Missing Data Treatments at the Second Level of Hierarchical Linear Models

ERIC Educational Resources Information Center

St. Clair, Suzanne W.

2011-01-01

The current study evaluated the performance of traditional versus modern MDTs in the estimation of fixed-effects and variance components for data missing at the second level of an hierarchical linear model (HLM) model across 24 different study conditions. Variables manipulated in the analysis included, (a) number of Level-2 variables with missing…

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…

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.

A Comprehensive Meta-Analysis of Triple P-Positive Parenting Program Using Hierarchical Linear Modeling: Effectiveness and Moderating Variables

ERIC Educational Resources Information Center

Nowak, Christoph; Heinrichs, Nina

2008-01-01

A meta-analysis encompassing all studies evaluating the impact of the Triple P-Positive Parenting Program on parent and child outcome measures was conducted in an effort to identify variables that moderate the program's effectiveness. Hierarchical linear models (HLM) with three levels of data were employed to analyze effect sizes. The results (N =…

Seeking Effectiveness and Equity in a Large College Chemistry Course: An HLM Investigation of Peer-Led Guided Inquiry

ERIC Educational Resources Information Center

Lewis, Scott E.; Lewis, Jennifer E.

2008-01-01

This study employed hierarchical linear models (HLM) to investigate Peer-Led Guided Inquiry (PLGI), a teaching practice combining cooperative learning and inquiry and tailored for a large class. Ultimately, the study provided an example of the effective introduction of a reform pedagogical approach in a large class setting. In the narrative, the…

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.

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.

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

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…

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…

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…

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

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…

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…

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.

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.

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

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

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.

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.

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

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

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.

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

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.

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

Measuring Teacher Effectiveness through Hierarchical Linear Models: Exploring Predictors of Student Achievement and Truancy

ERIC Educational Resources Information Center

Subedi, Bidya Raj; Reese, Nancy; Powell, Randy

2015-01-01

This study explored significant predictors of student's Grade Point Average (GPA) and truancy (days absent), and also determined teacher effectiveness based on proportion of variance explained at teacher level model. We employed a two-level hierarchical linear model (HLM) with student and teacher data at level-1 and level-2 models, respectively.…

Scale of association: hierarchical linear models and the measurement of ecological systems

Treesearch

Sean M. McMahon; Jeffrey M. Diez

2007-01-01

A fundamental challenge to understanding patterns in ecological systems lies in employing methods that can analyse, test and draw inference from measured associations between variables across scales. Hierarchical linear models (HLM) use advanced estimation algorithms to measure regression relationships and variance-covariance parameters in hierarchically structured...

Unpacking the Inequality among Turkish Schools: Findings from PISA 2006

ERIC Educational Resources Information Center

Alacaci, Cengiz; Erbas, Ayhan Kursat

2010-01-01

The study investigates the effects of certain school characteristics on students' mathematics performances in Turkey in the PISA 2006 while controlling for family background and demographic characteristics. Three models of Hierarchical Linear Modeling (HLM) are constructed. The results reveal that 55% of the variance is attributable to…

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.

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

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)

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.

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…

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.

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.

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.

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.

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…

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.

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

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…

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

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.

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,…

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…

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.

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.

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.

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

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…

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,…

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…

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…

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.

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…

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'…

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.

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

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.…

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.

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.

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…

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…

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

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.

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,…

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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

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)

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)

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

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.

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

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.

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.

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

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.

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

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.

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.

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

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)

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

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.

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.

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.

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)

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

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.

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.

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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…

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.

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.

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

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.

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.

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

[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.

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.

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.

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.

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.

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

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

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

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

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.

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

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.

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

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

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.

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

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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).

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.

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.

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

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.

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.

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

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

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

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.

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).

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.

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.

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.

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

High-throughput, 384-well, LC-MS/MS CYP inhibition assay using automation, cassette-analysis technique, and streamlined data analysis.

PubMed

Halladay, Jason S; Delarosa, Erlie Marie; Tran, Daniel; Wang, Leslie; Wong, Susan; Khojasteh, S Cyrus

2011-08-01

Here we describe a high capacity and high-throughput, automated, 384-well CYP inhibition assay using well-known HLM-based MS probes. We provide consistently robust IC(50) values at the lead optimization stage of the drug discovery process. Our method uses the Agilent Technologies/Velocity11 BioCel 1200 system, timesaving techniques for sample analysis, and streamlined data processing steps. For each experiment, we generate IC(50) values for up to 344 compounds and positive controls for five major CYP isoforms (probe substrate): CYP1A2 (phenacetin), CYP2C9 ((S)-warfarin), CYP2C19 ((S)-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4/5 (testosterone and midazolam). Each compound is incubated separately at four concentrations with each CYP probe substrate under the optimized incubation condition. Each incubation is quenched with acetonitrile containing the deuterated internal standard of the respective metabolite for each probe substrate. To minimize the number of samples to be analyzed by LC-MS/MS and reduce the amount of valuable MS runtime, we utilize timesaving techniques of cassette analysis (pooling the incubation samples at the end of each CYP probe incubation into one) and column switching (reducing the amount of MS runtime). Here we also report on the comparison of IC(50) results for five major CYP isoforms using our method compared to values reported in the literature.

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.

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.

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.

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

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.

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.

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.

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.

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).

Association of Inflammatory and Non-Inflammatory Breast Cancer with Socioeconomic Characteristics in the Surveillance, Epidemiology, and End Results Database, 2000–2007

PubMed Central

Schlichting, Jennifer A.; Soliman, Amr S.; Schairer, Catherine; Banerjee, Mousumi; Rozek, Laura S.; Schottenfeld, David; Harford, Joe B.; Merajver, Sofia D.

2011-01-01

Background Inflammatory breast cancer (IBC) is a rare and highly aggressive form of primary breast cancer. Little is known regarding risk factors for IBC, specifically the association with socioeconomic position (SEP). Methods The association between breast cancer type (IBC vs. non-IBC) with county-level SEP in the Surveillance, Epidemiology, and End Results database for cases diagnosed from 2000–2007 was examined. County-level SEP characteristics included metropolitan vs. non- metropolitan residence, percent below the poverty level, percent less than high school graduate,and an index combining the poverty and high school variables. IBC and non-IBC age-adjusted incidence rates (IRs) were calculated, stratified on SEP and race/ethnicity. The odds of IBC vs. non-IBC given a particular SEP characteristic, adjusting for age and race/ethnicity, was examined through fitting of hierarchical logistic regression models (HLMs). Results IRs for IBC generally increased as SEP decreased, while the opposite was found for non-IBC. HLM results showed low SEP is associated with higher odds of IBC: Highest (≥ 20%) vs. lowest (<10%) persons below the poverty level Odds Ratio (95% Confidence Interval) = 1.25 (1.09–1.43); Highest (>28.76%) vs. lowest (≤15.99%) persons less than high school graduate = 1.25 (1.10–1.42); Low SEP as measured by poverty-high school index vs. high SEP = 1.26 (1.11–1.44). Conclusion Overall breast cancer has been found to be positively associated with SEP, whereas in this analysis IBC was associated with decreasing SEP. Impact Studies focused on understanding the disparity in IBC incidence, as well as interventions to eliminate these differences are needed. PMID:22028401

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

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

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.

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.

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).

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).

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

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.

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.

Cluster randomized trial in smoking cessation with intensive advice in diabetic patients in primary care. ITADI Study

PubMed Central

2010-01-01

Background It is a priority to achieve smoking cessation in diabetic smokers, given that this is a group of patients with elevated cardiovascular risk. Furthermore, tobacco has a multiplying effect on micro and macro vascular complications. Smoking abstinence rates increase as the intensity of the intervention, length of the intervention and number and diversity of contacts with the healthcare professional during the intervention increases. However, there are few published studies about smoking cessation in diabetics in primary care, a level of healthcare that plays an essential role in these patients. Therefore, the aim of the present study is to evaluate the effectiveness of an intensive smoking cessation intervention in diabetic patients in primary care. Methods/Design Cluster randomized trial, controlled and multicentric. Randomization unit: Primary Care Team. Study population: 546 diabetic smokers older than 14 years of age whose disease is controlled by one of the primary care teams in the study. Outcome Measures: Continuous tobacco abstinence (a person who has not smoked for at least six months and with a CO level of less than 6 ppm measured by a cooximeter) , evolution in the Prochaska and DiClemente's Transtheoretical Model of Change, number of cigarettes/day, length of the visit. Point of assessment: one- year post- inclusion in the study. Intervention: Brief motivational interview for diabetic smokers at the pre-contemplation and contemplation stage, intensive motivational interview with pharmacotherapy for diabetic smokers in the preparation-action stage and reinforcing intevention in the maintenance stage. Statistical Analysis: A descriptive analysis of all variables will be done, as well as a multilevel logistic regression and a Poisson regression. All analyses will be done with an intention to treatment basis and will be fitted for potential confounding factors and variables of clinical importance. Statistical packages: SPSS15, STATA10 y HLM6. Discussion The present study will try to describe the profile of a diabetic smoker who receives the most benefit from an intensive intervention in primary care. The results will be useful for primary care professionals in their usual clinical practice. Trial Registration Clinical Trials.gov Identifier: NCT00954967 PMID:20132540

Correlates of sedentary time in children: a multilevel modelling approach.

