overall (i.e., between-person) levels of intentions-to-drink; that is, individuals who reported higher levels of these impulsivity-related constructs were more likely to intend to drink across the 10-days and, in turn, consumed more alcohol. Findings from the study suggest that treatment providers could address drinking intentions among individuals higher in impulsivity and work to establish potential replacement behaviors to reduce alcohol consumption in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predictors and Trajectories of Morning Fatigue Are Distinct from Evening Fatigue

PubMed Central

Wright, Fay; Melkus, Gail D’Eramo; Hammer, Marilyn; Schmidt, Brian L.; Knobf, M. Tish; Paul, Steven M.; Cartwright, Frances; Mastick, Judy; Cooper, Bruce A.; Chen, Lee-May; Melisko, Michelle; Levine, Jon D.; Kober, Kord; Aouizerat, Bradley E.; Miaskowski, Christine

2015-01-01

Context Fatigue is the most common symptom in oncology patients during chemotherapy (CTX). Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients. Objectives An evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue. Methods A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N=586) completed demographic and symptom questionnaires a total of six times over two cycles of CTX. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling (HLM) was used to answer the study objectives. Results A large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index (BMI), who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance and depressive symptoms, reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients’ ethnicity and younger age. Conclusion The modifiable risk factors that were associated with only morning fatigue were BMI, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors. PMID:25828559

Trajectories of Evening Fatigue in Oncology Outpatients Receiving Chemotherapy

PubMed Central

Wright, Fay; Melkus, Gail D’Eramo; Hammer, Marilyn; Schmidt, Brian L.; Knobf, M. Tish; Paul, Steven M.; Cartwright, Frances; Mastick, Judy; Cooper, Bruce A.; Chen, Lee-May; Melisko, Michelle; Levine, Jon D.; Kober, Kord; Aouizerat, Bradley E.; Miaskowski, Christine

2015-01-01

Context Fatigue is a distressing, persistent sense of physical tiredness that is not proportional to a person’s recent activity. Fatigue impacts patients’ treatment decisions and can limit their self-care activities. While significant interindividual variability in fatigue severity has been noted, little is known about predictors of interindividual variability in initial levels and trajectories of evening fatigue severity in oncology patients receiving chemotherapy (CTX). Objectives To determine whether demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of evening fatigue. Methods A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N=586) completed demographic and symptom questionnaires a total of six times over two cycles of CTX. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling (HLM) was used to answer the study objectives. Results A large amount of interindividual variability was found in the evening fatigue trajectories. A piecewise model fit the data best. Patients who were White, diagnosed with breast, gynecological, or lung cancer, and who had more years of education, child care responsibilities, lower functional status, and higher levels of sleep disturbance and depression reported higher levels of evening fatigue at enrollment. Conclusion This study identified both non-modifiable (e.g., ethnicity) and modifiable (e.g., child care responsibilities, depressive symptoms, sleep disturbance) risk factors for more severe evening fatigue. Using this information, clinicians can identify patients at higher risk for more severe evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors. PMID:25828560

ASCA Position Statement: Student Rights: A Right to Due Process

ERIC Educational Resources Information Center

School Counselor, 1978

1978-01-01

Presents the American School Counselor Association position statement on student rights by declaring its support of "the rights of all students to be guaranteed the protections of due process as provided by the United States Constitution." The role of the counselor is also discussed. (Author/HLM)

Influence of Contextual Challenges and Constraints on Learning-Centered Leadership

ERIC Educational Resources Information Center

Tan, Cheng Yong

2014-01-01

The present study examines from the contingency opportunities perspective the influence of contextual factors on principals' learning-centered leadership using HLM. Participants were 18,641 school principals from 73 jurisdictions who participated in the Programme for International Student Assessment (PISA) 2009. Results showed that principals were…

Secondary School Counselors As Their Students See Them At Different Grade Levels

ERIC Educational Resources Information Center

McCandless, C. E.; Pope, Henry D.

1976-01-01

In this study of high school student perceptions of counselors, perception most frequently differed between freshmen/sophomores and juniors/seniors. All students perceived the counselor's activities as being primarily directed toward educational and career guidance functions rather than as an assistant with personal problems. (Author/HLM)

Episodic and Individual Effects of Elementary Students' Optimal Experience: An HLM Study

ERIC Educational Resources Information Center

Cheng, Chao-Yang; Chen, Sherry Y.; Lin, Sunny S. J.

2017-01-01

The authors defined optimal experience as a functional state of a relatively high level of concentration, time distortion, satisfaction, and enjoyment (Csikszentmihalyi, 1992) and collected data through the Day Reconstruction Method. In three random days, 147 fifth-grade students answered questionnaires for each school event in the previous day…

Advanced mortar coatings for cultural heritage protection. Durability towards prolonged UV and outdoor exposure.

PubMed

Pino, F; Fermo, P; La Russa, M; Ruffolo, S; Comite, V; Baghdachi, J; Pecchioni, E; Fratini, F; Cappelletti, G

2017-05-01

In the present work, two kinds of hybrid polymeric-inorganic coatings containing TiO 2 or SiO 2 particles and prepared starting from two commercial resins (Alpha®SI30 and Bluesil®BP9710) were developed and applied to two kinds of mortars (an air-hardening calcic lime mortar [ALM] and a natural hydraulic lime mortar [HLM]) to achieve better performances in terms of water repellence and consequently damage resistance. The two pure commercial resins were also applied for comparison purposes. Properties of the coated materials and their performance were studied using different techniques such as contact angle measurements, capillary absorption test, mercury intrusion porosimetry, surface free energy, colorimetric measurements and water vapour permeability tests. Tests were also performed to determine the weathering effects on both the commercial and the hybrid coatings in order to study their durability. Thus, exposures to UV radiation, to UV radiation/condensed water cycles and to a real polluted atmospheric environment have been performed. The effectiveness of the hybrid SiO 2 based coating was demonstrated, especially in the case of the HLM mortar.

Social context, parental monitoring, and multisystemic therapy outcomes.

PubMed

Robinson, Brittany A; Winiarski, D Anne; Brennan, Patricia A; Foster, Sharon L; Cunningham, Phillippe B; Whitmore, Elizabeth A

2015-03-01

Multisystemic therapy (MST) and other evidence-based treatments targeting juvenile delinquency have been well substantiated in the literature. Although these treatments have been demonstrated to be effective overall at reducing juvenile delinquency, it is well known that they do not benefit all treated youth. Research has yet to examine the potential influence of contextual factors, such as socioeconomic status (SES) and neighborhood characteristics, on treatment outcomes, particularly as they influence parental monitoring, which is often a focus of interventions targeting juvenile delinquency. A primary goal of these treatments is to help parents develop the requisite skills to adequately monitor and discipline their children; however, this goal may be compromised by contextual factors affecting parental effectiveness and, ultimately, treatment efficacy. The objective of this study was to explore the role of SES and neighborhood factors in moderating the effects of parental monitoring across treatment. Using hierarchical linear modeling (HLM), we analyzed these contextual and family predictors of response to MST treatment within a sample of 185 youth (65.4% male) ages 12-18 (M = 15.35; SD = 1.28). Neighborhood factors interacted with parental monitoring, such that monitoring predicted decreases in externalizing behavior only for youth residing in better neighborhoods. In contrast, SES was unrelated to changes in externalizing behaviors in response to MST. Taken together, these results demonstrate a need for further understanding the potential role of the youth's larger social context in predicting MST outcomes. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Experience, cortisol reactivity, and the coordination of emotional responses to skydiving

PubMed Central

Meyer, Vanessa J.; Lee, Yoojin; Böttger, Christian; Leonbacher, Uwe; Allison, Amber L.; Shirtcliff, Elizabeth A.

2015-01-01

Physiological habituation to laboratory stressors has previously been demonstrated, although the literature remains equivocal. Previous studies have found skydiving to be a salient naturalistic stressor that elicits a robust subjective and physiological stress response. However, it is uncertain whether (or how) stress reactivity habituates to this stressor given that skydiving remains a risky, life-threatening challenge with every jump despite experience. While multiple components of the stress response have been documented, it is unclear whether an individual’s subjective emotions are related to their physiological responses. Documenting coordinated responsivity would lend insight into shared underlying mechanisms for the nature of habituation of both subjective (emotion) and objective (cortisol) stress responses. Therefore, we examined subjective emotion and cortisol responses in first-time compared to experienced skydivers in a predominantly male sample (total n = 44; males = 32, females = 12). Hierarchical linear modeling (HLM) revealed that experienced skydivers showed less reactivity and faster recovery compared to first-time skydivers. Subjective emotions were coordinated with physiological responses primarily within first-time skydivers. Pre-jump anxiety predicted cortisol reactivity within first-time, but not experienced, skydivers. Higher post-jump happiness predicted faster cortisol recovery after jumping although this effect overlapped somewhat with the effect of experience. Results suggest that experience may modulate the coordination of emotional response with cortisol reactivity to skydiving. Prior experience does not appear to extinguish the stress response but rather alters the individual’s engagement of the HPA axis. PMID:25859199

Prevention of school bullying: the important role of autonomy-supportive teaching and internalization of pro-social values.

PubMed

Roth, Guy; Kanat-Maymon, Yaniv; Bibi, Uri

2011-12-01

This study examined students' perceptions of autonomy-supportive teaching (AST) and its relations to internalization of pro-social values and bullying in class. We hypothesized that: (1) teachers' AST, which involves provision of rationale and taking the student's perspective, would relate positively to students' identified internalization of considerateness towards classmates, and would relate negatively to external regulation (considerateness to obtain rewards or avoid punishments); (2) students' identified regulation would relate negatively to self-reported bullying in class, whereas external regulation would relate positively to bullying; and (3) the relation between teachers' AST and student bullying would be mediated by students' identification with the value of considerateness towards others. The sample consisted of 725 junior high school students (50% females) in Grades 7 and 8 from 27 classes in four schools serving students from lower-middle to middle-class socioeconomic backgrounds.   The participants completed questionnaires assessing the variables of interest. Correlational analysis supported the hypotheses. Moreover, mediational analyses using hierarchical linear modelling (HLM) demonstrated that identified regulation mediates the negative relation between AST and self-reported bullying in class. The mediational hypothesis was supported at the between-class level and at the within-class level.   The findings suggest that school policy aimed at bullying reduction should go beyond external control that involves external rewards and sanctions and should help teachers acquire autonomy-supportive practices focusing on students' meaningful internalization. ©2010 The British Psychological Society.

N-demethylation of N-methyl-4-aminoantipyrine, the main metabolite of metamizole.

PubMed

Bachmann, Fabio; Duthaler, Urs; Rudin, Deborah; Krähenbühl, Stephan; Haschke, Manuel

2018-05-08

Metamizole is an old analgesic used frequently in some countries. Active metabolites of metamizole are the non-enzymatically generated N-methyl-4-aminoantipyrine (4-MAA) and its demethylation product 4-aminoantipyrine (4-AA). Previous studies suggested that 4-MAA demethylation can be performed by hepatic cytochrome P450 (CYP) 3A4, but the possible contribution of other CYPs remains unclear. Using human liver microsomes (HLM), liver homogenate and HepaRG cells, we could confirm 4-MAA demethylation by CYPs. Based on CYP induction (HepaRG cells) and CYP inhibition (HLM) we could identify CYP2B6, 2C8, 2C9 and 3A4 as major contributors to 4-MAA demethylation. The 4-MAA demethylation rate by HLM was 280 pmol/mg protein/h, too low to account for in vivo 4-MAA demethylation in humans. Since peroxidases can perform N-demethylation, we investigated horseradish peroxidase and human myeloperoxidase (MPO). Horse radish peroxidase efficiently demethylated 4-MAA, depending on the hydrogen peroxide concentration. This was also true for MPO; this reaction was saturable with a K m of 22.5 μM and a maximal velocity of 14 nmol/min/mg protein. Calculation of the entire body MPO capacity revealed that the demethylation capacity by granulocyte/granulocyte precursors was approximately 600 times higher than the liver capacity and could account for 4-MAA demethylation in humans. 4-MAA demethylation could also be demonstrated in MPO-expressing granulocyte precursor cells (HL-60). In conclusion, 4-MAA can be demethylated in the liver by several CYPs, but hepatic metabolism cannot fully explain 4-MAA demethylation in humans. The current study suggests that the major part of 4-MAA is demethylated by circulating granulocytes and granulocyte precursors in bone marrow. Copyright © 2018 Elsevier B.V. All rights reserved.

Estimating regression to the mean and true effects of an intervention in a four-wave panel study.

PubMed

Gmel, Gerhard; Wicki, Matthias; Rehm, Jürgen; Heeb, Jean-Luc

2008-01-01

First, to analyse whether a taxation-related decrease in spirit prices had a similar effect on spirit consumption for low-, medium- and high-level drinkers. Secondly, as the relationship between baseline values and post-intervention changes is confounded with regression to the mean (RTM) effects, to apply different approaches for estimating the RTM effect and true change. Consumption of spirits and total alcohol consumption were analysed in a four-wave panel study (one pre-intervention and three post-intervention measurements) of 889 alcohol consumers sampled from the general population of Switzerland. Two correlational methods, one method quantitatively estimating the RTM effect and one growth curve approach based on hierarchical linear models (HLM), were used to estimate RTM effects among low-, medium- and high-level drinkers. Adjusted for RTM effects, high-level drinkers increased consumption more than lighter drinkers in the short term, but this was not a persisting effect. Changes in taxation affected mainly light and moderate drinkers in the long term. All methods concurred that RTM effects were present to a considerable degree, and methods quantifying the RTM effect or adjusting for it yielded similar estimates. Intervention studies have to consider RTM effects both in the study design and in the evaluation methods. Observed changes can be adjusted for RTM effects and true change can be estimated. The recommended method, particularly if the aim is to estimate change not only for the sample as a whole, but for groups of drinkers with different baseline consumption levels, is growth curve modelling. If reliability of measurement instruments cannot be increased, the incorporation of more than one pre-intervention measurement point may be a valuable adjustment of the study design.

Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery.

PubMed

Williams, Wesley; McKinney, Christopher; Martinez, Larry; Benson, Carmela

2016-01-01

This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders. Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving ≥6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider's (Recovery Markers Inventory [RMI]) and patient's (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI. A total of 219 patients were identified and included in the study. Results of the final three-level HLMs indicated an overall increase in CRM scores (p < 0.05), an overall increase (p < 0.01), and an increased rate of change (p < 0.05) in RMI scores during the paliperidone palmitate LAI treatment period vs the pre-treatment period. This study contained a retrospective, non-comparative design, and did not adjust for multiplicity Conclusions: The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug's use as schizophrenia treatment from a recovery-oriented perspective.

Parents' Reactions to Finding Out That Their Children Have Average or above Average IQ Scores.

ERIC Educational Resources Information Center

Dirks, Jean; And Others

1983-01-01

Parents of 41 children who had been given an individually-administered intelligence test were contacted 19 months after testing. Parents of average IQ children were less accurate in their memory of test results. Children with above average IQ experienced extremely low frequencies of sibling rivalry, conceit or pressure. (Author/HLM)

Examining the Impact of Critical Feedback on Learner Engagement in Secondary Mathematics Classrooms: A Multi-Level Analysis

ERIC Educational Resources Information Center

Kearney, W. Sean; Webb, Michael; Goldhorn, Jeff; Peters, Michelle L.

2013-01-01

This article presents a quantitative study utilizing HLM to analyze classroom walkthrough data completed by principals within 87 secondary mathematics classrooms across 9 public schools in Texas. This research is based on the theoretical framework of learner engagement as established by Argryis & Schon (1996), and refined by Marks (2000). It…

Global Proteomic Analysis of Human Liver Microsomes: Rapid Characterization and Quantification of Hepatic Drug-Metabolizing Enzymes.

PubMed

Achour, Brahim; Al Feteisi, Hajar; Lanucara, Francesco; Rostami-Hodjegan, Amin; Barber, Jill

2017-06-01

Many genetic and environmental factors lead to interindividual variations in the metabolism and transport of drugs, profoundly affecting efficacy and toxicity. Precision dosing, that is, targeting drug dose to a well characterized subpopulation, is dependent on quantitative models of the profiles of drug-metabolizing enzymes (DMEs) and transporters within that subpopulation, informed by quantitative proteomics. We report the first use of ion mobility-mass spectrometry for this purpose, allowing rapid, robust, label-free quantification of human liver microsomal (HLM) proteins from distinct individuals. Approximately 1000 proteins were identified and quantified in four samples, including an average of 70 DMEs. Technical and biological variabilities were distinguishable, with technical variability accounting for about 10% of total variability. The biological variation between patients was clearly identified, with samples showing a range of expression profiles for cytochrome P450 and uridine 5'-diphosphoglucuronosyltransferase enzymes. Our results showed excellent agreement with previous data from targeted methods. The label-free method, however, allowed a fuller characterization of the in vitro system, showing, for the first time, that HLMs are significantly heterogeneous. Further, the traditional units of measurement of DMEs (pmol mg -1 HLM protein) are shown to introduce error arising from variability in unrelated, highly abundant proteins. Simulations of this variability suggest that up to 1.7-fold variation in apparent CYP3A4 abundance is artifactual, as are background positive correlations of up to 0.2 (Spearman correlation coefficient) between the abundances of DMEs. We suggest that protein concentrations used in pharmacokinetic predictions and scaling to in vivo clinical situations (physiologically based pharmacokinetics and in vitro-in vivo extrapolation) should be referenced instead to tissue mass. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Parental Perceptions toward and Practices of Heritage Language Maintenance: Focusing on the United States and Canada

ERIC Educational Resources Information Center

Liang, Feng

2018-01-01

This study reviews 17 studies since the year of 2000 on the perceptions and practices of immigrant parents who reside in the United States or Canada with respect to their children's heritage language maintenance (HLM). The findings suggest that parental perceptions may change due to practical considerations and vary with different degrees of…

Gender Differences in Context: The Impact of Track Position on Study Involvement in Flemish Secondary Education

ERIC Educational Resources Information Center

Van Houtte, Mieke

2017-01-01

This study examines whether the influence of track position on study involvement is gendered and whether gender differences in study involvement according to track position are associated with school misconduct and rather poor future perspectives. Three-level analyses (HLM 6) of data gathered in 2004-2005 from 11,872 third- and fifth-grade…

Exploring Factors Affecting Learner's Perception of Learning Information and Communication Technology: A HLM Analysis of a National Farmers' Training Program in Taiwan

ERIC Educational Resources Information Center

Yueh, Hsiu-Ping; Chen, Tzy-Ling; Chiu, Li-An; Lin, Wei-Chien

2013-01-01

The present study, pertaining to a national information literacy training program for both farmers and rural communities in Taiwan, explores factors that affect learners' perception of learning information and communication technology (ICT). It further analyzes effects of individual characteristics and varied training designs on learners'…

Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes.

PubMed

Schmidt, Jan; Kotnik, Petra; Trontelj, Jurij; Knez, Željko; Mašič, Lucija Peterlin

2013-06-01

Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para-hydroxy group on both benzene rings. Bisphenol A (BPA) can induce an uterotrophic response in immature CD-1 mice and elicits estrogenic responses in many other experimental systems. Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and/or produce oxidative stress. We used a liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) for the detection of metabolites and glutathione conjugates of BPA and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes (HLM) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent. We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes. These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs.

PubMed

Ruokolainen, Miina; Gul, Turan; Permentier, Hjalmar; Sikanen, Tiina; Kostiainen, Risto; Kotiaho, Tapio

2016-02-15

The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off. Copyright © 2015 Elsevier B.V. All rights reserved.

Impacts of Social Network on Therapeutic Community Participation: A Follow-up Survey of Data Gathered after Ya'an Earthquake.

PubMed

Li, Zhichao; Chen, Yao; Suo, Liming

2015-01-01

In recent years, natural disasters and the accompanying health risks have become more frequent, and rehabilitation work has become an important part of government performance. On one hand, social networks play an important role in participants' therapeutic community participation and physical & mental recovery. On the other hand, therapeutic communities with widespread participation can also contribute to community recovery after disaster. This paper described a field study in an earthquake-stricken area of Ya'an. A set of 3-stage follow-up data was obtained concerning with the villagers' participation in therapeutic community, social network status, demographic background, and other factors. The Hierarchical linear Model (HLM) method was used to investigate the determinants of social network on therapeutic community participation. First, social networks have significantly impacts on the annual changes of therapeutic community participation. Second, there were obvious differences in education between groups mobilized by the self-organization and local government. However, they all exerted the mobilization force through the acquaintance networks. Third, local cadre networks of villagers could negatively influence the activities of self-organized therapeutic community, while with positively influence in government-organized therapeutic activities. This paper suggests that relevant government departments need to focus more on the reconstruction and cultivation of villagers' social network and social capital in the process of post-disaster recovery. These findings contribute to better understandings of how social networks influence therapeutic community participation, and what role local government can play in post-disaster recovery and public health improvement after natural disasters.

Impacts of Social Network on Therapeutic Community Participation: A Follow-up Survey of Data Gathered after Ya’an Earthquake

PubMed Central

LI, Zhichao; CHEN, Yao; SUO, Liming

2015-01-01

Abstract Background In recent years, natural disasters and the accompanying health risks have become more frequent, and rehabilitation work has become an important part of government performance. On one hand, social networks play an important role in participants’ therapeutic community participation and physical & mental recovery. On the other hand, therapeutic communities with widespread participation can also contribute to community recovery after disaster. Methods This paper described a field study in an earthquake-stricken area of Ya’an. A set of 3-stage follow-up data was obtained concerning with the villagers’ participation in therapeutic community, social network status, demographic background, and other factors. The Hierarchical linear Model (HLM) method was used to investigate the determinants of social network on therapeutic community participation. Results First, social networks have significantly impacts on the annual changes of therapeutic community participation. Second, there were obvious differences in education between groups mobilized by the self-organization and local government. However, they all exerted the mobilization force through the acquaintance networks. Third, local cadre networks of villagers could negatively influence the activities of self-organized therapeutic community, while with positively influence in government-organized therapeutic activities. Conclusion This paper suggests that relevant government departments need to focus more on the reconstruction and cultivation of villagers’ social network and social capital in the process of post-disaster recovery. These findings contribute to better understandings of how social networks influence therapeutic community participation, and what role local government can play in post-disaster recovery and public health improvement after natural disasters. PMID:26060778

Associations among state and local organizational contexts: Use of evidence-based practices in the criminal justice system.

PubMed

Henderson, Craig E; Young, Douglas W; Farrell, Jill; Taxman, Faye S

2009-08-01

This study used hierarchical linear modeling (HLM) to examine the extent to which the organizational characteristics of state corrections agencies and local criminal justice facilities interacted in their associations with the extent to which local facilities are using evidence-based substance abuse treatment practices (EBPs). The study used data collected from two nationally representative surveys - one of state executives and the other of local prison wardens, justice administrators, and treatment directors - which were conducted as part of the National Criminal Justice Treatment Practices survey [NCJTP; Taxman, F.S., Young, D., Wiersema, B., Mitchell, S., Rhodes, A.G., 2007. The National Criminal Justice Treatment Practices Survey: Multi-level survey methods and procedures. J. Subst. Abuse Treat. 32, 225-238], and includes both adult criminal and juvenile justice samples. Results indicated that several state organizational characteristics were either associated with more EBP use or interacted with local organizational characteristics in associations with EBP use, including: (1) systems integration at the state level was associated with greater EBP use; (2) state staffing adequacy and stability accentuated the association between local training and resources for new programs and EBP use (i.e., in states with better staffing, the relationship between training/resources and EBP use in local facilities was stronger); and (3) state executives' attitudes regarding the missions and goals of corrections tended to diminish the extent to which corresponding local administrator attitudes were associated with EBP use. The study has implications for future research focused on EBP diffusion and implementation in correctional environments, particularly attempts to influence EBP use by working through state agencies.

Understanding the Factors that Influence Perceptions of Post-Wildfire Landscape Recovery Across 25 Wildfires in the Northwestern United States.

PubMed

Kooistra, C; Hall, T E; Paveglio, T; Pickering, M

2018-01-01

Disturbances such as wildfire are important features of forested landscapes. The trajectory of changes following wildfires (often referred to as landscape recovery) continues to be an important research topic among ecologists and wildfire scientists. However, the landscape recovery process also has important social dimensions that may or may not correspond to ecological or biophysical perspectives. Perceptions of landscape recovery may affect people's attitudes and behaviors related to forest and wildfire management. We explored the variables that influence people's perceptions of landscape recovery across 25 fires that occurred in 2011 or 2012 in the United States of Washington, Oregon, Idaho, and Montana and that represented a range of fire behavior characteristics and landscape impacts. Residents near each of the 25 fires were randomly selected to receive questionnaires about their experiences with the nearby fire, including perceived impacts and how the landscape had recovered since the fire. People generally perceived landscapes as recovering, even though only one to two years had passed. Regression analysis suggested that perceptions of landscape recovery were positively related to stronger beliefs about the ecological role of fire and negatively related to loss of landscape attachment, concern about erosion, increasing distance from the fire perimeter, and longer lasting fires. Hierarchical linear modeling (HLM) analysis indicated that the above relationships were largely consistent across fires. These findings highlight that perceptions of post-fire landscape recovery are influenced by more than vegetation changes and include emotional and cognitive factors. We discuss the management implications of these findings.

Psychological Well-Being in Italian Families: An Exploratory Approach to the Study of Mental Health Across the Adult Life Span in the Blue Zone

PubMed Central

Hitchcott, Paul Kenneth; Fastame, Maria Chiara; Ferrai, Jessica; Penna, Maria Pietronilla

2017-01-01

Self-reported measures of psychological well-being and depressive symptoms were examined across differently aged family members, while controlling for the impact of marital status and personal satisfaction about family and non-family relations. Twenty-one grandchildren (i.e., ages 21-36 years) were recruited with their parents (i.e., 48-66 years old) and grandparents (i.e., 75-101 years of age) in the ‘blue zone’ of Ogliastra, an Italian area known for the longevity of its inhabitants. Each participant was individually presented a battery of questionnaires assessing their lifestyle and several perceived mental health indices, including the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS, Tennant et al., 2007), and the Center for Epidemiologic Studies Depression Scale (i.e., CES-D, Radloff, 1977). After assessing the level of concordance among adults sharing the same context, the Hierarchical Linear Modeling (HLM) approach was used to assess the nested dataset. It was found that family membership (i.e., grandchildren versus parents and grandparents) predicted the WEMWBS score but not the CES-D when the impact of marital status and personal satisfaction about social (i.e., family and non-family) ties was controlled for. Moreover, two separate repeated-measure Analyses of Variance (ANOVAs) documented similar level of personal satisfaction about social relationships across the three family groups. In conclusions, satisfying social ties with friends and family members together with an active socially oriented life style seems to contribute to the promotion of mental health in adult span. PMID:28904594

Reductions in Hard Drug Use Among Homeless Youth Receiving a Strength-Based Outreach Intervention: Comparing the Long-Term Effects of Shelter Linkage Versus Drop-in Center Linkage.

PubMed

Guo, Xiamei; Slesnick, Natasha

2017-06-07

The current study sought to test hard drug use outcomes for youth receiving a strengths-based outreach and advocacy intervention that linked youth to either a shelter or a drop-in center. Homeless youth (14-24 years old) were engaged by research assistants (RAs) at soup kitchens, parks, libraries, and other locations that homeless youth were known to frequent. Youth were randomly assigned to receive six months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). Follow-up assessments were conducted at 3, 6, and 9 months post-baseline. Hard drug use over time was the main outcome. Intervention condition and service connection were used as predictors for the baseline level and the slope of change in hard drug use over time. Data analysis was conducted with Bernoulli Hierarchical Generalized Linear Modeling in HLM7. The current study found that those who were in the drop-in linkage condition exhibited a greater reduction in their odds of using hard drugs during the follow-up points than their counterparts in the shelter linkage condition. And finally, those who utilized services more often during the follow-ups were those who exhibited less hard drug use at baseline and less reduction in their odds of using hard drugs. This study suggests that drop-in centers, which are often characterized by low-demand programming and few behavioral restrictions, are effective for addressing hard drug use among homeless youth.

Understanding the Factors that Influence Perceptions of Post-Wildfire Landscape Recovery Across 25 Wildfires in the Northwestern United States

NASA Astrophysics Data System (ADS)

Kooistra, C.; Hall, T. E.; Paveglio, T.; Pickering, M.

2018-01-01

Disturbances such as wildfire are important features of forested landscapes. The trajectory of changes following wildfires (often referred to as landscape recovery) continues to be an important research topic among ecologists and wildfire scientists. However, the landscape recovery process also has important social dimensions that may or may not correspond to ecological or biophysical perspectives. Perceptions of landscape recovery may affect people's attitudes and behaviors related to forest and wildfire management. We explored the variables that influence people's perceptions of landscape recovery across 25 fires that occurred in 2011 or 2012 in the United States of Washington, Oregon, Idaho, and Montana and that represented a range of fire behavior characteristics and landscape impacts. Residents near each of the 25 fires were randomly selected to receive questionnaires about their experiences with the nearby fire, including perceived impacts and how the landscape had recovered since the fire. People generally perceived landscapes as recovering, even though only one to two years had passed. Regression analysis suggested that perceptions of landscape recovery were positively related to stronger beliefs about the ecological role of fire and negatively related to loss of landscape attachment, concern about erosion, increasing distance from the fire perimeter, and longer lasting fires. Hierarchical linear modeling (HLM) analysis indicated that the above relationships were largely consistent across fires. These findings highlight that perceptions of post-fire landscape recovery are influenced by more than vegetation changes and include emotional and cognitive factors. We discuss the management implications of these findings.

Variation in Emergency Medical Services Workplace Safety Culture

PubMed Central

Patterson, P. Daniel; Huang, David T.; Fairbanks, Rollin J.; Simeone, Scott; Weaver, Matthew; Wang, Henry E.

2010-01-01

Introduction Workplace attitude, beliefs and culture may impact the safety of patient care. This study characterized perceptions of safety culture in a nationwide sample of Emergency Medical Services (EMS) agencies. Methods We conducted a cross-sectional survey involving 61 Advanced Life Support EMS agencies in North America. We administered a modified version of the Safety Attitudes Questionnaire (SAQ), a survey instrument measuring dimensions of workplace safety culture (Safety Climate, Teamwork Climate, Perceptions of Management, Job Satisfaction, Working Conditions, and Stress Recognition). We included full-time and part-time paramedics and Emergency Medical Technicians. We determined the variation in safety culture scores across EMS agencies. Using Hierarchical Linear Models (HLM), we determined associations between safety culture scores and individual and EMS agency characteristics. Results We received 1,715 completed surveys from 61 EMS agencies (mean agency response rate 47%; 95% CI 10%, 83%). There was wide variation in safety culture scores across EMS agencies [mean (min, max)]: Safety Climate 74.5 (Min 49.9, Max 89.7), Teamwork Climate 71.2 (Min 45.1, Max 90.1), Perceptions of Management 67.2 (Min 31.1, Max 92.2), Job Satisfaction 75.4 (Min 47.5, Max 93.8), Working Conditions 66.9 (Min 36.6, Max 91.4), Stress Recognition 55.1 (Min 31.3, Max 70.6). Air medical EMS agencies tended to score higher across all safety culture domains. Lower safety culture scores were associated with increased annual patient contacts. Safety climate domain scores were not associated with other individual or EMS agency characteristics. Conclusion In this sample, workplace safety culture varies between EMS agencies. PMID:20809688

Reducing turnover is not enough: The need for proficient organizational cultures to support positive youth outcomes in child welfare.

PubMed

Williams, Nathaniel J; Glisson, Charles

2013-11-01

High caseworker turnover has been identified as a factor in the poor outcomes of child welfare services. However, almost no empirical research has examined the relationship between caseworker turnover and youth outcomes in child welfare systems and there is an important knowledge gap regarding whether, and how, caseworker turnover relates to outcomes for youth. We hypothesized that the effects of caseworker turnover are moderated by organizational culture such that reduced caseworker turnover is only associated with improved youth outcomes in organizations with proficient cultures. The study applied hierarchical linear models (HLM) analysis to the second National Survey of Child and Adolescent Well-being (NSCAW II) with a U.S. nationwide sample of 2,346 youth aged 1.5- to 18-years-old and 1,544 caseworkers in 73 child welfare agencies. Proficient organizational culture was measured by caseworkers' responses to the Organizational Social Context (OSC) measure; staff turnover was reported by the agencies' directors; and youth outcomes were measured as total problems in psychosocial functioning with the Child Behavior Checklist (CBCL) completed by the youths' caregivers at intake and at 18 month follow-up. The association between caseworker turnover and youth outcomes was moderated by organizational culture. Youth outcomes were improved with lower staff turnover in proficient organizational cultures and the best outcomes occurred in organizations with low turnover and high proficiency. To be successful, efforts to improve child welfare services by lowering staff turnover must also create proficient cultures that expect caseworkers to be competent and responsive to the needs of the youth and families they serve.

Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10

PubMed Central

Ramírez, Jacqueline; Mirkov, Snezana; House, Larry K.

2015-01-01

OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing clinical testing as antineoplastic agent. We aimed to identify the UDP-glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the relationship between UGT genetic polymorphisms and hepatic OTS167 glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs. Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human liver (HLM) (Km = 3.4 ± 0.2 µM), intestinal microsomes (HIM) (Km = 1.7 ± 0.1 µM), and UGTs. UGT1A1 (64 µl/min/mg) and UGT1A8 (72 µl/min/mg) exhibited the highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51 µl/min/mg) and UGT1A10 (47 µl/min/mg); UGT1A9 was a minor contributor. OTS167 glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r = 0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide according to mass spectrometry. A significant association was found between rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition (range: 0–21%) was observed using clinically relevant OTS167 concentrations (0.4–2 µM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may contribute to first-pass OTS167 metabolism after oral administration. PMID:25870101

Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10.

PubMed

Ramírez, Jacqueline; Mirkov, Snezana; House, Larry K; Ratain, Mark J

2015-07-01

OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing clinical testing as antineoplastic agent. We aimed to identify the UDP-glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the relationship between UGT genetic polymorphisms and hepatic OTS167 glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs. Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human liver (HLM) (Km = 3.4 ± 0.2 µM), intestinal microsomes (HIM) (Km = 1.7 ± 0.1 µM), and UGTs. UGT1A1 (64 µl/min/mg) and UGT1A8 (72 µl/min/mg) exhibited the highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51 µl/min/mg) and UGT1A10 (47 µl/min/mg); UGT1A9 was a minor contributor. OTS167 glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r = 0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide according to mass spectrometry. A significant association was found between rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition (range: 0-21%) was observed using clinically relevant OTS167 concentrations (0.4-2 µM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may contribute to first-pass OTS167 metabolism after oral administration. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Enantioselective N-demethylation and hydroxylation of sibutramine in human liver microsomes and recombinant cytochrome p-450 isoforms.

PubMed

Shinde, Dhananjay D; Kim, Min-Jung; Jeong, Eun-Sook; Kim, Yang-Weon; Lee, Ji-Woo; Shin, Jae-Gook; Kim, Dong-Hyun

2014-01-01

The enantioselective metabolism of sibutramine was examined using human liver microsomes (HLM) and recombinant cytochrome P-450 (CYP) isoforms. This drug is metabolized to N-mono-desmethyl- (M1) and N,N-di-desmethylsibutramine (M2), and subsequent hydroxylation results in hydroxyl M1 (HM1) and hydroxyl M2 (HM2). No significant difference was noted in formation of M1from sibutramine between R- and S-sibutramine in HLM. However, S-enantiomers of M1 and M2 were preferentially metabolized to M2, HM1, and HM2compared to R-enantiomers in HLM, and intrinsic clearance (Clint) ratios of S-enantiomers/R-enantiomers were 1.97, 4.83, and 9.94 for M2, HM1, and HM2, respectively. CYP3A4 and CYP3A5 were only involved in the formation of M1, whereas CYP2B6 and CYP2C19 were responsible for all metabolic reactions of sibutramine. CYP2C19 and CYP3A5 displayed catalytic preference for S-sibutramine to S-M1, whereas CYP2B6 and CYP3A4 showed little or no stereoselectivity in metabolism of sibutramine to M1. In the case of M2 formation, CYP2B6 metabolized S-M1 more rapidly than R-M1 with a Clint ratio of 2.14. However, CYP2C19 catalyzed less S-M1 than R-M1 and the Clint ratio of S-M1 to R-M1 was 0.65. The most significant enantioselectivity was observed in formation of HM1 from M1, and HM2 from M2. CYP2B6 and CYP2C19 exhibited preferential catalysis of formation of hydroxyl metabolites from S-enantiomers rather than R-enantiomers. These results indicate that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibutramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramine and co-administered drugs.

Examining school effectiveness at the fourth grade: A hierarchical analysis of the Third International Mathematics and Science Study (TIMSS)

NASA Astrophysics Data System (ADS)

Stemler, Steven Edward

This study explored school effectiveness in mathematics and science at the fourth grade using data from IEA's Third International Mathematics and Science Study (TIMSS). Fourteen of the 26 countries participating in TIMSS at the fourth grade possessed sufficient between-school variability in mathematics achievement to justify the creation of explanatory models of school effectiveness while 13 countries possessed sufficient between-school variability in science achievement. Exploratory models were developed using variables drawn from student, teacher, and school questionnaires. The variables were chosen to represent the domains of student involvement, instructional methods, classroom organization, school climate, and school structure. Six explanatory models for each subject were analyzed using two-level hierarchical linear modeling (HLM) and were compared to models using only school mean SES as an explanatory variable. The amount of variability in student achievement in mathematics attributable to differences between schools ranged from 16% in Cyprus to 56% in Latvia, while the amount of between-school variance in science achievement ranged from 12% in Korea to 59% in Latvia. In general, about one-quarter of the variability in mathematics and science achievement was found to lie between schools. The research findings revealed that after adjusting for differences in student backgrounds across schools, the most effective schools in mathematics and science had students who reported seeing a positive relationship between hard work, belief in their own abilities, and achievement. In addition, more effective schools had students who reported less frequent use of computers and calculators in the classroom. These relationships were found to be stable across explanatory models, cultural contexts, and subject areas. This study has contributed a unique element to the literature by examining school effectiveness at the fourth grade across two subject areas and across 14 different countries. The results indicate that further exploration of the relationship between school effectiveness and student locus of control warrants serious consideration. Future research on school effectiveness is recommended, perhaps using trend data and looking at different grade levels.

The Effects of Learning Strategies on Mathematical Literacy: A Comparison between Lower and Higher Achieving Countries

ERIC Educational Resources Information Center

Magen-Nagar, Noga

2016-01-01

The purpose of the current study is to explore the effects of learning strategies on Mathematical Literacy (ML) of students in higher and lower achieving countries. To address this issue, the study utilizes PISA2002 data to conduct a multi-level analysis (HLM) of Hong Kong and Israel students. In PISA2002, Israel was rated 31st in Mathematics,…

[Hepatotoxicity of emodin based on UGT1A1 enzyme-mediated bilirubin in liver microsomes].

PubMed

Wang, Qi; Dai, Zhong; Zhang, Yu-Jie; Ma, Shuang-Cheng

2016-12-01

To study the hepatotoxicity of emodin based on bilirubin metabolism mediated by glucuronidation of UGT1A1 enzyme. In this study, three different incubation systems were established by using RLM, HLM, and rUGT1A1, with bilirubin as the substrate. Different concentrations of bilirubin and emodin were added in the incubation systems. The double reciprocal Michaelis equation was drawn based on the total amount of bilirubin glucuronidation. The apparent inhibition constant Ki was then calculated with the slope curve to predict the hepatotoxicity. The results indicated that emodin had a significant inhibition to the UGT1A1 enzyme in all of the three systems, with Ki=5.400±0.956(P<0.05) in HLM system, Ki =10.020±0.611(P<0.05) in RLM system, Ki=4.850±0.528(P<0.05) in rUGT1A1 system. Meanwhile, emodin had no significant difference between rat and human in terms of inhibition of UGT1A1 enzyme. Emodin had a potential risk of the hepatotoxicity by inhibiting the UGT1A1 enzyme activity. And the method established in this study provides a new thought and new method to evaluate hepatotoxicity and safety of traditional Chinese medicines. Copyright© by the Chinese Pharmaceutical Association.

The Current Global State of Key Lifestyle Characteristics: Health and Economic Implications.

PubMed

Arena, Ross; McNeil, Amy; Sagner, Michael; Hills, Andrew P

The chronic disease crisis we currently face must be addressed in rapid fashion. Cardiovascular (CV) and pulmonary diseases, diabetes as well as several forms of cancer are leading causes of morbidity and mortality globally. Collectively, these conditions have a significant impact on the quality of life of individuals, families and communities, placing an unsustainable burden on health systems. There is hope for the chronic disease crisis in that these conditions are largely preventable or can be delayed to much later in life through a timeless medicine, healthy living. Specifically, physical activity (PA), healthy nutrition, not smoking and maintaining a healthy body weight, the latter of which being predominantly influenced by PA and nutrition, are the key healthy living medicine (HLM) ingredients. Unfortunately, there is much work to be done, the unhealthy living phenotype is running rampant across the globe. Without improvements in PA, nutrition, tobacco use and body habitus patterns, there is little hope for curtailing the chronic disease epidemic that has been brought about by the dramatic increase in unhealthy living behaviors. This review highlights current trends in lifestyle behaviors, benefits associated with reversing those behaviors and potential paths to promote the increased utilization of HLM. Copyright © 2017 Elsevier Inc. All rights reserved.

Sustaining new parents in home visitation services: key participant and program factors.