PubMed

Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Santos, Daniel; Pereira, Sara; Chaves, Raquel; Katzmarzyk, Peter Todd; Maia, José

2014-08-30

Sedentary behaviour (SB) has been implicated as a potential risk factor for chronic disease. Since children spend most of their awake time in schools, this study aimed to identify individual- and school-level correlates of sedentary time using a multilevel approach, and to determine if these correlates have a similar effect in normal weight (NW) and overweight/obese (O/O) children. Sample comprised 686 Portuguese children aged 9-10 years from 23 schools that took part in the ISCOLE project. Actigraph GT3X + accelerometers were used 24 hours/day for 7 days to assess sedentary time (daily minutes <100 counts/min); BMI was computed and WHO cut-points were used to classify subjects as NW or O/O. Sex, BMI, number of siblings, family income, computer use on school days, and sleep time on school days were used as individual-level correlates. At the school level, school size (number of students), percentage of students involved in sports or physical activity (PA) clubs, school promotion of active transportation, and students' access to equipment outside school hours were used. All multilevel modelling analysis was done in SPSS, WINPEPI, and HLM. School-level correlates explain ≈ 6.0% of the total variance in sedentary time. Results (β ± SE) showed that boys (-30.85 ± 5.23), children with more siblings (-8.56 ± 2.71) and those who sleep more (-17.78 ± 3.06) were less sedentary, while children with higher family income were more sedentary (4.32 ± 1.68). At the school level, no variable was significantly correlated with sedentary time. Among weight groups, variables related to sedentary time in NW were sex, sleep time and family income, while in O/O sex, number of siblings and sleep time were significant correlates. No school-level predictors were significantly associated in either of the weight groups. Notwithstanding the relevance of the school environment in the reduction of children's sedentary time, individual and family characteristics played a more relevant role than the school context in this study.

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.

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

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.

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.

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.

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.

Gender Differences in Introductory University Physics Performance: The Influence of High School Physics Preparation and Affect

NASA Astrophysics Data System (ADS)

Hazari, Zahra

2006-12-01

The attrition of females studying physics after high school has been a continuing concern for the physics education community. If females are well prepared, feel confident, and do well in introductory college physics, they may be inclined to study physics further. This quantitative study uses HLM to identify factors from high school physics preparation (content, pedagogy, and assessment) and the affective domain that predict female and male performance in introductory college physics. The study includes controls for student demographic and academic background characteristics, and the final dataset consists of 1973 surveys from 54 introductory college physics classes. The results highlight high school physics and affective experiences that differentially predict female and male performance. These experiences include: learning requirements, computer graphing/analysis, long written problems, everyday world examples, community projects cumulative tests/quizzes, father's encouragement, family's belief that science leads to a better career, and the length of time students believe that high school physics would help in university physics. There were also experiences that similarly predict female and male performance. The results paint a dynamic picture of the factors from high school physics and the affective domain that influence the future physics performance of females and males. The implication is that there are many aspects to the teaching of physics in high school that, although widely used and thought to be effective, need reform in their implementation in order to be fully beneficial to females and/or males in college.

Prediction of biotransformation products of the fungicide fluopyram by electrochemistry coupled online to liquid chromatography-mass spectrometry and comparison with in vitro microsomal assays.

PubMed

Mekonnen, Tessema F; Panne, Ulrich; Koch, Matthias

2018-04-01

Biotransformation processes of fluopyram (FLP), a new succinate dehydrogenase inhibitor (SDHI) fungicide, were investigated by electrochemistry (EC) coupled online to liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS). Oxidative phase I metabolite production was achieved using an electrochemical flow-through cell equipped with a boron-doped diamond (BDD) electrode. Structural elucidation and prediction of oxidative metabolism pathways were assured by retention time, isotopic patterns, fragmentation, and accurate mass measurements using EC/LC/MS, LC-MS/MS, and/or high-resolution mass spectrometry (HRMS). The results obtained by EC were compared with conventional in vitro studies by incubating FLP with rat and human liver microsomes (RLM, HLM). Known phase I metabolites of FLP (benzamide, benzoic acid, 7-hydroxyl, 8-hydroxyl, 7,8-dihydroxyl FLP, lactam FLP, pyridyl acetic acid, and Z/E-olefin FLP) were successfully simulated by EC/LC/MS. New metabolites including an imide, hydroxyl lactam, and 7-hydroxyl pyridyl acetic acid oxidative metabolites were predicted for the first time in our study using EC/LC/MS and liver microsomes. We found oxidation by dechlorination to be one of the major metabolism mechanisms of FLP. Thus, our results revealed that EC/LC/MS-based metabolic elucidation was more advantageous on time and cost of analysis and enabled matrix-free detection with valuable information about the mechanisms and intermediates of metabolism processes. Graphical abstract Oxidative metabolism of fluopyram.

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).

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.

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

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.

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.

[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.

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.

Cluster randomized trial in smoking cessation with intensive advice in diabetic patients in primary care. ITADI Study.

PubMed

Roig, Lydia; Perez, Santiago; Prieto, Gemma; Martin, Carlos; Advani, Mamta; Armengol, Angelina; Roura, Pilar; Manresa, Josep Maria; Briones, Elena

2010-02-04

It is a priority to achieve smoking cessation in diabetic smokers, given that this is a group of patients with elevated cardiovascular risk. Furthermore, tobacco has a multiplying effect on micro and macro vascular complications. Smoking abstinence rates increase as the intensity of the intervention, length of the intervention and number and diversity of contacts with the healthcare professional during the intervention increases. However, there are few published studies about smoking cessation in diabetics in primary care, a level of healthcare that plays an essential role in these patients. Therefore, the aim of the present study is to evaluate the effectiveness of an intensive smoking cessation intervention in diabetic patients in primary care. Cluster randomized trial, controlled and multicentric. Randomization unit: Primary Care Team. 546 diabetic smokers older than 14 years of age whose disease is controlled by one of the primary care teams in the study. Continuous tobacco abstinence (a person who has not smoked for at least six months and with a CO level of less than 6 ppm measured by a cooximeter) , evolution in the Prochaska and DiClemente's Transtheoretical Model of Change, number of cigarettes/day, length of the visit. Point of assessment: one- year post- inclusion in the study. Brief motivational interview for diabetic smokers at the pre-contemplation and contemplation stage, intensive motivational interview with pharmacotherapy for diabetic smokers in the preparation-action stage and reinforcing intevention in the maintenance stage. A descriptive analysis of all variables will be done, as well as a multilevel logistic regression and a Poisson regression. All analyses will be done with an intention to treatment basis and will be fitted for potential confounding factors and variables of clinical importance. Statistical packages: SPSS15, STATA10 y HLM6. The present study will try to describe the profile of a diabetic smoker who receives the most benefit from an intensive intervention in primary care. The results will be useful for primary care professionals in their usual clinical practice. Clinical Trials.gov Identifier: NCT00954967.

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

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.

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.

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

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

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.

In vitro and in vivo metabolic investigation of the Palbociclib by UHPLC-Q-TOF/MS/MS and in silico toxicity studies of its metabolites.

PubMed

Chavan, Balasaheb B; Tiwari, Shristy; G, Shankar; Nimbalkar, Rakesh D; Garg, Prabha; R, Srinivas; Talluri, M V N Kumar

2018-05-14

Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug. The in vitro metabolism studies were carried out by using microsomes (HLM and RLM) and S9 fractions (Human and rat). The in vivo metabolism of the drug was studied by administration of the PAB orally to the Sprague-Dawley rats followed by analysis of urine, faeces and plasma samples. The sample preparation includes simple protein precipitation (PP) followed by solid phase extraction (SPE). The extracted samples were analyzed by ultrahigh-performance liquid chromatography-quadruple time-of-flight tandem mass spectrometry (UHPLC/Q-TOF/MS/MS). A total of 14 metabolites were detected in in vivo matrices. The PAB was metabolized via hydroxylation, oxidation, sulphation, N-dealkylation, acetylation and carbonylation pathways. A few of the metabolites were also detected in in vitro samples. Metabolite identification and characterization were performed by using UHPLC/Q-TOF/MS/MS in combination with HRMS data. To identify the toxicity potential of these metabolites, in silico toxicity assessment was carried out using TOPKAT and DEREK softwares. Copyright © 2018. Published by Elsevier B.V.

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.

Disentangling the change-alliance relationship: Observational assessment of the therapeutic alliance during change and stuck episodes.

PubMed

Mellado, Augusto; Suárez, Nicolás; Altimir, Carolina; Martínez, Claudio; Pérez, Janet; Krause, Mariane; Horvath, Adam

2017-09-01

The therapeutic alliance is considered the most robust process variable associated with positive therapeutic outcome in a variety of psychotherapeutic models [Alexander, L. B., & Luborsky, L. (1986). The Penn Helping Alliance Scales. In L. S. Greenberg & W. M. Pinsoff (Eds.), The psychotherapeutic process: A research handbook (pp. 325-356). New York: Guilford Press; Horvath, A. O., Gaston, L., & Luborsky, L. (1993). The alliance as predictor of benefits of counseling and therapy. In N. Miller, L. Luborsky, J. Barber, & J. P. Docherty (Eds.), Psychodynamic treatment research: A handbook for clinical practice (pp. 247-274). New York, NY: Basic Books; Horvath, A. O., Del Re, A. C., Flückiger, C., & Symonds, D. (2011). Alliance in individual psychotherapy. Psychotherapy, 48, 9-16; Orlinky, D., Grawe, K., & Parks, B. (1994). Process and outcome in psychotherapy: Noch einmal. In A. Bergin & J. S. Garfield (Eds.), Handbook of psychotherapy and behaviour change (4th ed., pp. 270-378). New York, NY: Wiley and Sons]. The relationship between alliance and outcome has traditionally been studied based on measures that assess these therapy factors at a global level. However, the specific variations of the alliance process and their association with therapy segments that are relevant for change have not yet been fully examined. The present study examines the variations in the therapeutic alliance in 73 significant in-session events: 35 change and 38 stuck episodes identified through the observation of 14 short-term therapies of different theoretical orientations. Variations in the alliance were assessed using the VTAS-SF [Shelef, K., & Diamond, G. (2008). Short form of the revised Vanderbilt Therapeutic Alliance Scale: Development, reliability, and validity. Psychotherapy Research, 18, 433-443]. Nested analyses (HLM) indicate a statistically significant better quality of the alliance during change episodes.

Using Objective, Real-Time Measures to Investigate the Effect of Actual Physical Activity on Affective States in Everyday Life Differentiating the Contexts of Working and Leisure Time in a Sample with Students

PubMed Central

Kanning, Martina

2013-01-01

Multiple studies suggest that physical activity causes positive affective reactions and reduces depressive mood. However, studies and interventions focused mostly on structured activity programs, but rarely on actual physical activity (aPA) in daily life. Furthermore, they seldom account for the context in which the aPA occur (e.g., work, leisure). Using a prospective, real-time assessment design (ambulatory assessment), we investigated the effects of aPA on affective states (valence, energetic arousal, calmness) in real-time during everyday life while controlling for the context. Eighty-seven undergraduates students (Age: M = 24.6; SD = 3.2, females: 54%) participated in this study. aPA was assessed through accelerometers during 24-h. Palmtop devices prompted subjects approximately every 45 min during a 14-h daytime period to assess their affective states and the context. We analyzed within- and between-person effects with hierarchical modeling (HLM 6.0). Multilevel analyses revealed that both aPA and context influenced subsequent affective states. The interaction of aPA and context did predict energetic arousal only. State levels of affects did not differ between men and women. For both men and women, aPA in everyday life has an effect on individual’s affective states. For valence and calmness, it seems to be independent of the context in which the aPA occur. For energetic arousal, men reported to have lower feelings of energy and women reported to have more feelings of energy during leisure time compared to working episodes. PMID:23346064

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

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.

Preliminary research on flow rate and free surface of the accelerator driven subcritical system gravity-driven dense granular-flow target

PubMed Central

Li, Xiaodong; Wan, Jiangfeng; Zhang, Sheng; Lin, Ping; Zhang, Yanshi; Yang, Guanghui; Wang, Mengke; Duan, Wenshan; Sun, Jian’an

2017-01-01

A spallation target is one of the three core parts of the accelerator driven subcritical system (ADS), which has already been investigated for decades. Recently, a gravity-driven Dense Granular-flow Target (DGT) is proposed, which consists of a cylindrical hopper and an internal coaxial cylindrical beam pipe. The research on the flow rate and free surface are important for the design of the target whether in Heavy Liquid Metal (HLM) targets or the DGT. In this paper, the relations of flow rate and the geometry of the DGT are investigated. Simulations based on the discrete element method (DEM) implementing on Graphics Processing Units (GPUs) and experiments are both performed. It is found that the existence of an internal pipe doesn’t influence the flow rate when the distance from the bottom of the pipe to orifice is large enough even in a larger system. Meanwhile, snapshots of the free surface formed just below the beam pipe are given. It is observed that the free surface is stable over time. The entire research is meaningful for the design of DGT. PMID:29095910

Preliminary research on flow rate and free surface of the accelerator driven subcritical system gravity-driven dense granular-flow target.

PubMed

Li, Xiaodong; Wan, Jiangfeng; Zhang, Sheng; Lin, Ping; Zhang, Yanshi; Yang, Guanghui; Wang, Mengke; Duan, Wenshan; Sun, Jian'an; Yang, Lei

2017-01-01

A spallation target is one of the three core parts of the accelerator driven subcritical system (ADS), which has already been investigated for decades. Recently, a gravity-driven Dense Granular-flow Target (DGT) is proposed, which consists of a cylindrical hopper and an internal coaxial cylindrical beam pipe. The research on the flow rate and free surface are important for the design of the target whether in Heavy Liquid Metal (HLM) targets or the DGT. In this paper, the relations of flow rate and the geometry of the DGT are investigated. Simulations based on the discrete element method (DEM) implementing on Graphics Processing Units (GPUs) and experiments are both performed. It is found that the existence of an internal pipe doesn't influence the flow rate when the distance from the bottom of the pipe to orifice is large enough even in a larger system. Meanwhile, snapshots of the free surface formed just below the beam pipe are given. It is observed that the free surface is stable over time. The entire research is meaningful for the design of DGT.

The role of organizational context and individual nurse characteristics in explaining variation in use of information technologies in evidence based practice

PubMed Central

2012-01-01

Background There is growing awareness of the role of information technology in evidence-based practice. The purpose of this study was to investigate the role of organizational context and nurse characteristics in explaining variation in nurses’ use of personal digital assistants (PDAs) and mobile Tablet PCs for accessing evidence-based information. The Promoting Action on Research Implementation in Health Services (PARIHS) model provided the framework for studying the impact of providing nurses with PDA-supported, evidence-based practice resources, and for studying the organizational, technological, and human resource variables that impact nurses’ use patterns. Methods A survey design was used, involving baseline and follow-up questionnaires. The setting included 24 organizations representing three sectors: hospitals, long-term care (LTC) facilities, and community organizations (home care and public health). The sample consisted of 710 participants (response rate 58%) at Time 1, and 469 for whom both Time 1 and Time 2 follow-up data were obtained (response rate 66%). A hierarchical regression model (HLM) was used to evaluate the effect of predictors from all levels simultaneously. Results The Chi square result indicated PDA users reported using their device more frequently than Tablet PC users (p = 0.001). Frequency of device use was explained by ‘breadth of device functions’ and PDA versus Tablet PC. Frequency of Best Practice Guideline use was explained by ‘willingness to implement research,’ ‘structural and electronic resources,’ ‘organizational slack time,’ ‘breadth of device functions’ (positive effects), and ‘slack staff’ (negative effect). Frequency of Nursing Plus database use was explained by ‘culture,’ ‘structural and electronic resources,’ and ‘breadth of device functions’ (positive effects), and ‘slack staff’ (negative). ‘Organizational culture’ (positive), ‘breadth of device functions’ (positive), and ‘slack staff ‘(negative) were associated with frequency of Lexi/PEPID drug dictionary use. Conclusion Access to PDAs and Tablet PCs supported nurses’ self-reported use of information resources. Several of the organizational context variables and one individual nurse variable explained variation in the frequency of information resource use. PMID:23276201

CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48.

PubMed

Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

2015-09-01

Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.

Oral Health-Related Quality of Life and Traumatic Dental Injuries in Young Permanent Incisors in Brazilian Schoolchildren: A Multilevel Approach.

PubMed

Freire-Maia, Fernanda Bartolomeo; Auad, Sheyla Márcia; Abreu, Mauro Henrique Nogueira Guimarães de; Sardenberg, Fernanda; Martins, Milene Torres; Paiva, Saul Martins; Pordeus, Isabela Almeida; Vale, Míriam Pimenta

2015-01-01

Traumatic dental injury (TDI) during childhood may negatively impact the quality of life of children. To describe the association of oral health-related quality of life (OHRQoL) and domains (oral symptons, functional limitation, emotional- and social-well-being) of children with individual and contextual variables. A cross-sectional study was performed using a representative sample of 1,201 schoolchildren, 8-10 years-old, from public and private schools of Belo Horizonte, Brazil. The CPQ8-10 was used to assess OHRQoL, dichotomized in low and high impact. Sociodemographic information was collected through questionnaires to parents. Children were examined at schools, using the Andreasen criteria. Individual variables were gender, age, number of residents in home, parents/caregivers' level of education, family income, and TDI (dichotomized into without trauma/mild trauma and severe trauma). Dental caries and malocclusion were considered co-variables. Contextual variables were the Social Vulnerability Index and type of school. Ethical approval and consent forms were obtained. Data were analyzed using SPSS for Windows 19.0 and HLM 6.06, including frequency distribution, chi-squared test and multilevel approach (p < 0.05). The prevalence of a negative impact on OHRQoL in children with severe trauma was 55.9%. The TDI negatively impacted emotional and social domains of OHRQoL. A multilevel analysis revealed a significant difference in OHRQoL according to the type of school and showed that 16% of the total variance was due to contextual characteristics (p < 0.001; ICC = 0.16). The negative impact on OHRQoL was higher in girls (p = 0.009), younger children (p = 0.023), with severe TDI (p = 0.014), those from public schools (p = 0.017) and whose parents had a lower education level (p = 0.001). Severe trauma impacts OHRQoL on emotional and social domains. Contextual dimensions add information to individual variability to explain higher impact, emphasizing socioeconomic inequalities.