PubMed

Daro, Deborah; McCurdy, Karen; Falconnier, Lydia; Stojanovic, Daniela

2003-10-01

As prevention efforts have adopted more intensive service models, concerns over initial enrollment and retention rates have become more salient. This study examines the participant, provider and program factors that contribute to a longer length of stay and greater number of home visits for new parents enrolling in one national home visitation program. Retrospective data were collected on a random sample of 816 participants served by one of 17 Healthy Families America (HFA) program sites around the country. Using case record reviews, research staff documented each participant's characteristics and service experiences. To capture relevant staff and program information, research staff collected basic descriptive information from published documents and interviews with program managers. All home visitors who had contact with sample families also completed a self-assessment instrument regarding personal and professional characteristics. Hierarchical linear modeling allowed us to examine the unique role of participant, provider and program characteristics while recognizing the lack of independence among these three sets of variables. The combined provider and program levels in the HLM model accounted for one-third of the variance in service duration and one-quarter of the variance in the number of home visits. Older participants, those unemployed, and those who enrolled in the program early in their pregnancy were more likely to remain in services longer and to complete a greater number of home visits. Compared to White participants, African Americans and Hispanics were significantly more likely to remain in services longer and, in the case of African Americans, to receive a greater number of home visits. Participants who were enrolled in school were more likely to remain in services longer. Age was the only consistent provider characteristic associated with positive results in both models, with younger home visitors performing better. Prior experience showed a significant relationship only in the service dosage model and African American workers demonstrated greater success than White home visitors did in retaining families in service. At the program level, programs with lower caseloads and greater success in matching their participants and providers on parenting status and race/ethnicity were significantly more likely to demonstrate stronger enrollment patterns.

Application of Rapid Visco Analyser (RVA) viscograms and chemometrics for maize hardness characterisation.

PubMed

Guelpa, Anina; Bevilacqua, Marta; Marini, Federico; O'Kennedy, Kim; Geladi, Paul; Manley, Marena

2015-04-15

It has been established in this study that the Rapid Visco Analyser (RVA) can describe maize hardness, irrespective of the RVA profile, when used in association with appropriate multivariate data analysis techniques. Therefore, the RVA can complement or replace current and/or conventional methods as a hardness descriptor. Hardness modelling based on RVA viscograms was carried out using seven conventional hardness methods (hectoliter mass (HLM), hundred kernel mass (HKM), particle size index (PSI), percentage vitreous endosperm (%VE), protein content, percentage chop (%chop) and near infrared (NIR) spectroscopy) as references and three different RVA profiles (hard, soft and standard) as predictors. An approach using locally weighted partial least squares (LW-PLS) was followed to build the regression models. The resulted prediction errors (root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP)) for the quantification of hardness values were always lower or in the same order of the laboratory error of the reference method. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrating technology, curriculum, and online resources: A multilevel model study of impacts on science teachers and students

NASA Astrophysics Data System (ADS)

Ye, Lei

This scale-up study investigated the impact of a teacher technology tool (Curriculum Customization Service, CCS), curriculum, and online resources on earth science teachers' attitudes, beliefs, and practices and on students' achievement and engagement with science learning. Participants included 73 teachers and over 2,000 ninth-grade students within five public school districts in the western U.S. To assess the impact on teachers, changes between pre- and postsurveys were examined. Results suggest that the CCS tool appeared to significantly increase both teachers' awareness of other earth science teachers' practices and teachers' frequency of using interactive resources in their lesson planning and classroom teaching. A standard multiple regression model was developed. In addition to "District," "Training condition" (whether or not teachers received CCS training) appeared to predict teachers' attitudes, beliefs, and practices. Teachers who received CCS training tended to have lower postsurvey scores than their peers who had no CCS training. Overall, usage of the CCS tool tended to be low, and there were differences among school districts. To assess the impact on students, changes were examined between pre- and postsurveys of (1) knowledge assessment and (2) students' engagement with science learning. Students showed pre- to postsurvey improvements in knowledge assessment, with small to medium effect sizes. A nesting effect (students clustered within teachers) in the Earth's Dynamic Geosphere (EDG) knowledge assessment was identified and addressed by fitting a two-level hierarchical linear model (HLM). In addition, significant school district differences existed for student post-knowledge assessment scores. On the student engagement questionnaire, students tended to be neutral or to slightly disagree that science learning was important in terms of using science in daily life, stimulating their thinking, discovering science concepts, and satisfying their own curiosity. Students did not appear to change their self-reported engagement level after the intervention. Additionally, three multiple regression models were developed. Factors from the district, teacher, and student levels were identified to predict student post-knowledge assessments and their engagement with science learning. The results provide information to both the research community and practitioners.

Do brief motivational interventions reduce drinking game frequency in mandated students? An analysis of data from two randomized controlled trials.

PubMed

Fernandez, Anne C; Yurasek, Ali M; Merrill, Jennifer E; Miller, Mary Beth; Zamboanga, Byron L; Carey, Kate B; Borsari, Brian

2017-02-01

College students frequently engage in drinking games (DGs) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMIs) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from 2 randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Associations among state and local organizational contexts: Use of evidence-based practices in the criminal justice system

PubMed Central

Henderson, Craig E.; Young, Douglas W.; Farrell, Jill; Taxman, Faye S.

2016-01-01

This study used hierarchical linear modeling (HLM) to examine the extent to which the organizational characteristics of state corrections agencies and local criminal justice facilities interacted in their associations with the extent to which local facilities are using evidence-based substance abuse treatment practices (EBPs). The study used data collected from two nationally representative surveys – one of state executives and the other of local prison wardens, justice administrators, and treatment directors – which were conducted as part of the National Criminal Justice Treatment Practices survey [NCJTP; Taxman, F.S., Young, D., Wiersema, B., Mitchell, S., Rhodes, A.G., 2007. The National Criminal Justice Treatment Practices Survey: Multi-level survey methods and procedures. J. Subst. Abuse Treat. 32, 225–238], and includes both adult criminal and juvenile justice samples. Results indicated that several state organizational characteristics were either associated with more EBP use or interacted with local organizational characteristics in associations with EBP use, including: (1) systems integration at the state level was associated with greater EBP use; (2) state staffing adequacy and stability accentuated the association between local training and resources for new programs and EBP use (i.e., in states with better staffing, the relationship between training/resources and EBP use in local facilities was stronger); and (3) state executives’ attitudes regarding the missions and goals of corrections tended to diminish the extent to which corresponding local administrator attitudes were associated with EBP use. The study has implications for future research focused on EBP diffusion and implementation in correctional environments, particularly attempts to influence EBP use by working through state agencies. PMID:19174321

Relationships between college settings and student alcohol use before, during and after events: a multi-level study.

PubMed

Paschall, Mallie J; Saltz, Robert F

2007-11-01

We examined how alcohol risk is distributed based on college students' drinking before, during and after they go to certain settings. Students attending 14 California public universities (N=10,152) completed a web-based or mailed survey in the fall 2003 semester, which included questions about how many drinks they consumed before, during and after the last time they went to six settings/events: fraternity or sorority party, residence hall party, campus event (e.g. football game), off-campus party, bar/restaurant and outdoor setting (referent). Multi-level analyses were conducted in hierarchical linear modeling (HLM) to examine relationships between type of setting and level of alcohol use before, during and after going to the setting, and possible age and gender differences in these relationships. Drinking episodes (N=24,207) were level 1 units, students were level 2 units and colleges were level 3 units. The highest drinking levels were observed during all settings/events except campus events, with the highest number of drinks being consumed at off-campus parties, followed by residence hall and fraternity/sorority parties. The number of drinks consumed before a fraternity/sorority party was higher than other settings/events. Age group and gender differences in relationships between type of setting/event and 'before,''during' and 'after' drinking levels also were observed. For example, going to a bar/restaurant (relative to an outdoor setting) was positively associated with 'during' drinks among students of legal drinking age while no relationship was observed for underage students. Findings of this study indicate differences in the extent to which college settings are associated with student drinking levels before, during and after related events, and may have implications for intervention strategies targeting different types of settings.

Development of cortisol circadian rhythm in infancy.

PubMed

de Weerth, Carolina; Zijl, Robbert H; Buitelaar, Jan K

2003-08-01

Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set. Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling). The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that affect cortisol (i.e. time of sampling, feeding, etc.). Although the choice of analysis method influences the age of appearance obtained, our use of HLM shows that the infants' own variability in onset and stability of the cortisol circadian rhythm greatly contributes to the different results.

Non-suicidal self-injury within the school context: Multilevel analysis of teachers' support and peer climate.

PubMed

Madjar, N; Ben Shabat, S; Elia, R; Fellner, N; Rehavi, M; Rubin, S E; Segal, N; Shoval, G

2017-03-01

Recent studies regarding non-suicidal self-injury (NSSI) among adolescents have focused primarily on individual characteristics (e.g., depressive symptoms) and background factors (e.g., parental relationship), whereas less emphasis has been given to the role of school-related factors in NSSI. Therefore, the purpose of the current study was to explore the relationships between teachers' support, peer climate, and NSSI within the school context. The sample consisted of 594 high school students nested within 27 regular classes (54.4% boys; mean age 14.96, SD=1.33 years). The students were evaluated for NSSI behaviors, perception of teacher support, peer climate, relationships with mothers, and depressive symptoms using validated scales. The primary analysis used hierarchical linear modeling (HLM), controlling for gender and age. The main findings indicated that teacher support was positively associated with NSSI at the classroom-level (OR=6.15, 95% CI=2.05-18.5) but negatively associated at the student-level (OR=0.66, 95% CI=0.49-0.89). There was a trend toward an association between positive peer climate and NSSI at the classroom-level (OR=0.43, 95% CI=0.18-1.05), while negative peer climate was associated with NSSI at the student-level (OR=1.37, 95% CI=1.00-1.87). School-related factors are associated with NSSI behaviors among students. Teachers and educators should focus on both individual-level and classroom-level perceptions of school context. Students who feel supported by their teachers and who are exposed to a positive peer climate are less likely to engage in NSSI. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Reducing turnover is not enough: The need for proficient organizational cultures to support positive youth outcomes in child welfare

PubMed Central

Glisson, Charles

2013-01-01

Objective High caseworker turnover has been identified as a factor in the poor outcomes of child welfare services. However, almost no empirical research has examined the relationship between caseworker turnover and youth outcomes in child welfare systems and there is an important knowledge gap regarding whether, and how, caseworker turnover relates to outcomes for youth. We hypothesized that the effects of caseworker turnover are moderated by organizational culture such that reduced caseworker turnover is only associated with improved youth outcomes in organizations with proficient cultures. Methods The study applied hierarchical linear models (HLM) analysis to the second National Survey of Child and Adolescent Well-being (NSCAW II) with a U.S. nationwide sample of 2,346 youth aged 1.5- to 18-years-old and 1,544 caseworkers in 73 child welfare agencies. Proficient organizational culture was measured by caseworkers’ responses to the Organizational Social Context (OSC) measure; staff turnover was reported by the agencies’ directors; and youth outcomes were measured as total problems in psychosocial functioning with the Child Behavior Checklist (CBCL) completed by the youths’ caregivers at intake and at 18 month follow-up. Results The association between caseworker turnover and youth outcomes was moderated by organizational culture. Youth outcomes were improved with lower staff turnover in proficient organizational cultures and the best outcomes occurred in organizations with low turnover and high proficiency. Conclusions To be successful, efforts to improve child welfare services by lowering staff turnover must also create proficient cultures that expect caseworkers to be competent and responsive to the needs of the youth and families they serve. PMID:24273363

A protocol for a cluster-randomized controlled trial of a self-help psycho-education programme to reduce diagnosis delay in women with breast cancer symptoms in Indonesia.

PubMed

Setyowibowo, Hari; Sijbrandij, Marit; Iskandarsyah, Aulia; Hunfeld, Joke A M; Sadarjoen, Sawitri S; Badudu, Dharmayanti F; Suardi, Drajat R; Passchier, Jan

2017-04-20

Breast cancer (BC) is the most frequent cancer occurring in women across the world. Its mortality rate in low-middle income countries (LMICs) is higher than in high-income countries (HICs), and in Indonesia BC is the leading cause of cancer deaths among women. Delay in breast cancer diagnosis negatively impacts cancer prognosis. Only about 30% of patients who come to the hospital to check on their breast abnormalities, continue thorough examination to biopsy to get a diagnosis based on the results of anatomical pathology. Many Indonesian women with breast cancer were already in an advanced stage when starting treatment. Therefore, delay in diagnosis is a serious problem that needs to be addressed. The present study will investigate whether our newly developed self-help psycho-educational programme, "PERANTARA", for women with breast cancer symptoms is effective to reduce patient diagnosis delay in Indonesia. A cluster-randomized controlled trial will be conducted in 106 patients in four hospitals in Bandung, West Java, Indonesia. Data will be collected at baseline (pre-assessment), 7 days after the intervention (post-assessment), and at 3 months (follow-up assessments). The primary outcome is delay in diagnosis and treatment. Secondary outcomes are breast cancer knowledge, anxiety and depression, and quality of life. Exploratively, adherence with treatment will be measured too. Data will be analysed by hierarchical linear modelling (HLM) to assess differential change over time. If proven effective, PERANTARA will be evaluated and implemented in a diversity of settings for local cares (such as in POSYANDU, PUSKESMAS) that provide health education/psycho-education for women with breast symptoms. ISRCTN12570738 . Date: November 19th, 2016.

Predictors of Information Technology Integration in Secondary Schools: Evidence from a Large Scale Study of More than 30,000 Students

PubMed Central

Hew, Khe Foon; Tan, Cheng Yong

2016-01-01

The present study examined the predictors of information technology (IT) integration in secondary school mathematics lessons. The predictors pertained to IT resource availability in schools, school contextual/institutional variables, accountability pressure faced by schools, subject culture in mathematics, and mathematics teachers’ pedagogical beliefs and practices. Data from 32,256 secondary school students from 2,519 schools in 16 developed economies who participated in the Program for International Student Assessment (PISA) 2012 were analyzed using hierarchical linear modeling (HLM). Results showed that after controlling for student-level (gender, prior academic achievement and socioeconomic status) and school-level (class size, number of mathematics teachers) variables, students in schools with more computers per student, with more IT resources, with higher levels of IT curricular expectations, with an explicit policy on the use of IT in mathematics, whose teachers believed in student-centered teaching-learning, and whose teachers provided more problem-solving activities in class reported higher levels of IT integration. On the other hand, students who studied in schools with more positive teacher-related school learning climate, and with more academically demanding parents reported lower levels of IT integration. Student-related school learning climate, principal leadership behaviors, schools’ public posting of achievement data, tracking of school’s achievement data by administrative authorities, and pedagogical and curricular differentiation in mathematics lessons were not related to levels of IT integration. Put together, the predictors explained a total of 15.90% of the school-level variance in levels of IT integration. In particular, school IT resource availability, and mathematics teachers’ pedagogical beliefs and practices stood out as the most important determinants of IT integration in mathematics lessons. PMID:27997593

Predictors of Information Technology Integration in Secondary Schools: Evidence from a Large Scale Study of More than 30,000 Students.

PubMed

Hew, Khe Foon; Tan, Cheng Yong

2016-01-01

The present study examined the predictors of information technology (IT) integration in secondary school mathematics lessons. The predictors pertained to IT resource availability in schools, school contextual/institutional variables, accountability pressure faced by schools, subject culture in mathematics, and mathematics teachers' pedagogical beliefs and practices. Data from 32,256 secondary school students from 2,519 schools in 16 developed economies who participated in the Program for International Student Assessment (PISA) 2012 were analyzed using hierarchical linear modeling (HLM). Results showed that after controlling for student-level (gender, prior academic achievement and socioeconomic status) and school-level (class size, number of mathematics teachers) variables, students in schools with more computers per student, with more IT resources, with higher levels of IT curricular expectations, with an explicit policy on the use of IT in mathematics, whose teachers believed in student-centered teaching-learning, and whose teachers provided more problem-solving activities in class reported higher levels of IT integration. On the other hand, students who studied in schools with more positive teacher-related school learning climate, and with more academically demanding parents reported lower levels of IT integration. Student-related school learning climate, principal leadership behaviors, schools' public posting of achievement data, tracking of school's achievement data by administrative authorities, and pedagogical and curricular differentiation in mathematics lessons were not related to levels of IT integration. Put together, the predictors explained a total of 15.90% of the school-level variance in levels of IT integration. In particular, school IT resource availability, and mathematics teachers' pedagogical beliefs and practices stood out as the most important determinants of IT integration in mathematics lessons.

Effect of smoking regulations in local restaurants on smokers' anti‐smoking attitudes and quitting behaviours

PubMed Central

Albers, Alison B; Siegel, Michael; Cheng, Debbie M; Biener, Lois; Rigotti, Nancy A

2007-01-01

Objective To examine the effect of smoking regulations in local restaurants on anti‐smoking attitudes and quitting behaviours among adult smokers. Design Hierarchical linear modelling (HLM) was used to assess the relationship between baseline strength of town‐level restaurant smoking regulation and follow‐up (1) perceptions of the social acceptability of smoking and (2) quitting behaviours. Setting Each of the 351 Massachusetts towns was classified as having strong (complete smoking ban) or weak (all other and no smoking restrictions) restaurant smoking regulations. Subjects 1712 adult smokers of Massachusetts aged ⩾18 years at baseline who were interviewed via random‐digit‐dial telephone survey in 2001–2 and followed up 2 years later. Main outcome measures Perceived social acceptability of smoking in restaurants and bars, and making a quit attempt and quitting smoking. Results Among adult smokers who had made a quit attempt at baseline, living in a town with a strong regulation was associated with a threefold increase in the odds of making a quit attempt at follow‐up (OR = 3.12; 95% CI 1.51 to 6.44). Regulation was found to have no effect on cessation at follow‐up. A notable, although marginal, effect of regulation was observed for perceiving smoking in bars as socially unacceptable only among smokers who reported at baseline that smoking in bars was socially unacceptable. Conclusions Although local restaurant smoking regulations did not increase smoking cessation rates, they did increase the likelihood of making a quit attempt among smokers who had previously tried to quit, and seem to reinforce anti‐social smoking norms among smokers who already viewed smoking in bars as socially unacceptable. PMID:17400947

Do Brief Motivational Interventions Reduce Drinking Game Frequency in Mandated Students? An analysis of data from two randomized controlled trials

PubMed Central

Fernandez, Anne C.; Yurasek, Allison M.; Merrill, Jennifer E.; Miller, Mary Beth; Zamboanga, Byron L.; Carey, Kate B.; Borsari, Brian

2016-01-01

Purpose College students frequently engage in drinking games (DG) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMI) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from two randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Methods Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Results Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both Trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Conclusions Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. PMID:27936818

The effects of school policies and practices on eighth-grade science achievement: A multilevel analysis of TIMSS

NASA Astrophysics Data System (ADS)

Smyth, Carol Ann Mary

Identifying the relative importance of both alterable school policies and fairly stable contextual factors as they relate to middle level science achievement, a domain of identified national concern, requires simultaneous investigation of multilevel predictors (i.e., student level and school level) specific to the grade level and academic subject area. The school level factors are predictors associated with both the school (e.g., average socioeconomic status, tracking, and instructional time) and the classroom (e.g., average academic press of peers, teacher collaboration, and instructional strategies). The current study assessed the effects of school policies, practices, and contextual factors on the science achievement of eighth grade students. These influences were considered to be both additive (i.e., influencing the mean achievement in a school after controlling for student characteristics) and interactive (i.e., affecting the relationships between student background characteristics and individual achievement). To account for the nested structure of predictors and cross level interactions among predictors, a multilevel model for middle level science achievement was estimated using hierarchical linear modeling (HLM) with data collected from eighth grade students, science teachers, and administrators in 1995 as part of the Third International Mathematics and Science Study (TIMSS). The major findings of this research suggest that although average eighth grade science achievement in a school was primarily associated with the contextual characteristics of the classroom and the school (e.g., average socioeconomic status and average academic press), both the academic differentiating influence of prior achievement and the social differentiating influence of parental education on the science achievement of eighth grade students were related not only to contextual characteristics of the classroom and the school, but also to the instructional policies of the classroom. Using these results, policy makers can identify factors that can be modified to advance academic excellence in eighth grade science while promoting an equitable distribution of that achievement across students of varying backgrounds.

New psychoactive substances: Studies on the metabolism of XLR-11, AB-PINACA, FUB-PB-22, 4-methoxy-α-PVP, 25-I-NBOMe, and meclonazepam using human liver preparations in comparison to primary human hepatocytes, and human urine.

PubMed

Richter, Lilian H J; Maurer, Hans H; Meyer, Markus R

2017-10-05

New psychoactive substances (NPS) are an increasing problem in clinical and forensic toxicology. The knowledge of their metabolism is important for toxicological risk assessment and for developing toxicological urine screenings. Considering the huge numbers of NPS annually appearing on the market, metabolism studies should be realized in a fast, simple, cost efficient, and reliable way. Primary human hepatocytes (PHH) were recommended to be the gold standard for in vitro metabolism studies as they are expected to contain natural enzyme clusters, co-substrates, and drug transporters. In addition, they were already successfully used for metabolism studies of NPS. However, they also have disadvantages such as high costs and limited applicability without special equipment. The aims of the present study were therefore first to investigate exemplarily the phase I and phase II metabolism of six NPS (XLR-11, AB-PINACA, FUB-PB-22, 4-methoxy-α-PVP, 25-I-NBOMe, and meclonazepam) from different drug classes using pooled human S9 fraction (pS9) or pooled human liver microsomes combined with cytosol (pHLM/pHLC) after addition of the co-substrates for the main metabolic phase I and II reactions. Second to compare results to published data generated using primary human hepatocytes and human urine samples. Results of the incubations with pS9 or pHLM/pHLC were comparable in number and abundance of metabolites. Formation of metabolites, particularly after multi-step reactions needed a longer incubation time. However, incubations using human liver preparations resulted in a lower number of total detected metabolites compared to PHH, but they were still able to allow the identification of the main human urinary excretion products. Human liver preparations and particularly the pooled S9 fraction could be shown to be a sufficient and more cost-efficient alternative in context of metabolism studies also for developing toxicological urine screenings. It might be recommended to use the slightly cheaper pS9 fraction instead of a pHLM/pHLC combination. As formation of some metabolites needed a long incubation time, two sampling points at 60 and 360min should be recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro metabolism and drug-drug interaction potential of UTL-5g, a novel chemo- and radioprotective agent.

PubMed

Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick; Li, Jing

2014-12-01

N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute(-1)·mM(-1), respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

In Vitro Metabolism and Drug-Drug Interaction Potential of UTL-5g, a Novel Chemo- and Radioprotective Agent

PubMed Central

Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick

2014-01-01

N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute−1·mM−1, respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. PMID:25249693

Combined modified en bloc corpectomy with replacement of the aorta in curative interdisciplinary treatment of a large osteosarcoma infiltrating the aorta.

PubMed

Pilger, Amrei; Tsilimparis, Nikolaos; Bockhorn, Maximilian; Trepel, Martin; Dreimann, Marc

2016-05-01

We report a case of a large three-level spinal osteosarcoma infiltrating the adjacent aorta. This is the first case in which a combined modified three-level en bloc corpectomy with resection and replacement of the adjacent aorta was successful as a part of interdisciplinary curative treatment. Case report. The surgical procedure was performed as a two-step treatment. A heart lung machine (HLM) was not used, in order to avoid cerebral and spinal ischemia and to decrease the risk of hematogenous tumor metastases. Instead, a bypass from the left subclavian artery the distal descending aorta was used. We modified the en bloc corpectomy procedure, leaving a dorsal segment of the vertebral bodies to enable rapid surgery. The procedure was successful and the en bloc resection of the vertebral body with aortal resection could be achieved. Except for pallhypesthesia in the left dermatomes Th7-Th10, the patient does not have any postoperative neurologic deficits. Combined corpectomy with aortic replacement should be considered as a reasonable option in the curative treatment of osteosarcoma with consideration of the immense surgical risks. The use of an HLM is not necessary, especially considering the inherent risk of hematogenous tumor metastases. Modified corpectomy leaving a dorsal vertebral body segment was considered a reasonable variation since tumor-free margins could still be expected.

On the role of hydrophobic Si-based protective coatings in limiting mortar deterioration.

PubMed

Cappelletti, G; Fermo, P; Pino, F; Pargoletti, E; Pecchioni, E; Fratini, F; Ruffolo, S A; La Russa, M F

2015-11-01

In order to avoid both natural and artificial stone decay, mainly due to the interaction with atmospheric pollutants (both gases such as NOx and SO2 and particulate matter), polymeric materials have been widely studied as protective coatings enable to limit the penetration of fluids into the bulk material. In the current work, an air hardening calcic lime mortar (ALM) and a natural hydraulic lime mortar (HLM) were used as substrates, and commercially available Si-based resins (Alpha®SI30 and Silres®BS16) were adopted as protective agents to give hydrophobicity features to the artificial stones. Surface properties of coatings and their performance as hydrophobic agents were studied using different techniques such as contact angle measurements, capillary absorption test, mercury intrusion porosimetry, surface free energy, colorimetric measurements and water vapour permeability tests. Finally, some exposure tests to UV radiation and to real polluted atmospheric environments (a city centre and an urban background site) were carried out during a wintertime period (when the concentrations of the main atmospheric pollutants are higher) in order to study the durability of the coating systems applied. The effectiveness of the two commercial resins in reducing salt formation (sulphate and nitrate), induced by the interaction of the mortars with the atmospheric pollutants, was demonstrated in the case of the HLM mortar. Graphical Abstract ᅟ.

Emotion Regulation in Emerging Adult Couples: Temperament, Attachment, and HPA Response to Conflict

PubMed Central

Laurent, Heidemarie; Powers, Sally

2007-01-01

Difficulty managing the stress of conflict in close relationships can lead to mental and physical health problems, possibly through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine stress response system. Temperament, an individual characteristic, and attachment, a dyadic characteristic, have both been implicated in emotion regulation processes and physiological reactivity, yet there is no clear consensus on how the two work together to influence the stress response, especially after childhood. The present study investigated the ways in which temperament and attachment together predict HPA response in emerging adult couples. Analyses using multilevel modeling (HLM) found that partners' dyadic fit on attachment avoidance impacted females' cortisol response patterns, and attachment avoidance further moderated the effect of males' emotionality on both their own and their partners' cortisol. Results are discussed in terms of emotional coregulation processes in romantic attachment. PMID:17681662

The Competition-Violence Hypothesis: Sex, Marriage, and Male Aggression*

PubMed Central

Seffrin, Patrick M.

2018-01-01

Sexually active men, who are not in a monogamous relationship, may be at a greater risk for violence than men who are sexually active within monogamous relationships and men who are not sexually active. The current study examines changes in sexual behavior and violence in adolescence to early adulthood. Data on male (n = 4,597) and female (n = 5,523) respondents were drawn from four waves of the National Longitudinal Study of Adolescent and Adult Health (Add Health). HLM regression models indicate that men who transition to a monogamous, or less competitive, mode of sexual behavior (fewer partners since last wave), reduce their risk for violence. The same results were not replicated for females. Further, results were not accounted for by marital status or other more readily accepted explanations of violence. Findings suggest that competition for sex be further examined as a potential cause of male violence. PMID:29706687

Towed Thermistor Chain Observations in JASIN,

DTIC Science & Technology

1980-07-01

Lij LiJ - S -Ky LJDC cYcc Ql I- 6? F-L T cy D- Hl-m L-L Lo i -,7W LOu CT KK _ _4 C7) 63 -) Ln CD Ln ;Lf FE - CS -JN V LO WLJCNK ua- -~ Lfl CO F (YD... DBD C _W2 + D2 Integrating (A5) yields: G8 bW -1 2cs + b z(s) = (- - 2c 3 / 2 [sinh (d - sinh- (-)] (a7) +- [(A + bs + cs) - /a]c where d = 4ac - b

On the Multilevel Nature of Meta-Analysis: A Tutorial, Comparison of Software Programs, and Discussion of Analytic Choices.

PubMed

Pastor, Dena A; Lazowski, Rory A

2018-01-01

The term "multilevel meta-analysis" is encountered not only in applied research studies, but in multilevel resources comparing traditional meta-analysis to multilevel meta-analysis. In this tutorial, we argue that the term "multilevel meta-analysis" is redundant since all meta-analysis can be formulated as a special kind of multilevel model. To clarify the multilevel nature of meta-analysis the four standard meta-analytic models are presented using multilevel equations and fit to an example data set using four software programs: two specific to meta-analysis (metafor in R and SPSS macros) and two specific to multilevel modeling (PROC MIXED in SAS and HLM). The same parameter estimates are obtained across programs underscoring that all meta-analyses are multilevel in nature. Despite the equivalent results, not all software programs are alike and differences are noted in the output provided and estimators available. This tutorial also recasts distinctions made in the literature between traditional and multilevel meta-analysis as differences between meta-analytic choices, not between meta-analytic models, and provides guidance to inform choices in estimators, significance tests, moderator analyses, and modeling sequence. The extent to which the software programs allow flexibility with respect to these decisions is noted, with metafor emerging as the most favorable program reviewed.

A methodological approach to short-term tracking of youth physical fitness: the Oporto Growth, Health and Performance Study.

PubMed

Souza, Michele; Eisenmann, Joey; Chaves, Raquel; Santos, Daniel; Pereira, Sara; Forjaz, Cláudia; Maia, José

2016-10-01

In this paper, three different statistical approaches were used to investigate short-term tracking of cardiorespiratory and performance-related physical fitness among adolescents. Data were obtained from the Oporto Growth, Health and Performance Study and comprised 1203 adolescents (549 girls) divided into two age cohorts (10-12 and 12-14 years) followed for three consecutive years, with annual assessment. Cardiorespiratory fitness was assessed with 1-mile run/walk test; 50-yard dash, standing long jump, handgrip, and shuttle run test were used to rate performance-related physical fitness. Tracking was expressed in three different ways: auto-correlations, multilevel modelling with crude and adjusted model (for biological maturation, body mass index, and physical activity), and Cohen's Kappa (κ) computed in IBM SPSS 20.0, HLM 7.01 and Longitudinal Data Analysis software, respectively. Tracking of physical fitness components was (1) moderate-to-high when described by auto-correlations; (2) low-to-moderate when crude and adjusted models were used; and (3) low according to Cohen's Kappa (κ). These results demonstrate that when describing tracking, different methods should be considered since they provide distinct and more comprehensive views about physical fitness stability patterns.

Preclinical evaluation of the potential for cytochrome P450 inhibition and induction of the selective ALK inhibitor, alectinib.

PubMed

Sekiguchi, Nobuo; Nagao, Shunsuke; Takanashi, Kenji; Kato, Motohiro; Kaneko, Akihisa; Morita, Keiichi; Shindoh, Hidetoshi; Ishigai, Masaki

2017-12-01

1. A novel selective anaplastic lymphoma kinase (ALK) inhibitor, alectinib, has shown remarkable efficacy and safety in patients with ALK-positive non-small-cell lung cancer (NSCLC). The purpose of this study was to evaluate in vitro the potential to inhibit and induce cytochrome P450 (CYP) isoforms for alectinib and its major metabolite M4. 2. Alectinib and M4 did not show the meaningful direct inhibition of six major CYP isoforms (CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4) in human liver microsomes (HLM). Alectinib, but not M4, competitively inhibited CYP2C8, by which few marketed drugs are exclusively metabolized, with an inhibition constant of 1.98 μM. 3. Out of the seven CYP isoforms in HLM, alectinib and M4 showed time-dependent inhibition (TDI) of only CYP3A4, which suggests low TDI potential due to low inactivation efficiency. 4. Alectinib exhibited quite smaller induction of mRNA expression of CYP1A2, 2B6 and 3A4 genes in human hepatocytes compared to the respective positive controls, suggesting a low potential of enzyme induction. 5. In summary, the risk of alectinib causing drug-drug interactions with coadministered drugs is expected to be low due to the weak potential of CYP inhibition and induction estimated in the preclinical studies.

Characterization of in Vitro ADME Properties of Diosgenin and Dioscin from Dioscorea villosa

PubMed Central

Manda, Vamshi K.; Avula, Bharathi; Ali, Zulfiqar; Wong, Yan-Hong; Smillie, Troy J.; Khan, Ikhlas A.; Khan, Shabana I.

2017-01-01

Dioscorea villosa (wild yam) is native to North America and has been widely used as a natural alternative for estrogen replacement therapy to improve women’s health as well as to treat inflammation, muscle spasm, and asthma. Diosgenin and dioscin (glycoside form of diosgenin) are reported to be the pharmacologically active compounds. Despite the reports of significant pharmacological properties of dioscin and diosgenin in conditions related to inflammation, cancer, diabetes, and gastrointestinal ailments, no reports are available on ADME properties of these compounds. This study was carried out to determine ADME properties of diosgenin and dioscin and their effects on major drug metabolizing enzymes (CYP 3A4, 2D6, 2C9, and 1A2). The stability was determined in simulated gastric and intestinal fluids (SGF, pH 1.2 and SIF, pH 6.8), and intestinal transport was evaluated in Caco-2 model. Phase I and phase II metabolic stability was determined in human liver microsomes and S9 fractions, respectively. Quantitative analysis of dioscin and diosgenin was performed by UPLC-MS system. Dioscin degraded up to 28.3% in SGF and 12.4% in SIF, which could be accounted for by its conversion to diosgenin (24.2%. in SGF and 2.4% in SIF). The depletion of diosgenin in SGF and SIF was < 10%. Diosgenin was stable in HLM but disappeared in S9 fraction with a half-life of 11.3 min. In contrast, dioscin was stable in both HLM and S9 fractions. Dioscin showed higher permeability across Caco-2 monolayer with no significant efflux, while diosgenin was subjected to efflux mediated by P-glycoprotein. Diosgenin and dioscin inhibited CYP3A4 with IC50 values of 17 and 33 μM, respectively, while other CYP enzymes were not affected. In conclusion, dioscin showed better intestinal permeability. Conversion of dioscin to diosgenin was observed in both gastric and intestinal fluids. No phase I metabolism was detected for both compounds. The disappearance of diosgenin in S9 fraction indicated phase II metabolism. PMID:23970424

Long term corrosion on T91 and AISI1 316L steel in flowing lead alloy and corrosion protection barrier development: Experiments and models

NASA Astrophysics Data System (ADS)

Weisenburger, A.; Schroer, C.; Jianu, A.; Heinzel, A.; Konys, J.; Steiner, H.; Müller, G.; Fazio, C.; Gessi, A.; Babayan, S.; Kobzova, A.; Martinelli, L.; Ginestar, K.; Balbaud-Célerier, F.; Martín-Muñoz, F. J.; Soler Crespo, L.

2011-08-01

Considering the status of knowledge on corrosion and corrosion protection and especially the need for long term compatibility data of structural materials in HLM a set of experiments to generate reliable long term data was defined and performed. The long term corrosion behaviour of the two structural materials foreseen in ADS, 316L and T91, was investigated in the design relevant temperature field, i.e. from 300 to 550 °C. The operational window of the two steels in this temperature range was identified and all oxidation data were used to develop and validate the models of oxide scale growth in PbBi. A mechanistic model capable to predict the oxidation rate applying some experimentally fitted parameters has been developed. This model assumes parabolic oxidation and might be used for design and safety relevant investigations in future. Studies on corrosion barrier development allowed to define the required Al content for the formation of thin alumina scales in LBE. These results as well as future steps and required improvements are discussed. Variation of experimental conditions clearly showed that specific care has to be taken with respect to local flow conditions and oxygen concentrations.

A Hydrologic Routing Model Based on Geomorphological Characteristics of the River Network

NASA Astrophysics Data System (ADS)

Krajewski, W. F.; Quintero, F.; Ghimire, G.; Rojas, M.

2017-12-01

The Iowa Flood Center (IFC) provides streamflow forecasts for about 2000 locations in Iowa using a real-time distributed hydrologic model, forced with radar and raingage rainfall information. The model structure is based on ordinary differential equations that represent the flow of water from the hillslopes to the channels of the river network. The formulation of the routing of water across the rivers constitutes a fundamental aspect of the model, because this component is mostly responsible for providing estimates of the time-to-peak and peak magnitude. The routing model structure of the system is based on the scaling properties of river velocity with the discharge and drainage area of the channel, which can be written in terms of a power-law function. This study examines how this scaling relation is connected to the Horton-Strahler order of the channel network. This evaluation represents a step forward towards formulating model structures that are based on characteristics that are invariant across spatial scales. We proposed a routing model for every different Horton orders of the network, by adjusting a power-law function to available observations of velocity and discharge provided by USGS. The models were implemented into the Hillslope-Link Model (HLM) of the IFC for offline evaluation. Model simulations were compared to discharge observations to assess their performance, and compared to simulations obtained with other hydrologic routing schemes, to determine if the new formulation improves performance of the model.

Estimating multilevel logistic regression models when the number of clusters is low: a comparison of different statistical software procedures.

PubMed

Austin, Peter C

2010-04-22

Multilevel logistic regression models are increasingly being used to analyze clustered data in medical, public health, epidemiological, and educational research. Procedures for estimating the parameters of such models are available in many statistical software packages. There is currently little evidence on the minimum number of clusters necessary to reliably fit multilevel regression models. We conducted a Monte Carlo study to compare the performance of different statistical software procedures for estimating multilevel logistic regression models when the number of clusters was low. We examined procedures available in BUGS, HLM, R, SAS, and Stata. We found that there were qualitative differences in the performance of different software procedures for estimating multilevel logistic models when the number of clusters was low. Among the likelihood-based procedures, estimation methods based on adaptive Gauss-Hermite approximations to the likelihood (glmer in R and xtlogit in Stata) or adaptive Gaussian quadrature (Proc NLMIXED in SAS) tended to have superior performance for estimating variance components when the number of clusters was small, compared to software procedures based on penalized quasi-likelihood. However, only Bayesian estimation with BUGS allowed for accurate estimation of variance components when there were fewer than 10 clusters. For all statistical software procedures, estimation of variance components tended to be poor when there were only five subjects per cluster, regardless of the number of clusters.

The unique, optically-dominated quasar jet of PKS 1421-490

NASA Astrophysics Data System (ADS)

Gelbord, J. M.; Marshall, H. L.; Worrall, D. M.; Birkinshaw, M.; Lovell, J. E. J.; Ojha, R.; Godfrey, L.; Schwartz, D. A.; Perlman, E. S.; Georganopoulos, M.; Murphy, D. W.; Jauncey, D. L.

2004-12-01

The unique, optically-dominated quasar jet of PKS 1421-490 We report the discovery of extremely strong optical and X-ray emission associated with a knot in the radio jet of PKS 1421-490. The SDSS g' = 17.8 magnitude makes this the second-brightest optical jet known. The jet-to-core flux ratio in the X-ray band is unusually large (3.7), and the optical flux ratio ( ˜300) is unprecedented. The broad-band spectrum of the knot is flat from the radio through the optical bands, and has a similar slope with a lower normalization in the X-ray band. This emission is difficult to interpret without resorting to extreme model parameters or physically unlikely scenarios (flat electron distributions, non-equipartition magnetic fields, huge Doppler factors, etc.). We discuss several alternative models for the radio-to-X-ray continuum, including pure synchrotron, synchrotron plus inverse Compton scattering of cosmic microwave background photons, and a decelerating jet. JMG was supported under Chandra grant GO4-5124X to MIT from the CXC. HLM was supported under NASA contract SAO SV1-61010 for the Chandra X-Ray Center (CXC).

Bioactivation of cinnamic alcohol forms several strong skin sensitizers.

PubMed

Niklasson, Ida B; Ponting, David J; Luthman, Kristina; Karlberg, Ann-Therese

2014-04-21

Cinnamic alcohol is a frequent contact allergen, causing allergic contact dermatitis (ACD) in a substantial number of individuals sensitized from contacts with fragrances. Hence, cinnamic alcohol is one of the constituents in fragrance mix I (FM I) used for screening contact allergy in dermatitis patients. Cinnamic alcohol lacks structural alerts for protein reactivity and must therefore be activated by either air oxidation or bioactivation to be able to act as a sensitizer. In the present study, we explored the bioactivation of cinnamic alcohol using human liver microsomes (HLM), and the potential pathways for these reactions were modeled by in silico (DFT) techniques. Subsequently, the reactivity of cinnamic alcohol and its metabolites toward a model hexapeptide were investigated. In addition to cinnamic aldehyde and cinnamic acid, two highly sensitizing epoxides previously unobserved in studies of bioactivation were detected in the incubations with HLMs. Formation of epoxy cinnamic aldehyde was shown (both by the liver microsomal experiments, in which no depletion of epoxy cinnamic alcohol was observed after initial formation, and by the very high activation energy found for the oxidation thereof by calculations) to proceed via cinnamic aldehyde and not epoxy cinnamic alcohol.

Effectiveness of Motivational Incentives for Adolescent Marijuana Users in a School-Based Intervention.