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.

Factors significantly related to science achievement of Malaysian middle school students: An analysis of TIMSS 1999 data

NASA Astrophysics Data System (ADS)

Mokshein, Siti Eshah

The importance of science and technology in the global economy has led to growing emphasis on math and science achievement all over the world. In this study, I seek to identify variables at the student-level and school-level that account for the variation in science achievement of the eighth graders in Malaysia. Using the Third International Math and Science Study (TIMSS) 1999 for Malaysia, a series of HLM analysis was performed. Results indicate that (1) variation in overall science achievement is greater between schools than within schools; (2) both the selected student-level and school-level factors are Important in explaining the variation in the eight graders' achievement In science; (3) the selected student-level variables explain about 13% of the variation in students' achievement within schools, but as an aggregate, they account for a much larger proportion of the between-school variance; (4) the selected school-level variables account for about 55% of the variation between schools; (5) within schools, the effects of self-concept In science, awareness of the social implications of science, gender, and home educational resources are significantly related to achievement; (6) the effects of self-concept in science and awareness of social implications of science are significant even after controlling for the effects of SES; (7) between schools, the effects of the mean of home educational resources, mean of parents' education, mean of awareness of the social implications of science, and emphasis on conducting experiments are significantly related to achievement; (8) the effects of SES variables explain about 50% of the variation in the school means achievement; and (9) the effects of emphasis on conducting experiments on achievement are significant even after controlling for the effects of SES. Since it is hard to change the society, it is recommended that efforts to Improve science achievement be focused more at the school-level, concentrating on variables that can be changed. This includes Increasing students' awareness of the social Implications of science and improving students' self-concepts In science, strengthening evaluation systems, and finding ways to compensate for the lack of home educational resources among disadvantaged students. The study further suggests that emphasis be given to proper implementation of science experiments. Besides, the prominent effects of SES variables on the school mean achievement is something worthwhile to be further researched.

Potent and selective inhibition of magnolol on catalytic activities of UGT1A7 and 1A9.

PubMed

Zhu, Liangliang; Ge, Guangbo; Liu, Yong; He, Guiyuan; Liang, Sicheng; Fang, Zhongze; Dong, Peipei; Cao, Yunfeng; Yang, Ling

2012-10-01

1. Human exposure to magnolol can reach a high dose in daily life. Our previous studies indicated that magnolol showed high affinities to several UDP-glucuronosyltransferases (UGTs) This study was designed to examine the in vitro inhibitory effects of magnolol on UGTs, and further to evaluate the possibility of the in vivo inhibition that might happen. 2. Assays with recombinant UGTs and human liver microsomes (HLM) indicated that magnolol (10 µM) can selectively inhibit activities of UGT1A9 and extra-hepatic UGT1A7. Inhibition of magnolol on UGT1A7 followed competitive inhibition mechanism, while the inhibition on UGT1A9 obeyed either competitive or mixed inhibition mechanism, depending on substrates. The K(i) values for UGT1A7 and 1A9 are all in nanomolar ranges, lower than possible magnolol concentrations in human gut lumen and blood, indicating the in vivo inhibition on these two enzymes would likely occur. 3. In conclusion, UGT1A7 and 1A9 can be strongly inhibited by magnolol, raising the alarm for safe application of magnolol and traditional Chinese medicines containing magnolol. Additionally, given that UGT1A7 is an extra-hepatic enzyme, magnolol can serve as a selective UGT1A9 inhibitor that will act as a new useful tool in future hepatic glucuronidation phenotyping.

New copper(I) complexes bearing lomefloxacin motif: Spectroscopic properties, in vitro cytotoxicity and interactions with DNA and human serum albumin.

PubMed

Komarnicka, Urszula K; Starosta, Radosław; Kyzioł, Agnieszka; Płotek, Michał; Puchalska, Małgorzata; Jeżowska-Bojczuk, Małgorzata

2016-12-01

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar-phosphate backbone of plasmid DNA. The addition of H 2 O 2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of a Booster Intervention Three Years after Acute Treatment for Early-Onset Disruptive Behavior Disorders

PubMed Central

Lindhiem, Oliver; Hart, Jonathan; Bukstein, Oscar G.

2013-01-01

This study examines the impact of a brief booster treatment administered three years after the delivery of an acute treatment in a group (N = 118) of clinically referred boys and girls (ages 6 to 11) originally diagnosed with Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD). At the conclusion of the acute treatment and three-year follow-up period (i.e., study month 42), the sample was re-randomized into Booster treatment or Enhanced Usual Care and then assessed at four later timepoints (i.e., post-booster, and 6-, 12- and 24-month booster follow-up). Booster treatment was directed towards addressing individualized problems and some unique developmental issues of adolescence based on the same original protocol content and treatment setting, whereas the no-booster condition involved providing clinical recommendations based on the assessment and an outside referral for services. HLM analyses identified no significant group differences and few time effects across child, parent, and teacher reports on a broad range of child functioning and impairment outcomes. Analyses examining the role of putative moderators or mediators (e.g., severity of externalizing behavior, dose of treatment) were likewise non-significant. We discuss the nature and implications of these novel findings regarding the role and timing of booster treatment to address the continuity of DBD over time. PMID:23494526

Investigating Female Sexual Concordance: Do Sexual Excitation and Sexual Inhibition Moderate the Agreement of Genital and Subjective Sexual Arousal in Women?

PubMed

Velten, Julia; Scholten, Saskia; Graham, Cynthia A; Adolph, Dirk; Margraf, Jürgen

2016-11-01

The agreement of subjective and genital sexual response, also referred to as sexual concordance, shows substantial variability between women. Identifying predictors of sexual arousal and sexual concordance is important to improve our understanding of female sexual response and its relationship to sexual function or dysfunction. The aim of this study was to assess the relevance of sexual excitation and sexual inhibition as predictors of subjective sexual arousal, genital arousal, and sexual concordance. In a laboratory setting, sexual arousal was induced by erotic video stimuli. Subjective sexual arousal was assessed continuously during stimulus presentation and genital arousal was measured with vaginal photoplethysmography. Data of 58 women (M age = 24.95, SD = 4.65) were analyzed using multilevel analyses (HLM). This data analytic technique estimates the within-subject associations of subjective and genital arousal, by controlling for between-subject differences. An interaction term of sexual excitation and sexual inhibition significantly predicted genital sexual arousal. In exploratory analyses, two lower order factors of sexual inhibition (Concerns about Sexual Function and Arousal Contingency) were predictive of sexual concordance. Further examination of these associations might increase our knowledge of female sexual function and deepen our understanding of how sexual excitation and sexual inhibition affect sexual arousal and consequently, impact sexual behaviors, in women.

Fluid-induced Crystallization of Majoritic Garnet During Deep Continental Subduction (Western Gneiss Region, Norway)

NASA Astrophysics Data System (ADS)

Scambelluri, M.; Pettke, T.; van Roermund, H. L.

2008-12-01

In ultrahigh pressure (UHP) rocks, garnet containing pyroxene exsolutions derives from breakdown of majorite crystallized at depths > 200 km. Presence of microdiamonds in some of these rocks [1], including those of the Western Gneiss Region (WGR) of Norway [2], may suggest a fluid-bearing environment for the genesis of majorite. The WGR UHP gneisses host garnet peridotite and websterite recording uplift from extraordinary depths prior to uptake in a subducting slab [2]. These ultramafic rocks (islands of Otrøy and Bardane) derive from depleted Archean transition-zone mantle (350 km depth) upwelled and accreted to a cratonic lithosphere (M2 stage). Evidence for this are decimetric garnets (grt) preserved in Otrøy, hosting up to 20 volume% orthopyroxene (opx) and clinopyroxene (cpx) exsolved from precursor majoritic garnet (M1 stage). The pyroxene lamellae (20-30 ¥ìm thick, hundreds of ¥ìm long) [3] were exsolved under high-T, as shown by the garnet/cpx REE distribution [4]. This Archean-mid Proterozoic record is overprinted by the 425- 390 Ma Scandian continental subduction (M3 stage), forming new grt + cpx + opx + phlogopite (phl) + spinel (sp) that contain diamond-bearing micro-inclusions witnessing deep COH subduction fluids [2]. Here we document formation of new majoritic garnet in the M3 assemblage and in veins at Bardane [5]. Textural characteristics, together with the LREE and LILE enrichments of the M3 minerals, indicate that the new majorite is linked to infiltration of subduction fluids during renewed burial towards sub-lithospheric depths. It represents the deepest occurrence of fluid-related microstructures in mantle rocks. The new majoritic garnet crystallized at grain boundaries and in micro-veins at 7 Gpa and 900-1000 °C. It hosts thin pyroxene needles (5 mm thick, 100 mm long) exsolved under comparatively low-T, as indicated by the garnet/cpx REE distribution. The trace element signature of the majorite-bearing subduction assemblage is LREE- (cpx La/Yb = 220) and LILE-enriched (appreciable Li, B, Rb, Ba, Pb, U, Th in cpx and phl), to indicate addition of crustal components. The interstitial and vein M3 majoritic garnet has flat REE patterns (La 1xChondrite; La/Yb= 0.35) and lacks the LREE depletion characteristic of common grt. The px component of majorite thus allows LREE and subordinate LILE storage in this mineral, which becomes a relevant trace element repository in the deep mantle. The REE enriched signature of M3 majorite contrasts the depleted nature of M1 (+ M2) grt: this indicates the presence of two generations of majorite in these rocks and suggests the re-fertilization of initially depleted peridotite by subduction fluid at 200 km depth. Distinct generations of majoritic garnet thus survive in the same terrain, displaying distinct textures, compositions, and exsolution T. The majorite microstructures and compositions enable to discriminate between crystallization environments: hot sub- cratonic lithosphere vs. colder subduction settings. 1 Mposkos ED, Kostopoulos DK, 2001, EPSL 192, 497- 506; 2 Van Roermund HLM. et al., 2002, Geology 30, 959-962; 3 Van Roermund HLM, Drury M., 1998, Terra Nova 10, 295-301; 4 Spengler D. et al., 2006, Nature 440, 913-917; 5 Scambelluri M. et al., 2008, Geology 36, 59-62.

In vitro biotransformation of tris(2-butoxyethyl) phosphate (TBOEP) in human liver and serum

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

Van den Eede, Nele, E-mail: nele.vandeneede@uantwerpen.be; Erratico, Claudio; Exarchou, Vassiliki

Tris(2-butoxyethyl) phosphate (TBOEP) is a plasticizer present in indoor dust, reaching levels of several micrograms per gram. Such levels could lead to significant daily exposure of adults and children. Currently, no toxicokinetic data are available to estimate TBOEP clearance in humans after uptake and therefore, one objective of this study was to investigate intrinsic clearance of TBOEP by human liver microsome (HLM) and serum enzymes. Another objective was to generate information to identify and prioritize several metabolites of TBOEP for investigation of human exposure by biomonitoring. 1D and 2D-NMR methodologies were successfully applied on a mixture of the metabolites tomore » confirm the structure of 3-HO-TBOEP (bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate) and to tentatively assign structures to 1-HO-TBOEP and 2-HO-TBOEP. HO-TBOEP isomers and bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were further monitored by liquid chromatography–tandem mass spectrometry. Rates of formation of BBOEHEP and HO-TBOEP metabolites by liver enzymes were best described by the Michaelis–Menten model. Apparent K{sub m} values for BBOEHEP, 3-HO-TBOEP, and sum of 1- and 2-HO-TBOEP isomer formation were 152, 197 and 148 μM, respectively. Apparent V{sub max} values for the formation of BBOEHEP, 3-HO-TBOEP, and the sum of 1- and 2-HO-TBOEP isomers were 2560, 643, and 254 pmol/min/mg protein, respectively. No detectable formation of BBOEP occurred with liver or serum enzymes. Our findings indicate that intrinsic clearance of TBOEP is mainly catalyzed by oxidative enzymes in the liver and that its major in vitro metabolite is BBOEHEP. These findings can be applied in human biomonitoring studies and risk assessment. - Highlights: • First steps in the elucidation of TBOEP toxicokinetics • Quantification of TBOEP metabolites in human serum and liver microsomes • No detectable formation of BBOEP occurred with liver or serum enzymes. • Oxidative dealkylation to BBOEHEP was likely the major metabolic pathway. • 1D-NMR and 2D-NMR were used to tentatively assign structures of HO-TBOEP isomers.« less

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.

Development and validation of a highly sensitive LC-ESI-MS/MS method for estimation of IIIM-MCD-211, a novel nitrofuranyl methyl piperazine derivative with potential activity against tuberculosis: Application to drug development.

PubMed

Magotra, Asmita; Sharma, Anjna; Gupta, Ajai Prakash; Wazir, Priya; Sharma, Shweta; Singh, Parvinder Pal; Tikoo, Manoj Kumar; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

2017-08-15

In the present study, a simple, sensitive, specific and rapid liquid chromatography (LC) tandem mass spectrometry (MS/MS) method was developed and validated according to the Food and Drug Administration (FDA) guidelines for estimation of IIIM-MCD-211 (a potent oral candidate with promising action against tuberculosis) in mice plasma using carbamazepine as internal standard (IS). Bioanalytical method consisted of one step protein precipitation for sample preparation followed by quantitation in LC-MS/MS using positive electrospray ionization technique (ESI) operating in multiple reaction monitoring (MRM) mode. Elution was achieved in gradient mode on High Resolution Chromolith RP-18e column with mobile phase comprised of acetonitrile and 0.1% (v/v) formic acid in water at the flow rate of 0.4mL/min. Precursor to product ion transitions (m/z 344.5/218.4 and m/z 237.3/194.2) were used to measure analyte and IS, respectively. All validation parameters were well within the limit of acceptance criteria. The method was successfully applied to assess the pharmacokinetics of the candidate in mice following oral (10mg/kg) and intravenous (IV; 2.5mg/kg) administration. It was also effectively used to quantitate metabolic stability of the compound in mouse liver microsomes (MLM) and human liver microsomes (HLM) followed by its in-vitro-in-vivo extrapolation. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicokinetics of new psychoactive substances: plasma protein binding, metabolic stability, and human phase I metabolism of the synthetic cannabinoid WIN 55,212-2 studied using in vitro tools and LC-HR-MS/MS.

PubMed

Mardal, Marie; Gracia-Lor, Emma; Leibnitz, Svenja; Castiglioni, Sara; Meyer, Markus R

2016-10-01

The new psychoactive substance WIN 55,212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone) is a potent synthetic cannabinoid receptor agonist. The metabolism of WIN 55,212-2 in man has never been reported. Therefore, the aim of this study was to identify the human in vitro metabolites of WIN 55,212-2 using pooled human liver microsomes and liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS) to provide targets for toxicological, doping, and environmental screening procedures. Moreover, a metabolic stability study in pooled human liver microsomes (pHLM) was carried out. In total, 19 metabolites were identified and the following partly overlapping metabolic steps were deduced: degradation of the morpholine ring via hydroxylation, N- and O-dealkylation, and oxidative deamination, hydroxylations on either the naphthalene or morpholine ring or the alkyl spacer with subsequent oxidation, epoxide formation with subsequent hydrolysis, or combinations. In conclusion, WIN 55,212-2 was extensively metabolized in human liver microsomes incubations and the calculated hepatic clearance was comparably high, indicating a fast and nearly complete metabolism in vivo. This is in line with previous findings on other synthetic cannabinoids. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolites of 5F-AKB-48, a synthetic cannabinoid receptor agonist, identified in human urine and liver microsomal preparations using liquid chromatography high-resolution mass spectrometry.

PubMed

Holm, Niels Bjerre; Pedersen, Anders Just; Dalsgaard, Petur Weihe; Linnet, Kristian

2015-03-01

New types of synthetic cannabinoid designer drugs are constantly introduced to the illicit drug market to circumvent legislation. Recently, N-​(1-Adamant​yl)-​1-​(5-​fluoropentyl)-​1H-​indazole-​3-​carboxamide (5F-AKB-48), also known as 5F-APINACA, was identified as an adulterant in herbal products. This compound deviates from earlier JHW-type synthetic cannabinoids by having an indazole ring connected to an adamantyl group via a carboxamide linkage. Synthetic cannabinoids are completely metabolized, and identification of the metabolites is thus crucial when using urine as the sample matrix. Using an authentic urine sample and high-resolution accurate-mass Fourier transform Orbitrap mass spectrometry, we identified 16 phase-I metabolites of 5F-AKB-48. The modifications included mono-, di-, and trihydroxylation on the adamantyl ring alone or in combination with hydroxylation on the N-fluoropentylindazole moiety, dealkylation of the N-fluoropentyl side chain, and oxidative loss of fluorine as well as combinations thereof. The results were compared to human liver microsomal (HLM) incubations, which predominantly showed time-dependent formation of mono-, di-, and trihydroxylated metabolites having the hydroxyl groups on the adamantyl ring. The results presented here may be used to select metabolites specific of 5F-AKB-48 for use in clinical and forensic screening. Copyright © 2014 John Wiley & Sons, Ltd.

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.

10 Years Later: Changes in Food Access Disparities in New Orleans since Hurricane Katrina.

PubMed

Mundorf, Adrienne R; Willits-Smith, Amelia; Rose, Donald

2015-08-01

Inadequate access to healthy food is a problem in many urban neighborhoods, particularly for racial-ethnic minorities and low-income groups who are more likely to reside in food deserts. Although substantial research throughout the country has documented the existence of these disparities, few studies have focused on how this access changes over time or is affected by environmental shocks. This study examined citywide supermarket access in New Orleans as well as racial-ethnic disparities in this access, prior to Hurricane Katrina and at three times afterwards. On-the-ground verification of supermarket locations was conducted in 2004-2005, 2007, 2009, and 2014 and was mapped with secondary demographic data. Census tracts were defined as predominantly African-American neighborhoods if 80 % or more of the population identified as such. HLM Poisson regression analyses were conducted in 2014 to identify the difference in likelihood of finding supermarkets in a neighborhood by race-ethnicity and across all years of interest. Racial-ethnic disparities existed before the storm and worsened after it (IRR = 0.35; 95 % CI = 0.21, 0.60). Improvements in disparities to pre-storm levels were not seen until 2009, 4 years after the storm. By 2014, supermarket access, on average, was not significantly different in African-American neighborhoods than in others (IRR = 0.90; 95 % CI = 0.65, 1.26). The slow recovery of New Orleans' retail food infrastructure after Hurricane Katrina highlights the need for an increased focus on long-term planning to address disparities, especially those that may be exaggerated by shocks.