PubMed

Stewart, David G; Felleman, Benjamin I; Arger, Christopher A

2015-11-01

This study examined whether adolescents receiving Motivational Interviewing (MI) intervention have different outcomes compared to those receiving Motivational Incentives (Motivational Interviewing combined with Contingency Management; MI+CM). A total of 136 adolescents (from a parent study of 220 adolescents) with problematic substance use were recruited from 8 high schools in Washington State, where they completed either 8-weeks of MI or MI+CM. Frequency of marijuana use was assessed at baseline, at the end-of-treatment, and at 16-week follow-up. A balanced and matched sample was created using propensity scores, then analyzed using Hierarchical Linear Modeling (HLM). Multilevel regression analyses revealed that adolescents who received MI+CM exhibited a greater reduction in use across time (p<.05). Reductions at the end-of-treatment were greater for the MI+CM condition (Cohen's d=-.82) compared to MI alone (Cohen's d=-.33), but did not differ at 16-week follow-up. Adolescents receiving MI+CM showed significantly fewer negative consequences of marijuana use at the end-of-treatment (t1, 124=2.26, p<.05), higher use of coping strategies (t1, 124=3.01, p<.01), and increased likelihood to attend additional treatment for substance use (χ2 1, 124=4.12 p<.05), though hypothesized improvements in motivation and school attendance were not found. Use of coping strategies at the end-of-treatment had a significant indirect effect on the relationship between the intervention condition and marijuana use at the end-of-treatment (F3, 121=10.20, R2=.20, p<.01). These results suggest that the inclusion of contingencies into adolescent marijuana treatment decreases the end-of-treatment frequency of marijuana use and related consequences while increasing the use of coping strategies and the pursuit of additional treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

“Blurred Lines?”1 Sexual Aggression and Barroom Culture

PubMed Central

Graham, Kathryn; Bernards, Sharon; Osgood, D. Wayne; Abbey, Antonia; Parks, Michael; Flynn, Andrea; Dumas, Tara; Wells, Samantha

2014-01-01

Background Meeting potential sexual/romantic partners for mutual pleasure is one of the main reasons young adults go to bars. However, not all sexual contacts are positive and consensual, and aggression related to sexual advances is a common experience. Sometimes such aggression is related to misperceptions in making and receiving sexual advances while other times aggression reflects intentional harassment or other sexually aggressive acts. The present study uses objective observational research to assess quantitatively gender of initiators and targets and the extent that sexual aggression involves intentional aggression by the initiator, the nature of responses by targets, and the role of third parties and intoxication. Methods We analyzed 258 aggressive incidents involving sexual advances observed as part of a larger study on aggression in large capacity bars and clubs, using variables collected as part of the original research (gender, intoxication, intent) and variables coded from narrative descriptions (invasiveness, persistence, targets’ responses, role of third parties). Hierarchical Linear Modeling (HLM) analyses were used to account for nesting on incidents in evening and bars. Results 90% of incidents involved male initiators and female targets, with almost all incidents involving intentional or probably intentional aggression. Targets mostly responded nonaggressively, usually using evasion to end the incident. Staff rarely intervened; patron third parties intervened in 21% of incidents, usually to help the target but sometimes to encourage the initiator. Initiators’ level of invasiveness was related to intoxication of the targets but not their own intoxication, suggesting intoxicated women were being targeted. Conclusions Sexual aggression is a major problem in bars often reflecting intentional sexual invasiveness and unwanted persistence rather than misperceptions in sexual advances. Prevention needs to focus on addressing masculinity norms of male patrons and staff that support sexual aggression and better management of the highly sexualized and sexist environments of most bars. PMID:24588839

One-to-one iPad technology in the middle school mathematics and science classrooms

NASA Astrophysics Data System (ADS)

Bixler, Sharon G.

Science, technology, engineering, and mathematics (STEM) education has become an emphasized component of PreK-12 education in the United States. The US is struggling to produce enough science, mathematics, and technology experts to meet its national and global needs, and the mean scores of science and mathematics students are not meeting the expected levels desired by our leaders (Hossain & Robinson, 2011). In an effort to improve achievement scores in mathematics and science, school districts must consider many components that can contribute to the development of a classroom where students are engaged and growing academically. Computer technology (CT) for student use is a popular avenue for school districts to pursue in their goal to attain higher achievement. The purpose of this study is to examine the use of iPads in a one-to-one setting, where every student has his own device 24/7, to determine the effects, if any, on academic achievement in the areas of mathematics and science. This comparison study used hierarchical linear modeling (HLM) to examine three middle schools in a private school district. Two of the schools have implemented a one-to-one iPad program with their sixth through eighth grades and the third school uses computers on limited occasions in the classroom and in a computer lab setting. The questions addressed were what effect, if any, do the implementation of a one-to-one iPad program and a teacher's perception of his use of constructivist teaching strategies have on student academic achievement in the mathematics and science middle school classrooms. The research showed that although the program helped promote the use of constructivist activities through the use of technology, the one-to-one iPad initiative had no effect on academic achievement in the middle school mathematics and science classrooms.

Using conventional and in situ transmission electron microscopy techniques to understand nanoscale crystallography

NASA Astrophysics Data System (ADS)

Hudak, Bethany M.

Science, technology, engineering, and mathematics (STEM) education has become an emphasized component of PreK-12 education in the United States. The US is struggling to produce enough science, mathematics, and technology experts to meet its national and global needs, and the mean scores of science and mathematics students are not meeting the expected levels desired by our leaders (Hossain & Robinson, 2011). In an effort to improve achievement scores in mathematics and science, school districts must consider many components that can contribute to the development of a classroom where students are engaged and growing academically. Computer technology (CT) for student use is a popular avenue for school districts to pursue in their goal to attain higher achievement. The purpose of this study is to examine the use of iPads in a one-to-one setting, where every student has his own device 24/7, to determine the effects, if any, on academic achievement in the areas of mathematics and science. This comparison study used hierarchical linear modeling (HLM) to examine three middle schools in a private school district. Two of the schools have implemented a one-to-one iPad program with their sixth through eighth grades and the third school uses computers on limited occasions in the classroom and in a computer lab setting. The questions addressed were what effect, if any, do the implementation of a one-to-one iPad program and a teacher's perception of his use of constructivist teaching strategies have on student academic achievement in the mathematics and science middle school classrooms. The research showed that although the program helped promote the use of constructivist activities through the use of technology, the one-to-one iPad initiative had no effect on academic achievement in the middle school mathematics and science classrooms.

Changes in and predictors of severity of fatigue in women with breast cancer: A longitudinal study.

PubMed

Huang, Hsiang-Ping; Chen, Mei-Ling; Liang, Jersey; Miaskowski, Christine

2014-04-01

Fatigue is the most common symptom experienced by cancer patients. However, longitudinal studies of changes in the severity and predictors of fatigue are limited. The purposes of this study were to evaluate changes in fatigue severity in women with breast cancer prior to and for twelve months after surgery. Factors that affected the severity and the trajectory of fatigue were identified. This observational prospective study approached 334 women who were scheduled for breast cancer surgery in a medical center located in northern Taiwan. Among the 334 women, 239 met the inclusion/exclusion criteria. The final sample size used for the data analysis was 200. Fatigue, depressive symptom, and symptom distress were evaluated in women prior to and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 months after surgery for breast cancer. Hierarchical linear modeling (HLM) was applied where level-1 data consisted of repeated observations of study variables within each subject and level-2 data consisted of static characteristics of individual subject. The fatigue levels ranged from 1.92 to 3.09. Changes in fatigue severity demonstrated a quadratic trajectory that increased and reached the peak at the second month after the surgery, followed by a gradual decreased. After adjusting for the effect of receipt of chemotherapy, symptom distress, and depressive symptom, the quadratic change pattern for fatigue became imperceptible. Women who had a partial mastectomy (P=0.028), had a higher educational level (P=0.048), were married (P=0.043), and had poorer functional performance at diagnosis (P=0.043) had higher levels of fatigue. Patients who underwent surgery for breast cancer reported mild to moderate levels of fatigue over a period of 12 months. Fatigue levels fluctuated with patients' level of depressive symptoms, symptom distress, and receipt of chemotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification and characterization of naturally occurring inhibitors against UDP-glucuronosyltransferase 1A1 in Fructus Psoraleae (Bu-gu-zhi)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xin-Xin; Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023; Lv, Xia

As an edible traditional Chinese herb, Fructus psoraleae (FP) has been widely used in Asia for the treatment of vitiligo, bone fracture and osteoporosis. Several cases on markedly elevated bilirubin and acute liver injury following administration of FP and its related proprietary medicine have been reported, but the mechanism in FP-associated toxicity has not been well investigated yet. This study aimed to investigate the inhibitory effects of FP extract and its major constituents against human UDP-glucuronosyltransferase 1A1 (UGT1A1), the key enzyme responsible for metabolic elimination of bilirubin. To this end, N-(3-carboxy propyl)-4-hydroxy-1,8-naphthalimide (NCHN), a newly developed specific fluorescent probe formore » UGT1A1, was used to evaluate the inhibitory effects of FP extract or its fractions in human liver microsomes (HLM), while LC-UV fingerprint and UGT1A1 inhibition profile were combined to identity and characterize the naturally occurring inhibitors of UGT1A1 in FP. Our results demonstrated that both the extract of FP and five major components of FP displayed evident inhibitory effects on UGT1A1 in HLM. Among these five identified naturally occurring inhibitors, bavachin and corylifol A were found to be strong inhibitors of UGT1A1 with the inhibition kinetic parameters (K{sub i}) values lower than 1 μM, while neobavaisoflavone, isobavachalcone, and bavachinin displayed moderate inhibitory effects against UGT1A1 in HLM, with the K{sub i} values ranging from 1.61 to 9.86 μM. These findings suggested that FP contains natural compounds with potent inhibitory effects against human UGT1A1, which may be one of the important reasons for triggering FP-associated toxicity, including elevated bilirubin levels and liver injury. - Graphical abstract: LC-UV fingerprint and UGT1A1 inhibition profiles were combined to identity and characterize the natural inhibitors of UGT1A1 in F. psoraleae for the first time. Five major components in F. psoraleae were identified as strong inhibitors against UGT1A1 in human liver microsomes, with the K{sub i} values ranging from 1.18–9.86 μM. - Highlights: • A method for rapid identification of UGT1A1 inhibitors from herbals was developed. • Fructus psoraleae (FP) extract displayed strong inhibitory effects on UGT1A1. • Five UGT1A1 inhibitory constituents in FP were identified for the first time. • The inhibition mechanism and the inhibition constant were well-characterized.« less

Global Regulation of Plant Immunity by Histone Lysine Methyl Transferases

PubMed Central

Lee, Sanghun; Xu, Siming; Lee, Sang Yeol; Yun, Dae-Jin; Mengiste, Tesfaye

2016-01-01

Posttranslational modification of histones modulates gene expression affecting diverse biological functions. We showed that the Arabidopsis thaliana histone methyl transferases SET DOMAIN GROUP8 (SDG8) and SDG25 regulate pep1-, flg22-, and effector-triggered immunity as well as systemic acquired resistance. Genome-wide basal and induced transcriptome changes regulated by SDG8 and/or SDG25 showed that two genes of the SDG-dependent transcriptome, CAROTENOID ISOMERASE2 (CCR2) and ECERIFERUM3 (CER3), were also required for plant immunity, establishing mechanisms in defense functions for SDG8 and SDG25. CCR2 catalyzes the biosynthesis of carotenoids, whereas CER3 is involved in the biosynthesis of cuticular wax. SDG8 and SDG25 affected distinct and overlapping global and locus-specific histone H3 lysine 4 (H3K4) and histone H3 lysine 36 (H3K36) methylations. Loss of immunity in sdg mutants was attributed to altered global and CCR2- and CER3-specific histone lysine methylation (HLM). Loss of immunity in sdg, ccr2, and cer3 mutants was also associated with diminished accumulation of lipids and loss of cuticle integrity. In addition, sdg8 and sdg25 mutants were impaired in H2B ubiquitination (H2Bubn) at CCR2, CER3, and H2Bubn regulated R gene, SNC1, revealing crosstalk between the two types of histone modifications. In summary, SDG8 and SDG25 contribute to plant immunity directly through HLM or indirectly through H2Bubn and by regulating expression of plant immunity genes, accumulation of lipids, biosynthesis of carotenoids, and maintenance of cuticle integrity. PMID:27354553

Global Regulation of Plant Immunity by Histone Lysine Methyl Transferases.

PubMed

Lee, Sanghun; Fu, Fuyou; Xu, Siming; Lee, Sang Yeol; Yun, Dae-Jin; Mengiste, Tesfaye

2016-07-01

Posttranslational modification of histones modulates gene expression affecting diverse biological functions. We showed that the Arabidopsis thaliana histone methyl transferases SET DOMAIN GROUP8 (SDG8) and SDG25 regulate pep1-, flg22-, and effector-triggered immunity as well as systemic acquired resistance. Genome-wide basal and induced transcriptome changes regulated by SDG8 and/or SDG25 showed that two genes of the SDG-dependent transcriptome, CAROTENOID ISOMERASE2 (CCR2) and ECERIFERUM3 (CER3), were also required for plant immunity, establishing mechanisms in defense functions for SDG8 and SDG25. CCR2 catalyzes the biosynthesis of carotenoids, whereas CER3 is involved in the biosynthesis of cuticular wax. SDG8 and SDG25 affected distinct and overlapping global and locus-specific histone H3 lysine 4 (H3K4) and histone H3 lysine 36 (H3K36) methylations. Loss of immunity in sdg mutants was attributed to altered global and CCR2- and CER3-specific histone lysine methylation (HLM). Loss of immunity in sdg, ccr2, and cer3 mutants was also associated with diminished accumulation of lipids and loss of cuticle integrity. In addition, sdg8 and sdg25 mutants were impaired in H2B ubiquitination (H2Bubn) at CCR2, CER3, and H2Bubn regulated R gene, SNC1, revealing crosstalk between the two types of histone modifications. In summary, SDG8 and SDG25 contribute to plant immunity directly through HLM or indirectly through H2Bubn and by regulating expression of plant immunity genes, accumulation of lipids, biosynthesis of carotenoids, and maintenance of cuticle integrity. © 2016 American Society of Plant Biologists. All rights reserved.

Efavirenz Primary and Secondary Metabolism In Vitro and In Vivo: Identification of Novel Metabolic Pathways and Cytochrome P450 2A6 as the Principal Catalyst of Efavirenz 7-Hydroxylation

PubMed Central

Ogburn, Evan T.; Jones, David R.; Masters, Andrea R.; Xu, Cong; Guo, Yingying

2010-01-01

Efavirenz primary and secondary metabolism was investigated in vitro and in vivo. In human liver microsome (HLM) samples, 7- and 8-hydroxyefavirenz accounted for 22.5 and 77.5% of the overall efavirenz metabolism, respectively. Kinetic, inhibition, and correlation analyses in HLM samples and experiments in expressed cytochrome P450 show that CYP2A6 is the principal catalyst of efavirenz 7-hydroxylation. Although CYP2B6 was the main enzyme catalyzing efavirenz 8-hydroxylation, CYP2A6 also seems to contribute. Both 7- and 8-hydroxyefavirenz were further oxidized to novel dihydroxylated metabolite(s) primarily by CYP2B6. These dihydroxylated metabolite(s) were not the same as 8,14-dihydroxyefavirenz, a metabolite that has been suggested to be directly formed via 14-hydroxylation of 8-hydroxyefavirenz, because 8,14-dihydroxyefavirenz was not detected in vitro when efavirenz, 7-, or 8-hydroxyefavirenz were used as substrates. Efavirenz and its primary and secondary metabolites that were identified in vitro were quantified in plasma samples obtained from subjects taking a single 600-mg oral dose of efavirenz. 8,14-Dihydroxyefavirenz was detected and quantified in these plasma samples, suggesting that the glucuronide or the sulfate of 8-hydroxyefavirenz might undergo 14-hydroxylation in vivo. In conclusion, efavirenz metabolism is complex, involving unique and novel secondary metabolism. Although efavirenz 8-hydroxylation by CYP2B6 remains the major clearance mechanism of efavirenz, CYP2A6-mediated 7-hydroxylation (and to some extent 8-hydroxylation) may also contribute. Efavirenz may be a valuable dual phenotyping tool to study CYP2B6 and CYP2A6, and this should be further tested in vivo. PMID:20335270

Role of UDP-glucuronosyltransferase isoforms in 13-cis retinoic acid metabolism in humans.

PubMed

Rowbotham, Sophie E; Illingworth, Nicola A; Daly, Ann K; Veal, Gareth J; Boddy, Alan V

2010-07-01

13-cis Retinoic acid (13cisRA, isotretinoin) is an important drug in both dermatology, and the treatment of high-risk neuroblastoma. 13cisRA is known to undergo cytochrome P450-mediated oxidation, mainly by CYP2C8, but phase II metabolic pathways have not been characterized. In the present study, the glucuronidation activities of human liver (HLM) and intestinal microsomes (HIM), as well as a panel of human UDP-glucuronosyltransferases (UGTs) toward both 13cisRA and the 4-oxo metabolite, 4-oxo 13cisRA, were compared using high-performance liquid chromatography. Both HLM and, to a greater extent, HIM catalyzed the glucuronidation of 13cisRA and 4-oxo 13cisRA. Based on the structures of 13cisRA and 4-oxo 13cisRA, the glucuronides formed are conjugated at the terminal carboxylic acid. Further analysis revealed that UGT1A1, UGT1A3, UGT1A7, UGT1A8, and UGT1A9 were the major isoforms responsible for the glucuronidation of both substrates. For 13cisRA, a pronounced substrate inhibition was observed with individual UGTs and with HIM. UGT1A3 exhibited the highest rate of activity toward both substrates, and a high rate of activity toward 13cisRA glucuronidation was also observed with UGT1A7. However, for both substrates, K(m) values were above concentrations reported in clinical studies. Therefore, UGT1A9 is likely to be the most important enzyme in the glucuronidation of both substrates as this enzyme had the lowest K(m) and is expressed in both the intestine and at high levels in the liver.

In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS.

PubMed

Boumrah, Yacine; Humbert, Luc; Phanithavong, Melodie; Khimeche, Kamel; Dahmani, Abdallah; Allorge, Delphine

2016-02-01

One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false-negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP- and UGT-dependent metabolites of the 2-(4-bromo-2,5-dimethoxy-phenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra-high performance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry detector (UHPLC-Q-TOF/MS). On-line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified. O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B-NBOMe and allow us to detect 25B-MBOMe users. Copyright © 2015 John Wiley & Sons, Ltd.

Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

PubMed Central

Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

2013-01-01

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

Benzydamine N-oxidation as an index reaction reflecting FMO activity in human liver microsomes and impact of FMO3 polymorphisms on enzyme activity

PubMed Central

Störmer, Elke; Roots, Ivar; Brockmöller, Jürgen

2000-01-01

Aims The role of flavin containing monooxygenases (FMO) on the disposition of many drugs has been insufficiently explored. In vitro and in vivo tests are required to study FMO activity in humans. Benzydamine (BZD) N-oxidation was evaluated as an index reaction for FMO as was the impact of genetic polymorphisms of FMO3 on activity. Methods BZD was incubated with human liver microsomes (HLM) and recombinant enzymes. Human liver samples were genotyped using PCR-RFLP. Results BZD N-oxide formation rates in HLM followed Michaelis-Menten kinetics (mean Km = 64.0 μm, mean Vmax = 6.9 nmol mg−1 protein min−1; n = 35). N-benzylimidazole, a nonspecific CYP inhibitor, and various CYP isoform selective inhibitors did not affect BZD N-oxidation. In contrast, formation of BZD N-oxide was almost abolished by heat treatment of microsomes in the absence of NADPH and strongly inhibited by methimazole, a competitive FMO inhibitor. Recombinant FMO3 and FMO1 (which is not expressed in human liver), but not FMO5, showed BZD N-oxidase activity. Respective Km values for FMO3 and FMO1 were 40.4 μm and 23.6 μm, and respective Vmax values for FMO3 and FMO1 were 29.1 and 40.8 nmol mg−1 protein min−1. Human liver samples (n = 35) were analysed for six known FMO3 polymorphisms. The variants I66M, P135L and E305X were not detected. Samples homozygous for the K158 variant showed significantly reduced vmax values (median 2.7 nmol mg−1 protein min−1) compared to the carriers of at least one wild type allele (median 6.2 nmol mg−1 protein min−1) (P<0.05, Mann–Whitney- U-test). The V257M and E308G substitutions had no effect on enzyme activity. Conclusions BZD N-oxidation in human liver is mainly catalysed by FMO3 and enzyme activity is affected by FMO3 genotype. BZD may be used as a model substrate for human liver FMO3 activity in vitro and may be further developed as an in vivo probe reflecting FMO3 activity. PMID:11136294

Quinolone-based HDAC inhibitors.

PubMed

Balasubramanian, Gopalan; Kilambi, Narasimhan; Rathinasamy, Suresh; Rajendran, Praveen; Narayanan, Shridhar; Rajagopal, Sridharan

2014-08-01

HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.

Childhood and Adult Trauma Experiences of Incarcerated Persons and Their Relationship to Adult Behavioral Health Problems and Treatment

PubMed Central

Wolff, Nancy; Shi, Jing

2012-01-01

Rates of childhood and adult trauma are high among incarcerated persons. In addition to criminality, childhood trauma is associated with the risk for emotional disorders (e.g., depression and anxiety) and co-morbid conditions such as alcohol and drug abuse and antisocial behaviors in adulthood. This paper develops rates of childhood and adult trauma and examines the impact of age-of-onset and type-specific trauma on emotional problems and behavior for a sample of incarcerated males (N~4,000). Prevalence estimates for types of trauma were constructed by age at time of trauma, race and types of behavioral health treatment received while incarcerated. HLM models were used to explore the association between childhood and adult trauma and depression, anxiety, substance use, interpersonal problems, and aggression problems (each model estimated separately and controlling for age, gender, race, time incarcerated, and index offense). Rates of physical, sexual, and emotional trauma were higher in childhood than adulthood and ranged from 44.7% (physical trauma in childhood) to 4.5% (sexual trauma in adulthood). Trauma exposure was found to be strongly associated with a wide range of behavioral problems and clinical symptoms. Given the sheer numbers of incarcerated men and the strength of these associations, targeted intervention is critical. PMID:22754481

Childhood and adult trauma experiences of incarcerated persons and their relationship to adult behavioral health problems and treatment.

PubMed

Wolff, Nancy; Shi, Jing

2012-05-01

Rates of childhood and adult trauma are high among incarcerated persons. In addition to criminality, childhood trauma is associated with the risk for emotional disorders (e.g., depression and anxiety) and co-morbid conditions such as alcohol and drug abuse and antisocial behaviors in adulthood. This paper develops rates of childhood and adult trauma and examines the impact of age-of-onset and type-specific trauma on emotional problems and behavior for a sample of incarcerated males (N~4,000). Prevalence estimates for types of trauma were constructed by age at time of trauma, race and types of behavioral health treatment received while incarcerated. HLM models were used to explore the association between childhood and adult trauma and depression, anxiety, substance use, interpersonal problems, and aggression problems (each model estimated separately and controlling for age, gender, race, time incarcerated, and index offense). Rates of physical, sexual, and emotional trauma were higher in childhood than adulthood and ranged from 44.7% (physical trauma in childhood) to 4.5% (sexual trauma in adulthood). Trauma exposure was found to be strongly associated with a wide range of behavioral problems and clinical symptoms. Given the sheer numbers of incarcerated men and the strength of these associations, targeted intervention is critical.

A cross-cultural, multilevel study of inquiry-based instruction effects on conceptual understanding and motivation in physics

NASA Astrophysics Data System (ADS)

Negishi, Meiko

Student achievement and motivation to learn physics is highly valued in many industrialized countries including the United States and Japan. Science education curricula in these countries emphasize the importance and encourage classroom teachers to use an inquiry approach. This dissertation investigated high school students' motivational orientations and their understanding of physics concepts in a context of inquiry-based instruction. The goals were to explore the patterns of instructional effects on motivation and learning in each country and to examine cultural differences and similarities. Participants consisted of 108 students (55 females, 53 males) and 9 physics teachers in the United States and 616 students (203 females and 413 males) and 11 physics teachers in Japan. Students were administered (a) Force Concept Inventory measuring physics conceptual understanding and (b) Attitudes about Science Questionnaire measuring student motivational orientations. Teachers were given a survey regarding their use of inquiry teaching practices and background information. Additionally, three teachers in each country were interviewed and observed in their classrooms. For the data analysis, two-level hierarchical linear modeling (HLM) methods were used to examine individual student differences (i.e., learning, motivation, and gender) within each classroom (i.e., inquiry-based teaching, teaching experience, and class size) in the U.S. and Japan, separately. Descriptive statistical analyses were also conducted. The results indicated that there was a cultural similarity in that current teaching practices had minimal influence on conceptual understanding as well as motivation of high school students between the U.S. and Japan. In contrast, cultural differences were observed in classroom structures and instructional approaches. Furthermore, this study revealed gender inequity in Japanese students' conceptual understanding and self-efficacy. Limitations of the study, as well as implications for high school physics teachers are discussed. Future research in this line could explore students' use of cognitive strategies to overcome misconceptions in Western and Eastern cultures. Also, exploring the best practices in changing student misconceptions and promoting motivation across cultures would enrich our understanding and current teaching practices.

Prevalence of Suicidal Ideation and Its Association with Positive Affect in Working Women: A Day Reconstruction Study

PubMed Central

Tian, Lili; Yang, Ying; Yang, Huijing; Huebner, E. Scott

2017-01-01

The suicide rate for females in China is the second highest worldwide, and China is the only country in the world in which the rate of suicides is higher for women than men. Affective instability has been shown to be a strong predictor of suicidal ideation, particularly among women. However, prior research has mainly focused on the impact of women's negative affect on suicidal ideation, ignoring the influence of positive affect on suicidal ideation. Studies have revealed that hopelessness, which is 1.3 times more important than depression for explaining suicidal ideation, is driven more by low levels of positive affect than by high levels of negative affect. Although positive affect has also been found to be related to suicidal ideation, and it demonstrates independent, beneficial effects on mental health, much remains to be learned about the association between positive affective instability and suicidal ideation. Therefore, we investigated the prevalence of suicidal ideation among Chinese working women and explored the differences between working women with and without suicidal ideation in the intensity and daily variability of positive affect. A total of 222 young working women of ages 22–36 years (M = 27.64, SD = 3.73) were recruited from a free weekend psychology lecture. The women subsequently completed a daily diary Day Reconstruction Method (DRM) as well as a suicidal ideation questionnaire. We used hierarchical linear modeling (HLM) to analyze the data, and the results showed that: (1) 10.81% of participates reported suicidal ideation, the intensity of positive affect (happiness, warmth/friendliness, interest and relaxation/calmness) was significantly lower for women with suicidal ideation compared to women without suicidal ideation; (2) differing diurnal patterns of positive emotions were observed between women with and without suicidal ideation; women with suicidal ideation demonstrated a significantly lower trend of growth and a higher volatility in happiness, warmth/friendliness, relaxation/calmness. Given that lower intensity of positive affect and greater affective instability significantly predicted suicidal ideation in Chinese women, researchers should pay more attention to the role of positive affect in female suicide prevention research and intervention efforts in the future. PMID:28377731

The connection between students' out-of-school experiences and science learning

NASA Astrophysics Data System (ADS)

Tran, Natalie A.

This study sought to understand the connection between students' out-of-school experiences and their learning in science. This study addresses the following questions: (a) What effects does contextualized information have on student achievement and engagement in science? (b) To what extent do students use their out-of-school activities to construct their knowledge and understanding about science? (c) To what extent do science teachers use students' skills and knowledge acquired in out-of-school settings to inform their instructional practices? This study integrates mixed methods using both quantitative and qualitative approaches to answer the research questions. It involves the use of survey questionnaire and science assessment and features two-level hierarchical analyses of student achievement outcomes nested within classrooms. Hierarchical Linear Model (HLM) analyses were used to account for the cluster effect of students nested within classrooms. Interviews with students and teachers were also conducted to provide information about how learning opportunities that take place in out-of-school settings can be used to facilitate student learning in science classrooms. The results of the study include the following: (a) Controlling for student and classroom factors, students' ability to transfer science learning across contexts is associated with positive learning outcomes such as achievement, interest, career in science, self-efficacy, perseverance, and effort. Second, teacher practice using students' out-of-school experiences is associated with decrease in student achievement in science. However, as teachers make more connection to students' out-of-school experiences, the relationship between student effort and perseverance in science learning and transfer gets weaker, thus closing the gaps on these outcomes between students who have more ability to establish the transfer of learning across contexts and those who have less ability to do so. Third, science teachers have limited information about students' out-of-school experiences thus rarely integrate these experiences into their instructional practices. Fourth, the lack of learning objectives for activities structured in out-of-school settings coupled with the limited opportunities to integrate students' out of school experiences into classroom instructions are factors that may prevent students from making further connection of science learning across contexts.

Prevalence of Suicidal Ideation and Its Association with Positive Affect in Working Women: A Day Reconstruction Study.

PubMed

Tian, Lili; Yang, Ying; Yang, Huijing; Huebner, E Scott

2017-01-01

The suicide rate for females in China is the second highest worldwide, and China is the only country in the world in which the rate of suicides is higher for women than men. Affective instability has been shown to be a strong predictor of suicidal ideation, particularly among women. However, prior research has mainly focused on the impact of women's negative affect on suicidal ideation, ignoring the influence of positive affect on suicidal ideation. Studies have revealed that hopelessness, which is 1.3 times more important than depression for explaining suicidal ideation, is driven more by low levels of positive affect than by high levels of negative affect. Although positive affect has also been found to be related to suicidal ideation, and it demonstrates independent, beneficial effects on mental health, much remains to be learned about the association between positive affective instability and suicidal ideation. Therefore, we investigated the prevalence of suicidal ideation among Chinese working women and explored the differences between working women with and without suicidal ideation in the intensity and daily variability of positive affect. A total of 222 young working women of ages 22-36 years ( M = 27.64, SD = 3.73) were recruited from a free weekend psychology lecture. The women subsequently completed a daily diary Day Reconstruction Method (DRM) as well as a suicidal ideation questionnaire. We used hierarchical linear modeling (HLM) to analyze the data, and the results showed that: (1) 10.81% of participates reported suicidal ideation, the intensity of positive affect (happiness, warmth/friendliness, interest and relaxation/calmness) was significantly lower for women with suicidal ideation compared to women without suicidal ideation; (2) differing diurnal patterns of positive emotions were observed between women with and without suicidal ideation; women with suicidal ideation demonstrated a significantly lower trend of growth and a higher volatility in happiness, warmth/friendliness, relaxation/calmness. Given that lower intensity of positive affect and greater affective instability significantly predicted suicidal ideation in Chinese women, researchers should pay more attention to the role of positive affect in female suicide prevention research and intervention efforts in the future.

Sustained skeletal benefit from childhood mechanical loading

PubMed Central

Scerpella, T. A.; Dowthwaite, J. N.; Rosenbaum, P. F.

2011-01-01

Summary Preliminary prospective, longitudinal results suggest that pre-menarcheal exposure to artistic gymnastics is associated with greater radius BMC, aBMD, and projected area throughout growth and into early adulthood, more than 4 years after activity cessation. Any loss of benefit associated with de-training appears to be temporary. Introduction Mechanical loading may enhance bone accrual during growth, but prospective evidence of benefit retention is limited. This prospective, longitudinal cohort study tests whether gymnastics is linked to distal radius advantages during growth and four or more years post-training cessation. Methods Semi-annually, female ex/gymnasts and non-gymnasts underwent height and weight measurements; questionnaires assessed calcium intake, physical activity, and maturation. Annual dual energy X-ray absorptiometry scans (Hologic QDR 4500W) measured total body fat-free mass, skull areal density (aBMD), and bone mineral content (BMC); forearm scans measured ultradistal and 1/3 radius area, BMC, and aBMD. Analysis inclusion criteria were: (1) achievement of gynecological age >4 years and (2) for gymnasts, >2 years of pre-menarcheal training (>6 h/week), ceasing between 0.5 year pre-menarche and 1 year post-menarche. Hierarchical linear modeling (HLM v6.0) evaluated outcomes for ex/gymnasts versus non-gymnasts; a slope/intercept discontinuity evaluated de-training effects. Results Data from 14 non-gymnasts and six ex/gymnasts represented outcomes from 4 years pre-menarche to 9 years post-menarche. All adjusted distal radius parameters were higher in ex/gymnasts than non-gymnasts (p<0.02). Ultradistal BMC, ultradistal aBMD, and 1/3 aBMD temporarily decreased with gymnastic cessation (p<0.04); ultradistal area, 1/3 area, and 1/3 BMC did not change significantly. Skull outcomes did not differ between groups or change with activity cessation. Conclusion Gymnastic exposure during childhood and early puberty is associated with greater radius bone mass, size, and aBMD. Despite brief de-training losses in density and mass, significant skeletal benefits are manifested throughout growth and at least 4 years beyond activity cessation into early adulthood. PMID:20838772

VX-509 (Decernotinib)-Mediated CYP3A Time-Dependent Inhibition: An Aldehyde Oxidase Metabolite as a Perpetrator of Drug-Drug Interactions.

PubMed

Zetterberg, Craig; Maltais, Francois; Laitinen, Leena; Liao, Shengkai; Tsao, Hong; Chakilam, Ananthsrinivas; Hariparsad, Niresh

2016-08-01

(R)-2-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide (VX-509, decernotinib) is an oral Janus kinase 3 inhibitor that has been studied in patients with rheumatoid arthritis. Patients with rheumatoid arthritis often receive multiple medications, such as statins and steroids, to manage the signs and symptoms of comorbidities, which increases the chances of drug-drug interactions (DDIs). Mechanism-based inhibition is a subset of time-dependent inhibition (TDI) and occurs when a molecule forms a reactive metabolite which irreversibly binds and inactivates drug-metabolizing enzymes, potentially increasing the systemic load to toxic concentrations. Traditionally, perpetrating compounds are screened using human liver microsomes (HLMs); however, this system may be inadequate when the precipitant is activated by a non-cytochrome P450 (P450)-mediated pathway. Even though studies assessing competitive inhibition and TDI using HLM suggested a low risk for CYP3A4-mediated DDI in the clinic, VX-509 increased the area under the curve of midazolam, atorvastatin, and methyl-prednisolone by approximately 12.0-, 2.7-, and 4.3-fold, respectively. Metabolite identification studies using human liver cytosol indicated that VX-509 is converted to an oxidative metabolite, which is the perpetrator of the DDIs observed in the clinic. As opposed to HLM, hepatocytes contain the full complement of drug-metabolizing enzymes and transporters and can be used to assess TDI arising from non-P450-mediated metabolic pathways. In the current study, we highlight the role of aldehyde oxidase in the formation of the hydroxyl-metabolite of VX-509, which is involved in clinically significant TDI-based DDIs and represents an additional example in which a system-dependent prediction of TDI would be evident. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.

PubMed

Cheng, Yaofeng; Wang, Lifei; Iacono, Lisa; Zhang, Donglu; Chen, Weiqi; Gong, Jiachang; Humphreys, William Griffith; Gan, Jinping

2018-01-01

BMS-823778 is an inhibitor of 11β-hydroxysteroid dehydrogenase type-1, and thus a potential candidate for Type 2 diabetes treatment. Here, we investigated the metabolism and pharmacokinetics of BMS-823778 to understand its pharmacokinetic variations in early clinical trials. The metabolism of BMS-823778 was characterized in multiple in vitro assays. Pharmacokinetics were evaluated in healthy volunteers, prescreened as CYP2C19 extensive metabolizers (EM) or poor metabolizers (PM), with a single oral dose of [ 14 C]BMS-823778 (10 mg, 80 μCi). Three metabolites (<5%) were identified in human hepatocytes and liver microsomes (HLM) incubations, including two hydroxylated metabolites (M1 and M2) and one glucuronide conjugate (M3). As the most abundant metabolite, M1 was formed mainly through CYP2C19. M1 formation was also correlated with CYP2C19 activities in genotyped HLM. In humans, urinary excretion of dosed radioactivity was significantly higher in EM (68.8%; 95% confidence interval 61.3%, 76.3%) than in PM (47.0%; 43.5%, 50.6%); only small portions (<2%) were present in faeces or bile from both genotypes. In plasma, BMS-823778 exposure in PM was significantly (5.3-fold, P = 0.0097) higher than in EM. Furthermore, total radioactivity exposure was significantly higher (P < 0.01) than BMS-823778 exposure in all groups, indicating the presence of metabolites. M1 was the only metabolite observed in plasma, and much lower in PM. In urine, the amount of M1 and its oxidative metabolite in EM was 7-fold of that in PM, while more glucuronide conjugates of BMS-823778 and M1 were excreted in PM. CYP2C19 polymorphisms significantly impacted systemic exposure and metabolism pathways of BMS-823778 in humans. © 2017 The British Pharmacological Society.

In vitro-in vivo correlation and translation to the clinical outcome for CJ-13,610, a novel inhibitor of 5-lipoxygenase.

PubMed

Matthew Hutzler, J; Linder, Collette D; Melton, Roger J; Vincent, John; Daniels, J Scott

2010-07-01

The metabolism of the 5-lipoxygenase inhibitor, 4-(3-(4-(2-methyl-1H-imidazol-1-yl)phenylthio)phenyl)-tetrahydro-2H-pyran-4-carboxamide (CJ-13,610), was investigated in liver microsomes from human and preclinical species in an effort to compare metabolite profiles and evaluate the in vitro-in vivo correlation for metabolic clearance. Overall, the metabolite profile of CJ-13,610 was comparable across the species tested with multiple oxidative metabolites observed, including sulfoxidation. The sulfoxidation kinetics characterized in rat, dog, and human liver microsomes (HLM) indicated a low apparent Michaelis-Menten constant (K(m, app)) of 4 to 5 microM. Results from cDNA-expressed cytochrome P450 (P450) studies indicated that the metabolism in HLM was primarily mediated by CYP3A4 and 3A5. A subsequent in vitro study using ketoconazole as an inhibitor of CJ-13,610 sulfoxidation corroborated the CYP3A4/5-mediated pathway (IC(50) = 7 nM). Assessment of multiple methods for predicting the human pharmacokinetic profile observed with CJ-13,610 after a 30-mg single oral dose indicated that clearance scaled from human liver microsomes yielded a better prediction when coupled with a Vd(ss) term that was scaled from dog [area under the concentration-time curve (AUC) and half-life within 1.3-fold of actual] versus a Vd(ss) term obtained from rat. Single-species allometric scaling of clearance and Vd(ss) from dog pharmacokinetic studies was equally predictive, whereas scaling from rat resulted in underpredictions of both AUC and maximal concentration (C(max)). Results from these studies support the strategy of predicting human pharmacokinetics using human liver microsomal intrinsic clearance data. More importantly, results from the present investigation enabled the selection of alternative drug candidates from the chemical series via in vitro screening, while subsequently eliminating costly routine preclinical in vivo studies.

Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH.

PubMed

Nielsen, Line Marie; Holm, Niels Bjerre; Leth-Petersen, Sebastian; Kristensen, Jesper Langgaard; Olsen, Lars; Linnet, Kristian

2017-05-01

The dimethoxyphenyl-N-((2-methoxyphenyl)methyl)ethanamine (NBOMe) compounds are potent serotonin 5-HT2A receptor agonists and have recently been subject to recreational use due to their hallucinogenic effects. Use of NBOMe compounds has been known since 2011, and several non-fatal and fatal intoxication cases have been reported in the scientific literature. The aim of this study was to determine the importance of the different cytochrome P450 enzymes (CYP) involved in the metabolism of 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2methoxybenzyl)ethanamine (25I-NBOMe) and 2-[[2-(4-iodo-2,5dimethoxyphenyl)ethylamino]methyl]phenol (25I-NBOH) and to characterize the metabolites. The following approaches were used to identify the main enzymes involved in primary metabolism: incubation with a panel of CYP and monoamine oxidase (MAO) enzymes and incubation in pooled human liver microsomes (HLM) with and without specific CYP chemical inhibitors. The study was further substantiated by an evaluation of 25I-NBOMe and 25I-NBOH metabolism in single donor HLM. The metabolism pathways of 25I-NBOMe and 25I-NBOH were NADPHdependent with intrinsic clearance values of (CLint) of 70.1 and 118.7 mL/min/kg, respectively. The biotransformations included hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, and combinations thereof. The most abundant metabolites were all identified by retention time and spectrum matching with synthesized reference standards. The major CYP enzymes involved in the metabolism of 25I-NBOMe and 25INBOH were identified as CYP3A4 and CYP2D6, respectively. The compound 25I-NBOH was also liable to direct glucuronidation, which may diminish the impact of CYP2D6 genetic polymorphism. Users of 25I-NBOMe may be subject to drug-drug interactions (DDI) if 25I-NBOMe is taken with a strong CYP3A4 inhibitor. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, “LC-(High Resolution)-MSn” and “LC-(High Resolution)-MS/MS”

PubMed Central

Michely, Julian A.; Manier, Sascha K.; Caspar, Achim T.; Brandt, Simon D.; Wallach, Jason; Maurer, Hans. H.

2017-01-01

Background: 3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM) the identification of the cytochrome P450 (CYP) isoenzymes involved and the detectability using standard urine screening approaches (SUSA) after intake of common users’ doses using gas chromatography-mass spectrometry (GC-MS) liquid chromatography-multi-stage mass spectrometry (LC-MSn) and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) Methods: For metabolism studies rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn the phase I and II metabolites were identified Results: Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring single aromatic hydroxylation carboxylation after ring opening O-demethylation and glucuronidation. The transferability from rat to human was investigated by pHLM incubations where O-demethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved pharmacogenomic variations might occur but clinical data are needed to confirm the relevance. The detectability studies showed that the authors’ SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites PMID:27758707

In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A.

PubMed

Polasek, Thomas M; Sadagopal, Janani S; Elliot, David J; Miners, John O

2010-03-01

To evaluate zolpidem as a mechanism-based inactivator of human CYP3A in vitro, and to assess its metabolic interaction potential with CYP3A drugs (in vitro-in vivo extrapolation; IV-IVE). A co- vs. pre-incubation strategy was used to quantify time-dependent inhibition of human liver microsomal (HLM) and recombinant CYP3A4 (rCYP3A4) by zolpidem. Experiments involving a 10-fold dilution step were employed to determine the kinetic constants of inactivation (K (I) and k (inact)) and to assess the in vitro mechanism-based inactivation (MBI) criteria. Inactivation data were entered into the Simcyp population-based ADME simulator to predict the increase in the area under the plasma concentration-time curve (AUC) for orally administered midazolam. Consistent with MBI, the inhibitory potency of zolpidem toward CYP3A was increased following pre-incubation. In HLMs, the concentration required for half maximal inactivation (K (I)) was 122 microM and the maximal rate of inactivation (k (inact)) was 0.094 min(-1). In comparison, K (I) and k (inact) values with rCYP3A4 were 50 microM and 0.229 min(-1), respectively. Zolpidem fulfilled all other in vitro MBI criteria, including irreversible inhibition. The mean oral AUC for midazolam in healthy volunteers was predicted to increase 1.1- to 1.7-fold due to the inhibition of metabolic clearance by zolpidem. Elderly subjects were more sensitive to the interaction, with mean increases in midazolam AUC of 1.2- and 2.2-fold for HLM IV-IVE and rCYP3A4 IV-IVE, respectively. Zolpidem is a relatively weak mechanism-based inactivator of human CYP3A in vitro. Zolpidem is unlikely to act as a significant perpetrator of metabolic interactions involving CYP3A.