Sexual compulsivity, state affect, and sexual risk behavior in a daily diary study of gay and bisexual men.

PubMed

Grov, Christian; Golub, Sarit A; Mustanski, Brian; Parsons, Jeffrey T

2010-09-01

Researchers have identified a strong link between sexual compulsivity (SC) and risky sexual behavior among men who have sex with men (MSM). Meanwhile, affect/mood has also been connected with negative sexual health outcomes (sexually transmitted infection/human immunodeficiency virus [HIV] transmission, sexual risk, sex under the influence of drugs/alcohol). Given that SC is characterized by marked distress around one's own sexual behavior, affect may play a central role in SC and HIV risk behavior. Data were taken from the Pillow Talk Project, a pilot study conducted in 2008-2009 with 50 highly sexually active MSM (9 or more male sex partners, ≤ 90 days), of which half displayed SC symptoms and half did not. Forty-seven men completed a daily diary online for 30 days (n = 1,060 diary days), reporting on their sexual behavior and concurrent affect: positive activation, negative activation, anxious arousal, and sexual activation. We conducted HLM analyses using daily affect (Level 1, within subjects) and SC and HIV status (Level 2, between subjects) to predict sexual behavior outcomes. Increased negative activation (characterized by fear, sadness, anger, and disgust) was associated with reduced sexual risk behavior, but less so among sexually compulsive MSM. Sexual activation was associated with increased sexual risk taking, but less so among sexually compulsive MSM. Anxious arousal was associated with increased sexual behavior, but not necessarily sexual risk taking. Findings indicate that affect plays key roles in sexual behavior and sexual risk taking; however, the association between affect and behavior may be different for sexually compulsive and non-sexually compulsive MSM.

Controlled comparison of family cognitive behavioral therapy and psychoeducation/relaxation training for child obsessive-compulsive disorder.

PubMed

Piacentini, John; Bergman, R Lindsey; Chang, Susanna; Langley, Audra; Peris, Tara; Wood, Jeffrey J; McCracken, James

2011-11-01

To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD). A total of 71 youngsters 8 to 17 years of age (mean 12.2 years; range, 8-17 years, 37% male, 78% Caucasian) with primary OCD were randomized (70:30) to 12 sessions over 14 weeks of FCBT or PRT. Blind raters assessed outcomes with responders followed for 6 months to assess treatment durability. FCBT led to significantly higher response rates than PRT in ITT (57.1% vs 27.3%) and completer analyses (68.3% vs. 35.3%). Using HLM, FCBT was associated with significantly greater change in OCD severity and child-reported functional impairment than PRT and marginally greater change in parent-reported accommodation of symptoms. These findings were confirmed in some, but not all, secondary analyses. Clinical remission rates were 42.5% for FCBT versus 17.6% for PRT. Reduction in family accommodation temporally preceded improvement in OCD for both groups and child functional status for FCBT only. Treatment gains were maintained at 6 months. FCBT is effective for reducing OCD severity and impairment. Importantly, treatment also reduced parent-reported involvement in symptoms with reduced accommodation preceding reduced symptom severity and functional impairment. CLINICAL TRIALS REGISTRY INFORMATION: Behavior Therapy for Children and Adolescents with Obsessive-Compulsive Disorder (OCD); http://www.clinicaltrials.gov; NCT00000386. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

'I'm a consumer, I'm not a scientist': Cultivating Student Domain Identification, Agency, and Affect through Engagement in Scientific Practices

NASA Astrophysics Data System (ADS)

Scalone, Giovanna

This study investigates the potential benefits of redesigning hands-on, commercial inquiry science kits for fifth grade that afford agency and the development of science identities by leveraging youth's interests, personal or shared concerns, challenges or desires. Science identification is considered in relation to learning processes of being, becoming, knowing and doing. As identities are constructed dialogically through engagement, emotion, intentionality, innovation, and solidarity, students' agency is mediated and conceptualized as it develops in practice. The study is introduced in Chapter 1 by acknowledging how agency and identity are constructed from an ideological frame, thus problematizing the current neo-liberal policies undergirding educational reform. The conceptual argument in Chapter 2 outlines a theoretical synthesis of agency and learning. Subsequently, I leveraged a theory of semiosis to highlight how these perspectives on agency and identity contribute to the meaning-making processes of language, culture, and mind. Finally, conceptualizations of agency and identity are mapped to the sociology of scientific knowledge perspective. Chapter 3 situates the study context within a design-based implementation research model where the existing science curriculum units serve as comparisons (Inquiry group) to the experimental units (Agency group). The findings first demonstrate how student and teacher positioning are revealed during the turns of exchange by using functional grammar as a method to analyze how discourse works to construe experience and enact social relationships. Secondly, I analyze youth positioning across conditions highlighting the importance of raising student consciousness to the variegated ways scientists practice science and inducts students into how scientists intentionally and purposefully employ genres to engage in scientific ways of communicating. Student's perspectives, positioning, and emotional investments are then analyzed using appraisal analysis to show how students talking about their images of science yield different ways of knowing and dispositions in science. Thirdly, by tracing the inclination and obligation of doing science, I illustrate how subjectivity versus materiality/objectivity in science impact how students perceive science. Fourth, student images of science, ways of identifying with science and having agency in science are analyzed using a thematic analysis to identify patterns and emerging themes. Next, I assess students' developing understanding of scientific inquiry using HLM to determine whether the Agency units versus the Inquiry units predicted students' learning outcomes based on the inquiry assessment. Finally, I discuss the implications of these analyses. This study accounts for how youth develop practice-linked identities in science entails the fleeting identity performances and language choices made for and by youth in the science classroom. Central to this notion of identity is agency where positionality as well as material and symbolic, interactional and situational resources constrain or enable identity development. In a learning context, these choices and values inherent in language use are relational to learner agency outside of language, but ensouled in performative curating where solidarity, intention, creativity, emotion, accountability, anticipation, cognition, and rewards enable the capacity to transform the self, others, and communities. This dissertation demonstrates how design features embedded in curriculum related to personal relevance and the societal context for science affords teachers to engage youth in agentic science learning in the classroom in ways that become more meaningful and supportive of science identification than traditional inquiry approaches to teaching science.

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.

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.

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22.

PubMed

Diao, Xingxing; Scheidweiler, Karl B; Wohlfarth, Ariane; Pang, Shaokun; Kronstrand, Robert; Huestis, Marilyn A

2016-03-01

In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 μM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 μM was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after β-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after β-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.

Cytochrome P450 Isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica.

PubMed

Zhang, Jinhui; Li, Li; Tang, Suni; Hale, Thomas W; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 (CYP) enzymes, whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal (HLM) preparation, the general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol (NBN) and ketoconazole substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic (PK) study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0-48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0-48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D.

The paraoxonase-1 pathway is not a major bioactivation pathway of clopidogrel in vitro

PubMed Central

Ancrenaz, V; Desmeules, J; James, R; Fontana, P; Reny, J-L; Dayer, P; Daali, Y

2012-01-01

BACKGROUND AND PURPOSE Clopidogrel is a prodrug bioactivated by cytochrome P450s (CYPs). More recently, paraoxonase-1 (PON1) has been proposed as a major contributor to clopidogrel metabolism. The purpose of this study was to assess the relative contribution of CYPs and PON1 to clopidogrel metabolism in vitro. EXPERIMENTAL APPROACH Clopidogrel metabolism was studied in human serum, recombinant PON1 enzyme (rePON1), pooled human liver microsomes (HLMs), HLMs with the CYP2C19*1/*1 genotype and HLMs with the CYP2C19*2/*2 genotype. Inhibition studies were also performed using specific CYP inhibitors and antibodies. Clopidogrel and its metabolites were measured using LC/MS/MS method. KEY RESULTS PON1 activity was highest in the human serum and there was no difference in PON1 activity between any of the HLM groups. The production of clopidogrel's active metabolite (clopidogrel-AM) from 2-oxo-clopidogrel in pooled HLMs was approximately 500 times that in serum. When 2-oxo-clopidogrel was incubated with rePON1, clopidogrel-AM was not detected. Clopidogrel-AM production from 2-oxo-clopidogrel was lower in CYP2C19*2/*2 HLMs compared with CYP2C19*1/*1 HLMs, while PON1 activity in HLMs with both genotypes was similar. Moreover, incubation with inhibitors of CYP3A, CYP2B6 and CYP2C19 significantly reduced clopidogrel bioactivation while a PON1 inhibitor, EDTA, had only a weak inhibitory effect. CONCLUSION AND IMPLICATIONS This in vitro study shows that the contribution of PON1 to clopidogrel metabolism is limited at clinically relevant concentrations. Moreover, CYP2C19, CYP2B6 and CYP3A play important roles in the bioactivation of clopidogrel. PMID:22428615

Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine

PubMed Central

Manda, Vamshi K.; Avula, Bharathi; Dale, Olivia R.; Chittiboyina, Amar G.; Khan, Ikhlas A.; Walker, Larry A.; Khan, Shabana I.

2015-01-01

Abstract Background Vinpocetine, a semi-synthetic derivative of vincamine, is a popular dietary supplement used for the treatment of several central nervous system related disorders. Despite its wide use, no pharmacokinetic drug interaction studies are reported in the literature. Due to increasing use of dietary supplements in combination with conventional drugs, the risk of adverse effects is on the rise. As a preliminary step to predict a possibility of drug interaction during concomitant use of vinpocetine and conventional drugs, this study was carried out to evaluate the effects of vinpocetine on three main regulators of pharmacokinetic drug interactions namely, cytochromes P450 (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR). Methods Inhibition of CYPs was evaluated by employing recombinant enzymes. The inhibition of P-gp was determined by calcein-AM uptake method in transfected and wild type MDCKII cells. Modulation of PXR activity was monitored through a reporter gene assay in HepG2 cells. Results Vinpocetine showed a strong inhibition of P-gp (EC50 8 μM) and a moderate inhibition of recombinant CYP3A4 and CYP2D6 (IC50 2.8 and 6.5 μM) with no activity towards CYP2C9, CYP2C19 and CYP1A2 enzymes. In HLM, competitive inhibition of CYP3A4 (IC50 54 and Ki 19 μM) and non-competitive inhibition of CYP2D6 (IC50 19 and Ki 26 μM) was observed. Activation of PXR was observed only at the highest tested concentration of vinpocetine (30 μM) while lower doses were ineffective. Conclusion Strong inhibition of P-gp by vinpocetine is indicative of a possibility of drug interactions by altering the pharmacokinetics of drugs, which are the substrates of P-gp. However, the effects on CYPs and PXR indicate that vinpocetine may not affect CYP-mediated metabolism of drugs, as the inhibitory concentrations are much greater than the expected plasma concentrations in humans. PMID:28930203

Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine.

PubMed

Manda, Vamshi K; Avula, Bharathi; Dale, Olivia R; Chittiboyina, Amar G; Khan, Ikhlas A; Walker, Larry A; Khan, Shabana I

2015-06-05

Background: Vinpocetine, a semi-synthetic derivative of vincamine, is a popular dietary supplement used for the treatment of several central nervous system related disorders. Despite its wide use, no pharmacokinetic drug interaction studies are reported in the literature. Due to increasing use of dietary supplements in combination with conventional drugs, the risk of adverse effects is on the rise. As a preliminary step to predict a possibility of drug interaction during concomitant use of vinpocetine and conventional drugs, this study was carried out to evaluate the effects of vinpocetine on three main regulators of pharmacokinetic drug interactions namely, cytochromes P450 (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR). Methods: Inhibition of CYPs was evaluated by employing recombinant enzymes. The inhibition of P-gp was determined by calcein-AM uptake method in transfected and wild type MDCKII cells. Modulation of PXR activity was monitored through a reporter gene assay in HepG2 cells. Results: Vinpocetine showed a strong inhibition of P-gp (EC 50 8 µM) and a moderate inhibition of recombinant CYP3A4 and CYP2D6 (IC 50 2.8 and 6.5 µM) with no activity towards CYP2C9, CYP2C19 and CYP1A2 enzymes. In HLM, competitive inhibition of CYP3A4 (IC 50 54 and K i 19 µM) and non-competitive inhibition of CYP2D6 (IC 50 19 and K i 26 µM) was observed. Activation of PXR was observed only at the highest tested concentration of vinpocetine (30 µM) while lower doses were ineffective. Conclusion: Strong inhibition of P-gp by vinpocetine is indicative of a possibility of drug interactions by altering the pharmacokinetics of drugs, which are the substrates of P-gp. However, the effects on CYPs and PXR indicate that vinpocetine may not affect CYP-mediated metabolism of drugs, as the inhibitory concentrations are much greater than the expected plasma concentrations in humans.

The effect of chlorpyrifos-oxon and other xenobiotics on the human cytochrome P450-dependent metabolism of naphthalene and deet.

PubMed

Cho, Taehyeon M; Rose, Randy L; Hodgson, Ernest

2007-01-01

Chlorpyrifos-oxon (CPO), a metabolite of chlorpyrifos, is a potent inhibitor of acetylcholinesterase and, although the neurotoxicological impact of this organophosphorus compound has been broadly studied both in vitro and in vivo, there are few studies of metabolic interactions of CPO with other xenobiotics. CPO significantly activated the production of 1-naphthol (5-fold), 2-naphthol (10-fold), trans-1,2-dihydro-1,2-naphthalenediol (1.5-fold), and 1,4-naphthoquinone from naphthalene by human liver microsomes (HLM). It was further demonstrated that the production of naphthalene metabolites by CYP2C8, 2C9*(1), 2C19, 2D6*(1), 3A4, 3A5, and 3A7 was activated by CPO, while the production of naphthalene metabolites by CYP1A1, 1A2, 1B1, and 2B6 was inhibited by CPO. CPO inhibited CYP1A2 production of naphthalene metabolites, while activating their production by CYP3A4. Similarly, CPO inhibited the production of N,N-diethyl-m-hydroxymethylbenzamide (BALC) from DEET by human liver microsomes, but activated the production of N-ethyl-m-toluamide (ET) from this substrate. CYP2B6, the most efficient isoform for BALC production, was inhibited by CPO, while CYP3A4, the most efficient isoform for ET production, was activated by CPO. CPO inhibited CYP2B6 production of both BALC and ET from DEET, but activated CYP3A4 production of ET, while inhibiting CYP3A4 BALC production. CPO appears to facilitate the binding of naphthalene to CYP3A4. This metabolic activation is independent of cytochrome b5, suggesting that activation of CYP3A4 by CPO is associated with a conformational change of the isoform rather than facilitating electron transfer.

Metabolism of endosulfan-alpha by human liver microsomes and its utility as a simultaneous in vitro probe for CYP2B6 and CYP3A4.

PubMed

Casabar, Richard C T; Wallace, Andrew D; Hodgson, Ernest; Rose, Randy L

2006-10-01

Endosulfan-alpha is metabolized to a single metabolite, endosulfan sulfate, in pooled human liver microsomes (Km = 9.8 microM, Vmax = 178.5 pmol/mg/min). With the use of recombinant cytochrome P450 (P450) isoforms, we identified CYP2B6 (Km = 16.2 microM, Vmax = 11.4 nmol/nmol P450/min) and CYP3A4 (Km = 14.4 microM, Vmax = 1.3 nmol/nmol P450/min) as the primary enzymes catalyzing the metabolism of endosulfan-alpha, although CYP2B6 had an 8-fold higher intrinsic clearance rate (CL(int) = 0.70 microl/min/pmol P450) than CYP3A4 (CL(int) = 0.09 microl/min/pmol P450). Using 16 individual human liver microsomes (HLMs), a strong correlation was observed with endosulfan sulfate formation and S-mephenytoin N-demethylase activity of CYP2B6 (r(2) = 0.79), whereas a moderate correlation with testosterone 6 beta-hydroxylase activity of CYP3A4 (r(2) = 0.54) was observed. Ticlopidine (5 microM), a potent CYP2B6 inhibitor, and ketoconazole (10 microM), a selective CYP3A4 inhibitor, together inhibited approximately 90% of endosulfan-alpha metabolism in HLMs. Using six HLM samples, the percentage total normalized rate (% TNR) was calculated to estimate the contribution of each P450 in the total metabolism of endosulfan-alpha. In five of the six HLMs used, the percentage inhibition with ticlopidine and ketoconazole in the same incubation correlated with the combined % TNRs for CYP2B6 and CYP3A4. This study shows that endosulfan-alpha is metabolized by HLMs to a single metabolite, endosulfan sulfate, and that it has potential use, in combination with inhibitors, as an in vitro probe for CYP2B6 and 3A4 catalytic activities.

The Cytochrome P450 Enzyme Responsible for the Production of (Z)-Norendoxifen in vitro.