The effect of simulated narratives that leverage EMR data on shared decision-making: a pilot study.

PubMed

Zeng-Treitler, Qing; Gibson, Bryan; Hill, Brent; Butler, Jorie; Christensen, Carrie; Redd, Douglas; Shao, Yijun; Bray, Bruce

2016-07-22

Shared decision-making can improve patient satisfaction and outcomes. To participate in shared decision-making, patients need information about the potential risks and benefits of treatment options. Our team has developed a novel prototype tool for shared decision-making called hearts like mine (HLM) that leverages EHR data to provide personalized information to patients regarding potential outcomes of different treatments. These potential outcomes are presented through an Icon array and/or simulated narratives for each "person" in the display. In this pilot project we sought to determine whether the inclusion of simulated narratives in the display affects individuals' decision-making. Thirty subjects participated in this block-randomized study in which they used a version of HLM with simulated narratives and a version without (or in the opposite order) to make a hypothetical therapeutic decision. After each decision, participants completed a questionnaire that measured decisional confidence. We used Chi square tests to compare decisions across conditions and Mann-Whitney U tests to examine the effects of narratives on decisional confidence. Finally, we calculated the mean of subjects' post-experiment rating of whether narratives were helpful in their decision-making. In this study, there was no effect of simulated narratives on treatment decisions (decision 1: Chi squared = 0, p = 1.0; decision 2: Chi squared = 0.574, p = 0.44) or Decisional confidence (decision 1, w = 105.5, p = 0.78; decision 2, w = 86.5, p = 0.28). Post-experiment, participants reported that narratives helped them to make decisions (mean = 3.3/4). We found that simulated narratives had no measurable effect on decisional confidence or decisions and most participants felt that the narratives were helpful to them in making therapeutic decisions. The use of simulated stories holds promise for promoting shared decision-making while minimizing their potential biasing effect.

Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

PubMed

Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

2016-01-01

Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the produced information enables the implementation of new target analytes into routine doping controls and expands the focus of anti-doping efforts concerning this new anabolic agent.

Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases.

PubMed

Guo, Bin; Fang, Zhongze; Yang, Lu; Xiao, Ling; Xia, Yangliu; Gonzalez, Frank J; Zhu, Liangliang; Cao, Yunfeng; Ge, Guangbo; Yang, Ling; Sun, Hongzhi

2015-04-25

Glabridin (GA) has gained wide application in the cosmetics and food industry. This study was performed to investigate its metabolic inactivation and elimination by glucuronidation by use of liver and intestine microsomes from humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4 positions of the B ring are conjugated to generate two mono-glucuronides (M1 and M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation with intrinsic clearance values (Clint) above 2000 μL/min/mg, with little measurable M1 formation activity. DLM displayed considerable activity both in M1 and M2 formation, with Clint values of 71 and 214 μL/min/mg, respectively, while HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with Clint values all below 20 μL/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7, 2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the highest activity with a Clint value more than 5-fold higher than the other isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9, 2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal GA glucuronidation in humans. In summary, this in vitro study demonstrated large species differences in GA glucuronidation by liver and intestinal microsomes, and that intestinal UGTs are important for the pathway in humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evidences for CYP3A4 autoactivation in the desulfuration of dimethoate by the human liver.

PubMed

Buratti, Franca M; Testai, Emanuela

2007-11-20

Dimethoate (DIM) is an organophosphorothionate (OPT) pesticide used worldwide as a systemic insecticide and acaricide. It is characterized by low-to-moderate acute mammalian toxicity; similarly to the other OPT pesticides, its mode of action is mediated by the inhibition of acetylcholinesterase (AChE), exerted by its toxic metabolite dimethoate-oxon or omethoate (OME), which is also used as a direct acting pesticide. Human hepatic DIM bioactivation to the toxic metabolite OME has been characterized by using c-DNA expressed human CYPs and human liver microsomes (HLM) also in the presence of CYP-specific chemical inhibitors, with a method based on AChE inhibition. The obtained kinetic parameters and AChE IC(50) have been compared with those previously obtained with other OPTs, indicating a lower efficiency in DIM desulfuration reaction and a lower potency in inhibiting AChE. Results showed that, similarly to the other OPTs tested so far, at low DIM concentration OME formation is mainly catalysed by CYP1A2, while the role of 3A4 is relevant at high DIM levels. Differently from the other OPTs, DIM desulfuration reaction showed an atypical kinetic profile, likely due to CYP3A4 autoactivation. The sigmoidicity degree of the activity curve increased with the level of CYP3A4 in HLM or disappeared in the presence of a CYP3A4 chemical inhibitor. This atypical kinetic behaviour can be considered one of the possible explanations for the recent findings that among patients hospitalized following OPT intoxication, DIM ingestion gave different symptoms and more severe poisoning (23.1% of fatal cases versus total) than chlorpyrifos (8% of deaths), which has a lower LD(50) value. Since DIM-poisoned patients poorly responded to pralidoxime, the possibility to use CYP3A4 inhibitors could be considered as a complementary treatment.

EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2011-01-01

Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

UPLC/MS MS data of testosterone metabolites in human and zebrafish liver microsomes and whole zebrafish larval microsomes.

PubMed

Saad, Moayad; Bijttebier, Sebastiaan; Matheeussen, An; Verbueken, Evy; Pype, Casper; Casteleyn, Christophe; Van Ginneken, Chris; Maes, Louis; Cos, Paul; Van Cruchten, Steven

2018-02-01

This article represents data regarding a study published in Toxicology in vitro entitled " in vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human reference compounds" (Saad et al., 2017) [1]. Data were acquired with ultra-performance liquid chromatography - accurate mass mass spectrometry (UPLC-amMS). A full spectrum scan was conducted for the testosterone (TST) metabolites from the microsomal stability assay in zebrafish and humans. The microsomal proteins were extracted from adult zebrafish male (MLM) and female (FLM) livers, whole body homogenates of 96 h post fertilization larvae (EM) and a pool of human liver microsomes from 50 donors (HLM). Data are expressed as the abundance from the extracted ion chromatogram of the metabolites.

Water Remedial Investigation Report, Version 3.3. Volume 2

DTIC Science & Technology

1989-07-01

the Third Quarter FY 1987 water table contour map, S(Page 9 of 13) Water Level "KaU._ID LiaMAUan 26143 5175.9 26145 -999,9 27002 5095.3 27003 5098.0...26125 5146.9 26127 5164.6 26133 5147.0 26143 5175.9 4 26145 5140.9 ID 27001 5093.2 27002 5094.8 27003 51.08 -1 27004 B-105 20,43.7 27005 5094.2 27006...ML Po 1IM A- T .0 cO16 Folcm Iscale ’ 𔃾 IV*- C. [LA \\S Y4 6 It. ISO . 4:- 4~ 1A . 6 IAT sti ~~~~~ If*1 l H 44 - . C-99 0 S S 0 040 0 s HtHLm.01 0O

The relationship between club drug use and other drug use: a survey of New York City middle school students.

PubMed

Goldsamt, Lloyd A; O'Brien, Julie; Clatts, Michael C; McGuire, Laura Silver

2005-01-01

In order to explore the relationship between use of club drugs (crystal methamphetamine, ecstasy, GHB, ketamine), and use of other drugs, survey data collected from 23,780 middle school students in New York City during 2002-2003 was examined. Results of HGLM analyses (a generalization of HLM to accommodate nonlinear outcomes), controlling for the effect of school, indicate that Black students are less likely than White students to use club drugs depending on the timeframe of use. The use of alcohol and/or marijuana predict club drug use regardless of the timeframe of use, and lifetime cigarette use predicts lifetime club drug use. Recommendations for future research and prevention efforts are discussed.

On protolith-, metamorphic overprint, microstructure and rheology of mineral assemblages in orogenic peridotites of the central Scandinavian Caledonides

NASA Astrophysics Data System (ADS)

Gilio, Mattia; Clos, Frediano; Van Roermund, Herman L. M.

2013-04-01

The Scandinavian Caledonides (SC) are a deeply eroded Alpine-type orogenic belt formed by closure of the Iapetus ocean and collision between Baltica and Laurentia (500-380 Ma). The SC consists of a stack of Nappe Complexes (from bottom to top called Lower, Middle, Upper and Uppermost Allochthons) thrusted to the east over the Baltic Shield (Brueckner and Van Roermund, 2004; Gee et al., 2008). Fossil lithospheric mantle fragments, called orogenic peridotites, have been found within the (upper part of) middle, upper and uppermost Allochthons, as well as in the reworked basement gneisses (a.o Western Gneiss Complex (WGC)) along the Norwegian west coast. They occur as isolated lenses that contain diverse mineral parageneses and/or bulk rock compositions. Crustal incorporation of orogenic peridotite is classically interpreted to be the result of plate collisional processes related to orogeny (Brueckner and Medaris, 2000). The WGC and parts of the upper part of the Middle Allochthon (a.o. Seve Nappe Complex (SNC) in N Jämtland/S Västerbotten, central Sweden), are well known for the occurrence of high (HP) and ultrahigh pressure (UHP) metamorphic terranes (of Caledonian age). The (U)HPM evidence clearly demonstrates the deep metamorphic origin of these rocks interpreted to be caused by continental subduction and/or collision. Other metamorphic rocks (of Caledonian age) exposed in allochthonous nappes are solely characterised by greenschist-, amphibolite- and/or MP granulite "facies" mineral assemblages that can be interpreted, in the absence of retrogression, to have formed in less deeply subducted (and/or metamorphic) environments. This duality in metamorphic "facies" allows for a discrimination (at least theoretically) between "deep" versus "shallow" rooted nappes (in central parts of the Scandinavian Caledonides). Conform this reasoning, this duality should also be present within the Caledonian mineral assemblages (= metamorphic overprint) of orogenic peridotites (in central parts of the orogen), which, at least in the allochtonous nappes, have been interpreted to be "isofacial" with their host country rocks (Bucher, 1991). The latter strongly contrast to the interpretation of their "primary" (="protolith"- related) mineral assemblage(s) which clearly suggest a bimodal origin: here called thick (>80 km) versus thin (< 70 km) rooted lithospheric mantle protoliths. Distinction can be made on the basis of the presence of the stable (minimal Proterozoic) garnet-olivine assemblages in the protolith (i.e. much older than the Scandian collision event (Brueckner et al., 2010). For this reason orogenic garnet peridotite was first called "relict" garnet peridotite (Brueckner and Medaris, 2000), later rephrased into mantle wedge garnet peridotite (MWgp) by Van Roermund (2009). MWgp occurs in the WGC and in the SNC of the Upper Allochthon in central Sweden (Zhang et al., 2009). Most (All?) other protolith assemblages of orogenic peridotite in the CSC belong to the thin-rooted protolith subtype. No examples are known to us in which thin rooted prototypes became overprinted (during the Caledonian orogeny) by (U)HP metamorphic minerals, except for the subduction zone garnet peridotites (SZgp) in the WGC (Van Roermund, 2009). The latter can thus savely be interpreted as being enclosed within normal "MP" (or lower pressure) nappe sequences. As such it will be clear that this duality in protolith (and/or metamorphic) mineral assemblages of orogenic peridotite can be used to identify former, but now strongly retrogressed, (U)HP metamorphic terranes in other parts of the CSC (Gee et al, 2012). For this reason a comparative study has been made concerning field, (micro-)structural, mineral-chemical and/or geochemical aspects of two major orogenic peridotites from the SNC, central Sweden; here called the Friningen Garnet Peridotite (FGP) and the Kittelfjäll Spinel Peridotite (KSP), both exposed within the central belt of the SNC in central Sweden. The ultimate aim was to investigate whether the MWgp sub-type can be extended towards (Al-poor) spinel-bearing protolith assemblages or not. Results, including some hitherto unexpected mechanical effects, will be presented. References: Brueckner, H.K., Carswell, D.A., Griffin, W.L., Medaris, L.G., Van Roermund, H.L.M., Cuthbert, S.J. (2010). The mantle and crustal evolution of two garnet peridotite suites from the Western Gneiss Region, Norwegian Caledonides: An isotopic investigation. Lithos, 117, 1-19. doi:10.1016/j. Lithos.2010.01.011 Brueckner, H.K.and Medaris, L.G. (2000). A general model for the intrusion and evolution of "mantle" garnet peridotites in high-pressure and ultra-high-pressure metamorphic terranes. J. Metamorphic Geol., 18, 123-133. Brueckner H.K. and Van Roermund,H.L.M. (2004). Dunk tectonics: A multiple subduction//eduction model for the evolution of the Scandinavian Caledonides. Tectonics, 23, TC2004, doi:10.1029/2003tc001502. Bucher, K. (1991). Mantle fragments in the Scandinavian Caledonides. Tectonophysics, 190, 173-192. Gee, D.G., Fossen, H., Henriksen, N., Higgins, K. (2008). From the Early Paleozoic Platforms of Baltica and Laurentia to the Caledonide Orogen of Scandinavia and Greenland. Episodes, 31, 44-51. Gee, D.G., Janak, M., Majka, J., Robinson, P., Van Roermund, H.L.M (2012). UHP metamorphism along the Baltoscandian outer margin: evidence from the Seve Nappe Complex of the Swedish Caledonides. Lithosphere, in press. Janak, M., Van Roermund, H., Majka, J., Gee, D. (2012). UHP metamorphism recorded by kyanite-bearing eclogite in the Seve Nappe Complex of northern Jämtland, Swedish Caledonides. Gondwana Research, in press. Van Roermund, H.L.M. (2009). Mantle-wedge garnet peridotites from the northernmost ultra-high pressure domain of the Western Gneiss Region, SW Norway. Eur. J. Mineralogy, 21, 1085-1096. Zhang, C., Van Roermund, H.L.M., Zhang, L.F (2011). 16 - Orogenic Garnet Peridotites: Tools to Reconstruct Paleo-Geodynamic Settings of Fossil Continental Collision Zones. In: Ultrahigh Pressure Metamorphism, 25 Years After The Discovery Of Coesite And Diamond. London. Doi:10.1016/B978-0-12-385144-4.00015-1

The Influence of Classroom Aggression and Classroom Climate on Aggressive-Disruptive Behavior

PubMed Central

Thomas, Duane E.; Bierman, Karen L.; Powers, CJ

2011-01-01

Research suggests that early classroom experiences influence the socialization of aggression. Tracking changes in the aggressive behavior of 4179 children from kindergarten to second-grade (ages 5–8) this study examined the impact of two important features of the classroom context–aggregate peer aggression and climates characterized by supportive teacher-student interactions. The aggregate aggression scores of children assigned to first-grade classrooms predicted the level of classroom aggression (assessed by teacher ratings) and quality of classroom climate (assessed by observers) that emerged by the end of grade 1. HLM analyses revealed that first-grade classroom aggression and quality of classroom climate made independent contributions to changes in student aggression, as students moved from kindergarten to second grade. Implications for policy and practice are discussed. PMID:21434887

ETHICAL LEADERSHIP AND EMPLOYEE VOICE: EMPLOYEE SELF-EFFICACY AND SELF-IMPACT AS MEDIATORS.

PubMed

Wang, Duanxu; Gan, Chenjing; Wu, Chaoyan; Wang, Danqi

2015-06-01

Previous studies have used social learning theory to explain the influence of ethical leadership. This study continues the previous research by using social learning theory to explain the mediating effect of self-efficacy on the relationship between ethical leadership and employee voice. In addition, this study extends previous studies by introducing expectancy theory to explore whether self-impact also mediates the relationship between ethical leadership and employee voice. Ethical leadership, self-efficacy, self-impact, and employee voice were assessed using paired surveys among 59 supervisors and 295 subordinates employed at nine firms in the People's Republic of China. Using HLM and SEM analyses, the results revealed that ethical leadership was positively related to employee voice and that this relationship was partially mediated by both self-efficacy and self-impact.

Interaction of 5-HTTLPR and Idiographic Stressors Predicts Prospective Depressive Symptoms Specifically among Youth in a Multi-wave Design

PubMed Central

Hankin, Benjamin L.; Jenness, Jessica; Abela, John R.Z.; Smolen, Andrew

2011-01-01

5-HTTLPR, episodic stressors, depressive and anxious symptoms were assessed prospectively (child and parent report) every 3 months over 1 year (5 waves of data) among community youth ages 9–15 (n = 220). Lagged HLM analyses showed 5-HTTLPR interacted with idiographic stressors (increases relative to the child’s own average level over time), but not nomothetic stressors (higher stress exposure relative to the sample), to predict prospective elevations in depressive, but not anxious, symptoms. Youth with copies of the S or LG alleles of 5-HTTLPR, who experienced more stressors relative to their typical level, exhibited prospective increases in depressive symptoms over time. These findings suggest that 5-HTTLPR confers susceptibility to depression via stress reactivity. PMID:21722029

Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl-piperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione as potential antidepressant agents.

PubMed

Zagórska, Agnieszka; Bucki, Adam; Kołaczkowski, Marcin; Siwek, Agata; Głuch-Lutwin, Monika; Starowicz, Gabriela; Kazek, Grzegorz; Partyka, Anna; Wesołowska, Anna; Słoczyńska, Karolina; Pękala, Elżbieta; Pawłowski, Maciej

2016-01-01

A series of 2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4-21) were synthesized and evaluated for their serotonin (5-HT 1A /5-HT 7 ) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5-HT 1A , 5-HT 7 and mixed 5-HT 1A /5-HT 7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A. The tests have been completed with the determination of lipophilicity and metabolic stability using micellar electrokinetic chromatography (MEKC) system and human liver microsomes (HLM) model. In preliminary pharmacological in vivo studies, selected compound 8-(5-(4-(2-fluorophenyl)piperazin-1-yl)pentyl)-1,3,7-trimethyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (9) behaved as a potential antidepressant in forced swim test (FST) in mice. Moreover, potency of antianxiety effects evoked by 9 (2.5 mg/kg) is greater than that of the reference anxiolytic drug, diazepam. Molecular modeling revealed that fluorinated arylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione have major significance for the provision of lead compounds for antidepressant and/or anxiolytic application.

Application of a nonrandomized stepped wedge design to evaluate an evidence-based quality improvement intervention: a proof of concept using simulated data on patient-centered medical homes.

PubMed

Huynh, Alexis K; Lee, Martin L; Farmer, Melissa M; Rubenstein, Lisa V

2016-10-21

Stepped wedge designs have gained recognition as a method for rigorously assessing implementation of evidence-based quality improvement interventions (QIIs) across multiple healthcare sites. In theory, this design uses random assignment of sites to successive QII implementation start dates based on a timeline determined by evaluators. However, in practice, QII timing is often controlled more by site readiness. We propose an alternate version of the stepped wedge design that does not assume the randomized timing of implementation while retaining the method's analytic advantages and applying to a broader set of evaluations. To test the feasibility of a nonrandomized stepped wedge design, we developed simulated data on patient care experiences and on QII implementation that had the structures and features of the expected data from a planned QII. We then applied the design in anticipation of performing an actual QII evaluation. We used simulated data on 108,000 patients to model nonrandomized stepped wedge results from QII implementation across nine primary care sites over 12 quarters. The outcome we simulated was change in a single self-administered question on access to care used by Veterans Health Administration (VA), based in the United States, as part of its quarterly patient ratings of quality of care. Our main predictors were QII exposure and time. Based on study hypotheses, we assigned values of 4 to 11 % for improvement in access when sites were first exposed to implementation and 1 to 3 % improvement in each ensuing time period thereafter when sites continued with implementation. We included site-level (practice size) and respondent-level (gender, race/ethnicity) characteristics that might account for nonrandomized timing in site implementation of the QII. We analyzed the resulting data as a repeated cross-sectional model using HLM 7 with a three-level hierarchical data structure and an ordinal outcome. Levels in the data structure included patient ratings, timing of adoption of the QII, and primary care site. We were able to demonstrate a statistically significant improvement in adoption of the QII, as postulated in our simulation. The linear time trend while sites were in the control state was not significant, also as expected in the real life scenario of the example QII. We concluded that the nonrandomized stepped wedge design was feasible within the parameters of our planned QII with its data structure and content. Our statistical approach may be applicable to similar evaluations.

PARENTHOOD AND CRIME: THE ROLE OF WANTEDNESS, RELATIONSHIPS WITH PARTNERS, AND SES

PubMed Central

Giordano, Peggy C.; Seffrin, Patrick M.; Manning, Wendy D.; Longmore, Monica A.

2012-01-01

Purpose Parenthood may play a pivotal role in the criminal desistance process, but few studies have examined the conditions under which becoming a mother or father is most likely to lead to reductions in criminal behavior. Methods The current longitudinal study draws on four waves of adolescent and young adult interview data (N = 1,066) and HLM regression models to examine the impact of parenthood on criminal trajectories, as well as the degree to which the prosocial potential of parenthood is modified by socioeconomic factors, the nature of the relationship between the biological parents, and pregnancy wantedness. The analysis also draws on narrative life history accounts elicited from a subset of these respondents (N = 22). Results SES and the wantedness of the pregnancy condition the relationship between parenthood and criminal involvement, however some gender differences emerged. Status of the relationship (married or cohabiting and single) was in general not a strong predictor. Conclusions Highly disadvantaged young men and women are not as likely as more advantaged young adults to evidence lower levels of criminal behavior after becoming parents, however wanted pregnancies may reduce female involvement in crime regardless of socioeconomic status. In-depth qualitative data further elucidate the conditional nature of the parenthood-crime relationship. PMID:23805011

Early onset of delinquency and the trajectory of alcohol-impaired driving among young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2011-12-01

Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Why women perform better in college than admission scores would predict: Exploring the roles of conscientiousness and course-taking patterns.

PubMed

Keiser, Heidi N; Sackett, Paul R; Kuncel, Nathan R; Brothen, Thomas

2016-04-01

Women typically obtain higher subsequent college GPAs than men with the same admissions test score. A common reaction is to attribute this to a flaw in the admissions test. We explore the possibility that this underprediction of women's performance reflects gender differences in conscientiousness and college course-taking patterns. In Study 1, we focus on using the ACT to predict performance in a single, large course where performance is decomposed into cognitive (exam and quiz scores) and less cognitive, discretionary components (discussion and extra credit points). The ACT does not underpredict female's cognitive performance, but it does underpredict female performance on the less cognitive, discretionary components of academic performance, because it fails to measure and account for the personality trait of conscientiousness. In Study 2, we create 2 course-difficulty indices (Course Challenge and Mean Aptitude in Course) and add them to an HLM regression model to see if they reduce the degree to which SAT scores underpredict female performance. Including Course Challenge does result in a modest reduction of the gender coefficient; however, including Mean Aptitude in Course does not. Thus, differences in course-taking patterns is a partial (albeit small) explanation for the common finding of differential prediction by gender. (c) 2016 APA, all rights reserved).

New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, "LC-(High Resolution)-MSn" and "LC-(High Resolution)-MS/MS".

PubMed

A Michely, Julian A; Manier, Sascha K; Caspar, Achim T; Brandt, Simon D; Wallach, Jason; Maurer, Hans H

2017-01-01

3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeOPCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users' doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn, the phase I and II metabolites were identified. Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring, single aromatic hydroxylation, carboxylation after ring opening, O-demethylation, and glucuronidation. The transferability from rat to human was investigated by pHLM incubations, where Odemethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP, CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy, aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved, pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance. The detectability studies showed that the authors' SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Xia

2016-06-15

Tolcapone and entacapone are two potent catechol-O-methyltransferase (COMT) inhibitors with a similar skeleton and displaying similar pharmacological activities. However, entacapone is a very safe drug used widely in the treatment of Parkinson's disease, while tolcapone is only in limited use for Parkinson's patients and needs careful monitoring of hepatic functions due to hepatotoxicity. This study aims to investigate and compare the inhibitory effects of entacapone and tolcapone on human UDP-glucosyltransferases (UGTs), as well as to evaluate the potential risks from the view of drug-drug interactions (DDI). The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7,more » UGT1A9 and UGT1A10. In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. It is noteworthy that the inhibition constants (K{sub i}) of tolcapone and entacapone against bilirubin-O-glucuronidation in human liver microsomes (HLM) are determined as 0.68 μM and 30.82 μM, respectively, which means that the inhibition potency of tolcapone on UGT1A1 mediated bilirubin-O-glucuronidation in HLM is much higher than that of entacapone. Furthermore, the potential risks of tolcapone or entacapone via inhibition of human UGT1A1 were quantitatively predicted by the ratio of the areas under the plasma drug concentration-time curve (AUC). The results indicate that tolcapone may result in significant increase in AUC of bilirubin or the drugs primarily metabolized by UGT1A1, while entacapone is unlikely to cause a significant DDI through inhibition of UGT1A1. - Highlights: • Tolcapone and entacapone exhibited preferential inhibition against UGT1A enzymes. • In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on human UGT1A1, 1 A7 and 1 A10. • Tolcapone may lead to significant increase in AUC of bilirubin. • This study provided new insights into the underlying mechanisms of tolcapone induced hepatotoxicity.« less

Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: a cluster randomized trial study protocol.

PubMed

Aarons, Gregory A; Ehrhart, Mark G; Moullin, Joanna C; Torres, Elisa M; Green, Amy E

2017-03-03

Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12 months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered.

Precollege science achievement growth: Racial-ethnic and gender differences in cognitive and psychosocial constructs

NASA Astrophysics Data System (ADS)

Muller, Patricia Ann

The purpose of this study was to gain a more complete understanding of the differences in science, mathematics and engineering education among racial-ethnic and gender subgroups by exploring factors related to precollege science achievement growth rates. Using Hierarchical Linear Modeling (HLM) and multi-wave, longitudinal data from the first three waves of the National Education Longitudinal Study of 1988--1994 (NELS:88/94), this study examined precollege science achievement growth rates during the 8th to 10th grade period and the 10th to 12th grade period for African American males, African American females, Latino males, Latina females, Asian American males, Asian American females, White males and White females. For the 8th--10th grade period, previous grades were significantly and positively related to science achievement growth for all subgroups; and socio-economic status and high school program were significantly and positively related to science achievement growth for all subgroups except one (Latino males, and Asian American males respectively). For the 10th--12th grade period, the quantity of science courses completed (science units) was the only variable that was statistically significant for more than one racial-ethnic by gender subgroup. Science units taken were significantly and positively related to 10 th--12th grade growth rates for all racial-ethnic by gender subgroups except Latino males. Locus-of-control was the only cognitive or psychosocial factor included from Eccles, Adler, Futterman, Goff, Kaczala, Meece and Midgley's (1983) theoretical framework for achievement behaviors that appeared to exhibit any pattern across race-ethnicities. Locus-of-control was positively related to 8th--10 th grade science achievement growth for females across all racial-ethnic subgroups, as well as for African American males. However, for both the 8 th--10th grade and 10th--12 th grade periods, there was no consistency across racial-ethnic or gender subgroups in effects of the remaining cognitive and psychosocial factors on science achievement growth rates. Cognitive and psychosocial variables were statistically significant only for specific subgroups, and did not generally exhibit any commonalities across gender, or by race. The findings accentuated the importance of disaggregating data and analyses by both race-ethnicity and gender.

Out Drinking the Joneses: Neighborhood Factors Moderating the Effects of Drinking on Relationship Quality over the First Four Years of Marriage.

PubMed

Crasta, Dev; Funk, Janette L; Lee, Soonhee; Rogge, Ronald D

2017-12-27

Neighborhood quality has been cross-sectionally linked to both relationship behaviors and relationship well-being. Consistent with the Vulnerability Stress-Adaptation model of relationship functioning (Karney & Bradbury, 1995), we hypothesized that associations between social behaviors (e.g., drinking) and relationship quality could be moderated by neighborhood factors. Specifically, we characterized neighborhoods along multiple dimensions using multiple methods (self-report, census) to investigate how neighborhood factors might clarify ambiguous effects of alcohol use on marital functioning. A nationally recruited sample of 303 newlywed couples completed a baseline assessment around the time of marriage and was then assessed yearly across the first 4 years of marriage (94% retention). Three level HLM slope-intercept models were used to model changes in relationship satisfaction across the first 4 years of marriage. Results suggested that, for couples living in highly disordered neighborhoods, positive shifts in overall levels of drinking within specific waves of assessment were associated with corresponding negative shifts in satisfaction whereas in neighborhoods without perceived disorder, this effect was reversed. For couples living in neighborhoods with low levels of domestic structures (high census rates of single renters without children), within-couple discrepancies favoring higher rates of husband drinking in specific waves predicted poorer relationship quality for both partners in those same waves whereas those same discrepancies predicted higher satisfaction in high domesticity neighborhoods (high census rates of married homeowners with children). The findings provide insight into the different roles of alcohol use in relationship maintenance and highlight the importance of using external context to understand intradyadic processes. © 2017 Family Process Institute.

Genomic prediction based on data from three layer lines using non-linear regression models.

PubMed

Huang, Heyun; Windig, Jack J; Vereijken, Addie; Calus, Mario P L

2014-11-06

Most studies on genomic prediction with reference populations that include multiple lines or breeds have used linear models. Data heterogeneity due to using multiple populations may conflict with model assumptions used in linear regression methods. In an attempt to alleviate potential discrepancies between assumptions of linear models and multi-population data, two types of alternative models were used: (1) a multi-trait genomic best linear unbiased prediction (GBLUP) model that modelled trait by line combinations as separate but correlated traits and (2) non-linear models based on kernel learning. These models were compared to conventional linear models for genomic prediction for two lines of brown layer hens (B1 and B2) and one line of white hens (W1). The three lines each had 1004 to 1023 training and 238 to 240 validation animals. Prediction accuracy was evaluated by estimating the correlation between observed phenotypes and predicted breeding values. When the training dataset included only data from the evaluated line, non-linear models yielded at best a similar accuracy as linear models. In some cases, when adding a distantly related line, the linear models showed a slight decrease in performance, while non-linear models generally showed no change in accuracy. When only information from a closely related line was used for training, linear models and non-linear radial basis function (RBF) kernel models performed similarly. The multi-trait GBLUP model took advantage of the estimated genetic correlations between the lines. Combining linear and non-linear models improved the accuracy of multi-line genomic prediction. Linear models and non-linear RBF models performed very similarly for genomic prediction, despite the expectation that non-linear models could deal better with the heterogeneous multi-population data. This heterogeneity of the data can be overcome by modelling trait by line combinations as separate but correlated traits, which avoids the occasional occurrence of large negative accuracies when the evaluated line was not included in the training dataset. Furthermore, when using a multi-line training dataset, non-linear models provided information on the genotype data that was complementary to the linear models, which indicates that the underlying data distributions of the three studied lines were indeed heterogeneous.

Power differentials in bullying: individuals in a community context.

PubMed

Schumann, Lyndall; Craig, Wendy; Rosu, Andrei

2014-03-01

Central to the definition of bullying is the abuse of power. Power relationships are inherent in social groups, by virtue of differing size, strength, age, socioeconomic status (SES), or social connectedness of individuals. Beyond the influence of these individual characteristics, environmental factors have the potential to affect the power dynamic in bullying and victimization, but are a relatively unexplored research area. In particular, we know little about how the community-level factors relate to bullying in the adolescent population. The present study is guided by a social ecological perspective to gain a deeper understanding of the individual and built community characteristics (e.g., parks, recreational spaces, buildings that facilitate social interaction and community connectedness) that contribute to the power dynamics related to victimization or bullying in traditional and electronic contexts. Data were collected from 17,777 students in Grades 6 to 10 as part of the 2009/2010 Health Behavior in School-aged Children (HBSC) Survey, from Geographical Information Systems (GIS) data, and from 2006 Canadian Census data. Two nested models were run using HLM with age, gender, ethnicity, SES, social inclusion factors (e.g., collective efficacy), and community resource factors (e.g., access to recreation) as predictors. Characteristics of individuals that placed them at a power disadvantage (being younger, female, and having low SES) were linked to higher rates of victimization. Lower individual collective efficacy was also associated with higher rates of traditional and electronic victimization. Community recreational opportunities were associated with decreased victimization in both contexts. The relative importance of individual and built environmental factors and conceptualization of bullying interactions within a social ecology model are discussed.

LINEAR - DERIVATION AND DEFINITION OF A LINEAR AIRCRAFT MODEL

NASA Technical Reports Server (NTRS)

Duke, E. L.

1994-01-01

The Derivation and Definition of a Linear Model program, LINEAR, provides the user with a powerful and flexible tool for the linearization of aircraft aerodynamic models. LINEAR was developed to provide a standard, documented, and verified tool to derive linear models for aircraft stability analysis and control law design. Linear system models define the aircraft system in the neighborhood of an analysis point and are determined by the linearization of the nonlinear equations defining vehicle dynamics and sensors. LINEAR numerically determines a linear system model using nonlinear equations of motion and a user supplied linear or nonlinear aerodynamic model. The nonlinear equations of motion used are six-degree-of-freedom equations with stationary atmosphere and flat, nonrotating earth assumptions. LINEAR is capable of extracting both linearized engine effects, such as net thrust, torque, and gyroscopic effects and including these effects in the linear system model. The point at which this linear model is defined is determined either by completely specifying the state and control variables, or by specifying an analysis point on a trajectory and directing the program to determine the control variables and the remaining state variables. The system model determined by LINEAR consists of matrices for both the state and observation equations. The program has been designed to provide easy selection of state, control, and observation variables to be used in a particular model. Thus, the order of the system model is completely under user control. Further, the program provides the flexibility of allowing alternate formulations of both the state and observation equations. Data describing the aircraft and the test case is input to the program through a terminal or formatted data files. All data can be modified interactively from case to case. The aerodynamic model can be defined in two ways: a set of nondimensional stability and control derivatives for the flight point of interest, or a full non-linear aerodynamic model as used in simulations. LINEAR is written in FORTRAN and has been implemented on a DEC VAX computer operating under VMS with a virtual memory requirement of approximately 296K of 8 bit bytes. Both an interactive and batch version are included. LINEAR was developed in 1988.

Changes in Marital Conflict and Youths’ Responses Across Childhood and Adolescence: A Test of Sensitization

PubMed Central

Goeke-Morey, Marcie C.; Papp, Lauren M.; Cummings, E. Mark

2013-01-01

Although the sensitization hypothesis is fundamental to process-oriented explanations of the effects of marital conflict on children, few longitudinal tests of the theory’s propositions have been conducted. This prospective, longitudinal study (n = 297 families) used HLM to assess changes in dimensions of responding to conflict (i.e., emotional, cognitive, behavioral) for three consecutive years in youth between the ages of 8 and 19 years. Moreover, to test the notion of sensitization, analyses examined whether change in marital conflict predicted change in children’s responding across middle childhood and adolescence. Supporting the sensitization hypothesis, increases in exposure to hostile marital conflict were associated with increases in children’s negative emotionality, threat, self blame, and skepticism about resolution. With a few exceptions, effects were largely consistent for boys and girls, and for younger and older children. PMID:23398762

Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes

PubMed Central

Li, Jia; He, Chunyong; Fang, Lianxiang; Yang, Li; Wang, Zhengtao

2016-01-01

20(S)-protopanaxadiol (PPD), one of the representative aglycones of ginsenosides, has a broad spectrum of pharmacological activities. Although phase I metabolism has been investigated extensively, information regarding phase II metabolism of this compound remains to be elucidated. Here, a glucuronidated metabolite of PPD in human liver microsomes (HLMs) and rat liver microsomes (RLMs) was unambiguously identified as PPD-3-O-β-d-glucuronide by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. The chemical inhibition and recombinant human UDP-Glucuronosyltransferase (UGT) isoforms assay showed that the PPD glucuronidation was mainly catalyzed by UGT1A4 in HLM, whereas UGT1A3 showed weak catalytic activity. In conclusion, PPD-3-O-β-d-glucuronide was first identified as the principal glucuronidation metabolite of PPD in HLMs, which was catalyzed by UGT1A4. PMID:27005621

Multi-level risk factors and developmental assets associated with aggressive behavior in disadvantaged adolescents.

PubMed

Smokowski, Paul R; Guo, Shenyang; Cotter, Katie L; Evans, Caroline B R; Rose, Roderick A

2016-01-01

The current study examined multilevel risk factors and developmental assets on longitudinal trajectories of aggressive behavior in a diverse sample of rural adolescents. Using ecological and social capital theories, we explored the impact of positive and negative proximal processes, social capital, and contextual characteristics (i.e., school and neighborhood) on adolescent aggression. Data came from the Rural Adaptation Project, which is a 5-year longitudinal panel study of more than 4,000 middle and high school students from 40 public schools in two rural, low income counties in North Carolina. A three-level HLM model (N = 4,056 at Wave 1, 4,251 at Wave 2, and 4,256 at Wave 3) was estimated to predict factors affecting the change trajectories of aggression. Results indicated that negative proximal processes in the form of parent-adolescent conflict, friend rejection, peer pressure, delinquent friends, and school hassles were significant predictors of aggression. In addition, social capital in the form of ethnic identity, religious orientation, and school satisfaction served as buffers against aggression. Negative proximal processes were more salient predictors than positive proximal processes. School and neighborhood characteristics had a minimal impact on aggression. Overall, rates of aggression did not change significantly over the 3-year study window. Findings highlight the need to intervene in order to decrease negative interactions in the peer and parent domains. © 2015 Wiley Periodicals, Inc.

Comparison of linear and non-linear models for predicting energy expenditure from raw accelerometer data.

PubMed

Montoye, Alexander H K; Begum, Munni; Henning, Zachary; Pfeiffer, Karin A

2017-02-01

This study had three purposes, all related to evaluating energy expenditure (EE) prediction accuracy from body-worn accelerometers: (1) compare linear regression to linear mixed models, (2) compare linear models to artificial neural network models, and (3) compare accuracy of accelerometers placed on the hip, thigh, and wrists. Forty individuals performed 13 activities in a 90 min semi-structured, laboratory-based protocol. Participants wore accelerometers on the right hip, right thigh, and both wrists and a portable metabolic analyzer (EE criterion). Four EE prediction models were developed for each accelerometer: linear regression, linear mixed, and two ANN models. EE prediction accuracy was assessed using correlations, root mean square error (RMSE), and bias and was compared across models and accelerometers using repeated-measures analysis of variance. For all accelerometer placements, there were no significant differences for correlations or RMSE between linear regression and linear mixed models (correlations: r  =  0.71-0.88, RMSE: 1.11-1.61 METs; p  >  0.05). For the thigh-worn accelerometer, there were no differences in correlations or RMSE between linear and ANN models (ANN-correlations: r  =  0.89, RMSE: 1.07-1.08 METs. Linear models-correlations: r  =  0.88, RMSE: 1.10-1.11 METs; p  >  0.05). Conversely, one ANN had higher correlations and lower RMSE than both linear models for the hip (ANN-correlation: r  =  0.88, RMSE: 1.12 METs. Linear models-correlations: r  =  0.86, RMSE: 1.18-1.19 METs; p  <  0.05), and both ANNs had higher correlations and lower RMSE than both linear models for the wrist-worn accelerometers (ANN-correlations: r  =  0.82-0.84, RMSE: 1.26-1.32 METs. Linear models-correlations: r  =  0.71-0.73, RMSE: 1.55-1.61 METs; p  <  0.01). For studies using wrist-worn accelerometers, machine learning models offer a significant improvement in EE prediction accuracy over linear models. Conversely, linear models showed similar EE prediction accuracy to machine learning models for hip- and thigh-worn accelerometers and may be viable alternative modeling techniques for EE prediction for hip- or thigh-worn accelerometers.

Estimation of suspended-sediment rating curves and mean suspended-sediment loads

USGS Publications Warehouse

Crawford, Charles G.

1991-01-01

A simulation study was done to evaluate: (1) the accuracy and precision of parameter estimates for the bias-corrected, transformed-linear and non-linear models obtained by the method of least squares; (2) the accuracy of mean suspended-sediment loads calculated by the flow-duration, rating-curve method using model parameters obtained by the alternative methods. Parameter estimates obtained by least squares for the bias-corrected, transformed-linear model were considerably more precise than those obtained for the non-linear or weighted non-linear model. The accuracy of parameter estimates obtained for the biascorrected, transformed-linear and weighted non-linear model was similar and was much greater than the accuracy obtained by non-linear least squares. The improved parameter estimates obtained by the biascorrected, transformed-linear or weighted non-linear model yield estimates of mean suspended-sediment load calculated by the flow-duration, rating-curve method that are more accurate and precise than those obtained for the non-linear model.

User's manual for LINEAR, a FORTRAN program to derive linear aircraft models

NASA Technical Reports Server (NTRS)

Duke, Eugene L.; Patterson, Brian P.; Antoniewicz, Robert F.

1987-01-01

This report documents a FORTRAN program that provides a powerful and flexible tool for the linearization of aircraft models. The program LINEAR numerically determines a linear system model using nonlinear equations of motion and a user-supplied nonlinear aerodynamic model. The system model determined by LINEAR consists of matrices for both state and observation equations. The program has been designed to allow easy selection and definition of the state, control, and observation variables to be used in a particular model.

Latent log-linear models for handwritten digit classification.

PubMed

Deselaers, Thomas; Gass, Tobias; Heigold, Georg; Ney, Hermann

2012-06-01

We present latent log-linear models, an extension of log-linear models incorporating latent variables, and we propose two applications thereof: log-linear mixture models and image deformation-aware log-linear models. The resulting models are fully discriminative, can be trained efficiently, and the model complexity can be controlled. Log-linear mixture models offer additional flexibility within the log-linear modeling framework. Unlike previous approaches, the image deformation-aware model directly considers image deformations and allows for a discriminative training of the deformation parameters. Both are trained using alternating optimization. For certain variants, convergence to a stationary point is guaranteed and, in practice, even variants without this guarantee converge and find models that perform well. We tune the methods on the USPS data set and evaluate on the MNIST data set, demonstrating the generalization capabilities of our proposed models. Our models, although using significantly fewer parameters, are able to obtain competitive results with models proposed in the literature.

Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

PubMed

Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

2017-12-01

The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of the currently used methods for DON-biomarker analysis.

Simplified large African carnivore density estimators from track indices.

PubMed

Winterbach, Christiaan W; Ferreira, Sam M; Funston, Paul J; Somers, Michael J

2016-01-01

The range, population size and trend of large carnivores are important parameters to assess their status globally and to plan conservation strategies. One can use linear models to assess population size and trends of large carnivores from track-based surveys on suitable substrates. The conventional approach of a linear model with intercept may not intercept at zero, but may fit the data better than linear model through the origin. We assess whether a linear regression through the origin is more appropriate than a linear regression with intercept to model large African carnivore densities and track indices. We did simple linear regression with intercept analysis and simple linear regression through the origin and used the confidence interval for ß in the linear model y  =  αx  + ß, Standard Error of Estimate, Mean Squares Residual and Akaike Information Criteria to evaluate the models. The Lion on Clay and Low Density on Sand models with intercept were not significant ( P  > 0.05). The other four models with intercept and the six models thorough origin were all significant ( P  < 0.05). The models using linear regression with intercept all included zero in the confidence interval for ß and the null hypothesis that ß = 0 could not be rejected. All models showed that the linear model through the origin provided a better fit than the linear model with intercept, as indicated by the Standard Error of Estimate and Mean Square Residuals. Akaike Information Criteria showed that linear models through the origin were better and that none of the linear models with intercept had substantial support. Our results showed that linear regression through the origin is justified over the more typical linear regression with intercept for all models we tested. A general model can be used to estimate large carnivore densities from track densities across species and study areas. The formula observed track density = 3.26 × carnivore density can be used to estimate densities of large African carnivores using track counts on sandy substrates in areas where carnivore densities are 0.27 carnivores/100 km 2 or higher. To improve the current models, we need independent data to validate the models and data to test for non-linear relationship between track indices and true density at low densities.

Population response to climate change: linear vs. non-linear modeling approaches.

PubMed

Ellis, Alicia M; Post, Eric

2004-03-31

Research on the ecological consequences of global climate change has elicited a growing interest in the use of time series analysis to investigate population dynamics in a changing climate. Here, we compare linear and non-linear models describing the contribution of climate to the density fluctuations of the population of wolves on Isle Royale, Michigan from 1959 to 1999. The non-linear self excitatory threshold autoregressive (SETAR) model revealed that, due to differences in the strength and nature of density dependence, relatively small and large populations may be differentially affected by future changes in climate. Both linear and non-linear models predict a decrease in the population of wolves with predicted changes in climate. Because specific predictions differed between linear and non-linear models, our study highlights the importance of using non-linear methods that allow the detection of non-linearity in the strength and nature of density dependence. Failure to adopt a non-linear approach to modelling population response to climate change, either exclusively or in addition to linear approaches, may compromise efforts to quantify ecological consequences of future warming.

Comparison Between Linear and Non-parametric Regression Models for Genome-Enabled Prediction in Wheat

PubMed Central

Pérez-Rodríguez, Paulino; Gianola, Daniel; González-Camacho, Juan Manuel; Crossa, José; Manès, Yann; Dreisigacker, Susanne

2012-01-01

In genome-enabled prediction, parametric, semi-parametric, and non-parametric regression models have been used. This study assessed the predictive ability of linear and non-linear models using dense molecular markers. The linear models were linear on marker effects and included the Bayesian LASSO, Bayesian ridge regression, Bayes A, and Bayes B. The non-linear models (this refers to non-linearity on markers) were reproducing kernel Hilbert space (RKHS) regression, Bayesian regularized neural networks (BRNN), and radial basis function neural networks (RBFNN). These statistical models were compared using 306 elite wheat lines from CIMMYT genotyped with 1717 diversity array technology (DArT) markers and two traits, days to heading (DTH) and grain yield (GY), measured in each of 12 environments. It was found that the three non-linear models had better overall prediction accuracy than the linear regression specification. Results showed a consistent superiority of RKHS and RBFNN over the Bayesian LASSO, Bayesian ridge regression, Bayes A, and Bayes B models. PMID:23275882

Comparison between linear and non-parametric regression models for genome-enabled prediction in wheat.

PubMed

Pérez-Rodríguez, Paulino; Gianola, Daniel; González-Camacho, Juan Manuel; Crossa, José; Manès, Yann; Dreisigacker, Susanne

2012-12-01

In genome-enabled prediction, parametric, semi-parametric, and non-parametric regression models have been used. This study assessed the predictive ability of linear and non-linear models using dense molecular markers. The linear models were linear on marker effects and included the Bayesian LASSO, Bayesian ridge regression, Bayes A, and Bayes B. The non-linear models (this refers to non-linearity on markers) were reproducing kernel Hilbert space (RKHS) regression, Bayesian regularized neural networks (BRNN), and radial basis function neural networks (RBFNN). These statistical models were compared using 306 elite wheat lines from CIMMYT genotyped with 1717 diversity array technology (DArT) markers and two traits, days to heading (DTH) and grain yield (GY), measured in each of 12 environments. It was found that the three non-linear models had better overall prediction accuracy than the linear regression specification. Results showed a consistent superiority of RKHS and RBFNN over the Bayesian LASSO, Bayesian ridge regression, Bayes A, and Bayes B models.

The effects of student-level and classroom-level factors on elementary students' science achievement in five countries

NASA Astrophysics Data System (ADS)

Kaya, Sibel

The interest in raising levels of achievement in math and science has led to a focus on investigating the factors that shape achievement in these subjects (Lamb & Fullarton, 2002) as well as understanding how these factors operate across countries (Baker, Fabrega, Galindo, & Mishook, 2004). The current study examined the individual student factors and classroom factors on fourth grade science achievement within and across five countries. Guided by the previous school learning models, the elements of students' science learning were categorized as student-level and classroom-level factors. The student-level factors included gender, self-confidence in science, and home resources. The classroom-level factors included teacher characteristics, instructional variables and classroom composition. Results for the United States and four other countries, Singapore, Japan, Australia, and Scotland were reported. Multilevel effects of student and classroom variables were examined through Hierarchical Linear Modeling (HLM) using the Trends in International Mathematics and Science Study (TIMSS) 2003 fourth grade dataset. The outcome variable was the TIMSS 2003 science score. Overall, the results of this study showed that selected student background characteristics were consistently related to elementary science achievement in countries investigated. At the student-level, higher levels of home resources and self-confidence and at the classroom-level, higher levels of class mean home resources yielded higher science scores on the TIMSS 2003. In general, teacher and instructional variables were minimally related to science achievement. There was evidence of positive effects of teacher support in the U.S. and Singapore. The emphasis on science inquiry was positively related to science achievement in Singapore and negatively related in the U.S. and Australia. Experimental studies that investigate the impacts of teacher and instructional factors on elementary science achievement are needed. For all the countries investigated, with the exception of Singapore, the between-class variance was much smaller than the within-class variance. Japan had the smallest variation in science achievement among classrooms which indicates the homogeneity across classrooms in Japan. Increasing awareness and knowledge of gender neutral instructional techniques, providing a non-threatening, rich and supportive environment for both genders in classrooms by elementary teachers are to be encouraged. To improve students' self beliefs about science, it is recommended that teachers model science activities and accommodate students' needs and abilities (Bandura, 1997; Britner & Pajares, 2006). Schools and teachers are recommended to develop a successful home-school partnership for improved student learning and positive attitudes toward science (Eccles & Harold, 1996; Epstein & Salinas, 2004). Furthermore, developing a knowledge base for teachers regarding the influences of classroom and school composition is highlighted (Honig, Kahne, & McLaughlin, 2001; Murrel, 2001). At the classroom- and school-level, policy efforts could focus on the distribution of educational resources (Condron & Roscigno, 2003; Goesling, 2003) to compensate for poor family background.

Computing Linear Mathematical Models Of Aircraft

NASA Technical Reports Server (NTRS)

Duke, Eugene L.; Antoniewicz, Robert F.; Krambeer, Keith D.

1991-01-01

Derivation and Definition of Linear Aircraft Model (LINEAR) computer program provides user with powerful, and flexible, standard, documented, and verified software tool for linearization of mathematical models of aerodynamics of aircraft. Intended for use in software tool to drive linear analysis of stability and design of control laws for aircraft. Capable of both extracting such linearized engine effects as net thrust, torque, and gyroscopic effects, and including these effects in linear model of system. Designed to provide easy selection of state, control, and observation variables used in particular model. Also provides flexibility of allowing alternate formulations of both state and observation equations. Written in FORTRAN.

Modelling female fertility traits in beef cattle using linear and non-linear models.

PubMed

Naya, H; Peñagaricano, F; Urioste, J I

2017-06-01

Female fertility traits are key components of the profitability of beef cattle production. However, these traits are difficult and expensive to measure, particularly under extensive pastoral conditions, and consequently, fertility records are in general scarce and somehow incomplete. Moreover, fertility traits are usually dominated by the effects of herd-year environment, and it is generally assumed that relatively small margins are kept for genetic improvement. New ways of modelling genetic variation in these traits are needed. Inspired in the methodological developments made by Prof. Daniel Gianola and co-workers, we assayed linear (Gaussian), Poisson, probit (threshold), censored Poisson and censored Gaussian models to three different kinds of endpoints, namely calving success (CS), number of days from first calving (CD) and number of failed oestrus (FE). For models involving FE and CS, non-linear models overperformed their linear counterparts. For models derived from CD, linear versions displayed better adjustment than the non-linear counterparts. Non-linear models showed consistently higher estimates of heritability and repeatability in all cases (h 2  < 0.08 and r < 0.13, for linear models; h 2  > 0.23 and r > 0.24, for non-linear models). While additive and permanent environment effects showed highly favourable correlations between all models (>0.789), consistency in selecting the 10% best sires showed important differences, mainly amongst the considered endpoints (FE, CS and CD). In consequence, endpoints should be considered as modelling different underlying genetic effects, with linear models more appropriate to describe CD and non-linear models better for FE and CS. © 2017 Blackwell Verlag GmbH.

User's manual for interactive LINEAR: A FORTRAN program to derive linear aircraft models

NASA Technical Reports Server (NTRS)

Antoniewicz, Robert F.; Duke, Eugene L.; Patterson, Brian P.

1988-01-01

An interactive FORTRAN program that provides the user with a powerful and flexible tool for the linearization of aircraft aerodynamic models is documented in this report. The program LINEAR numerically determines a linear system model using nonlinear equations of motion and a user-supplied linear or nonlinear aerodynamic model. The nonlinear equations of motion used are six-degree-of-freedom equations with stationary atmosphere and flat, nonrotating earth assumptions. The system model determined by LINEAR consists of matrices for both the state and observation equations. The program has been designed to allow easy selection and definition of the state, control, and observation variables to be used in a particular model.

Development and validation of a general purpose linearization program for rigid aircraft models

NASA Technical Reports Server (NTRS)

Duke, E. L.; Antoniewicz, R. F.

1985-01-01

A FORTRAN program that provides the user with a powerful and flexible tool for the linearization of aircraft models is discussed. The program LINEAR numerically determines a linear systems model using nonlinear equations of motion and a user-supplied, nonlinear aerodynamic model. The system model determined by LINEAR consists of matrices for both the state and observation equations. The program has been designed to allow easy selection and definition of the state, control, and observation variables to be used in a particular model. Also, included in the report is a comparison of linear and nonlinear models for a high performance aircraft.

The determination of third order linear models from a seventh order nonlinear jet engine model

NASA Technical Reports Server (NTRS)

Lalonde, Rick J.; Hartley, Tom T.; De Abreu-Garcia, J. Alex

1989-01-01

Results are presented that demonstrate how good reduced-order models can be obtained directly by recursive parameter identification using input/output (I/O) data of high-order nonlinear systems. Three different methods of obtaining a third-order linear model from a seventh-order nonlinear turbojet engine model are compared. The first method is to obtain a linear model from the original model and then reduce the linear model by standard reduction techniques such as residualization and balancing. The second method is to identify directly a third-order linear model by recursive least-squares parameter estimation using I/O data of the original model. The third method is to obtain a reduced-order model from the original model and then linearize the reduced model. Frequency responses are used as the performance measure to evaluate the reduced models. The reduced-order models along with their Bode plots are presented for comparison purposes.

Development of a Linear Stirling Model with Varying Heat Inputs

NASA Technical Reports Server (NTRS)

Regan, Timothy F.; Lewandowski, Edward J.

2007-01-01

The linear model of the Stirling system developed by NASA Glenn Research Center (GRC) has been extended to include a user-specified heat input. Previously developed linear models were limited to the Stirling convertor and electrical load. They represented the thermodynamic cycle with pressure factors that remained constant. The numerical values of the pressure factors were generated by linearizing GRC s non-linear System Dynamic Model (SDM) of the convertor at a chosen operating point. The pressure factors were fixed for that operating point, thus, the model lost accuracy if a transition to a different operating point were simulated. Although the previous linear model was used in developing controllers that manipulated current, voltage, and piston position, it could not be used in the development of control algorithms that regulated hot-end temperature. This basic model was extended to include the thermal dynamics associated with a hot-end temperature that varies over time in response to external changes as well as to changes in the Stirling cycle. The linear model described herein includes not only dynamics of the piston, displacer, gas, and electrical circuit, but also the transient effects of the heater head thermal inertia. The linear version algebraically couples two separate linear dynamic models, one model of the Stirling convertor and one model of the thermal system, through the pressure factors. The thermal system model includes heat flow of heat transfer fluid, insulation loss, and temperature drops from the heat source to the Stirling convertor expansion space. The linear model was compared to a nonlinear model, and performance was very similar. The resulting linear model can be implemented in a variety of computing environments, and is suitable for analysis with classical and state space controls analysis techniques.

Application of Hierarchical Linear Models/Linear Mixed-Effects Models in School Effectiveness Research

ERIC Educational Resources Information Center

Ker, H. W.

2014-01-01

Multilevel data are very common in educational research. Hierarchical linear models/linear mixed-effects models (HLMs/LMEs) are often utilized to analyze multilevel data nowadays. This paper discusses the problems of utilizing ordinary regressions for modeling multilevel educational data, compare the data analytic results from three regression…

Comparison of all atom, continuum, and linear fitting empirical models for charge screening effect of aqueous medium surrounding a protein molecule

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Sugiura, Junnnosuke; Nagayama, Kuniaki

2002-05-01

To investigate the role hydration plays in the electrostatic interactions of proteins, the time-averaged electrostatic potential of the B1 domain of protein G in an aqueous solution was calculated with full atomic molecular dynamics simulations that explicitly considers every atom (i.e., an all atom model). This all atom calculated potential was compared with the potential obtained from an electrostatic continuum model calculation. In both cases, the charge-screening effect was fairly well formulated with an effective relative dielectric constant which increased linearly with increasing charge-charge distance. This simulated linear dependence agrees with the experimentally determined linear relation proposed by Pickersgill. Cut-off approximations for Coulomb interactions failed to reproduce this linear relation. Correlation between the all atom model and the continuum models was found to be better than the respective correlation calculated for linear fitting to the two models. This confirms that the continuum model is better at treating the complicated shapes of protein conformations than the simple linear fitting empirical model. We have tried a sigmoid fitting empirical model in addition to the linear one. When weights of all data were treated equally, the sigmoid model, which requires two fitting parameters, fits results of both the all atom and the continuum models less accurately than the linear model which requires only one fitting parameter. When potential values are chosen as weighting factors, the fitting error of the sigmoid model became smaller, and the slope of both linear fitting curves became smaller. This suggests the screening effect of an aqueous medium within a short range, where potential values are relatively large, is smaller than that expected from the linear fitting curve whose slope is almost 4. To investigate the linear increase of the effective relative dielectric constant, the Poisson equation of a low-dielectric sphere in a high-dielectric medium was solved and charges distributed near the molecular surface were indicated as leading to the apparent linearity.

The Overgeneralization of Linear Models among University Students' Mathematical Productions: A Long-Term Study

ERIC Educational Resources Information Center

Esteley, Cristina B.; Villarreal, Monica E.; Alagia, Humberto R.

2010-01-01

Over the past several years, we have been exploring and researching a phenomenon that occurs among undergraduate students that we called extension of linear models to non-linear contexts or overgeneralization of linear models. This phenomenon appears when some students use linear representations in situations that are non-linear. In a first phase,…

Piecewise Linear-Linear Latent Growth Mixture Models with Unknown Knots

ERIC Educational Resources Information Center

Kohli, Nidhi; Harring, Jeffrey R.; Hancock, Gregory R.

2013-01-01

Latent growth curve models with piecewise functions are flexible and useful analytic models for investigating individual behaviors that exhibit distinct phases of development in observed variables. As an extension of this framework, this study considers a piecewise linear-linear latent growth mixture model (LGMM) for describing segmented change of…

Predicting oropharyngeal tumor volume throughout the course of radiation therapy from pretreatment computed tomography data using general linear models.

PubMed

Yock, Adam D; Rao, Arvind; Dong, Lei; Beadle, Beth M; Garden, Adam S; Kudchadker, Rajat J; Court, Laurence E

2014-05-01

The purpose of this work was to develop and evaluate the accuracy of several predictive models of variation in tumor volume throughout the course of radiation therapy. Nineteen patients with oropharyngeal cancers were imaged daily with CT-on-rails for image-guided alignment per an institutional protocol. The daily volumes of 35 tumors in these 19 patients were determined and used to generate (1) a linear model in which tumor volume changed at a constant rate, (2) a general linear model that utilized the power fit relationship between the daily and initial tumor volumes, and (3) a functional general linear model that identified and exploited the primary modes of variation between time series describing the changing tumor volumes. Primary and nodal tumor volumes were examined separately. The accuracy of these models in predicting daily tumor volumes were compared with those of static and linear reference models using leave-one-out cross-validation. In predicting the daily volume of primary tumors, the general linear model and the functional general linear model were more accurate than the static reference model by 9.9% (range: -11.6%-23.8%) and 14.6% (range: -7.3%-27.5%), respectively, and were more accurate than the linear reference model by 14.2% (range: -6.8%-40.3%) and 13.1% (range: -1.5%-52.5%), respectively. In predicting the daily volume of nodal tumors, only the 14.4% (range: -11.1%-20.5%) improvement in accuracy of the functional general linear model compared to the static reference model was statistically significant. A general linear model and a functional general linear model trained on data from a small population of patients can predict the primary tumor volume throughout the course of radiation therapy with greater accuracy than standard reference models. These more accurate models may increase the prognostic value of information about the tumor garnered from pretreatment computed tomography images and facilitate improved treatment management.

Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

PubMed Central

Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

2014-01-01

Purpose The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency during anterior-posterior stretching. Method Three materially linear and three materially nonlinear models were created and stretched up to 10 mm in 1 mm increments. Phonation onset pressure (Pon) and fundamental frequency (F0) at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1 mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Results Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Conclusions Nonlinear synthetic models appear to more accurately represent the human vocal folds than linear models, especially with respect to F0 response. PMID:22271874

Frequency response of synthetic vocal fold models with linear and nonlinear material properties.

PubMed

Shaw, Stephanie M; Thomson, Scott L; Dromey, Christopher; Smith, Simeon

2012-10-01

The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F0) during anterior-posterior stretching. Three materially linear and 3 materially nonlinear models were created and stretched up to 10 mm in 1-mm increments. Phonation onset pressure (Pon) and F0 at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1-mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Nonlinear synthetic models appear to more accurately represent the human vocal folds than do linear models, especially with respect to F0 response.

Extending Linear Models to Non-Linear Contexts: An In-Depth Study about Two University Students' Mathematical Productions

ERIC Educational Resources Information Center

Esteley, Cristina; Villarreal, Monica; Alagia, Humberto

2004-01-01

This research report presents a study of the work of agronomy majors in which an extension of linear models to non-linear contexts can be observed. By linear models we mean the model y=a.x+b, some particular representations of direct proportionality and the diagram for the rule of three. Its presence and persistence in different types of problems…

Mathematical model for the contribution of individual organs to non-zero y-intercepts in single and multi-compartment linear models of whole-body energy expenditure.

PubMed

Kaiyala, Karl J

2014-01-01

Mathematical models for the dependence of energy expenditure (EE) on body mass and composition are essential tools in metabolic phenotyping. EE scales over broad ranges of body mass as a non-linear allometric function. When considered within restricted ranges of body mass, however, allometric EE curves exhibit 'local linearity.' Indeed, modern EE analysis makes extensive use of linear models. Such models typically involve one or two body mass compartments (e.g., fat free mass and fat mass). Importantly, linear EE models typically involve a non-zero (usually positive) y-intercept term of uncertain origin, a recurring theme in discussions of EE analysis and a source of confounding in traditional ratio-based EE normalization. Emerging linear model approaches quantify whole-body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys, heart, brain). Proponents of individual organ REE modeling hypothesize that multi-organ linear models may eliminate non-zero y-intercepts. This could have advantages in adjusting REE for body mass and composition. Studies reveal that individual organ REE is an allometric function of total body mass. I exploit first-order Taylor linearization of individual organ REEs to model the manner in which individual organs contribute to whole-body REE and to the non-zero y-intercept in linear REE models. The model predicts that REE analysis at the individual organ-tissue level will not eliminate intercept terms. I demonstrate that the parameters of a linear EE equation can be transformed into the parameters of the underlying 'latent' allometric equation. This permits estimates of the allometric scaling of EE in a diverse variety of physiological states that are not represented in the allometric EE literature but are well represented by published linear EE analyses.

Development of a Linear Stirling System Model with Varying Heat Inputs

NASA Technical Reports Server (NTRS)

Regan, Timothy F.; Lewandowski, Edward J.

2007-01-01

The linear model of the Stirling system developed by NASA Glenn Research Center (GRC) has been extended to include a user-specified heat input. Previously developed linear models were limited to the Stirling convertor and electrical load. They represented the thermodynamic cycle with pressure factors that remained constant. The numerical values of the pressure factors were generated by linearizing GRC's nonlinear System Dynamic Model (SDM) of the convertor at a chosen operating point. The pressure factors were fixed for that operating point, thus, the model lost accuracy if a transition to a different operating point were simulated. Although the previous linear model was used in developing controllers that manipulated current, voltage, and piston position, it could not be used in the development of control algorithms that regulated hot-end temperature. This basic model was extended to include the thermal dynamics associated with a hot-end temperature that varies over time in response to external changes as well as to changes in the Stirling cycle. The linear model described herein includes not only dynamics of the piston, displacer, gas, and electrical circuit, but also the transient effects of the heater head thermal inertia. The linear version algebraically couples two separate linear dynamic models, one model of the Stirling convertor and one model of the thermal system, through the pressure factors. The thermal system model includes heat flow of heat transfer fluid, insulation loss, and temperature drops from the heat source to the Stirling convertor expansion space. The linear model was compared to a nonlinear model, and performance was very similar. The resulting linear model can be implemented in a variety of computing environments, and is suitable for analysis with classical and state space controls analysis techniques.

Pseudo-second order models for the adsorption of safranin onto activated carbon: comparison of linear and non-linear regression methods.

PubMed

Kumar, K Vasanth

2007-04-02

Kinetic experiments were carried out for the sorption of safranin onto activated carbon particles. The kinetic data were fitted to pseudo-second order model of Ho, Sobkowsk and Czerwinski, Blanchard et al. and Ritchie by linear and non-linear regression methods. Non-linear method was found to be a better way of obtaining the parameters involved in the second order rate kinetic expressions. Both linear and non-linear regression showed that the Sobkowsk and Czerwinski and Ritchie's pseudo-second order models were the same. Non-linear regression analysis showed that both Blanchard et al. and Ho have similar ideas on the pseudo-second order model but with different assumptions. The best fit of experimental data in Ho's pseudo-second order expression by linear and non-linear regression method showed that Ho pseudo-second order model was a better kinetic expression when compared to other pseudo-second order kinetic expressions.

Linearized aerodynamic and control law models of the X-29A airplane and comparison with flight data

NASA Technical Reports Server (NTRS)

Bosworth, John T.

1992-01-01

Flight control system design and analysis for aircraft rely on mathematical models of the vehicle dynamics. In addition to a six degree of freedom nonlinear simulation, the X-29A flight controls group developed a set of programs that calculate linear perturbation models throughout the X-29A flight envelope. The models include the aerodynamics as well as flight control system dynamics and were used for stability, controllability, and handling qualities analysis. These linear models were compared to flight test results to help provide a safe flight envelope expansion. A description is given of the linear models at three flight conditions and two flight control system modes. The models are presented with a level of detail that would allow the reader to reproduce the linear results if desired. Comparison between the response of the linear model and flight measured responses are presented to demonstrate the strengths and weaknesses of the linear models' ability to predict flight dynamics.

From Spiking Neuron Models to Linear-Nonlinear Models

PubMed Central

Ostojic, Srdjan; Brunel, Nicolas

2011-01-01

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates. PMID:21283777

From spiking neuron models to linear-nonlinear models.

PubMed

Ostojic, Srdjan; Brunel, Nicolas

2011-01-20

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.

Second-order kinetic model for the sorption of cadmium onto tree fern: a comparison of linear and non-linear methods.

PubMed

Ho, Yuh-Shan

2006-01-01

A comparison was made of the linear least-squares method and a trial-and-error non-linear method of the widely used pseudo-second-order kinetic model for the sorption of cadmium onto ground-up tree fern. Four pseudo-second-order kinetic linear equations are discussed. Kinetic parameters obtained from the four kinetic linear equations using the linear method differed but they were the same when using the non-linear method. A type 1 pseudo-second-order linear kinetic model has the highest coefficient of determination. Results show that the non-linear method may be a better way to obtain the desired parameters.

Identification of UDP-glucuronosyltransferases 1A1, 1A3 and 2B15 as the main contributors to glucuronidation of bakuchiol, a natural biologically active compound.

PubMed

Li, Feng; Wang, Shuai; Lu, Danyi; Wang, Yifei; Dong, Dong; Wu, Baojian

2017-05-01

1. Bakuchiol, one of the main active compounds of Psoralea corylifolia, possesses a variety of pharmacological activities such as anti-tumor and anti-aging effects. Here, we aimed to characterize the glucuronidation of bakuchiol using human liver microsomes (HLM) and expressed UDP-glucuronosyltransferase (UGT) enzymes. 2. The glucuronide of bakuchiol was confirmed by liquid chromatography-mass spectrometry (LC-MS) and β-glucuronidase hydrolysis assay. Glucuronidation rates and kinetic parameters were derived by enzymatic incubation and model fitting. Activity correlation analyses were performed to identify the main UGT isoforms contributing to hepatic metabolism of bakuchiol. 3. Among the three UGT enzymes (i.e., UGT1A1, UGT1A3 and UGT2B15) capable of catalyzing bakuchiol glucuronidation, UGT2B15 showed the highest activity with a CL int value of 100 μl/min/nmol. Bakuchiol glucuronidation was strongly correlated with glucuronidation of 5-hydroxyrofecoxib (r = 0.933; p < 0.001), 3-O-glucuronidation of β-estradiol (r = 0.719; p < 0.01) and significantly correlated with 24-O-glucuronidation of CDCA (r = 0.594; p < 0.05). In addition, a marked species difference existed in hepatic glucuronidation of bakuchiol. 4. In conclusion, UGT1A1, UGT1A3 and UGT2B15 were identified as the main contributors to glucuronidation of bakuchiol.

Effects of Stochastic Traffic Flow Model on Expected System Performance

DTIC Science & Technology

2012-12-01

NSWC-PCD has made considerable improvements to their pedestrian flow modeling . In addition to the linear paths, the 2011 version now includes...using stochastic paths. 2.2 Linear Paths vs. Stochastic Paths 2.2.1 Linear Paths and Direct Maximum Pd Calculation Modeling pedestrian traffic flow...as a stochastic process begins with the linear path model . Let the detec- tion area be R x C voxels. This creates C 2 total linear paths, path(Cs

Statistical Methodology for the Analysis of Repeated Duration Data in Behavioral Studies.

PubMed

Letué, Frédérique; Martinez, Marie-José; Samson, Adeline; Vilain, Anne; Vilain, Coriandre

2018-03-15

Repeated duration data are frequently used in behavioral studies. Classical linear or log-linear mixed models are often inadequate to analyze such data, because they usually consist of nonnegative and skew-distributed variables. Therefore, we recommend use of a statistical methodology specific to duration data. We propose a methodology based on Cox mixed models and written under the R language. This semiparametric model is indeed flexible enough to fit duration data. To compare log-linear and Cox mixed models in terms of goodness-of-fit on real data sets, we also provide a procedure based on simulations and quantile-quantile plots. We present two examples from a data set of speech and gesture interactions, which illustrate the limitations of linear and log-linear mixed models, as compared to Cox models. The linear models are not validated on our data, whereas Cox models are. Moreover, in the second example, the Cox model exhibits a significant effect that the linear model does not. We provide methods to select the best-fitting models for repeated duration data and to compare statistical methodologies. In this study, we show that Cox models are best suited to the analysis of our data set.

Fast and local non-linear evolution of steep wave-groups on deep water: A comparison of approximate models to fully non-linear simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adcock, T. A. A.; Taylor, P. H.

2016-01-15

The non-linear Schrödinger equation and its higher order extensions are routinely used for analysis of extreme ocean waves. This paper compares the evolution of individual wave-packets modelled using non-linear Schrödinger type equations with packets modelled using fully non-linear potential flow models. The modified non-linear Schrödinger Equation accurately models the relatively large scale non-linear changes to the shape of wave-groups, with a dramatic contraction of the group along the mean propagation direction and a corresponding extension of the width of the wave-crests. In addition, as extreme wave form, there is a local non-linear contraction of the wave-group around the crest whichmore » leads to a localised broadening of the wave spectrum which the bandwidth limited non-linear Schrödinger Equations struggle to capture. This limitation occurs for waves of moderate steepness and a narrow underlying spectrum.« less

Constructing an Efficient Self-Tuning Aircraft Engine Model for Control and Health Management Applications

NASA Technical Reports Server (NTRS)

Armstrong, Jeffrey B.; Simon, Donald L.

2012-01-01

Self-tuning aircraft engine models can be applied for control and health management applications. The self-tuning feature of these models minimizes the mismatch between any given engine and the underlying engineering model describing an engine family. This paper provides details of the construction of a self-tuning engine model centered on a piecewise linear Kalman filter design. Starting from a nonlinear transient aerothermal model, a piecewise linear representation is first extracted. The linearization procedure creates a database of trim vectors and state-space matrices that are subsequently scheduled for interpolation based on engine operating point. A series of steady-state Kalman gains can next be constructed from a reduced-order form of the piecewise linear model. Reduction of the piecewise linear model to an observable dimension with respect to available sensed engine measurements can be achieved using either a subset or an optimal linear combination of "health" parameters, which describe engine performance. The resulting piecewise linear Kalman filter is then implemented for faster-than-real-time processing of sensed engine measurements, generating outputs appropriate for trending engine performance, estimating both measured and unmeasured parameters for control purposes, and performing on-board gas-path fault diagnostics. Computational efficiency is achieved by designing multidimensional interpolation algorithms that exploit the shared scheduling of multiple trim vectors and system matrices. An example application illustrates the accuracy of a self-tuning piecewise linear Kalman filter model when applied to a nonlinear turbofan engine simulation. Additional discussions focus on the issue of transient response accuracy and the advantages of a piecewise linear Kalman filter in the context of validation and verification. The techniques described provide a framework for constructing efficient self-tuning aircraft engine models from complex nonlinear simulations.Self-tuning aircraft engine models can be applied for control and health management applications. The self-tuning feature of these models minimizes the mismatch between any given engine and the underlying engineering model describing an engine family. This paper provides details of the construction of a self-tuning engine model centered on a piecewise linear Kalman filter design. Starting from a nonlinear transient aerothermal model, a piecewise linear representation is first extracted. The linearization procedure creates a database of trim vectors and state-space matrices that are subsequently scheduled for interpolation based on engine operating point. A series of steady-state Kalman gains can next be constructed from a reduced-order form of the piecewise linear model. Reduction of the piecewise linear model to an observable dimension with respect to available sensed engine measurements can be achieved using either a subset or an optimal linear combination of "health" parameters, which describe engine performance. The resulting piecewise linear Kalman filter is then implemented for faster-than-real-time processing of sensed engine measurements, generating outputs appropriate for trending engine performance, estimating both measured and unmeasured parameters for control purposes, and performing on-board gas-path fault diagnostics. Computational efficiency is achieved by designing multidimensional interpolation algorithms that exploit the shared scheduling of multiple trim vectors and system matrices. An example application illustrates the accuracy of a self-tuning piecewise linear Kalman filter model when applied to a nonlinear turbofan engine simulation. Additional discussions focus on the issue of transient response accuracy and the advantages of a piecewise linear Kalman filter in the context of validation and verification. The techniques described provide a framework for constructing efficient self-tuning aircraft engine models from complex nonlinear simulatns.

Non-linear scaling of a musculoskeletal model of the lower limb using statistical shape models.

PubMed

Nolte, Daniel; Tsang, Chui Kit; Zhang, Kai Yu; Ding, Ziyun; Kedgley, Angela E; Bull, Anthony M J

2016-10-03

Accurate muscle geometry for musculoskeletal models is important to enable accurate subject-specific simulations. Commonly, linear scaling is used to obtain individualised muscle geometry. More advanced methods include non-linear scaling using segmented bone surfaces and manual or semi-automatic digitisation of muscle paths from medical images. In this study, a new scaling method combining non-linear scaling with reconstructions of bone surfaces using statistical shape modelling is presented. Statistical Shape Models (SSMs) of femur and tibia/fibula were used to reconstruct bone surfaces of nine subjects. Reference models were created by morphing manually digitised muscle paths to mean shapes of the SSMs using non-linear transformations and inter-subject variability was calculated. Subject-specific models of muscle attachment and via points were created from three reference models. The accuracy was evaluated by calculating the differences between the scaled and manually digitised models. The points defining the muscle paths showed large inter-subject variability at the thigh and shank - up to 26mm; this was found to limit the accuracy of all studied scaling methods. Errors for the subject-specific muscle point reconstructions of the thigh could be decreased by 9% to 20% by using the non-linear scaling compared to a typical linear scaling method. We conclude that the proposed non-linear scaling method is more accurate than linear scaling methods. Thus, when combined with the ability to reconstruct bone surfaces from incomplete or scattered geometry data using statistical shape models our proposed method is an alternative to linear scaling methods. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Analysis of baseline, average, and longitudinally measured blood pressure data using linear mixed models.

PubMed

Hossain, Ahmed; Beyene, Joseph

2014-01-01

This article compares baseline, average, and longitudinal data analysis methods for identifying genetic variants in genome-wide association study using the Genetic Analysis Workshop 18 data. We apply methods that include (a) linear mixed models with baseline measures, (b) random intercept linear mixed models with mean measures outcome, and (c) random intercept linear mixed models with longitudinal measurements. In the linear mixed models, covariates are included as fixed effects, whereas relatedness among individuals is incorporated as the variance-covariance structure of the random effect for the individuals. The overall strategy of applying linear mixed models decorrelate the data is based on Aulchenko et al.'s GRAMMAR. By analyzing systolic and diastolic blood pressure, which are used separately as outcomes, we compare the 3 methods in identifying a known genetic variant that is associated with blood pressure from chromosome 3 and simulated phenotype data. We also analyze the real phenotype data to illustrate the methods. We conclude that the linear mixed model with longitudinal measurements of diastolic blood pressure is the most accurate at identifying the known single-nucleotide polymorphism among the methods, but linear mixed models with baseline measures perform best with systolic blood pressure as the outcome.

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

PubMed

Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

2017-06-01

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were observed for the SOBP scenario, both non-linear LET spectrum- and linear LET d based models should be further evaluated in clinically realistic scenarios. © 2017 American Association of Physicists in Medicine.

Mathematical Model for the Contribution of Individual Organs to Non-Zero Y-Intercepts in Single and Multi-Compartment Linear Models of Whole-Body Energy Expenditure

PubMed Central

Kaiyala, Karl J.

2014-01-01

Mathematical models for the dependence of energy expenditure (EE) on body mass and composition are essential tools in metabolic phenotyping. EE scales over broad ranges of body mass as a non-linear allometric function. When considered within restricted ranges of body mass, however, allometric EE curves exhibit ‘local linearity.’ Indeed, modern EE analysis makes extensive use of linear models. Such models typically involve one or two body mass compartments (e.g., fat free mass and fat mass). Importantly, linear EE models typically involve a non-zero (usually positive) y-intercept term of uncertain origin, a recurring theme in discussions of EE analysis and a source of confounding in traditional ratio-based EE normalization. Emerging linear model approaches quantify whole-body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys, heart, brain). Proponents of individual organ REE modeling hypothesize that multi-organ linear models may eliminate non-zero y-intercepts. This could have advantages in adjusting REE for body mass and composition. Studies reveal that individual organ REE is an allometric function of total body mass. I exploit first-order Taylor linearization of individual organ REEs to model the manner in which individual organs contribute to whole-body REE and to the non-zero y-intercept in linear REE models. The model predicts that REE analysis at the individual organ-tissue level will not eliminate intercept terms. I demonstrate that the parameters of a linear EE equation can be transformed into the parameters of the underlying ‘latent’ allometric equation. This permits estimates of the allometric scaling of EE in a diverse variety of physiological states that are not represented in the allometric EE literature but are well represented by published linear EE analyses. PMID:25068692

A Technique of Fuzzy C-Mean in Multiple Linear Regression Model toward Paddy Yield

NASA Astrophysics Data System (ADS)

Syazwan Wahab, Nur; Saifullah Rusiman, Mohd; Mohamad, Mahathir; Amira Azmi, Nur; Che Him, Norziha; Ghazali Kamardan, M.; Ali, Maselan

2018-04-01

In this paper, we propose a hybrid model which is a combination of multiple linear regression model and fuzzy c-means method. This research involved a relationship between 20 variates of the top soil that are analyzed prior to planting of paddy yields at standard fertilizer rates. Data used were from the multi-location trials for rice carried out by MARDI at major paddy granary in Peninsular Malaysia during the period from 2009 to 2012. Missing observations were estimated using mean estimation techniques. The data were analyzed using multiple linear regression model and a combination of multiple linear regression model and fuzzy c-means method. Analysis of normality and multicollinearity indicate that the data is normally scattered without multicollinearity among independent variables. Analysis of fuzzy c-means cluster the yield of paddy into two clusters before the multiple linear regression model can be used. The comparison between two method indicate that the hybrid of multiple linear regression model and fuzzy c-means method outperform the multiple linear regression model with lower value of mean square error.

Circuit transients due to negative bias arcs-II. [on solar cell power systems in low earth orbit

NASA Technical Reports Server (NTRS)

Metz, R. N.

1986-01-01

Two new models of negative-bias arcing on a solar cell power system in Low Earth Orbit are presented. One is an extended, analytical model and the other is a non-linear, numerical model. The models are based on an earlier analytical model in which the interactions between solar cell interconnects and the space plasma as well as the parameters of the power circuit are approximated linearly. Transient voltages due to arcs struck at the negative thermal of the solar panel are calculated in the time domain. The new models treat, respectively, further linear effects within the solar panel load circuit and non-linear effects associated with the plasma interactions. Results of computer calculations with the models show common-mode voltage transients of the electrically floating solar panel struck by an arc comparable to the early model but load transients that differ substantially from the early model. In particular, load transients of the non-linear model can be more than twice as great as those of the early model and more than twenty times as great as the extended, linear model.

State Estimation for Humanoid Robots

DTIC Science & Technology

2015-07-01

21 2.2.1 Linear Inverted Pendulum Model . . . . . . . . . . . . . . . . . . . 21 2.2.2 Planar Five-link Model...Linear Inverted Pendulum Model. LVDT Linear Variable Differential Transformers. MEMS Microelectromechanical Systems. MHE Moving Horizon Estimator. QP...

Digital Image Restoration Under a Regression Model - The Unconstrained, Linear Equality and Inequality Constrained Approaches

DTIC Science & Technology

1974-01-01

REGRESSION MODEL - THE UNCONSTRAINED, LINEAR EQUALITY AND INEQUALITY CONSTRAINED APPROACHES January 1974 Nelson Delfino d’Avila Mascarenha;? Image...Report 520 DIGITAL IMAGE RESTORATION UNDER A REGRESSION MODEL THE UNCONSTRAINED, LINEAR EQUALITY AND INEQUALITY CONSTRAINED APPROACHES January...a two- dimensional form adequately describes the linear model . A dis- cretization is performed by using quadrature methods. By trans

Defining a Family of Cognitive Diagnosis Models Using Log-Linear Models with Latent Variables

ERIC Educational Resources Information Center

Henson, Robert A.; Templin, Jonathan L.; Willse, John T.

2009-01-01

This paper uses log-linear models with latent variables (Hagenaars, in "Loglinear Models with Latent Variables," 1993) to define a family of cognitive diagnosis models. In doing so, the relationship between many common models is explicitly defined and discussed. In addition, because the log-linear model with latent variables is a general model for…

Three-dimensional modeling of flexible pavements : research implementation plan.

DOT National Transportation Integrated Search

2006-02-14

Many of the asphalt pavement analysis programs are based on linear elastic models. A linear viscoelastic models : would be superior to linear elastic models for analyzing the response of asphalt concrete pavements to loads. There : is a need to devel...

Equivalent linear damping characterization in linear and nonlinear force-stiffness muscle models.

PubMed

Ovesy, Marzieh; Nazari, Mohammad Ali; Mahdavian, Mohammad

2016-02-01

In the current research, the muscle equivalent linear damping coefficient which is introduced as the force-velocity relation in a muscle model and the corresponding time constant are investigated. In order to reach this goal, a 1D skeletal muscle model was used. Two characterizations of this model using a linear force-stiffness relationship (Hill-type model) and a nonlinear one have been implemented. The OpenSim platform was used for verification of the model. The isometric activation has been used for the simulation. The equivalent linear damping and the time constant of each model were extracted by using the results obtained from the simulation. The results provide a better insight into the characteristics of each model. It is found that the nonlinear models had a response rate closer to the reality compared to the Hill-type models.

A Constrained Linear Estimator for Multiple Regression

ERIC Educational Resources Information Center

Davis-Stober, Clintin P.; Dana, Jason; Budescu, David V.

2010-01-01

"Improper linear models" (see Dawes, Am. Psychol. 34:571-582, "1979"), such as equal weighting, have garnered interest as alternatives to standard regression models. We analyze the general circumstances under which these models perform well by recasting a class of "improper" linear models as "proper" statistical models with a single predictor. We…

Fuzzy bi-objective linear programming for portfolio selection problem with magnitude ranking function

NASA Astrophysics Data System (ADS)

Kusumawati, Rosita; Subekti, Retno

2017-04-01

Fuzzy bi-objective linear programming (FBOLP) model is bi-objective linear programming model in fuzzy number set where the coefficients of the equations are fuzzy number. This model is proposed to solve portfolio selection problem which generate an asset portfolio with the lowest risk and the highest expected return. FBOLP model with normal fuzzy numbers for risk and expected return of stocks is transformed into linear programming (LP) model using magnitude ranking function.

Comparison of linear and non-linear models for the adsorption of fluoride onto geo-material: limonite.

PubMed

Sahin, Rubina; Tapadia, Kavita

2015-01-01

The three widely used isotherms Langmuir, Freundlich and Temkin were examined in an experiment using fluoride (F⁻) ion adsorption on a geo-material (limonite) at four different temperatures by linear and non-linear models. Comparison of linear and non-linear regression models were given in selecting the optimum isotherm for the experimental results. The coefficient of determination, r², was used to select the best theoretical isotherm. The four Langmuir linear equations (1, 2, 3, and 4) are discussed. Langmuir isotherm parameters obtained from the four Langmuir linear equations using the linear model differed but they were the same when using the nonlinear model. Langmuir-2 isotherm is one of the linear forms, and it had the highest coefficient of determination (r² = 0.99) compared to the other Langmuir linear equations (1, 3 and 4) in linear form, whereas, for non-linear, Langmuir-4 fitted best among all the isotherms because it had the highest coefficient of determination (r² = 0.99). The results showed that the non-linear model may be a better way to obtain the parameters. In the present work, the thermodynamic parameters show that the absorption of fluoride onto limonite is both spontaneous (ΔG < 0) and endothermic (ΔH > 0). Scanning electron microscope and X-ray diffraction images also confirm the adsorption of F⁻ ion onto limonite. The isotherm and kinetic study reveals that limonite can be used as an adsorbent for fluoride removal. In future we can develop new technology for fluoride removal in large scale by using limonite which is cost-effective, eco-friendly and is easily available in the study area.

[Anlysis of foot biomechanics characteristic in 303 patients with type 2 diabetes mellitus].

PubMed

Li, Wen-Xia; Cao, Ying; Zou, Meng-Chen; Huang, Ying; Hu, Ping; Luo, Xiang-Rong; Jiang, Ya; Xue, Yao-Ming; Gao, Fang

2016-10-20

To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus. This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system. The maximum peak pressure of 10 regions decreased in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the left foot, and in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the right foot. The MPP in M1 region was higher in the right than in the left foot (P<0.05). The MPP in M3, M4, M5, and MF was higher in the left than in the right foot (P<0.05). The percentage of high-risk foot (defined by a total plantar pressure ≥70 N/cm 2 ) was 34% on the left and 17.7% on the right. An increased BMI was associated with a significant increase in high-risk foot, but not for the right foot in underweight patients. Foot flat phase was extended and forefoot push-off phase shortened in stance phase in the patients. Compared with the right foot, the left foot showed a significantly increased foot arch index and increased low and high arch rates with a decreased normal arch rate. Total plantar pressure was higher in of the left high arch foot than in normal arch foot. The foot angle was significantly larger on the right than on the left. The bilateral total plantar pressures were significantly greater in male patients (P<0.05) and increased with age but were not associated with the duration of DM, foot angle, or glycosylated hemoglobin level. Diabetic patients have obvious alterations in foot biomechanics with abnormalities of the plantar pressure, and the percentage of high-risk foot increases in overweight and obese patients, suggesting the need of body weight control in these patients when administering offloading treatment for prevention of diabetic foot ulcer.

Investigation on Constrained Matrix Factorization for Hyperspectral Image Analysis

DTIC Science & Technology

2005-07-25

analysis. Keywords: matrix factorization; nonnegative matrix factorization; linear mixture model ; unsupervised linear unmixing; hyperspectral imagery...spatial resolution permits different materials present in the area covered by a single pixel. The linear mixture model says that a pixel reflectance in...in r. In the linear mixture model , r is considered as the linear mixture of m1, m2, …, mP as nMαr += (1) where n is included to account for

Valuation of financial models with non-linear state spaces

NASA Astrophysics Data System (ADS)

Webber, Nick

2001-02-01

A common assumption in valuation models for derivative securities is that the underlying state variables take values in a linear state space. We discuss numerical implementation issues in an interest rate model with a simple non-linear state space, formulating and comparing Monte Carlo, finite difference and lattice numerical solution methods. We conclude that, at least in low dimensional spaces, non-linear interest rate models may be viable.

The Application of the Cumulative Logistic Regression Model to Automated Essay Scoring

ERIC Educational Resources Information Center

Haberman, Shelby J.; Sinharay, Sandip

2010-01-01

Most automated essay scoring programs use a linear regression model to predict an essay score from several essay features. This article applied a cumulative logit model instead of the linear regression model to automated essay scoring. Comparison of the performances of the linear regression model and the cumulative logit model was performed on a…

Estimation of the linear mixed integrated Ornstein–Uhlenbeck model

PubMed Central

Hughes, Rachael A.; Kenward, Michael G.; Sterne, Jonathan A. C.; Tilling, Kate

2017-01-01

ABSTRACT The linear mixed model with an added integrated Ornstein–Uhlenbeck (IOU) process (linear mixed IOU model) allows for serial correlation and estimation of the degree of derivative tracking. It is rarely used, partly due to the lack of available software. We implemented the linear mixed IOU model in Stata and using simulations we assessed the feasibility of fitting the model by restricted maximum likelihood when applied to balanced and unbalanced data. We compared different (1) optimization algorithms, (2) parameterizations of the IOU process, (3) data structures and (4) random-effects structures. Fitting the model was practical and feasible when applied to large and moderately sized balanced datasets (20,000 and 500 observations), and large unbalanced datasets with (non-informative) dropout and intermittent missingness. Analysis of a real dataset showed that the linear mixed IOU model was a better fit to the data than the standard linear mixed model (i.e. independent within-subject errors with constant variance). PMID:28515536

A comparison of linear and nonlinear statistical techniques in performance attribution.

PubMed

Chan, N H; Genovese, C R

2001-01-01

Performance attribution is usually conducted under the linear framework of multifactor models. Although commonly used by practitioners in finance, linear multifactor models are known to be less than satisfactory in many situations. After a brief survey of nonlinear methods, nonlinear statistical techniques are applied to performance attribution of a portfolio constructed from a fixed universe of stocks using factors derived from some commonly used cross sectional linear multifactor models. By rebalancing this portfolio monthly, the cumulative returns for procedures based on standard linear multifactor model and three nonlinear techniques-model selection, additive models, and neural networks-are calculated and compared. It is found that the first two nonlinear techniques, especially in combination, outperform the standard linear model. The results in the neural-network case are inconclusive because of the great variety of possible models. Although these methods are more complicated and may require some tuning, toolboxes are developed and suggestions on calibration are proposed. This paper demonstrates the usefulness of modern nonlinear statistical techniques in performance attribution.

Parameter estimation of Monod model by the Least-Squares method for microalgae Botryococcus Braunii sp

NASA Astrophysics Data System (ADS)

See, J. J.; Jamaian, S. S.; Salleh, R. M.; Nor, M. E.; Aman, F.

2018-04-01

This research aims to estimate the parameters of Monod model of microalgae Botryococcus Braunii sp growth by the Least-Squares method. Monod equation is a non-linear equation which can be transformed into a linear equation form and it is solved by implementing the Least-Squares linear regression method. Meanwhile, Gauss-Newton method is an alternative method to solve the non-linear Least-Squares problem with the aim to obtain the parameters value of Monod model by minimizing the sum of square error ( SSE). As the result, the parameters of the Monod model for microalgae Botryococcus Braunii sp can be estimated by the Least-Squares method. However, the estimated parameters value obtained by the non-linear Least-Squares method are more accurate compared to the linear Least-Squares method since the SSE of the non-linear Least-Squares method is less than the linear Least-Squares method.

Linear Logistic Test Modeling with R

ERIC Educational Resources Information Center

Baghaei, Purya; Kubinger, Klaus D.

2015-01-01

The present paper gives a general introduction to the linear logistic test model (Fischer, 1973), an extension of the Rasch model with linear constraints on item parameters, along with eRm (an R package to estimate different types of Rasch models; Mair, Hatzinger, & Mair, 2014) functions to estimate the model and interpret its parameters. The…

Mixed linear-non-linear inversion of crustal deformation data: Bayesian inference of model, weighting and regularization parameters

NASA Astrophysics Data System (ADS)

Fukuda, Jun'ichi; Johnson, Kaj M.

2010-06-01

We present a unified theoretical framework and solution method for probabilistic, Bayesian inversions of crustal deformation data. The inversions involve multiple data sets with unknown relative weights, model parameters that are related linearly or non-linearly through theoretic models to observations, prior information on model parameters and regularization priors to stabilize underdetermined problems. To efficiently handle non-linear inversions in which some of the model parameters are linearly related to the observations, this method combines both analytical least-squares solutions and a Monte Carlo sampling technique. In this method, model parameters that are linearly and non-linearly related to observations, relative weights of multiple data sets and relative weights of prior information and regularization priors are determined in a unified Bayesian framework. In this paper, we define the mixed linear-non-linear inverse problem, outline the theoretical basis for the method, provide a step-by-step algorithm for the inversion, validate the inversion method using synthetic data and apply the method to two real data sets. We apply the method to inversions of multiple geodetic data sets with unknown relative data weights for interseismic fault slip and locking depth. We also apply the method to the problem of estimating the spatial distribution of coseismic slip on faults with unknown fault geometry, relative data weights and smoothing regularization weight.

Anomaly General Circulation Models.

NASA Astrophysics Data System (ADS)

Navarra, Antonio

The feasibility of the anomaly model is assessed using barotropic and baroclinic models. In the barotropic case, both a stationary and a time-dependent model has been formulated and constructed, whereas only the stationary, linear case is considered in the baroclinic case. Results from the barotropic model indicate that a relation between the stationary solution and the time-averaged non-linear solution exists. The stationary linear baroclinic solution can therefore be considered with some confidence. The linear baroclinic anomaly model poses a formidable mathematical problem because it is necessary to solve a gigantic linear system to obtain the solution. A new method to find solution of large linear system, based on a projection on the Krylov subspace is shown to be successful when applied to the linearized baroclinic anomaly model. The scheme consists of projecting the original linear system on the Krylov subspace, thereby reducing the dimensionality of the matrix to be inverted to obtain the solution. With an appropriate setting of the damping parameters, the iterative Krylov method reaches a solution even using a Krylov subspace ten times smaller than the original space of the problem. This generality allows the treatment of the important problem of linear waves in the atmosphere. A larger class (nonzonally symmetric) of basic states can now be treated for the baroclinic primitive equations. These problem leads to large unsymmetrical linear systems of order 10000 and more which can now be successfully tackled by the Krylov method. The (R7) linear anomaly model is used to investigate extensively the linear response to equatorial and mid-latitude prescribed heating. The results indicate that the solution is deeply affected by the presence of the stationary waves in the basic state. The instability of the asymmetric flows, first pointed out by Simmons et al. (1983), is active also in the baroclinic case. However, the presence of baroclinic processes modifies the dominant response. The most sensitive areas are identified; they correspond to north Japan, the Pole and Greenland regions. A limited set of higher resolution (R15) experiments indicate that this situation is still present and enhanced at higher resolution. The linear anomaly model is also applied to a realistic case. (Abstract shortened with permission of author.).

Comparing Multiple-Group Multinomial Log-Linear Models for Multidimensional Skill Distributions in the General Diagnostic Model. Research Report. ETS RR-08-35

ERIC Educational Resources Information Center

Xu, Xueli; von Davier, Matthias

2008-01-01

The general diagnostic model (GDM) utilizes located latent classes for modeling a multidimensional proficiency variable. In this paper, the GDM is extended by employing a log-linear model for multiple populations that assumes constraints on parameters across multiple groups. This constrained model is compared to log-linear models that assume…

Linear models: permutation methods

USGS Publications Warehouse

Cade, B.S.; Everitt, B.S.; Howell, D.C.

2005-01-01

Permutation tests (see Permutation Based Inference) for the linear model have applications in behavioral studies when traditional parametric assumptions about the error term in a linear model are not tenable. Improved validity of Type I error rates can be achieved with properly constructed permutation tests. Perhaps more importantly, increased statistical power, improved robustness to effects of outliers, and detection of alternative distributional differences can be achieved by coupling permutation inference with alternative linear model estimators. For example, it is well-known that estimates of the mean in linear model are extremely sensitive to even a single outlying value of the dependent variable compared to estimates of the median [7, 19]. Traditionally, linear modeling focused on estimating changes in the center of distributions (means or medians). However, quantile regression allows distributional changes to be estimated in all or any selected part of a distribution or responses, providing a more complete statistical picture that has relevance to many biological questions [6]...

Comparing The Effectiveness of a90/95 Calculations (Preprint)

DTIC Science & Technology

2006-09-01

Nachtsheim, John Neter, William Li, Applied Linear Statistical Models , 5th ed., McGraw-Hill/Irwin, 2005 5. Mood, Graybill and Boes, Introduction...curves is based on methods that are only valid for ordinary linear regression. Requirements for a valid Ordinary Least-Squares Regression Model There... linear . For example is a linear model ; is not. 2. Uniform variance (homoscedasticity

Non-Linear Approach in Kinesiology Should Be Preferred to the Linear--A Case of Basketball.

PubMed

Trninić, Marko; Jeličić, Mario; Papić, Vladan

2015-07-01

In kinesiology, medicine, biology and psychology, in which research focus is on dynamical self-organized systems, complex connections exist between variables. Non-linear nature of complex systems has been discussed and explained by the example of non-linear anthropometric predictors of performance in basketball. Previous studies interpreted relations between anthropometric features and measures of effectiveness in basketball by (a) using linear correlation models, and by (b) including all basketball athletes in the same sample of participants regardless of their playing position. In this paper the significance and character of linear and non-linear relations between simple anthropometric predictors (AP) and performance criteria consisting of situation-related measures of effectiveness (SE) in basketball were determined and evaluated. The sample of participants consisted of top-level junior basketball players divided in three groups according to their playing time (8 minutes and more per game) and playing position: guards (N = 42), forwards (N = 26) and centers (N = 40). Linear (general model) and non-linear (general model) regression models were calculated simultaneously and separately for each group. The conclusion is viable: non-linear regressions are frequently superior to linear correlations when interpreting actual association logic among research variables.

Waveform Design for Wireless Power Transfer

NASA Astrophysics Data System (ADS)

Clerckx, Bruno; Bayguzina, Ekaterina

2016-12-01

Far-field Wireless Power Transfer (WPT) has attracted significant attention in recent years. Despite the rapid progress, the emphasis of the research community in the last decade has remained largely concentrated on improving the design of energy harvester (so-called rectenna) and has left aside the effect of transmitter design. In this paper, we study the design of transmit waveform so as to enhance the DC power at the output of the rectenna. We derive a tractable model of the non-linearity of the rectenna and compare with a linear model conventionally used in the literature. We then use those models to design novel multisine waveforms that are adaptive to the channel state information (CSI). Interestingly, while the linear model favours narrowband transmission with all the power allocated to a single frequency, the non-linear model favours a power allocation over multiple frequencies. Through realistic simulations, waveforms designed based on the non-linear model are shown to provide significant gains (in terms of harvested DC power) over those designed based on the linear model and over non-adaptive waveforms. We also compute analytically the theoretical scaling laws of the harvested energy for various waveforms as a function of the number of sinewaves and transmit antennas. Those scaling laws highlight the benefits of CSI knowledge at the transmitter in WPT and of a WPT design based on a non-linear rectenna model over a linear model. Results also motivate the study of a promising architecture relying on large-scale multisine multi-antenna waveforms for WPT. As a final note, results stress the importance of modeling and accounting for the non-linearity of the rectenna in any system design involving wireless power.

Image Processing Research

DTIC Science & Technology

1975-09-30

systems a linear model results in an object f being mappad into an image _ by a point spread function matrix H. Thus with noise j +Hf +n (1) The simplest... linear models for imaging systems are given by space invariant point spread functions (SIPSF) in which case H is block circulant. If the linear model is...Ij,...,k-IM1 is a set of two dimensional indices each distinct and prior to k. Modeling Procedare: To derive the linear predictor (block LP of figure

Linear time-varying models can reveal non-linear interactions of biomolecular regulatory networks using multiple time-series data.

PubMed

Kim, Jongrae; Bates, Declan G; Postlethwaite, Ian; Heslop-Harrison, Pat; Cho, Kwang-Hyun

2008-05-15

Inherent non-linearities in biomolecular interactions make the identification of network interactions difficult. One of the principal problems is that all methods based on the use of linear time-invariant models will have fundamental limitations in their capability to infer certain non-linear network interactions. Another difficulty is the multiplicity of possible solutions, since, for a given dataset, there may be many different possible networks which generate the same time-series expression profiles. A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells. The software used in this article is available from http://sbie.kaist.ac.kr/software

Non-linear analysis of wave progagation using transform methods and plates and shells using integral equations

NASA Astrophysics Data System (ADS)

Pipkins, Daniel Scott

Two diverse topics of relevance in modern computational mechanics are treated. The first involves the modeling of linear and non-linear wave propagation in flexible, lattice structures. The technique used combines the Laplace Transform with the Finite Element Method (FEM). The procedure is to transform the governing differential equations and boundary conditions into the transform domain where the FEM formulation is carried out. For linear problems, the transformed differential equations can be solved exactly, hence the method is exact. As a result, each member of the lattice structure is modeled using only one element. In the non-linear problem, the method is no longer exact. The approximation introduced is a spatial discretization of the transformed non-linear terms. The non-linear terms are represented in the transform domain by making use of the complex convolution theorem. A weak formulation of the resulting transformed non-linear equations yields a set of element level matrix equations. The trial and test functions used in the weak formulation correspond to the exact solution of the linear part of the transformed governing differential equation. Numerical results are presented for both linear and non-linear systems. The linear systems modeled are longitudinal and torsional rods and Bernoulli-Euler and Timoshenko beams. For non-linear systems, a viscoelastic rod and Von Karman type beam are modeled. The second topic is the analysis of plates and shallow shells under-going finite deflections by the Field/Boundary Element Method. Numerical results are presented for two plate problems. The first is the bifurcation problem associated with a square plate having free boundaries which is loaded by four, self equilibrating corner forces. The results are compared to two existing numerical solutions of the problem which differ substantially.

Descriptive Linear modeling of steady-state visual evoked response

NASA Technical Reports Server (NTRS)

Levison, W. H.; Junker, A. M.; Kenner, K.

1986-01-01

A study is being conducted to explore use of the steady state visual-evoke electrocortical response as an indicator of cognitive task loading. Application of linear descriptive modeling to steady state Visual Evoked Response (VER) data is summarized. Two aspects of linear modeling are reviewed: (1) unwrapping the phase-shift portion of the frequency response, and (2) parsimonious characterization of task-loading effects in terms of changes in model parameters. Model-based phase unwrapping appears to be most reliable in applications, such as manual control, where theoretical models are available. Linear descriptive modeling of the VER has not yet been shown to provide consistent and readily interpretable results.

Assessment of Poisson, probit and linear models for genetic analysis of presence and number of black spots in Corriedale sheep.

PubMed

Peñagaricano, F; Urioste, J I; Naya, H; de los Campos, G; Gianola, D

2011-04-01

Black skin spots are associated with pigmented fibres in wool, an important quality fault. Our objective was to assess alternative models for genetic analysis of presence (BINBS) and number (NUMBS) of black spots in Corriedale sheep. During 2002-08, 5624 records from 2839 animals in two flocks, aged 1 through 6 years, were taken at shearing. Four models were considered: linear and probit for BINBS and linear and Poisson for NUMBS. All models included flock-year and age as fixed effects and animal and permanent environmental as random effects. Models were fitted to the whole data set and were also compared based on their predictive ability in cross-validation. Estimates of heritability ranged from 0.154 to 0.230 for BINBS and 0.269 to 0.474 for NUMBS. For BINBS, the probit model fitted slightly better to the data than the linear model. Predictions of random effects from these models were highly correlated, and both models exhibited similar predictive ability. For NUMBS, the Poisson model, with a residual term to account for overdispersion, performed better than the linear model in goodness of fit and predictive ability. Predictions of random effects from the Poisson model were more strongly correlated with those from BINBS models than those from the linear model. Overall, the use of probit or linear models for BINBS and of a Poisson model with a residual for NUMBS seems a reasonable choice for genetic selection purposes in Corriedale sheep. © 2010 Blackwell Verlag GmbH.

Effective connectivity between superior temporal gyrus and Heschl's gyrus during white noise listening: linear versus non-linear models.

PubMed

Hamid, Ka; Yusoff, An; Rahman, Mza; Mohamad, M; Hamid, Aia

2012-04-01

This fMRI study is about modelling the effective connectivity between Heschl's gyrus (HG) and the superior temporal gyrus (STG) in human primary auditory cortices. MATERIALS #ENTITYSTARTX00026; Ten healthy male participants were required to listen to white noise stimuli during functional magnetic resonance imaging (fMRI) scans. Statistical parametric mapping (SPM) was used to generate individual and group brain activation maps. For input region determination, two intrinsic connectivity models comprising bilateral HG and STG were constructed using dynamic causal modelling (DCM). The models were estimated and inferred using DCM while Bayesian Model Selection (BMS) for group studies was used for model comparison and selection. Based on the winning model, six linear and six non-linear causal models were derived and were again estimated, inferred, and compared to obtain a model that best represents the effective connectivity between HG and the STG, balancing accuracy and complexity. Group results indicated significant asymmetrical activation (p(uncorr) < 0.001) in bilateral HG and STG. Model comparison results showed strong evidence of STG as the input centre. The winning model is preferred by 6 out of 10 participants. The results were supported by BMS results for group studies with the expected posterior probability, r = 0.7830 and exceedance probability, ϕ = 0.9823. One-sample t-tests performed on connection values obtained from the winning model indicated that the valid connections for the winning model are the unidirectional parallel connections from STG to bilateral HG (p < 0.05). Subsequent model comparison between linear and non-linear models using BMS prefers non-linear connection (r = 0.9160, ϕ = 1.000) from which the connectivity between STG and the ipsi- and contralateral HG is gated by the activity in STG itself. We are able to demonstrate that the effective connectivity between HG and STG while listening to white noise for the respective participants can be explained by a non-linear dynamic causal model with the activity in STG influencing the STG-HG connectivity non-linearly.

The Simplest Complete Model of Choice Response Time: Linear Ballistic Accumulation

ERIC Educational Resources Information Center

Brown, Scott D.; Heathcote, Andrew

2008-01-01

We propose a linear ballistic accumulator (LBA) model of decision making and reaction time. The LBA is simpler than other models of choice response time, with independent accumulators that race towards a common response threshold. Activity in the accumulators increases in a linear and deterministic manner. The simplicity of the model allows…

A network model of successive partitioning-limited solute diffusion through the stratum corneum.

PubMed

Schumm, Phillip; Scoglio, Caterina M; van der Merwe, Deon

2010-02-07

As the most exposed point of contact with the external environment, the skin is an important barrier to many chemical exposures, including medications, potentially toxic chemicals and cosmetics. Traditional dermal absorption models treat the stratum corneum lipids as a homogenous medium through which solutes diffuse according to Fick's first law of diffusion. This approach does not explain non-linear absorption and irregular distribution patterns within the stratum corneum lipids as observed in experimental data. A network model, based on successive partitioning-limited solute diffusion through the stratum corneum, where the lipid structure is represented by a large, sparse, and regular network where nodes have variable characteristics, offers an alternative, efficient, and flexible approach to dermal absorption modeling that simulates non-linear absorption data patterns. Four model versions are presented: two linear models, which have unlimited node capacities, and two non-linear models, which have limited node capacities. The non-linear model outputs produce absorption to dose relationships that can be best characterized quantitatively by using power equations, similar to the equations used to describe non-linear experimental data.

Tip-tilt disturbance model identification based on non-linear least squares fitting for Linear Quadratic Gaussian control

NASA Astrophysics Data System (ADS)

Yang, Kangjian; Yang, Ping; Wang, Shuai; Dong, Lizhi; Xu, Bing

2018-05-01

We propose a method to identify tip-tilt disturbance model for Linear Quadratic Gaussian control. This identification method based on Levenberg-Marquardt method conducts with a little prior information and no auxiliary system and it is convenient to identify the tip-tilt disturbance model on-line for real-time control. This identification method makes it easy that Linear Quadratic Gaussian control runs efficiently in different adaptive optics systems for vibration mitigation. The validity of the Linear Quadratic Gaussian control associated with this tip-tilt disturbance model identification method is verified by experimental data, which is conducted in replay mode by simulation.

Improved LTVMPC design for steering control of autonomous vehicle

NASA Astrophysics Data System (ADS)

Velhal, Shridhar; Thomas, Susy

2017-01-01

An improved linear time varying model predictive control for steering control of autonomous vehicle running on slippery road is presented. Control strategy is designed such that the vehicle will follow the predefined trajectory with highest possible entry speed. In linear time varying model predictive control, nonlinear vehicle model is successively linearized at each sampling instant. This linear time varying model is used to design MPC which will predict the future horizon. By incorporating predicted input horizon in each successive linearization the effectiveness of controller has been improved. The tracking performance using steering with front wheel and braking at four wheels are presented to illustrate the effectiveness of the proposed method.

Employment of CB models for non-linear dynamic analysis

NASA Technical Reports Server (NTRS)

Klein, M. R. M.; Deloo, P.; Fournier-Sicre, A.

1990-01-01

The non-linear dynamic analysis of large structures is always very time, effort and CPU consuming. Whenever possible the reduction of the size of the mathematical model involved is of main importance to speed up the computational procedures. Such reduction can be performed for the part of the structure which perform linearly. Most of the time, the classical Guyan reduction process is used. For non-linear dynamic process where the non-linearity is present at interfaces between different structures, Craig-Bampton models can provide a very rich information, and allow easy selection of the relevant modes with respect to the phenomenon driving the non-linearity. The paper presents the employment of Craig-Bampton models combined with Newmark direct integration for solving non-linear friction problems appearing at the interface between the Hubble Space Telescope and its solar arrays during in-orbit maneuvers. Theory, implementation in the FEM code ASKA, and practical results are shown.

Assessing the Tangent Linear Behaviour of Common Tracer Transport Schemes and Their Use in a Linearised Atmospheric General Circulation Model

NASA Technical Reports Server (NTRS)

Holdaway, Daniel; Kent, James

2015-01-01

The linearity of a selection of common advection schemes is tested and examined with a view to their use in the tangent linear and adjoint versions of an atmospheric general circulation model. The schemes are tested within a simple offline one-dimensional periodic domain as well as using a simplified and complete configuration of the linearised version of NASA's Goddard Earth Observing System version 5 (GEOS-5). All schemes which prevent the development of negative values and preserve the shape of the solution are confirmed to have nonlinear behaviour. The piecewise parabolic method (PPM) with certain flux limiters, including that used by default in GEOS-5, is found to support linear growth near the shocks. This property can cause the rapid development of unrealistically large perturbations within the tangent linear and adjoint models. It is shown that these schemes with flux limiters should not be used within the linearised version of a transport scheme. The results from tests using GEOS-5 show that the current default scheme (a version of PPM) is not suitable for the tangent linear and adjoint model, and that using a linear third-order scheme for the linearised model produces better behaviour. Using the third-order scheme for the linearised model improves the correlations between the linear and non-linear perturbation trajectories for cloud liquid water and cloud liquid ice in GEOS-5.

Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy

NASA Astrophysics Data System (ADS)

Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Brock, Kristy

2011-08-01

Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.

Linearized Poststall Aerodynamic and Control Law Models of the X-31A Aircraft and Comparison with Flight Data

NASA Technical Reports Server (NTRS)

Stoliker, Patrick C.; Bosworth, John T.; Georgie, Jennifer

1997-01-01

The X-31A aircraft has a unique configuration that uses thrust-vector vanes and aerodynamic control effectors to provide an operating envelope to a maximum 70 deg angle of attack, an inherently nonlinear portion of the flight envelope. This report presents linearized versions of the X-31A longitudinal and lateral-directional control systems, with aerodynamic models sufficient to evaluate characteristics in the poststall envelope at 30 deg, 45 deg, and 60 deg angle of attack. The models are presented with detail sufficient to allow the reader to reproduce the linear results or perform independent control studies. Comparisons between the responses of the linear models and flight data are presented in the time and frequency domains to demonstrate the strengths and weaknesses of the ability to predict high-angle-of-attack flight dynamics using linear models. The X-31A six-degree-of-freedom simulation contains a program that calculates linear perturbation models throughout the X-31A flight envelope. The models include aerodynamics and flight control system dynamics that are used for stability, controllability, and handling qualities analysis. The models presented in this report demonstrate the ability to provide reasonable linear representations in the poststall flight regime.

Study of Piezoelectric Vibration Energy Harvester with non-linear conditioning circuit using an integrated model

NASA Astrophysics Data System (ADS)

Manzoor, Ali; Rafique, Sajid; Usman Iftikhar, Muhammad; Mahmood Ul Hassan, Khalid; Nasir, Ali

2017-08-01

Piezoelectric vibration energy harvester (PVEH) consists of a cantilever bimorph with piezoelectric layers pasted on its top and bottom, which can harvest power from vibrations and feed to low power wireless sensor nodes through some power conditioning circuit. In this paper, a non-linear conditioning circuit, consisting of a full-bridge rectifier followed by a buck-boost converter, is employed to investigate the issues of electrical side of the energy harvesting system. An integrated mathematical model of complete electromechanical system has been developed. Previously, researchers have studied PVEH with sophisticated piezo-beam models but employed simplistic linear circuits, such as resistor, as electrical load. In contrast, other researchers have worked on more complex non-linear circuits but with over-simplified piezo-beam models. Such models neglect different aspects of the system which result from complex interactions of its electrical and mechanical subsystems. In this work, authors have integrated the distributed parameter-based model of piezo-beam presented in literature with a real world non-linear electrical load. Then, the developed integrated model is employed to analyse the stability of complete energy harvesting system. This work provides a more realistic and useful electromechanical model having realistic non-linear electrical load unlike the simplistic linear circuit elements employed by many researchers.

An R2 statistic for fixed effects in the linear mixed model.

PubMed

Edwards, Lloyd J; Muller, Keith E; Wolfinger, Russell D; Qaqish, Bahjat F; Schabenberger, Oliver

2008-12-20

Statisticians most often use the linear mixed model to analyze Gaussian longitudinal data. The value and familiarity of the R(2) statistic in the linear univariate model naturally creates great interest in extending it to the linear mixed model. We define and describe how to compute a model R(2) statistic for the linear mixed model by using only a single model. The proposed R(2) statistic measures multivariate association between the repeated outcomes and the fixed effects in the linear mixed model. The R(2) statistic arises as a 1-1 function of an appropriate F statistic for testing all fixed effects (except typically the intercept) in a full model. The statistic compares the full model with a null model with all fixed effects deleted (except typically the intercept) while retaining exactly the same covariance structure. Furthermore, the R(2) statistic leads immediately to a natural definition of a partial R(2) statistic. A mixed model in which ethnicity gives a very small p-value as a longitudinal predictor of blood pressure (BP) compellingly illustrates the value of the statistic. In sharp contrast to the extreme p-value, a very small R(2) , a measure of statistical and scientific importance, indicates that ethnicity has an almost negligible association with the repeated BP outcomes for the study.

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

NASA Astrophysics Data System (ADS)

Morén, B.; Larsson, T.; Carlsson Tedgren, Å.

2018-03-01

High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.

Non-linear dual-phase-lag model for analyzing heat transfer phenomena in living tissues during thermal ablation.

PubMed

Kumar, P; Kumar, Dinesh; Rai, K N

2016-08-01

In this article, a non-linear dual-phase-lag (DPL) bio-heat transfer model based on temperature dependent metabolic heat generation rate is derived to analyze the heat transfer phenomena in living tissues during thermal ablation treatment. The numerical solution of the present non-linear problem has been done by finite element Runge-Kutta (4,5) method which combines the essence of Runge-Kutta (4,5) method together with finite difference scheme. Our study demonstrates that at the thermal ablation position temperature predicted by non-linear and linear DPL models show significant differences. A comparison has been made among non-linear DPL, thermal wave and Pennes model and it has been found that non-linear DPL and thermal wave bio-heat model show almost same nature whereas non-linear Pennes model shows significantly different temperature profile at the initial stage of thermal ablation treatment. The effect of Fourier number and Vernotte number (relaxation Fourier number) on temperature profile in presence and absence of externally applied heat source has been studied in detail and it has been observed that the presence of externally applied heat source term highly affects the efficiency of thermal treatment method. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Linearized Prognostic Cloud Scheme in NASAs Goddard Earth Observing System Data Assimilation Tools

NASA Technical Reports Server (NTRS)

Holdaway, Daniel; Errico, Ronald M.; Gelaro, Ronald; Kim, Jong G.; Mahajan, Rahul

2015-01-01

A linearized prognostic cloud scheme has been developed to accompany the linearized convection scheme recently implemented in NASA's Goddard Earth Observing System data assimilation tools. The linearization, developed from the nonlinear cloud scheme, treats cloud variables prognostically so they are subject to linearized advection, diffusion, generation, and evaporation. Four linearized cloud variables are modeled, the ice and water phases of clouds generated by large-scale condensation and, separately, by detraining convection. For each species the scheme models their sources, sublimation, evaporation, and autoconversion. Large-scale, anvil and convective species of precipitation are modeled and evaporated. The cloud scheme exhibits linearity and realistic perturbation growth, except around the generation of clouds through large-scale condensation. Discontinuities and steep gradients are widely used here and severe problems occur in the calculation of cloud fraction. For data assimilation applications this poor behavior is controlled by replacing this part of the scheme with a perturbation model. For observation impacts, where efficiency is less of a concern, a filtering is developed that examines the Jacobian. The replacement scheme is only invoked if Jacobian elements or eigenvalues violate a series of tuned constants. The linearized prognostic cloud scheme is tested by comparing the linear and nonlinear perturbation trajectories for 6-, 12-, and 24-h forecast times. The tangent linear model performs well and perturbations of clouds are well captured for the lead times of interest.

Estimating linear temporal trends from aggregated environmental monitoring data

USGS Publications Warehouse

Erickson, Richard A.; Gray, Brian R.; Eager, Eric A.

2017-01-01

Trend estimates are often used as part of environmental monitoring programs. These trends inform managers (e.g., are desired species increasing or undesired species decreasing?). Data collected from environmental monitoring programs is often aggregated (i.e., averaged), which confounds sampling and process variation. State-space models allow sampling variation and process variations to be separated. We used simulated time-series to compare linear trend estimations from three state-space models, a simple linear regression model, and an auto-regressive model. We also compared the performance of these five models to estimate trends from a long term monitoring program. We specifically estimated trends for two species of fish and four species of aquatic vegetation from the Upper Mississippi River system. We found that the simple linear regression had the best performance of all the given models because it was best able to recover parameters and had consistent numerical convergence. Conversely, the simple linear regression did the worst job estimating populations in a given year. The state-space models did not estimate trends well, but estimated population sizes best when the models converged. We found that a simple linear regression performed better than more complex autoregression and state-space models when used to analyze aggregated environmental monitoring data.

Estimation of group means when adjusting for covariates in generalized linear models.

PubMed

Qu, Yongming; Luo, Junxiang

2015-01-01

Generalized linear models are commonly used to analyze categorical data such as binary, count, and ordinal outcomes. Adjusting for important prognostic factors or baseline covariates in generalized linear models may improve the estimation efficiency. The model-based mean for a treatment group produced by most software packages estimates the response at the mean covariate, not the mean response for this treatment group for the studied population. Although this is not an issue for linear models, the model-based group mean estimates in generalized linear models could be seriously biased for the true group means. We propose a new method to estimate the group mean consistently with the corresponding variance estimation. Simulation showed the proposed method produces an unbiased estimator for the group means and provided the correct coverage probability. The proposed method was applied to analyze hypoglycemia data from clinical trials in diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Composite Linear Models | Division of Cancer Prevention

Cancer.gov

By Stuart G. Baker The composite linear models software is a matrix approach to compute maximum likelihood estimates and asymptotic standard errors for models for incomplete multinomial data. It implements the method described in Baker SG. Composite linear models for incomplete multinomial data. Statistics in Medicine 1994;13:609-622. The software includes a library of thirty

Expanding the occupational health methodology: A concatenated artificial neural network approach to model the burnout process in Chinese nurses.

PubMed

Ladstätter, Felix; Garrosa, Eva; Moreno-Jiménez, Bernardo; Ponsoda, Vicente; Reales Aviles, José Manuel; Dai, Junming

2016-01-01

Artificial neural networks are sophisticated modelling and prediction tools capable of extracting complex, non-linear relationships between predictor (input) and predicted (output) variables. This study explores this capacity by modelling non-linearities in the hardiness-modulated burnout process with a neural network. Specifically, two multi-layer feed-forward artificial neural networks are concatenated in an attempt to model the composite non-linear burnout process. Sensitivity analysis, a Monte Carlo-based global simulation technique, is then utilised to examine the first-order effects of the predictor variables on the burnout sub-dimensions and consequences. Results show that (1) this concatenated artificial neural network approach is feasible to model the burnout process, (2) sensitivity analysis is a prolific method to study the relative importance of predictor variables and (3) the relationships among variables involved in the development of burnout and its consequences are to different degrees non-linear. Many relationships among variables (e.g., stressors and strains) are not linear, yet researchers use linear methods such as Pearson correlation or linear regression to analyse these relationships. Artificial neural network analysis is an innovative method to analyse non-linear relationships and in combination with sensitivity analysis superior to linear methods.

Numerical solution of non-linear dual-phase-lag bioheat transfer equation within skin tissues.

PubMed

Kumar, Dinesh; Kumar, P; Rai, K N

2017-11-01

This paper deals with numerical modeling and simulation of heat transfer in skin tissues using non-linear dual-phase-lag (DPL) bioheat transfer model under periodic heat flux boundary condition. The blood perfusion is assumed temperature-dependent which results in non-linear DPL bioheat transfer model in order to predict more accurate results. A numerical method of line which is based on finite difference and Runge-Kutta (4,5) schemes, is used to solve the present non-linear problem. Under specific case, the exact solution has been obtained and compared with the present numerical scheme, and we found that those are in good agreement. A comparison based on model selection criterion (AIC) has been made among non-linear DPL models when the variation of blood perfusion rate with temperature is of constant, linear and exponential type with the experimental data and it has been found that non-linear DPL model with exponential variation of blood perfusion rate is closest to the experimental data. In addition, it is found that due to absence of phase-lag phenomena in Pennes bioheat transfer model, it achieves steady state more quickly and always predict higher temperature than thermal and DPL non-linear models. The effect of coefficient of blood perfusion rate, dimensionless heating frequency and Kirchoff number on dimensionless temperature distribution has also been analyzed. The whole analysis is presented in dimensionless form. Copyright © 2017 Elsevier Inc. All rights reserved.

Biochemical methane potential prediction of plant biomasses: Comparing chemical composition versus near infrared methods and linear versus non-linear models.

PubMed

Godin, Bruno; Mayer, Frédéric; Agneessens, Richard; Gerin, Patrick; Dardenne, Pierre; Delfosse, Philippe; Delcarte, Jérôme

2015-01-01

The reliability of different models to predict the biochemical methane potential (BMP) of various plant biomasses using a multispecies dataset was compared. The most reliable prediction models of the BMP were those based on the near infrared (NIR) spectrum compared to those based on the chemical composition. The NIR predictions of local (specific regression and non-linear) models were able to estimate quantitatively, rapidly, cheaply and easily the BMP. Such a model could be further used for biomethanation plant management and optimization. The predictions of non-linear models were more reliable compared to those of linear models. The presentation form (green-dried, silage-dried and silage-wet form) of biomasses to the NIR spectrometer did not influence the performances of the NIR prediction models. The accuracy of the BMP method should be improved to enhance further the BMP prediction models. Copyright © 2014 Elsevier Ltd. All rights reserved.

A multiphase non-linear mixed effects model: An application to spirometry after lung transplantation.

PubMed

Rajeswaran, Jeevanantham; Blackstone, Eugene H

2017-02-01

In medical sciences, we often encounter longitudinal temporal relationships that are non-linear in nature. The influence of risk factors may also change across longitudinal follow-up. A system of multiphase non-linear mixed effects model is presented to model temporal patterns of longitudinal continuous measurements, with temporal decomposition to identify the phases and risk factors within each phase. Application of this model is illustrated using spirometry data after lung transplantation using readily available statistical software. This application illustrates the usefulness of our flexible model when dealing with complex non-linear patterns and time-varying coefficients.

Modeling of non-ideal hard permanent magnets with an affine-linear model, illustrated for a bar and a horseshoe magnet

NASA Astrophysics Data System (ADS)

Glane, Sebastian; Reich, Felix A.; Müller, Wolfgang H.

2017-11-01

This study is dedicated to continuum-scale material modeling of isotropic permanent magnets. An affine-linear extension to the commonly used ideal hard model for permanent magnets is proposed, motivated, and detailed. In order to demonstrate the differences between these models, bar and horseshoe magnets are considered. The structure of the boundary value problem for the magnetic field and related solution techniques are discussed. For the ideal model, closed-form analytical solutions were obtained for both geometries. Magnetic fields of the boundary value problems for both models and differently shaped magnets were computed numerically by using the boundary element method. The results show that the character of the magnetic field is strongly influenced by the model that is used. Furthermore, it can be observed that the shape of an affine-linear magnet influences the near-field significantly. Qualitative comparisons with experiments suggest that both the ideal and the affine-linear models are relevant in practice, depending on the magnetic material employed. Mathematically speaking, the ideal magnetic model is a special case of the affine-linear one. Therefore, in applications where knowledge of the near-field is important, the affine-linear model can yield more accurate results—depending on the magnetic material.

Convex set and linear mixing model

NASA Technical Reports Server (NTRS)

Xu, P.; Greeley, R.

1993-01-01

A major goal of optical remote sensing is to determine surface compositions of the earth and other planetary objects. For assessment of composition, single pixels in multi-spectral images usually record a mixture of the signals from various materials within the corresponding surface area. In this report, we introduce a closed and bounded convex set as a mathematical model for linear mixing. This model has a clear geometric implication because the closed and bounded convex set is a natural generalization of a triangle in n-space. The endmembers are extreme points of the convex set. Every point in the convex closure of the endmembers is a linear mixture of those endmembers, which is exactly how linear mixing is defined. With this model, some general criteria for selecting endmembers could be described. This model can lead to a better understanding of linear mixing models.

Nonlinear aeroacoustic characterization of Helmholtz resonators with a local-linear neuro-fuzzy network model

NASA Astrophysics Data System (ADS)

Förner, K.; Polifke, W.

2017-10-01

The nonlinear acoustic behavior of Helmholtz resonators is characterized by a data-based reduced-order model, which is obtained by a combination of high-resolution CFD simulation and system identification. It is shown that even in the nonlinear regime, a linear model is capable of describing the reflection behavior at a particular amplitude with quantitative accuracy. This observation motivates to choose a local-linear model structure for this study, which consists of a network of parallel linear submodels. A so-called fuzzy-neuron layer distributes the input signal over the linear submodels, depending on the root mean square of the particle velocity at the resonator surface. The resulting model structure is referred to as an local-linear neuro-fuzzy network. System identification techniques are used to estimate the free parameters of this model from training data. The training data are generated by CFD simulations of the resonator, with persistent acoustic excitation over a wide range of frequencies and sound pressure levels. The estimated nonlinear, reduced-order models show good agreement with CFD and experimental data over a wide range of amplitudes for several test cases.

Controls/CFD Interdisciplinary Research Software Generates Low-Order Linear Models for Control Design From Steady-State CFD Results

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.

1997-01-01

The NASA Lewis Research Center is developing analytical methods and software tools to create a bridge between the controls and computational fluid dynamics (CFD) disciplines. Traditionally, control design engineers have used coarse nonlinear simulations to generate information for the design of new propulsion system controls. However, such traditional methods are not adequate for modeling the propulsion systems of complex, high-speed vehicles like the High Speed Civil Transport. To properly model the relevant flow physics of high-speed propulsion systems, one must use simulations based on CFD methods. Such CFD simulations have become useful tools for engineers that are designing propulsion system components. The analysis techniques and software being developed as part of this effort are an attempt to evolve CFD into a useful tool for control design as well. One major aspect of this research is the generation of linear models from steady-state CFD results. CFD simulations, often used during the design of high-speed inlets, yield high resolution operating point data. Under a NASA grant, the University of Akron has developed analytical techniques and software tools that use these data to generate linear models for control design. The resulting linear models have the same number of states as the original CFD simulation, so they are still very large and computationally cumbersome. Model reduction techniques have been successfully applied to reduce these large linear models by several orders of magnitude without significantly changing the dynamic response. The result is an accurate, easy to use, low-order linear model that takes less time to generate than those generated by traditional means. The development of methods for generating low-order linear models from steady-state CFD is most complete at the one-dimensional level, where software is available to generate models with different kinds of input and output variables. One-dimensional methods have been extended somewhat so that linear models can also be generated from two- and three-dimensional steady-state results. Standard techniques are adequate for reducing the order of one-dimensional CFD-based linear models. However, reduction of linear models based on two- and three-dimensional CFD results is complicated by very sparse, ill-conditioned matrices. Some novel approaches are being investigated to solve this problem.

Predicting musically induced emotions from physiological inputs: linear and neural network models.

PubMed

Russo, Frank A; Vempala, Naresh N; Sandstrom, Gillian M

2013-01-01

Listening to music often leads to physiological responses. Do these physiological responses contain sufficient information to infer emotion induced in the listener? The current study explores this question by attempting to predict judgments of "felt" emotion from physiological responses alone using linear and neural network models. We measured five channels of peripheral physiology from 20 participants-heart rate (HR), respiration, galvanic skin response, and activity in corrugator supercilii and zygomaticus major facial muscles. Using valence and arousal (VA) dimensions, participants rated their felt emotion after listening to each of 12 classical music excerpts. After extracting features from the five channels, we examined their correlation with VA ratings, and then performed multiple linear regression to see if a linear relationship between the physiological responses could account for the ratings. Although linear models predicted a significant amount of variance in arousal ratings, they were unable to do so with valence ratings. We then used a neural network to provide a non-linear account of the ratings. The network was trained on the mean ratings of eight of the 12 excerpts and tested on the remainder. Performance of the neural network confirms that physiological responses alone can be used to predict musically induced emotion. The non-linear model derived from the neural network was more accurate than linear models derived from multiple linear regression, particularly along the valence dimension. A secondary analysis allowed us to quantify the relative contributions of inputs to the non-linear model. The study represents a novel approach to understanding the complex relationship between physiological responses and musically induced emotion.

A class of stochastic optimization problems with one quadratic & several linear objective functions and extended portfolio selection model

NASA Astrophysics Data System (ADS)

Xu, Jiuping; Li, Jun

2002-09-01

In this paper a class of stochastic multiple-objective programming problems with one quadratic, several linear objective functions and linear constraints has been introduced. The former model is transformed into a deterministic multiple-objective nonlinear programming model by means of the introduction of random variables' expectation. The reference direction approach is used to deal with linear objectives and results in a linear parametric optimization formula with a single linear objective function. This objective function is combined with the quadratic function using the weighted sums. The quadratic problem is transformed into a linear (parametric) complementary problem, the basic formula for the proposed approach. The sufficient and necessary conditions for (properly, weakly) efficient solutions and some construction characteristics of (weakly) efficient solution sets are obtained. An interactive algorithm is proposed based on reference direction and weighted sums. Varying the parameter vector on the right-hand side of the model, the DM can freely search the efficient frontier with the model. An extended portfolio selection model is formed when liquidity is considered as another objective to be optimized besides expectation and risk. The interactive approach is illustrated with a practical example.

A distributed lag approach to fitting non-linear dose-response models in particulate matter air pollution time series investigations.

PubMed

Roberts, Steven; Martin, Michael A

2007-06-01

The majority of studies that have investigated the relationship between particulate matter (PM) air pollution and mortality have assumed a linear dose-response relationship and have used either a single-day's PM or a 2- or 3-day moving average of PM as the measure of PM exposure. Both of these modeling choices have come under scrutiny in the literature, the linear assumption because it does not allow for non-linearities in the dose-response relationship, and the use of the single- or multi-day moving average PM measure because it does not allow for differential PM-mortality effects spread over time. These two problems have been dealt with on a piecemeal basis with non-linear dose-response models used in some studies and distributed lag models (DLMs) used in others. In this paper, we propose a method for investigating the shape of the PM-mortality dose-response relationship that combines a non-linear dose-response model with a DLM. This combined model will be shown to produce satisfactory estimates of the PM-mortality dose-response relationship in situations where non-linear dose response models and DLMs alone do not; that is, the combined model did not systemically underestimate or overestimate the effect of PM on mortality. The combined model is applied to ten cities in the US and a pooled dose-response model formed. When fitted with a change-point value of 60 microg/m(3), the pooled model provides evidence for a positive association between PM and mortality. The combined model produced larger estimates for the effect of PM on mortality than when using a non-linear dose-response model or a DLM in isolation. For the combined model, the estimated percentage increase in mortality for PM concentrations of 25 and 75 microg/m(3) were 3.3% and 5.4%, respectively. In contrast, the corresponding values from a DLM used in isolation were 1.2% and 3.5%, respectively.

A model of the extent and distribution of woody linear features in rural Great Britain.

PubMed

Scholefield, Paul; Morton, Dan; Rowland, Clare; Henrys, Peter; Howard, David; Norton, Lisa

2016-12-01

Hedges and lines of trees (woody linear features) are important boundaries that connect and enclose habitats, buffer the effects of land management, and enhance biodiversity in increasingly impoverished landscapes. Despite their acknowledged importance in the wider countryside, they are usually not considered in models of landscape function due to their linear nature and the difficulties of acquiring relevant data about their character, extent, and location. We present a model which uses national datasets to describe the distribution of woody linear features along boundaries in Great Britain. The method can be applied for other boundary types and in other locations around the world across a range of spatial scales where different types of linear feature can be separated using characteristics such as height or width. Satellite-derived Land Cover Map 2007 (LCM2007) provided the spatial framework for locating linear features and was used to screen out areas unsuitable for their occurrence, that is, offshore, urban, and forest areas. Similarly, Ordnance Survey Land-Form PANORAMA®, a digital terrain model, was used to screen out where they do not occur. The presence of woody linear features on boundaries was modelled using attributes from a canopy height dataset obtained by subtracting a digital terrain map (DTM) from a digital surface model (DSM). The performance of the model was evaluated against existing woody linear feature data in Countryside Survey across a range of scales. The results indicate that, despite some underestimation, this simple approach may provide valuable information on the extents and locations of woody linear features in the countryside at both local and national scales.

Item Purification in Differential Item Functioning Using Generalized Linear Mixed Models

ERIC Educational Resources Information Center

Liu, Qian

2011-01-01

For this dissertation, four item purification procedures were implemented onto the generalized linear mixed model for differential item functioning (DIF) analysis, and the performance of these item purification procedures was investigated through a series of simulations. Among the four procedures, forward and generalized linear mixed model (GLMM)…

Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts.

PubMed

Howe, Laura D; Tilling, Kate; Matijasevich, Alicia; Petherick, Emily S; Santos, Ana Cristina; Fairley, Lesley; Wright, John; Santos, Iná S; Barros, Aluísio Jd; Martin, Richard M; Kramer, Michael S; Bogdanovich, Natalia; Matush, Lidia; Barros, Henrique; Lawlor, Debbie A

2016-10-01

Childhood growth is of interest in medical research concerned with determinants and consequences of variation from healthy growth and development. Linear spline multilevel modelling is a useful approach for deriving individual summary measures of growth, which overcomes several data issues (co-linearity of repeat measures, the requirement for all individuals to be measured at the same ages and bias due to missing data). Here, we outline the application of this methodology to model individual trajectories of length/height and weight, drawing on examples from five cohorts from different generations and different geographical regions with varying levels of economic development. We describe the unique features of the data within each cohort that have implications for the application of linear spline multilevel models, for example, differences in the density and inter-individual variation in measurement occasions, and multiple sources of measurement with varying measurement error. After providing example Stata syntax and a suggested workflow for the implementation of linear spline multilevel models, we conclude with a discussion of the advantages and disadvantages of the linear spline approach compared with other growth modelling methods such as fractional polynomials, more complex spline functions and other non-linear models. © The Author(s) 2013.

Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts

PubMed Central

Tilling, Kate; Matijasevich, Alicia; Petherick, Emily S; Santos, Ana Cristina; Fairley, Lesley; Wright, John; Santos, Iná S.; Barros, Aluísio JD; Martin, Richard M; Kramer, Michael S; Bogdanovich, Natalia; Matush, Lidia; Barros, Henrique; Lawlor, Debbie A

2013-01-01

Childhood growth is of interest in medical research concerned with determinants and consequences of variation from healthy growth and development. Linear spline multilevel modelling is a useful approach for deriving individual summary measures of growth, which overcomes several data issues (co-linearity of repeat measures, the requirement for all individuals to be measured at the same ages and bias due to missing data). Here, we outline the application of this methodology to model individual trajectories of length/height and weight, drawing on examples from five cohorts from different generations and different geographical regions with varying levels of economic development. We describe the unique features of the data within each cohort that have implications for the application of linear spline multilevel models, for example, differences in the density and inter-individual variation in measurement occasions, and multiple sources of measurement with varying measurement error. After providing example Stata syntax and a suggested workflow for the implementation of linear spline multilevel models, we conclude with a discussion of the advantages and disadvantages of the linear spline approach compared with other growth modelling methods such as fractional polynomials, more complex spline functions and other non-linear models. PMID:24108269

Performance Metrics, Error Modeling, and Uncertainty Quantification

NASA Technical Reports Server (NTRS)

Tian, Yudong; Nearing, Grey S.; Peters-Lidard, Christa D.; Harrison, Kenneth W.; Tang, Ling

2016-01-01

A common set of statistical metrics has been used to summarize the performance of models or measurements-­ the most widely used ones being bias, mean square error, and linear correlation coefficient. They assume linear, additive, Gaussian errors, and they are interdependent, incomplete, and incapable of directly quantifying un­certainty. The authors demonstrate that these metrics can be directly derived from the parameters of the simple linear error model. Since a correct error model captures the full error information, it is argued that the specification of a parametric error model should be an alternative to the metrics-based approach. The error-modeling meth­odology is applicable to both linear and nonlinear errors, while the metrics are only meaningful for linear errors. In addition, the error model expresses the error structure more naturally, and directly quantifies uncertainty. This argument is further explained by highlighting the intrinsic connections between the performance metrics, the error model, and the joint distribution between the data and the reference.

A new adaptive multiple modelling approach for non-linear and non-stationary systems

NASA Astrophysics Data System (ADS)

Chen, Hao; Gong, Yu; Hong, Xia

2016-07-01

This paper proposes a novel adaptive multiple modelling algorithm for non-linear and non-stationary systems. This simple modelling paradigm comprises K candidate sub-models which are all linear. With data available in an online fashion, the performance of all candidate sub-models are monitored based on the most recent data window, and M best sub-models are selected from the K candidates. The weight coefficients of the selected sub-model are adapted via the recursive least square (RLS) algorithm, while the coefficients of the remaining sub-models are unchanged. These M model predictions are then optimally combined to produce the multi-model output. We propose to minimise the mean square error based on a recent data window, and apply the sum to one constraint to the combination parameters, leading to a closed-form solution, so that maximal computational efficiency can be achieved. In addition, at each time step, the model prediction is chosen from either the resultant multiple model or the best sub-model, whichever is the best. Simulation results are given in comparison with some typical alternatives, including the linear RLS algorithm and a number of online non-linear approaches, in terms of modelling performance and time consumption.

Australia's Next Top Fraction Model

ERIC Educational Resources Information Center

Gould, Peter

2013-01-01

Peter Gould suggests Australia's next top fraction model should be a linear model rather than an area model. He provides a convincing argument and gives examples of ways to introduce a linear model in primary classrooms.

An Application to the Prediction of LOD Change Based on General Regression Neural Network

NASA Astrophysics Data System (ADS)

Zhang, X. H.; Wang, Q. J.; Zhu, J. J.; Zhang, H.

2011-07-01

Traditional prediction of the LOD (length of day) change was based on linear models, such as the least square model and the autoregressive technique, etc. Due to the complex non-linear features of the LOD variation, the performances of the linear model predictors are not fully satisfactory. This paper applies a non-linear neural network - general regression neural network (GRNN) model to forecast the LOD change, and the results are analyzed and compared with those obtained with the back propagation neural network and other models. The comparison shows that the performance of the GRNN model in the prediction of the LOD change is efficient and feasible.

Non-linear Growth Models in Mplus and SAS

PubMed Central

Grimm, Kevin J.; Ram, Nilam

2013-01-01

Non-linear growth curves or growth curves that follow a specified non-linear function in time enable researchers to model complex developmental patterns with parameters that are easily interpretable. In this paper we describe how a variety of sigmoid curves can be fit using the Mplus structural modeling program and the non-linear mixed-effects modeling procedure NLMIXED in SAS. Using longitudinal achievement data collected as part of a study examining the effects of preschool instruction on academic gain we illustrate the procedures for fitting growth models of logistic, Gompertz, and Richards functions. Brief notes regarding the practical benefits, limitations, and choices faced in the fitting and estimation of such models are included. PMID:23882134

Comparison between Linear and Nonlinear Regression in a Laboratory Heat Transfer Experiment

ERIC Educational Resources Information Center

Gonçalves, Carine Messias; Schwaab, Marcio; Pinto, José Carlos

2013-01-01

In order to interpret laboratory experimental data, undergraduate students are used to perform linear regression through linearized versions of nonlinear models. However, the use of linearized models can lead to statistically biased parameter estimates. Even so, it is not an easy task to introduce nonlinear regression and show for the students…

Application of General Regression Neural Network to the Prediction of LOD Change

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Hong; Wang, Qi-Jie; Zhu, Jian-Jun; Zhang, Hao

2012-01-01

Traditional methods for predicting the change in length of day (LOD change) are mainly based on some linear models, such as the least square model and autoregression model, etc. However, the LOD change comprises complicated non-linear factors and the prediction effect of the linear models is always not so ideal. Thus, a kind of non-linear neural network — general regression neural network (GRNN) model is tried to make the prediction of the LOD change and the result is compared with the predicted results obtained by taking advantage of the BP (back propagation) neural network model and other models. The comparison result shows that the application of the GRNN to the prediction of the LOD change is highly effective and feasible.

Computation of linear acceleration through an internal model in the macaque cerebellum

PubMed Central

Laurens, Jean; Meng, Hui; Angelaki, Dora E.

2013-01-01

A combination of theory and behavioral findings has supported a role for internal models in the resolution of sensory ambiguities and sensorimotor processing. Although the cerebellum has been proposed as a candidate for implementation of internal models, concrete evidence from neural responses is lacking. Here we exploit un-natural motion stimuli, which induce incorrect self-motion perception and eye movements, to explore the neural correlates of an internal model proposed to compensate for Einstein’s equivalence principle and generate neural estimates of linear acceleration and gravity. We show that caudal cerebellar vermis Purkinje cells and cerebellar nuclei neurons selective for actual linear acceleration also encode erroneous linear acceleration, as expected from the internal model hypothesis, even when no actual linear acceleration occurs. These findings provide strong evidence that the cerebellum might be involved in the implementation of internal models that mimic physical principles to interpret sensory signals, as previously hypothesized by theorists. PMID:24077562

A comparison of linear versus non-linear models of aversive self-awareness, dissociation, and non-suicidal self-injury among young adults.

PubMed

Armey, Michael F; Crowther, Janis H

2008-02-01

Research has identified a significant increase in both the incidence and prevalence of non-suicidal self-injury (NSSI). The present study sought to test both linear and non-linear cusp catastrophe models by using aversive self-awareness, which was operationalized as a composite of aversive self-relevant affect and cognitions, and dissociation as predictors of NSSI. The cusp catastrophe model evidenced a better fit to the data, accounting for 6 times the variance (66%) of a linear model (9%-10%). These results support models of NSSI implicating emotion regulation deficits and experiential avoidance in the occurrence of NSSI and provide preliminary support for the use of cusp catastrophe models to study certain types of low base rate psychopathology such as NSSI. These findings suggest novel approaches to prevention and treatment of NSSI as well.

A Multiphase Non-Linear Mixed Effects Model: An Application to Spirometry after Lung Transplantation

PubMed Central

Rajeswaran, Jeevanantham; Blackstone, Eugene H.

2014-01-01

In medical sciences, we often encounter longitudinal temporal relationships that are non-linear in nature. The influence of risk factors may also change across longitudinal follow-up. A system of multiphase non-linear mixed effects model is presented to model temporal patterns of longitudinal continuous measurements, with temporal decomposition to identify the phases and risk factors within each phase. Application of this model is illustrated using spirometry data after lung transplantation using readily available statistical software. This application illustrates the usefulness of our flexible model when dealing with complex non-linear patterns and time varying coefficients. PMID:24919830

The Linear Bias in the Zeldovich Approximation and a Relation between the Number Density and the Linear Bias of Dark Halos

NASA Astrophysics Data System (ADS)

Fan, Zuhui

2000-01-01

The linear bias of the dark halos from a model under the Zeldovich approximation is derived and compared with the fitting formula of simulation results. While qualitatively similar to the Press-Schechter formula, this model gives a better description for the linear bias around the turnaround point. This advantage, however, may be compromised by the large uncertainty of the actual behavior of the linear bias near the turnaround point. For a broad class of structure formation models in the cold dark matter framework, a general relation exists between the number density and the linear bias of dark halos. This relation can be readily tested by numerical simulations. Thus, instead of laboriously checking these models one by one, numerical simulation studies can falsify a whole category of models. The general validity of this relation is important in identifying key physical processes responsible for the large-scale structure formation in the universe.

Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

ERIC Educational Resources Information Center

Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

2012-01-01

Purpose: The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F[subscript 0]) during anterior-posterior stretching. Method: Three materially linear and 3 materially nonlinear models were…

Smoothed Residual Plots for Generalized Linear Models. Technical Report #450.

ERIC Educational Resources Information Center

Brant, Rollin

Methods for examining the viability of assumptions underlying generalized linear models are considered. By appealing to the likelihood, a natural generalization of the raw residual plot for normal theory models is derived and is applied to investigating potential misspecification of the linear predictor. A smooth version of the plot is also…

An Expert System for the Evaluation of Cost Models

DTIC Science & Technology

1990-09-01

contrast to the condition of equal error variance, called homoscedasticity. (Reference: Applied Linear Regression Models by John Neter - page 423...normal. (Reference: Applied Linear Regression Models by John Neter - page 125) Click Here to continue -> Autocorrelation Click Here for the index - Index...over time. Error terms correlated over time are said to be autocorrelated or serially correlated. (REFERENCE: Applied Linear Regression Models by John

Effect of non-linearity in predicting doppler waveforms through a novel model

PubMed Central

Gayasen, Aman; Dua, Sunil Kumar; Sengupta, Amit; Nagchoudhuri, D

2003-01-01

Background In pregnancy, the uteroplacental vascular system develops de novo locally in utero and a systemic haemodynamic & bio-rheological alteration accompany it. Any abnormality in the non-linear vascular system is believed to trigger the onset of serious morbid conditions like pre-eclampsia and/or intrauterine growth restriction (IUGR). Exact Aetiopathogenesis is unknown. Advancement in the field of non-invasive doppler image analysis and simulation incorporating non-linearities may unfold the complexities associated with the inaccessible uteroplacental vessels. Earlier modeling approaches approximate it as a linear system. Method We proposed a novel electrical model for the uteroplacental system that uses MOSFETs as non-linear elements in place of traditional linear transmission line (TL) model. The model to simulate doppler FVW's was designed by including the inputs from our non-linear mathematical model. While using the MOSFETs as voltage-controlled switches, a fair degree of controlled-non-linearity has been introduced in the model. Comparative analysis was done between the simulated data and the actual doppler FVW's waveforms. Results & Discussion Normal pregnancy has been successfully modeled and the doppler output waveforms are simulated for different gestation time using the model. It is observed that the dicrotic notch disappears and the S/D ratio decreases as the pregnancy matures. Both these results are established clinical facts. Effects of blood density, viscosity and the arterial wall elasticity on the blood flow velocity profile were also studied. Spectral analysis on the output of the model (blood flow velocity) indicated that the Total Harmonic Distortion (THD) falls during the mid-gestation. Conclusion Total harmonic distortion (THD) is found to be informative in determining the Feto-maternal health. Effects of the blood density, the viscosity and the elasticity changes on the blood FVW are simulated. Future works are expected to concentrate mainly on improving the load with respect to varying non-linear parameters in the model. Heart rate variability, which accounts for the vascular tone, should also be included. We also expect the model to initiate extensive clinical or experimental studies in the near future. PMID:14561227

Relations Among Student Attention Behaviors, Teacher Practices, and Beginning Word Reading Skill

PubMed Central

Sáez, Leilani; Folsom, Jessica Sidler; Al Otaiba, Stephanie; Schatschneider, Christopher

2011-01-01

The role of student attention for predicting kindergarten word reading was investigated among 432 students. Using SWAN behavior rating scores, we conducted an exploratory factor analysis, which yielded three distinct factors that reflected selective attention. In this study, we focused on the role of one of these factors, which we labeled attention-memory behaviors, for predicting reading performance. Teacher ratings of attention predicted word reading above and beyond the contribution of phonological awareness and vocabulary knowledge. In addition, the relations between four teacher practices and attention ratings for predicting reading performance were examined. Using HLM, significant interactions between student attention and teacher practices observed during literacy instruction were found. In general, as ratings of attention improved, better kindergarten word reading performance was associated with high levels of classroom behavior management. However, by mid-year, better word reading performance was not associated with high levels of teacher task- orienting. A significant three-way interaction was also found among attention, individualized instruction, and teacher task re-directions. The role of regulating kindergarten student attention to support beginning word reading skill development is discussed. PMID:22207616

Thermodynamic properties and equation of state of liquid lead and lead bismuth eutectic

NASA Astrophysics Data System (ADS)

Sobolev, V. P.; Schuurmans, P.; Benamati, G.

2008-06-01

Since the 1950s, liquid lead (Pb) and lead-bismuth eutectic (Pb-Bi) have been studied in the USA, Canada and in the former-USSR as potential coolants for nuclear installations due to their very attractive thermophysical and neutronic properties. However, experimental data on the thermal properties of these coolants in the temperature range of interest are still incomplete and often contradictory. This makes it very difficult to perform design calculations and to analyse the normal and abnormal behaviour of nuclear installations where these coolants are expected to be used. Recently, a compilation of heavy liquid metal (HLM) properties along with recommendations for its use was prepared by the OECD/NEA Working Party on Fuel Cycle (WPFC) Expert Group on Lead-Bismuth Eutectic Technology. A brief review of this compilation and some new data are presented in this article. A set of correlations for the temperature dependence of the main thermodynamic properties of Pb and Pb-Bi(e) at normal pressure, and a set of simplified thermal and caloric equations of state for the liquid phase are proposed.

A model for rotorcraft flying qualities studies

NASA Technical Reports Server (NTRS)

Mittal, Manoj; Costello, Mark F.

1993-01-01

This paper outlines the development of a mathematical model that is expected to be useful for rotorcraft flying qualities research. A computer model is presented that can be applied to a range of different rotorcraft configurations. The algorithm computes vehicle trim and a linear state-space model of the aircraft. The trim algorithm uses non linear optimization theory to solve the nonlinear algebraic trim equations. The linear aircraft equations consist of an airframe model and a flight control system dynamic model. The airframe model includes coupled rotor and fuselage rigid body dynamics and aerodynamics. The aerodynamic model for the rotors utilizes blade element theory and a three state dynamic inflow model. Aerodynamics of the fuselage and fuselage empennages are included. The linear state-space description for the flight control system is developed using standard block diagram data.

Numerical studies on the electromagnetic properties of the nonlinear Lorentz Computational model for the dielectric media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, H.; Okuda, H.

We study linear and nonlinear properties of a new computer simulation model developed to study the propagation of electromagnetic waves in a dielectric medium in the linear and nonlinear regimes. The model is constructed by combining a microscopic model used in the semi-classical approximation for the dielectric media and the particle model developed for the plasma simulations. It is shown that the model may be useful for studying linear and nonlinear wave propagation in the dielectric media.

The NASA High Speed ASE Project: Computational Analyses of a Low-Boom Supersonic Configuration

NASA Technical Reports Server (NTRS)

Silva, Walter A.; DeLaGarza, Antonio; Zink, Scott; Bounajem, Elias G.; Johnson, Christopher; Buonanno, Michael; Sanetrik, Mark D.; Yoo, Seung Y.; Kopasakis, George; Christhilf, David M.;

Rank-based estimation in the {ell}1-regularized partly linear model for censored outcomes with application to integrated analyses of clinical predictors and gene expression data.

PubMed

Johnson, Brent A

2009-10-01

We consider estimation and variable selection in the partial linear model for censored data. The partial linear model for censored data is a direct extension of the accelerated failure time model, the latter of which is a very important alternative model to the proportional hazards model. We extend rank-based lasso-type estimators to a model that may contain nonlinear effects. Variable selection in such partial linear model has direct application to high-dimensional survival analyses that attempt to adjust for clinical predictors. In the microarray setting, previous methods can adjust for other clinical predictors by assuming that clinical and gene expression data enter the model linearly in the same fashion. Here, we select important variables after adjusting for prognostic clinical variables but the clinical effects are assumed nonlinear. Our estimator is based on stratification and can be extended naturally to account for multiple nonlinear effects. We illustrate the utility of our method through simulation studies and application to the Wisconsin prognostic breast cancer data set.

Comparison of linear and nonlinear models for coherent hemodynamics spectroscopy (CHS)

NASA Astrophysics Data System (ADS)

Sassaroli, Angelo; Kainerstorfer, Jana; Fantini, Sergio

2015-03-01

A recently proposed linear time-invariant hemodynamic model for coherent hemodynamics spectroscopy1 (CHS) relates the tissue concentrations of oxy- and deoxy-hemoglobin (outputs of the system) to given dynamics of the tissue blood volume, blood flow and rate constant of oxygen diffusion (inputs of the system). This linear model was derived in the limit of "small" perturbations in blood flow velocity. We have extended this model to a more general model (which will be referred to as the nonlinear extension to the original model) that yields the time-dependent changes of oxy and deoxy-hemoglobin concentrations in response to arbitrary dynamic changes in capillary blood flow velocity. The nonlinear extension to the model relies on a general solution of the partial differential equation that governs the spatio-temporal behavior of oxygen saturation of hemoglobin in capillaries and venules on the basis of dynamic (or time resolved) blood transit time. We show preliminary results where the CHS spectra obtained from the linear and nonlinear models are compared to quantify the limits of applicability of the linear model.

On the modelling of linear-assisted DC-DC voltage regulators for photovoltaic solar energy systems

NASA Astrophysics Data System (ADS)

Martínez-García, Herminio; García-Vílchez, Encarna

2017-11-01

This paper shows the modelling of linear-assisted or hybrid (linear & switching) DC/DC voltage regulators. In this kind of regulators, an auxiliary linear regulator is used, which objective is to cancel the ripple at the output voltage and provide fast responses for load variations. On the other hand, a switching DC/DC converter, connected in parallel with the linear regulator, allows to supply almost the whole output current demanded by the load. The objective of this topology is to take advantage of the suitable regulation characteristics that series linear voltage regulators have, but almost achieving the high efficiency that switching DC/DC converters provide. Linear-assisted DC/DC regulators are feedback systems with potential instability. Therefore, their modelling is mandatory in order to obtain design guidelines and assure stability of the implemented power supply system.

Linear regression crash prediction models : issues and proposed solutions.

DOT National Transportation Integrated Search

2010-05-01

The paper develops a linear regression model approach that can be applied to : crash data to predict vehicle crashes. The proposed approach involves novice data aggregation : to satisfy linear regression assumptions; namely error structure normality ...

Portfolio optimization by using linear programing models based on genetic algorithm

NASA Astrophysics Data System (ADS)

Sukono; Hidayat, Y.; Lesmana, E.; Putra, A. S.; Napitupulu, H.; Supian, S.

2018-01-01

In this paper, we discussed the investment portfolio optimization using linear programming model based on genetic algorithms. It is assumed that the portfolio risk is measured by absolute standard deviation, and each investor has a risk tolerance on the investment portfolio. To complete the investment portfolio optimization problem, the issue is arranged into a linear programming model. Furthermore, determination of the optimum solution for linear programming is done by using a genetic algorithm. As a numerical illustration, we analyze some of the stocks traded on the capital market in Indonesia. Based on the analysis, it is shown that the portfolio optimization performed by genetic algorithm approach produces more optimal efficient portfolio, compared to the portfolio optimization performed by a linear programming algorithm approach. Therefore, genetic algorithms can be considered as an alternative on determining the investment portfolio optimization, particularly using linear programming models.

Design of Linear-Quadratic-Regulator for a CSTR process

NASA Astrophysics Data System (ADS)

Meghna, P. R.; Saranya, V.; Jaganatha Pandian, B.

2017-11-01

This paper aims at creating a Linear Quadratic Regulator (LQR) for a Continuous Stirred Tank Reactor (CSTR). A CSTR is a common process used in chemical industries. It is a highly non-linear system. Therefore, in order to create the gain feedback controller, the model is linearized. The controller is designed for the linearized model and the concentration and volume of the liquid in the reactor are kept at a constant value as required.

Feedback linearization for control of air breathing engines

NASA Technical Reports Server (NTRS)

Phillips, Stephen; Mattern, Duane

1991-01-01

The method of feedback linearization for control of the nonlinear nozzle and compressor components of an air breathing engine is presented. This method overcomes the need for a large number of scheduling variables and operating points to accurately model highly nonlinear plants. Feedback linearization also results in linear closed loop system performance simplifying subsequent control design. Feedback linearization is used for the nonlinear partial engine model and performance is verified through simulation.

Linear mixed-effects models to describe individual tree crown width for China-fir in Fujian Province, southeast China.

PubMed

Hao, Xu; Yujun, Sun; Xinjie, Wang; Jin, Wang; Yao, Fu

2015-01-01

A multiple linear model was developed for individual tree crown width of Cunninghamia lanceolata (Lamb.) Hook in Fujian province, southeast China. Data were obtained from 55 sample plots of pure China-fir plantation stands. An Ordinary Linear Least Squares (OLS) regression was used to establish the crown width model. To adjust for correlations between observations from the same sample plots, we developed one level linear mixed-effects (LME) models based on the multiple linear model, which take into account the random effects of plots. The best random effects combinations for the LME models were determined by the Akaike's information criterion, the Bayesian information criterion and the -2logarithm likelihood. Heteroscedasticity was reduced by three residual variance functions: the power function, the exponential function and the constant plus power function. The spatial correlation was modeled by three correlation structures: the first-order autoregressive structure [AR(1)], a combination of first-order autoregressive and moving average structures [ARMA(1,1)], and the compound symmetry structure (CS). Then, the LME model was compared to the multiple linear model using the absolute mean residual (AMR), the root mean square error (RMSE), and the adjusted coefficient of determination (adj-R2). For individual tree crown width models, the one level LME model showed the best performance. An independent dataset was used to test the performance of the models and to demonstrate the advantage of calibrating LME models.

Recent Updates to the GEOS-5 Linear Model

NASA Technical Reports Server (NTRS)

Holdaway, Dan; Kim, Jong G.; Errico, Ron; Gelaro, Ronald; Mahajan, Rahul

2014-01-01

Global Modeling and Assimilation Office (GMAO) is close to having a working 4DVAR system and has developed a linearized version of GEOS-5.This talk outlines a series of improvements made to the linearized dynamics, physics and trajectory.Of particular interest is the development of linearized cloud microphysics, which provides the framework for 'all-sky' data assimilation.

Generalized Multilevel Structural Equation Modeling

ERIC Educational Resources Information Center

Rabe-Hesketh, Sophia; Skrondal, Anders; Pickles, Andrew

2004-01-01

A unifying framework for generalized multilevel structural equation modeling is introduced. The models in the framework, called generalized linear latent and mixed models (GLLAMM), combine features of generalized linear mixed models (GLMM) and structural equation models (SEM) and consist of a response model and a structural model for the latent…

On the Validity of the Streaming Model for the Redshift-Space Correlation Function in the Linear Regime

NASA Astrophysics Data System (ADS)

Fisher, Karl B.

1995-08-01

The relation between the galaxy correlation functions in real-space and redshift-space is derived in the linear regime by an appropriate averaging of the joint probability distribution of density and velocity. The derivation recovers the familiar linear theory result on large scales but has the advantage of clearly revealing the dependence of the redshift distortions on the underlying peculiar velocity field; streaming motions give rise to distortions of θ(Ω0.6/b) while variations in the anisotropic velocity dispersion yield terms of order θ(Ω1.2/b2). This probabilistic derivation of the redshift-space correlation function is similar in spirit to the derivation of the commonly used "streaming" model, in which the distortions are given by a convolution of the real-space correlation function with a velocity distribution function. The streaming model is often used to model the redshift-space correlation function on small, highly nonlinear, scales. There have been claims in the literature, however, that the streaming model is not valid in the linear regime. Our analysis confirms this claim, but we show that the streaming model can be made consistent with linear theory provided that the model for the streaming has the functional form predicted by linear theory and that the velocity distribution is chosen to be a Gaussian with the correct linear theory dispersion.

A Method for Generating Reduced-Order Linear Models of Multidimensional Supersonic Inlets

NASA Technical Reports Server (NTRS)

Chicatelli, Amy; Hartley, Tom T.

1998-01-01

Simulation of high speed propulsion systems may be divided into two categories, nonlinear and linear. The nonlinear simulations are usually based on multidimensional computational fluid dynamics (CFD) methodologies and tend to provide high resolution results that show the fine detail of the flow. Consequently, these simulations are large, numerically intensive, and run much slower than real-time. ne linear simulations are usually based on large lumping techniques that are linearized about a steady-state operating condition. These simplistic models often run at or near real-time but do not always capture the detailed dynamics of the plant. Under a grant sponsored by the NASA Lewis Research Center, Cleveland, Ohio, a new method has been developed that can be used to generate improved linear models for control design from multidimensional steady-state CFD results. This CFD-based linear modeling technique provides a small perturbation model that can be used for control applications and real-time simulations. It is important to note the utility of the modeling procedure; all that is needed to obtain a linear model of the propulsion system is the geometry and steady-state operating conditions from a multidimensional CFD simulation or experiment. This research represents a beginning step in establishing a bridge between the controls discipline and the CFD discipline so that the control engineer is able to effectively use multidimensional CFD results in control system design and analysis.

Linear and non-linear dynamic models of a geared rotor-bearing system

NASA Technical Reports Server (NTRS)

Kahraman, Ahmet; Singh, Rajendra

1990-01-01

A three degree of freedom non-linear model of a geared rotor-bearing system with gear backlash and radial clearances in rolling element bearings is proposed here. This reduced order model can be used to describe the transverse-torsional motion of the system. It is justified by comparing the eigen solutions yielded by corresponding linear model with the finite element method results. Nature of nonlinearities in bearings is examined and two approximate nonlinear stiffness functions are proposed. These approximate bearing models are verified by comparing their frequency responses with the results given by the exact form of nonlinearity. The proposed nonlinear dynamic model of the geared rotor-bearing system can be used to investigate the dynamic behavior and chaos.

Linear Equating for the NEAT Design: Parameter Substitution Models and Chained Linear Relationship Models

ERIC Educational Resources Information Center

Kane, Michael T.; Mroch, Andrew A.; Suh, Youngsuk; Ripkey, Douglas R.

2009-01-01

This paper analyzes five linear equating models for the "nonequivalent groups with anchor test" (NEAT) design with internal anchors (i.e., the anchor test is part of the full test). The analysis employs a two-dimensional framework. The first dimension contrasts two general approaches to developing the equating relationship. Under a "parameter…

Exploring compositional variations on the surface of Mars applying mixing modeling to a telescopic spectral image

NASA Technical Reports Server (NTRS)

Merenyi, E.; Miller, J. S.; Singer, R. B.

1992-01-01

The linear mixing model approach was successfully applied to data sets of various natures. In these sets, the measured radiance could be assumed to be a linear combination of radiance contributions. The present work is an attempt to analyze a spectral image of Mars with linear mixing modeling.

Some comparisons of complexity in dictionary-based and linear computational models.

PubMed

Gnecco, Giorgio; Kůrková, Věra; Sanguineti, Marcello

2011-03-01

Neural networks provide a more flexible approximation of functions than traditional linear regression. In the latter, one can only adjust the coefficients in linear combinations of fixed sets of functions, such as orthogonal polynomials or Hermite functions, while for neural networks, one may also adjust the parameters of the functions which are being combined. However, some useful properties of linear approximators (such as uniqueness, homogeneity, and continuity of best approximation operators) are not satisfied by neural networks. Moreover, optimization of parameters in neural networks becomes more difficult than in linear regression. Experimental results suggest that these drawbacks of neural networks are offset by substantially lower model complexity, allowing accuracy of approximation even in high-dimensional cases. We give some theoretical results comparing requirements on model complexity for two types of approximators, the traditional linear ones and so called variable-basis types, which include neural networks, radial, and kernel models. We compare upper bounds on worst-case errors in variable-basis approximation with lower bounds on such errors for any linear approximator. Using methods from nonlinear approximation and integral representations tailored to computational units, we describe some cases where neural networks outperform any linear approximator. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison of the Tangent Linear Properties of Tracer Transport Schemes Applied to Geophysical Problems.

NASA Technical Reports Server (NTRS)

Kent, James; Holdaway, Daniel

2015-01-01

A number of geophysical applications require the use of the linearized version of the full model. One such example is in numerical weather prediction, where the tangent linear and adjoint versions of the atmospheric model are required for the 4DVAR inverse problem. The part of the model that represents the resolved scale processes of the atmosphere is known as the dynamical core. Advection, or transport, is performed by the dynamical core. It is a central process in many geophysical applications and is a process that often has a quasi-linear underlying behavior. However, over the decades since the advent of numerical modelling, significant effort has gone into developing many flavors of high-order, shape preserving, nonoscillatory, positive definite advection schemes. These schemes are excellent in terms of transporting the quantities of interest in the dynamical core, but they introduce nonlinearity through the use of nonlinear limiters. The linearity of the transport schemes used in Goddard Earth Observing System version 5 (GEOS-5), as well as a number of other schemes, is analyzed using a simple 1D setup. The linearized version of GEOS-5 is then tested using a linear third order scheme in the tangent linear version.

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

Forcing Regression through a Given Point Using Any Familiar Computational Routine.

DTIC Science & Technology

1983-03-01

a linear model , Y =a + OX + e ( Model I) then adopt the principle of least squares; and use sample data to estimate the unknown parameters, a and 8...has an expected value of zero indicates that the "average" response is considered linear . If c varies widely, Model I, though conceptually correct, may...relationship is linear from the maximum observed x to x - a, then Model II should be used. To pro- ceed with the customary evaluation of Model I would be

A Bivariate Generalized Linear Item Response Theory Modeling Framework to the Analysis of Responses and Response Times.

PubMed

Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

2015-01-01

A generalized linear modeling framework to the analysis of responses and response times is outlined. In this framework, referred to as bivariate generalized linear item response theory (B-GLIRT), separate generalized linear measurement models are specified for the responses and the response times that are subsequently linked by cross-relations. The cross-relations can take various forms. Here, we focus on cross-relations with a linear or interaction term for ability tests, and cross-relations with a curvilinear term for personality tests. In addition, we discuss how popular existing models from the psychometric literature are special cases in the B-GLIRT framework depending on restrictions in the cross-relation. This allows us to compare existing models conceptually and empirically. We discuss various extensions of the traditional models motivated by practical problems. We also illustrate the applicability of our approach using various real data examples, including data on personality and cognitive ability.

Cost Estimation of Naval Ship Acquisition.

DTIC Science & Technology

1983-12-01

one a 9-sub- system model , the other a single total cost model . The models were developed using the linear least squares regression tech- nique with...to Linear Statistical Models , McGraw-Hill, 1961. 11. Helmer, F. T., Bibliography on Pricing Methodology and Cost Estimating, Dept. of Economics and...SUPPI.EMSaTARY NOTES IS. KWRo" (Cowaft. en tever aide of ..aesep M’ Idab~t 6 Week ONNa.) Cost estimation; Acquisition; Parametric cost estimate; linear

Non-linear models for the detection of impaired cerebral blood flow autoregulation.

PubMed

Chacón, Max; Jara, José Luis; Miranda, Rodrigo; Katsogridakis, Emmanuel; Panerai, Ronney B

2018-01-01

The ability to discriminate between normal and impaired dynamic cerebral autoregulation (CA), based on measurements of spontaneous fluctuations in arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable clinical relevance. We studied 45 normal subjects at rest and under hypercapnia induced by breathing a mixture of carbon dioxide and air. Non-linear models with BP as input and CBF velocity (CBFV) as output, were implemented with support vector machines (SVM) using separate recordings for learning and validation. Dynamic SVM implementations used either moving average or autoregressive structures. The efficiency of dynamic CA was estimated from the model's derived CBFV response to a step change in BP as an autoregulation index for both linear and non-linear models. Non-linear models with recurrences (autoregressive) showed the best results, with CA indexes of 5.9 ± 1.5 in normocapnia, and 2.5 ± 1.2 for hypercapnia with an area under the receiver-operator curve of 0.955. The high performance achieved by non-linear SVM models to detect deterioration of dynamic CA should encourage further assessment of its applicability to clinical conditions where CA might be impaired.

Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

PubMed

Cook, James P; Mahajan, Anubha; Morris, Andrew P

2017-02-01

Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

An approximate generalized linear model with random effects for informative missing data.

PubMed

Follmann, D; Wu, M

1995-03-01

This paper develops a class of models to deal with missing data from longitudinal studies. We assume that separate models for the primary response and missingness (e.g., number of missed visits) are linked by a common random parameter. Such models have been developed in the econometrics (Heckman, 1979, Econometrica 47, 153-161) and biostatistics (Wu and Carroll, 1988, Biometrics 44, 175-188) literature for a Gaussian primary response. We allow the primary response, conditional on the random parameter, to follow a generalized linear model and approximate the generalized linear model by conditioning on the data that describes missingness. The resultant approximation is a mixed generalized linear model with possibly heterogeneous random effects. An example is given to illustrate the approximate approach, and simulations are performed to critique the adequacy of the approximation for repeated binary data.

Experimental analysis of bidirectional reflectance distribution function cross section conversion term in direction cosine space.

PubMed

Butler, Samuel D; Nauyoks, Stephen E; Marciniak, Michael A

2015-06-01

Of the many classes of bidirectional reflectance distribution function (BRDF) models, two popular classes of models are the microfacet model and the linear systems diffraction model. The microfacet model has the benefit of speed and simplicity, as it uses geometric optics approximations, while linear systems theory uses a diffraction approach to compute the BRDF, at the expense of greater computational complexity. In this Letter, nongrazing BRDF measurements of rough and polished surface-reflecting materials at multiple incident angles are scaled by the microfacet cross section conversion term, but in the linear systems direction cosine space, resulting in great alignment of BRDF data at various incident angles in this space. This results in a predictive BRDF model for surface-reflecting materials at nongrazing angles, while avoiding some of the computational complexities in the linear systems diffraction model.

Generation of linear dynamic models from a digital nonlinear simulation

NASA Technical Reports Server (NTRS)

Daniele, C. J.; Krosel, S. M.

1979-01-01

The results and methodology used to derive linear models from a nonlinear simulation are presented. It is shown that averaged positive and negative perturbations in the state variables can reduce numerical errors in finite difference, partial derivative approximations and, in the control inputs, can better approximate the system response in both directions about the operating point. Both explicit and implicit formulations are addressed. Linear models are derived for the F 100 engine, and comparisons of transients are made with the nonlinear simulation. The problem of startup transients in the nonlinear simulation in making these comparisons is addressed. Also, reduction of the linear models is investigated using the modal and normal techniques. Reduced-order models of the F 100 are derived and compared with the full-state models.

Modeling and Inverse Controller Design for an Unmanned Aerial Vehicle Based on the Self-Organizing Map

NASA Technical Reports Server (NTRS)

Cho, Jeongho; Principe, Jose C.; Erdogmus, Deniz; Motter, Mark A.

2005-01-01

The next generation of aircraft will have dynamics that vary considerably over the operating regime. A single controller will have difficulty to meet the design specifications. In this paper, a SOM-based local linear modeling scheme of an unmanned aerial vehicle (UAV) is developed to design a set of inverse controllers. The SOM selects the operating regime depending only on the embedded output space information and avoids normalization of the input data. Each local linear model is associated with a linear controller, which is easy to design. Switching of the controllers is done synchronously with the active local linear model that tracks the different operating conditions. The proposed multiple modeling and control strategy has been successfully tested in a simulator that models the LoFLYTE UAV.

Linear and non-linear perturbations in dark energy models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escamilla-Rivera, Celia; Casarini, Luciano; Fabris, Júlio C.

2016-11-01

In this work we discuss observational aspects of three time-dependent parameterisations of the dark energy equation of state w ( z ). In order to determine the dynamics associated with these models, we calculate their background evolution and perturbations in a scalar field representation. After performing a complete treatment of linear perturbations, we also show that the non-linear contribution of the selected w ( z ) parameterisations to the matter power spectra is almost the same for all scales, with no significant difference from the predictions of the standard ΛCDM model.

Non-Linear Concentration-Response Relationships between Ambient Ozone and Daily Mortality.

PubMed

Bae, Sanghyuk; Lim, Youn-Hee; Kashima, Saori; Yorifuji, Takashi; Honda, Yasushi; Kim, Ho; Hong, Yun-Chul

2015-01-01

Ambient ozone (O3) concentration has been reported to be significantly associated with mortality. However, linearity of the relationships and the presence of a threshold has been controversial. The aim of the present study was to examine the concentration-response relationship and threshold of the association between ambient O3 concentration and non-accidental mortality in 13 Japanese and Korean cities from 2000 to 2009. We selected Japanese and Korean cities which have population of over 1 million. We constructed Poisson regression models adjusting daily mean temperature, daily mean PM10, humidity, time trend, season, year, day of the week, holidays and yearly population. The association between O3 concentration and mortality was examined using linear, spline and linear-threshold models. The thresholds were estimated for each city, by constructing linear-threshold models. We also examined the city-combined association using a generalized additive mixed model. The mean O3 concentration did not differ greatly between Korea and Japan, which were 26.2 ppb and 24.2 ppb, respectively. Seven out of 13 cities showed better fits for the spline model compared with the linear model, supporting a non-linear relationships between O3 concentration and mortality. All of the 7 cities showed J or U shaped associations suggesting the existence of thresholds. The range of city-specific thresholds was from 11 to 34 ppb. The city-combined analysis also showed a non-linear association with a threshold around 30-40 ppb. We have observed non-linear concentration-response relationship with thresholds between daily mean ambient O3 concentration and daily number of non-accidental death in Japanese and Korean cities.

A novel methodology for non-linear system identification of battery cells used in non-road hybrid electric vehicles

NASA Astrophysics Data System (ADS)

Unger, Johannes; Hametner, Christoph; Jakubek, Stefan; Quasthoff, Marcus

2014-12-01

An accurate state of charge (SoC) estimation of a traction battery in hybrid electric non-road vehicles, which possess higher dynamics and power densities than on-road vehicles, requires a precise battery cell terminal voltage model. This paper presents a novel methodology for non-linear system identification of battery cells to obtain precise battery models. The methodology comprises the architecture of local model networks (LMN) and optimal model based design of experiments (DoE). Three main novelties are proposed: 1) Optimal model based DoE, which aims to high dynamically excite the battery cells at load ranges frequently used in operation. 2) The integration of corresponding inputs in the LMN to regard the non-linearities SoC, relaxation, hysteresis as well as temperature effects. 3) Enhancements to the local linear model tree (LOLIMOT) construction algorithm, to achieve a physical appropriate interpretation of the LMN. The framework is applicable for different battery cell chemistries and different temperatures, and is real time capable, which is shown on an industrial PC. The accuracy of the obtained non-linear battery model is demonstrated on cells with different chemistries and temperatures. The results show significant improvement due to optimal experiment design and integration of the battery non-linearities within the LMN structure.

Phylogenetic mixtures and linear invariants for equal input models.

PubMed

Casanellas, Marta; Steel, Mike

2017-04-01

The reconstruction of phylogenetic trees from molecular sequence data relies on modelling site substitutions by a Markov process, or a mixture of such processes. In general, allowing mixed processes can result in different tree topologies becoming indistinguishable from the data, even for infinitely long sequences. However, when the underlying Markov process supports linear phylogenetic invariants, then provided these are sufficiently informative, the identifiability of the tree topology can be restored. In this paper, we investigate a class of processes that support linear invariants once the stationary distribution is fixed, the 'equal input model'. This model generalizes the 'Felsenstein 1981' model (and thereby the Jukes-Cantor model) from four states to an arbitrary number of states (finite or infinite), and it can also be described by a 'random cluster' process. We describe the structure and dimension of the vector spaces of phylogenetic mixtures and of linear invariants for any fixed phylogenetic tree (and for all trees-the so called 'model invariants'), on any number n of leaves. We also provide a precise description of the space of mixtures and linear invariants for the special case of [Formula: see text] leaves. By combining techniques from discrete random processes and (multi-) linear algebra, our results build on a classic result that was first established by James Lake (Mol Biol Evol 4:167-191, 1987).

OPLS statistical model versus linear regression to assess sonographic predictors of stroke prognosis.

PubMed

Vajargah, Kianoush Fathi; Sadeghi-Bazargani, Homayoun; Mehdizadeh-Esfanjani, Robab; Savadi-Oskouei, Daryoush; Farhoudi, Mehdi

2012-01-01

The objective of the present study was to assess the comparable applicability of orthogonal projections to latent structures (OPLS) statistical model vs traditional linear regression in order to investigate the role of trans cranial doppler (TCD) sonography in predicting ischemic stroke prognosis. The study was conducted on 116 ischemic stroke patients admitted to a specialty neurology ward. The Unified Neurological Stroke Scale was used once for clinical evaluation on the first week of admission and again six months later. All data was primarily analyzed using simple linear regression and later considered for multivariate analysis using PLS/OPLS models through the SIMCA P+12 statistical software package. The linear regression analysis results used for the identification of TCD predictors of stroke prognosis were confirmed through the OPLS modeling technique. Moreover, in comparison to linear regression, the OPLS model appeared to have higher sensitivity in detecting the predictors of ischemic stroke prognosis and detected several more predictors. Applying the OPLS model made it possible to use both single TCD measures/indicators and arbitrarily dichotomized measures of TCD single vessel involvement as well as the overall TCD result. In conclusion, the authors recommend PLS/OPLS methods as complementary rather than alternative to the available classical regression models such as linear regression.

A Comparison of Linear versus Non-Linear Models of Aversive Self-Awareness, Dissociation, and Non-Suicidal Self-Injury among Young Adults

ERIC Educational Resources Information Center

Armey, Michael F.; Crowther, Janis H.

2008-01-01

Research has identified a significant increase in both the incidence and prevalence of non-suicidal self-injury (NSSI). The present study sought to test both linear and non-linear cusp catastrophe models by using aversive self-awareness, which was operationalized as a composite of aversive self-relevant affect and cognitions, and dissociation as…

Nonlinearity measure and internal model control based linearization in anti-windup design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perev, Kamen

2013-12-18

This paper considers the problem of internal model control based linearization in anti-windup design. The nonlinearity measure concept is used for quantifying the control system degree of nonlinearity. The linearizing effect of a modified internal model control structure is presented by comparing the nonlinearity measures of the open-loop and closed-loop systems. It is shown that the linearization properties are improved by increasing the control system local feedback gain. However, it is emphasized that at the same time the stability of the system deteriorates. The conflicting goals of stability and linearization are resolved by solving the design problem in different frequencymore » ranges.« less

Perfect commuting-operator strategies for linear system games

NASA Astrophysics Data System (ADS)

Cleve, Richard; Liu, Li; Slofstra, William

2017-01-01

Linear system games are a generalization of Mermin's magic square game introduced by Cleve and Mittal. They show that perfect strategies for linear system games in the tensor-product model of entanglement correspond to finite-dimensional operator solutions of a certain set of non-commutative equations. We investigate linear system games in the commuting-operator model of entanglement, where Alice and Bob's measurement operators act on a joint Hilbert space, and Alice's operators must commute with Bob's operators. We show that perfect strategies in this model correspond to possibly infinite-dimensional operator solutions of the non-commutative equations. The proof is based around a finitely presented group associated with the linear system which arises from the non-commutative equations.

Modelling and Predicting Backstroke Start Performance Using Non-Linear and Linear Models.

PubMed

de Jesus, Karla; Ayala, Helon V H; de Jesus, Kelly; Coelho, Leandro Dos S; Medeiros, Alexandre I A; Abraldes, José A; Vaz, Mário A P; Fernandes, Ricardo J; Vilas-Boas, João Paulo

2018-03-01

Our aim was to compare non-linear and linear mathematical model responses for backstroke start performance prediction. Ten swimmers randomly completed eight 15 m backstroke starts with feet over the wedge, four with hands on the highest horizontal and four on the vertical handgrip. Swimmers were videotaped using a dual media camera set-up, with the starts being performed over an instrumented block with four force plates. Artificial neural networks were applied to predict 5 m start time using kinematic and kinetic variables and to determine the accuracy of the mean absolute percentage error. Artificial neural networks predicted start time more robustly than the linear model with respect to changing training to the validation dataset for the vertical handgrip (3.95 ± 1.67 vs. 5.92 ± 3.27%). Artificial neural networks obtained a smaller mean absolute percentage error than the linear model in the horizontal (0.43 ± 0.19 vs. 0.98 ± 0.19%) and vertical handgrip (0.45 ± 0.19 vs. 1.38 ± 0.30%) using all input data. The best artificial neural network validation revealed a smaller mean absolute error than the linear model for the horizontal (0.007 vs. 0.04 s) and vertical handgrip (0.01 vs. 0.03 s). Artificial neural networks should be used for backstroke 5 m start time prediction due to the quite small differences among the elite level performances.

Scoring and staging systems using cox linear regression modeling and recursive partitioning.

PubMed

Lee, J W; Um, S H; Lee, J B; Mun, J; Cho, H

2006-01-01

Scoring and staging systems are used to determine the order and class of data according to predictors. Systems used for medical data, such as the Child-Turcotte-Pugh scoring and staging systems for ordering and classifying patients with liver disease, are often derived strictly from physicians' experience and intuition. We construct objective and data-based scoring/staging systems using statistical methods. We consider Cox linear regression modeling and recursive partitioning techniques for censored survival data. In particular, to obtain a target number of stages we propose cross-validation and amalgamation algorithms. We also propose an algorithm for constructing scoring and staging systems by integrating local Cox linear regression models into recursive partitioning, so that we can retain the merits of both methods such as superior predictive accuracy, ease of use, and detection of interactions between predictors. The staging system construction algorithms are compared by cross-validation evaluation of real data. The data-based cross-validation comparison shows that Cox linear regression modeling is somewhat better than recursive partitioning when there are only continuous predictors, while recursive partitioning is better when there are significant categorical predictors. The proposed local Cox linear recursive partitioning has better predictive accuracy than Cox linear modeling and simple recursive partitioning. This study indicates that integrating local linear modeling into recursive partitioning can significantly improve prediction accuracy in constructing scoring and staging systems.

Action Centered Contextual Bandits.

PubMed

Greenewald, Kristjan; Tewari, Ambuj; Klasnja, Predrag; Murphy, Susan

2017-12-01

Contextual bandits have become popular as they offer a middle ground between very simple approaches based on multi-armed bandits and very complex approaches using the full power of reinforcement learning. They have demonstrated success in web applications and have a rich body of associated theoretical guarantees. Linear models are well understood theoretically and preferred by practitioners because they are not only easily interpretable but also simple to implement and debug. Furthermore, if the linear model is true, we get very strong performance guarantees. Unfortunately, in emerging applications in mobile health, the time-invariant linear model assumption is untenable. We provide an extension of the linear model for contextual bandits that has two parts: baseline reward and treatment effect. We allow the former to be complex but keep the latter simple. We argue that this model is plausible for mobile health applications. At the same time, it leads to algorithms with strong performance guarantees as in the linear model setting, while still allowing for complex nonlinear baseline modeling. Our theory is supported by experiments on data gathered in a recently concluded mobile health study.

Non-Linear Relationship between Economic Growth and CO2 Emissions in China: An Empirical Study Based on Panel Smooth Transition Regression Models

PubMed Central

Wang, Zheng-Xin; Hao, Peng; Yao, Pei-Yi

2017-01-01

The non-linear relationship between provincial economic growth and carbon emissions is investigated by using panel smooth transition regression (PSTR) models. The research indicates that, on the condition of separately taking Gross Domestic Product per capita (GDPpc), energy structure (Es), and urbanisation level (Ul) as transition variables, three models all reject the null hypothesis of a linear relationship, i.e., a non-linear relationship exists. The results show that the three models all contain only one transition function but different numbers of location parameters. The model taking GDPpc as the transition variable has two location parameters, while the other two models separately considering Es and Ul as the transition variables both contain one location parameter. The three models applied in the study all favourably describe the non-linear relationship between economic growth and CO2 emissions in China. It also can be seen that the conversion rate of the influence of Ul on per capita CO2 emissions is significantly higher than those of GDPpc and Es on per capita CO2 emissions. PMID:29236083

Accuracy assessment of the linear Poisson-Boltzmann equation and reparametrization of the OBC generalized Born model for nucleic acids and nucleic acid-protein complexes.

PubMed

Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

2015-04-05

The generalized Born model in the Onufriev, Bashford, and Case (Onufriev et al., Proteins: Struct Funct Genet 2004, 55, 383) implementation has emerged as one of the best compromises between accuracy and speed of computation. For simulations of nucleic acids, however, a number of issues should be addressed: (1) the generalized Born model is based on a linear model and the linearization of the reference Poisson-Boltmann equation may be questioned for highly charged systems as nucleic acids; (2) although much attention has been given to potentials, solvation forces could be much less sensitive to linearization than the potentials; and (3) the accuracy of the Onufriev-Bashford-Case (OBC) model for nucleic acids depends on fine tuning of parameters. Here, we show that the linearization of the Poisson Boltzmann equation has mild effects on computed forces, and that with optimal choice of the OBC model parameters, solvation forces, essential for molecular dynamics simulations, agree well with those computed using the reference Poisson-Boltzmann model. © 2015 Wiley Periodicals, Inc.

Non-Linear Relationship between Economic Growth and CO₂ Emissions in China: An Empirical Study Based on Panel Smooth Transition Regression Models.

PubMed

Wang, Zheng-Xin; Hao, Peng; Yao, Pei-Yi

2017-12-13

The non-linear relationship between provincial economic growth and carbon emissions is investigated by using panel smooth transition regression (PSTR) models. The research indicates that, on the condition of separately taking Gross Domestic Product per capita (GDPpc), energy structure (Es), and urbanisation level (Ul) as transition variables, three models all reject the null hypothesis of a linear relationship, i.e., a non-linear relationship exists. The results show that the three models all contain only one transition function but different numbers of location parameters. The model taking GDPpc as the transition variable has two location parameters, while the other two models separately considering Es and Ul as the transition variables both contain one location parameter. The three models applied in the study all favourably describe the non-linear relationship between economic growth and CO₂ emissions in China. It also can be seen that the conversion rate of the influence of Ul on per capita CO₂ emissions is significantly higher than those of GDPpc and Es on per capita CO₂ emissions.

A General Accelerated Degradation Model Based on the Wiener Process.

PubMed

Liu, Le; Li, Xiaoyang; Sun, Fuqiang; Wang, Ning

2016-12-06

Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses.

A General Accelerated Degradation Model Based on the Wiener Process

PubMed Central

Liu, Le; Li, Xiaoyang; Sun, Fuqiang; Wang, Ning

2016-01-01

Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses. PMID:28774107

Aircraft Airframe Cost Estimation Using a Random Coefficients Model

DTIC Science & Technology

1979-12-01

approach will also be used here. 2 Model Formulation Several different types of equations could be used for the basic form of the CER, such as linear ...5) Marcotte developed several CER’s for fighter aircraft airframes using the log- linear model . A plot of the residuals from the CER for recurring...of the natural logarithm. Ordinary Least Squares The ordinary least squares procedure starts with the equation for the general linear model . The

Comparison of linear and nonlinear implementation of the compartmental tissue uptake model for dynamic contrast-enhanced MRI.

PubMed

Kallehauge, Jesper F; Sourbron, Steven; Irving, Benjamin; Tanderup, Kari; Schnabel, Julia A; Chappell, Michael A

2017-06-01

Fitting tracer kinetic models using linear methods is much faster than using their nonlinear counterparts, although this comes often at the expense of reduced accuracy and precision. The aim of this study was to derive and compare the performance of the linear compartmental tissue uptake (CTU) model with its nonlinear version with respect to their percentage error and precision. The linear and nonlinear CTU models were initially compared using simulations with varying noise and temporal sampling. Subsequently, the clinical applicability of the linear model was demonstrated on 14 patients with locally advanced cervical cancer examined with dynamic contrast-enhanced magnetic resonance imaging. Simulations revealed equal percentage error and precision when noise was within clinical achievable ranges (contrast-to-noise ratio >10). The linear method was significantly faster than the nonlinear method, with a minimum speedup of around 230 across all tested sampling rates. Clinical analysis revealed that parameters estimated using the linear and nonlinear CTU model were highly correlated (ρ ≥ 0.95). The linear CTU model is computationally more efficient and more stable against temporal downsampling, whereas the nonlinear method is more robust to variations in noise. The two methods may be used interchangeably within clinical achievable ranges of temporal sampling and noise. Magn Reson Med 77:2414-2423, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Modeling of salt and pH gradient elution in ion-exchange chromatography.

PubMed

Schmidt, Michael; Hafner, Mathias; Frech, Christian

2014-01-01

The separation of proteins by internally and externally generated pH gradients in chromatofocusing on ion-exchange columns is a well-established analytical method with a large number of applications. In this work, a stoichiometric displacement model was used to describe the retention behavior of lysozyme on SP Sepharose FF and a monoclonal antibody on Fractogel SO3 (S) in linear salt and pH gradient elution. The pH dependence of the binding charge B in the linear gradient elution model is introduced using a protein net charge model, while the pH dependence of the equilibrium constant is based on a thermodynamic approach. The model parameter and pH dependences are calculated from linear salt gradient elutions at different pH values as well as from linear pH gradient elutions at different fixed salt concentrations. The application of the model for the well-characterized protein lysozyme resulted in almost identical model parameters based on either linear salt or pH gradient elution data. For the antibody, only the approach based on linear pH gradients is feasible because of the limited pH range useful for salt gradient elution. The application of the model for the separation of an acid variant of the antibody from the major monomeric form is discussed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimation of the standardized ileal digestible valine to lysine ratio required for 25- to 120-kilogram pigs fed low crude protein diets supplemented with crystalline amino acids.

PubMed

Liu, X T; Ma, W F; Zeng, X F; Xie, C Y; Thacker, P A; Htoo, J K; Qiao, S Y

2015-10-01

Four 28-d experiments were conducted to determine the standardized ileal digestible (SID) valine (Val) to lysine (Lys) ratio required for 26- to 46- (Exp. 1), 49- to 70- (Exp. 2), 71- to 92- (Exp. 3), and 94- to 119-kg (Exp. 4) pigs fed low CP diets supplemented with crystalline AA. The first 3 experiments utilized 150 pigs (Duroc × Landrace × Large White), while Exp. 4 utilized 90 finishing pigs. Pigs in all 4 experiments were randomly allocated to 1 of 5 diets with 6 pens per treatment (3 pens of barrows and 3 pens of gilts) and 5 pigs per pen for the first 3 experiments and 3 pigs per pen for Exp. 4. Diets for all experiments were formulated to contain SID Val to Lys ratios of 0.55, 0.60, 0.65, 0.70, or 0.75. In Exp. 1 (26 to 46 kg), ADG increased (linear, = 0.039; quadratic, = 0.042) with an increasing dietary Val:Lys ratio. The SID Val:Lys ratio to maximize ADG was 0.62 using a linear broken-line model and 0.71 using a quadratic model. In Exp. 2 (49 to 70 kg), ADG increased (linear, = 0.021; quadratic, = 0.042) as the SID Val:Lys ratio increased. G:F improved (linear, = 0.039) and serum urea nitrogen (SUN) decreased (linear, = 0.021; quadratic, = 0.024) with an increased SID Val:Lys ratio. The SID Val:Lys ratios to maximize ADG as well as to minimize SUN levels were 0.67 and 0.65, respectively, using a linear broken-line model and 0.72 and 0.71, respectively, using a quadratic model. In Exp. 3 (71 to 92 kg), ADG increased (linear, = 0.007; quadratic, = 0.022) and SUN decreased (linear, = 0.011; quadratic, = 0.034) as the dietary SID Val:Lys ratio increased. The SID Val:Lys ratios to maximize ADG as well as to minimize SUN levels were 0.67 and 0.67, respectively, using a linear broken-line model and 0.72 and 0.74, respectively, using a quadratic model. In Exp. 4 (94 to 119 kg), ADG increased (linear, = 0.041) and G:F was improved (linear, = 0.004; quadratic, = 0.005) as the dietary SID Val:Lys ratio increased. The SID Val:Lys ratio to maximize G:F was 0.68 using a linear broken-line model and 0.72 using a quadratic model. Carcass traits and muscle quality were not influenced by SID Val:Lys ratio. In conclusion, the dietary SID Val:Lys ratios required for 26- to 46-, 49- to 70-, 71- to 92-, and 94- to 119-kg pigs were estimated to be 0.62, 0.66, 0.67, and 0.68, respectively, using a linear broken-line model and 0.71, 0.72, 0.73, and 0.72, respectively, using a quadratic model.

The Fermi-Pasta-Ulam Problem and Its Underlying Integrable Dynamics: An Approach Through Lyapunov Exponents

NASA Astrophysics Data System (ADS)

Benettin, G.; Pasquali, S.; Ponno, A.

2018-05-01

FPU models, in dimension one, are perturbations either of the linear model or of the Toda model; perturbations of the linear model include the usual β -model, perturbations of Toda include the usual α +β model. In this paper we explore and compare two families, or hierarchies, of FPU models, closer and closer to either the linear or the Toda model, by computing numerically, for each model, the maximal Lyapunov exponent χ . More precisely, we consider statistically typical trajectories and study the asymptotics of χ for large N (the number of particles) and small ɛ (the specific energy E / N), and find, for all models, asymptotic power laws χ ˜eq Cɛ ^a, C and a depending on the model. The asymptotics turns out to be, in general, rather slow, and producing accurate results requires a great computational effort. We also revisit and extend the analytic computation of χ introduced by Casetti, Livi and Pettini, originally formulated for the β -model. With great evidence the theory extends successfully to all models of the linear hierarchy, but not to models close to Toda.

Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

PubMed Central

2011-01-01

Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task. PMID:21867520

Protein linear indices of the 'macromolecular pseudograph alpha-carbon atom adjacency matrix' in bioinformatics. Part 1: prediction of protein stability effects of a complete set of alanine substitutions in Arc repressor.

PubMed

Marrero-Ponce, Yovani; Medina-Marrero, Ricardo; Castillo-Garit, Juan A; Romero-Zaldivar, Vicente; Torrens, Francisco; Castro, Eduardo A

2005-04-15

A novel approach to bio-macromolecular design from a linear algebra point of view is introduced. A protein's total (whole protein) and local (one or more amino acid) linear indices are a new set of bio-macromolecular descriptors of relevance to protein QSAR/QSPR studies. These amino-acid level biochemical descriptors are based on the calculation of linear maps on Rn[f k(xmi):Rn-->Rn] in canonical basis. These bio-macromolecular indices are calculated from the kth power of the macromolecular pseudograph alpha-carbon atom adjacency matrix. Total linear indices are linear functional on Rn. That is, the kth total linear indices are linear maps from Rn to the scalar R[f k(xm):Rn-->R]. Thus, the kth total linear indices are calculated by summing the amino-acid linear indices of all amino acids in the protein molecule. A study of the protein stability effects for a complete set of alanine substitutions in the Arc repressor illustrates this approach. A quantitative model that discriminates near wild-type stability alanine mutants from the reduced-stability ones in a training series was obtained. This model permitted the correct classification of 97.56% (40/41) and 91.67% (11/12) of proteins in the training and test set, respectively. It shows a high Matthews correlation coefficient (MCC=0.952) for the training set and an MCC=0.837 for the external prediction set. Additionally, canonical regression analysis corroborated the statistical quality of the classification model (Rcanc=0.824). This analysis was also used to compute biological stability canonical scores for each Arc alanine mutant. On the other hand, the linear piecewise regression model compared favorably with respect to the linear regression one on predicting the melting temperature (tm) of the Arc alanine mutants. The linear model explains almost 81% of the variance of the experimental tm (R=0.90 and s=4.29) and the LOO press statistics evidenced its predictive ability (q2=0.72 and scv=4.79). Moreover, the TOMOCOMD-CAMPS method produced a linear piecewise regression (R=0.97) between protein backbone descriptors and tm values for alanine mutants of the Arc repressor. A break-point value of 51.87 degrees C characterized two mutant clusters and coincided perfectly with the experimental scale. For this reason, we can use the linear discriminant analysis and piecewise models in combination to classify and predict the stability of the mutant Arc homodimers. These models also permitted the interpretation of the driving forces of such folding process, indicating that topologic/topographic protein backbone interactions control the stability profile of wild-type Arc and its alanine mutants.

Pseudo second order kinetics and pseudo isotherms for malachite green onto activated carbon: comparison of linear and non-linear regression methods.

PubMed

Kumar, K Vasanth; Sivanesan, S

2006-08-25

Pseudo second order kinetic expressions of Ho, Sobkowsk and Czerwinski, Blanachard et al. and Ritchie were fitted to the experimental kinetic data of malachite green onto activated carbon by non-linear and linear method. Non-linear method was found to be a better way of obtaining the parameters involved in the second order rate kinetic expressions. Both linear and non-linear regression showed that the Sobkowsk and Czerwinski and Ritchie's pseudo second order model were the same. Non-linear regression analysis showed that both Blanachard et al. and Ho have similar ideas on the pseudo second order model but with different assumptions. The best fit of experimental data in Ho's pseudo second order expression by linear and non-linear regression method showed that Ho pseudo second order model was a better kinetic expression when compared to other pseudo second order kinetic expressions. The amount of dye adsorbed at equilibrium, q(e), was predicted from Ho pseudo second order expression and were fitted to the Langmuir, Freundlich and Redlich Peterson expressions by both linear and non-linear method to obtain the pseudo isotherms. The best fitting pseudo isotherm was found to be the Langmuir and Redlich Peterson isotherm. Redlich Peterson is a special case of Langmuir when the constant g equals unity.

A simple method for identifying parameter correlations in partially observed linear dynamic models.

PubMed

Li, Pu; Vu, Quoc Dong

2015-12-14

Parameter estimation represents one of the most significant challenges in systems biology. This is because biological models commonly contain a large number of parameters among which there may be functional interrelationships, thus leading to the problem of non-identifiability. Although identifiability analysis has been extensively studied by analytical as well as numerical approaches, systematic methods for remedying practically non-identifiable models have rarely been investigated. We propose a simple method for identifying pairwise correlations and higher order interrelationships of parameters in partially observed linear dynamic models. This is made by derivation of the output sensitivity matrix and analysis of the linear dependencies of its columns. Consequently, analytical relations between the identifiability of the model parameters and the initial conditions as well as the input functions can be achieved. In the case of structural non-identifiability, identifiable combinations can be obtained by solving the resulting homogenous linear equations. In the case of practical non-identifiability, experiment conditions (i.e. initial condition and constant control signals) can be provided which are necessary for remedying the non-identifiability and unique parameter estimation. It is noted that the approach does not consider noisy data. In this way, the practical non-identifiability issue, which is popular for linear biological models, can be remedied. Several linear compartment models including an insulin receptor dynamics model are taken to illustrate the application of the proposed approach. Both structural and practical identifiability of partially observed linear dynamic models can be clarified by the proposed method. The result of this method provides important information for experimental design to remedy the practical non-identifiability if applicable. The derivation of the method is straightforward and thus the algorithm can be easily implemented into a software packet.

Nonlinear time series modeling and forecasting the seismic data of the Hindu Kush region

NASA Astrophysics Data System (ADS)

Khan, Muhammad Yousaf; Mittnik, Stefan

2018-01-01

In this study, we extended the application of linear and nonlinear time models in the field of earthquake seismology and examined the out-of-sample forecast accuracy of linear Autoregressive (AR), Autoregressive Conditional Duration (ACD), Self-Exciting Threshold Autoregressive (SETAR), Threshold Autoregressive (TAR), Logistic Smooth Transition Autoregressive (LSTAR), Additive Autoregressive (AAR), and Artificial Neural Network (ANN) models for seismic data of the Hindu Kush region. We also extended the previous studies by using Vector Autoregressive (VAR) and Threshold Vector Autoregressive (TVAR) models and compared their forecasting accuracy with linear AR model. Unlike previous studies that typically consider the threshold model specifications by using internal threshold variable, we specified these models with external transition variables and compared their out-of-sample forecasting performance with the linear benchmark AR model. The modeling results show that time series models used in the present study are capable of capturing the dynamic structure present in the seismic data. The point forecast results indicate that the AR model generally outperforms the nonlinear models. However, in some cases, threshold models with external threshold variables specification produce more accurate forecasts, indicating that specification of threshold time series models is of crucial importance. For raw seismic data, the ACD model does not show an improved out-of-sample forecasting performance over the linear AR model. The results indicate that the AR model is the best forecasting device to model and forecast the raw seismic data of the Hindu Kush region.

Evaluation of linearly solvable Markov decision process with dynamic model learning in a mobile robot navigation task.

PubMed

Kinjo, Ken; Uchibe, Eiji; Doya, Kenji

2013-01-01

Linearly solvable Markov Decision Process (LMDP) is a class of optimal control problem in which the Bellman's equation can be converted into a linear equation by an exponential transformation of the state value function (Todorov, 2009b). In an LMDP, the optimal value function and the corresponding control policy are obtained by solving an eigenvalue problem in a discrete state space or an eigenfunction problem in a continuous state using the knowledge of the system dynamics and the action, state, and terminal cost functions. In this study, we evaluate the effectiveness of the LMDP framework in real robot control, in which the dynamics of the body and the environment have to be learned from experience. We first perform a simulation study of a pole swing-up task to evaluate the effect of the accuracy of the learned dynamics model on the derived the action policy. The result shows that a crude linear approximation of the non-linear dynamics can still allow solution of the task, despite with a higher total cost. We then perform real robot experiments of a battery-catching task using our Spring Dog mobile robot platform. The state is given by the position and the size of a battery in its camera view and two neck joint angles. The action is the velocities of two wheels, while the neck joints were controlled by a visual servo controller. We test linear and bilinear dynamic models in tasks with quadratic and Guassian state cost functions. In the quadratic cost task, the LMDP controller derived from a learned linear dynamics model performed equivalently with the optimal linear quadratic regulator (LQR). In the non-quadratic task, the LMDP controller with a linear dynamics model showed the best performance. The results demonstrate the usefulness of the LMDP framework in real robot control even when simple linear models are used for dynamics learning.

Linear and Nonlinear Thinking: A Multidimensional Model and Measure

ERIC Educational Resources Information Center

Groves, Kevin S.; Vance, Charles M.

2015-01-01

Building upon previously developed and more general dual-process models, this paper provides empirical support for a multidimensional thinking style construct comprised of linear thinking and multiple dimensions of nonlinear thinking. A self-report assessment instrument (Linear/Nonlinear Thinking Style Profile; LNTSP) is presented and…

Women's Endorsement of Models of Sexual Response: Correlates and Predictors.

PubMed

Nowosielski, Krzysztof; Wróbel, Beata; Kowalczyk, Robert

2016-02-01

Few studies have investigated endorsement of female sexual response models, and no single model has been accepted as a normative description of women's sexual response. The aim of the study was to establish how women from a population-based sample endorse current theoretical models of the female sexual response--the linear models and circular model (partial and composite Basson models)--as well as predictors of endorsement. Accordingly, 174 heterosexual women aged 18-55 years were included in a cross-sectional study: 74 women diagnosed with female sexual dysfunction (FSD) based on DSM-5 criteria and 100 non-dysfunctional women. The description of sexual response models was used to divide subjects into four subgroups: linear (Masters-Johnson and Kaplan models), circular (partial Basson model), mixed (linear and circular models in similar proportions, reflective of the composite Basson model), and a different model. Women were asked to choose which of the models best described their pattern of sexual response and how frequently they engaged in each model. Results showed that 28.7% of women endorsed the linear models, 19.5% the partial Basson model, 40.8% the composite Basson model, and 10.9% a different model. Women with FSD endorsed the partial Basson model and a different model more frequently than did non-dysfunctional controls. Individuals who were dissatisfied with a partner as a lover were more likely to endorse a different model. Based on the results, we concluded that the majority of women endorsed a mixed model combining the circular response with the possibility of an innate desire triggering a linear response. Further, relationship difficulties, not FSD, predicted model endorsement.

A numerical study of linear and nonlinear kinematic models in fish swimming with the DSD/SST method

NASA Astrophysics Data System (ADS)

Tian, Fang-Bao

2015-03-01

Flow over two fish (modeled by two flexible plates) in tandem arrangement is investigated by solving the incompressible Navier-Stokes equations numerically with the DSD/SST method to understand the differences between the geometrically linear and nonlinear models. In the simulation, the motions of the plates are reconstructed from a vertically flowing soap film tunnel experiment with linear and nonlinear kinematic models. Based on the simulations, the drag, lift, power consumption, vorticity and pressure fields are discussed in detail. It is found that the linear and nonlinear models are able to reasonably predict the forces and power consumption of a single plate in flow. Moreover, if multiple plates are considered, these two models yield totally different results, which implies that the nonlinear model should be used. The results presented in this work provide a guideline for future studies in fish swimming.

The non-linear response of a muscle in transverse compression: assessment of geometry influence using a finite element model.

PubMed

Gras, Laure-Lise; Mitton, David; Crevier-Denoix, Nathalie; Laporte, Sébastien

2012-01-01

Most recent finite element models that represent muscles are generic or subject-specific models that use complex, constitutive laws. Identification of the parameters of such complex, constitutive laws could be an important limit for subject-specific approaches. The aim of this study was to assess the possibility of modelling muscle behaviour in compression with a parametric model and a simple, constitutive law. A quasi-static compression test was performed on the muscles of dogs. A parametric finite element model was designed using a linear, elastic, constitutive law. A multi-variate analysis was performed to assess the effects of geometry on muscle response. An inverse method was used to define Young's modulus. The non-linear response of the muscles was obtained using a subject-specific geometry and a linear elastic law. Thus, a simple muscle model can be used to have a bio-faithful, biomechanical response.

Informativeness of Wind Data in Linear Madden-Julian Oscillation Prediction

DTIC Science & Technology

2016-08-15

Linear inverse models (LIMs) are used to explore predictability and information content of the Madden–Julian Oscillation (MJO). Hindcast skill for...mostly at the largest scales, adds 1–2 days of skill. Keywords: linear inverse modeling; Madden–Julian Oscillation; sub-seasonal prediction 1...tion that may reflect on the MJO’s incompletely under- stood dynamics. Cavanaugh et al. (2014, hereafter C14) explored the skill of linear inverse

Optimization of isotherm models for pesticide sorption on biopolymer-nanoclay composite by error analysis.

PubMed

Narayanan, Neethu; Gupta, Suman; Gajbhiye, V T; Manjaiah, K M

2017-04-01

A carboxy methyl cellulose-nano organoclay (nano montmorillonite modified with 35-45 wt % dimethyl dialkyl (C 14 -C 18 ) amine (DMDA)) composite was prepared by solution intercalation method. The prepared composite was characterized by infrared spectroscopy (FTIR), X-Ray diffraction spectroscopy (XRD) and scanning electron microscopy (SEM). The composite was utilized for its pesticide sorption efficiency for atrazine, imidacloprid and thiamethoxam. The sorption data was fitted into Langmuir and Freundlich isotherms using linear and non linear methods. The linear regression method suggested best fitting of sorption data into Type II Langmuir and Freundlich isotherms. In order to avoid the bias resulting from linearization, seven different error parameters were also analyzed by non linear regression method. The non linear error analysis suggested that the sorption data fitted well into Langmuir model rather than in Freundlich model. The maximum sorption capacity, Q 0 (μg/g) was given by imidacloprid (2000) followed by thiamethoxam (1667) and atrazine (1429). The study suggests that the degree of determination of linear regression alone cannot be used for comparing the best fitting of Langmuir and Freundlich models and non-linear error analysis needs to be done to avoid inaccurate results. Copyright © 2017 Elsevier Ltd. All rights reserved.