PubMed

Ma, Jianli; Chu, Zhong; Lu, Jessica Bo Li; Liu, Jinzhong; Zhang, Qingyuan; Liu, Zhaoliang; Tang, Dabei

2018-01-01

Norendoxifen, an active metabolite of tamoxifen, is a potent aromatase inhibitor. Little information is available regarding production of norendoxifen in vitro. Here, we conducted a series of kinetic and inhibition studies in human liver microsomes (HLMs) and expressed P450s to study the metabolic disposition of norendoxifen. To validate that norendoxifen was the metabolite of endoxifen, metabolites in HLMs incubates of endoxifen were measured using a HPLC/MS/MS method. To further probe the specific isoforms involved in the metabolic route, endoxifen was incubated with recombinant P450s (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 3A5 and CYP4A11). Formation rates of norendoxifen were evaluated in the absence and presence of P450 isoform specific inhibitors using HLMs. The peak of norendoxifen was found in the incubations consisting of endoxifen, HLMs, and cofactors. The retention times of norendoxifen, endoxifen, and the internal standard (diphenhydramine) were 7.81, 7.97, and 5.86 min, respectively. The K m (app) and V max (app) values of norendoxifen formation from endoxifen in HLM was 47.8 μm and 35.39 pmol min -1 mg -1 . The apparent hepatic intrinsic clearances of norendoxifen formation were 0.74 μl mg -1 min. CYP3A5 and CYP2D6 were the major enzymes capable of norendoxifen formation from endoxifen with the rates of 0.26 and 0.86 pmol pmol -1 P450 × min. CYP1A2, 3A2, 2C9, and 2C19 also contributed to norendoxifen formation, but the contributions were at least 6-fold lower. One micromolar ketoconazole (CYP3A inhibitor) showed an inhibitory effect on the rates of norendoxifen formation by 45%, but 1 μm quinidine (CYP2D6 inhibitor) does not show any inhibitory effect. Norendoxifen, metabolism from endoxifen by multiple P450s that including CYP3A5. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes

PubMed Central

Yang, Junling; He, Minxia M; Niu, Wei; Wrighton, Steven A; Li, Li; Liu, Yang; Li, Chuan

2012-01-01

AIM The most common causes of variability in drug response include differences in drug metabolism, especially when the hepatic cytochrome P450 (CYP) enzymes are involved. The current study was conducted to assess the differences in CYP activities in human liver microsomes (HLM) of Chinese or Caucasian origin. METHODS The metabolic capabilities of CYP enzymes in 30 Chinese liver microsomal samples were compared with those of 30 Caucasian samples utilizing enzyme kinetics. Phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, amodiaquine N-desethylation, diclofenac 4′-hydroxylation (S)-mephenytoin 4′-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and midazolam 1′-hydroxylation/testosterone 6β-hydroxylation were used as probes for activities of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Mann-Whitney U test was used to assess the differences. RESULTS The samples of the two ethnic groups were not significantly different in cytochrome-b5 concentrations but were significantly different in total CYP concentrations and NADPH-P450 reductase activity (P < 0.05). Significant ethnic differences in intrinsic clearance were observed for CYP1A2, CYP2C9, CYP2C19 and CYP2E1; the median values of the Chinese group were 54, 58, 26, and 35% of the corresponding values of the Caucasian group, respectively. These differences were associated with differences in Michaelis constant or maximum velocity. Despite negligible difference in intrinsic clearance, the Michaelis constant of CYP2B6 appeared to have a significant ethnic difference. No ethnic difference was observed for CYP2A6, CYP2C8, CYP2D6 and CYP3A. CONCLUSIONS These data extend our knowledge on the ethnic differences in CYP enzymes and will have implications for drug discovery and drug therapy for patients from different ethnic origins. PMID:21815912

The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes.

PubMed

Albassam, Ahmed A; Frye, Reginald F; Markowitz, John S

2017-06-01

Milk thistle is a widely-consumed botanical used for an array of purported health benefits. The primary extract of milk thistle is termed silymarin, a complex mixture that contains a number of structurally-related flavonolignans, the flavonoid, taxifolin, and a number of other constituents. The major flavonolignans present in most extracts are silybin A, silybin B, isosilybin A and isosilybin B, silydianin, silychristin and isosilychristin. Silymarin itself has been reported to inhibit CYP2C8 activity in vitro, but the effect of the individual flavonolignans on this enzyme has not been studied. To investigate the effects of milk thistle extract and its main flavonolignans (silybin A, silybin B, isosilybin A and isosilybin B) on CYP2C8 activity at relevant concentrations, the effect of milk thistle extract and the flavonolignans on CYP2C8 enzyme activity was studied in vitro using human liver microsomes (HLM) incorporating an enzyme-selective substrate for CYP2C8, amodiaquine. Metabolite formation was analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). The concentration causing 50% inhibition of enzyme activity (IC 50 ) was used to express the degree of inhibition. Isosilibinin, a mixture of the diastereoisomers isosilybin A and isosilybin B, was found to be the most potent inhibitor, followed by isosilybin B with IC 50 values (mean ± SE) of 1.64 ± 0.66 μg/mL and 2.67 ± 1.18 μg/mL, respectively. The rank order of observed inhibitory potency after isosilibinin was silibinin > isosilybin A > silybin A > milk thistle extract > and silybin B. These in vitro results suggest a potentially significant inhibitory effect of isosilibinin and isosilybin B on CYP2C8 activity. However, the observed IC 50 values are unlikely to be achieved in humans supplemented with orally administered milk thistle extracts due to the poor bioavailability of flavonolignans documented with most commercially available formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

A catalog of automated analysis methods for enterprise models.

PubMed

Florez, Hector; Sánchez, Mario; Villalobos, Jorge

2016-01-01

Enterprise models are created for documenting and communicating the structure and state of Business and Information Technologies elements of an enterprise. After models are completed, they are mainly used to support analysis. Model analysis is an activity typically based on human skills and due to the size and complexity of the models, this process can be complicated and omissions or miscalculations are very likely. This situation has fostered the research of automated analysis methods, for supporting analysts in enterprise analysis processes. By reviewing the literature, we found several analysis methods; nevertheless, they are based on specific situations and different metamodels; then, some analysis methods might not be applicable to all enterprise models. This paper presents the work of compilation (literature review), classification, structuring, and characterization of automated analysis methods for enterprise models, expressing them in a standardized modeling language. In addition, we have implemented the analysis methods in our modeling tool.

40 CFR 52.1490 - Original identification of plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

... measures. (ii) A modeling analysis indicating 1982 attainment. (iii) Documentation of the modeling analysis... agencies, (ii) Additional supporting documentation for the 1982 attainment modeling analysis which included... factors for the model. (iii) A revised 1982 attainment modeling analysis and supporting documentation...

40 CFR 52.1490 - Original identification of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... measures. (ii) A modeling analysis indicating 1982 attainment. (iii) Documentation of the modeling analysis... agencies, (ii) Additional supporting documentation for the 1982 attainment modeling analysis which included... factors for the model. (iii) A revised 1982 attainment modeling analysis and supporting documentation...

40 CFR 52.1490 - Original identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... measures. (ii) A modeling analysis indicating 1982 attainment. (iii) Documentation of the modeling analysis... agencies, (ii) Additional supporting documentation for the 1982 attainment modeling analysis which included... factors for the model. (iii) A revised 1982 attainment modeling analysis and supporting documentation...

Ascertaining Validity in the Abstract Realm of PMESII Simulation Models: An Analysis of the Peace Support Operations Model (PSOM)

DTIC Science & Technology

2009-06-01

simulation is the campaign-level Peace Support Operations Model (PSOM). This thesis provides a quantitative analysis of PSOM. The results are based ...multiple potential outcomes , further development and analysis is required before the model is used for large scale analysis . 15. NUMBER OF PAGES 159...multiple potential outcomes , further development and analysis is required before the model is used for large scale analysis . vi THIS PAGE

An Integrated Analysis of the Physiological Effects of Space Flight: Executive Summary

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

A large array of models were applied in a unified manner to solve problems in space flight physiology. Mathematical simulation was used as an alternative way of looking at physiological systems and maximizing the yield from previous space flight experiments. A medical data analysis system was created which consist of an automated data base, a computerized biostatistical and data analysis system, and a set of simulation models of physiological systems. Five basic models were employed: (1) a pulsatile cardiovascular model; (2) a respiratory model; (3) a thermoregulatory model; (4) a circulatory, fluid, and electrolyte balance model; and (5) an erythropoiesis regulatory model. Algorithms were provided to perform routine statistical tests, multivariate analysis, nonlinear regression analysis, and autocorrelation analysis. Special purpose programs were prepared for rank correlation, factor analysis, and the integration of the metabolic balance data.

Load Model Verification, Validation and Calibration Framework by Statistical Analysis on Field Data

NASA Astrophysics Data System (ADS)

Jiao, Xiangqing; Liao, Yuan; Nguyen, Thai

2017-11-01

Accurate load models are critical for power system analysis and operation. A large amount of research work has been done on load modeling. Most of the existing research focuses on developing load models, while little has been done on developing formal load model verification and validation (V&V) methodologies or procedures. Most of the existing load model validation is based on qualitative rather than quantitative analysis. In addition, not all aspects of model V&V problem have been addressed by the existing approaches. To complement the existing methods, this paper proposes a novel load model verification and validation framework that can systematically and more comprehensively examine load model's effectiveness and accuracy. Statistical analysis, instead of visual check, quantifies the load model's accuracy, and provides a confidence level of the developed load model for model users. The analysis results can also be used to calibrate load models. The proposed framework can be used as a guidance to systematically examine load models for utility engineers and researchers. The proposed method is demonstrated through analysis of field measurements collected from a utility system.

On Two-Dimensional ARMA Models for Image Analysis.

DTIC Science & Technology

1980-03-24

2-D ARMA models for image analysis . Particular emphasis is placed on restoration of noisy images using 2-D ARMA models. Computer results are...is concluded that the models are very effective linear models for image analysis . (Author)

Error Propagation Analysis in the SAE Architecture Analysis and Design Language (AADL) and the EDICT Tool Framework

NASA Technical Reports Server (NTRS)

LaValley, Brian W.; Little, Phillip D.; Walter, Chris J.

2011-01-01

This report documents the capabilities of the EDICT tools for error modeling and error propagation analysis when operating with models defined in the Architecture Analysis & Design Language (AADL). We discuss our experience using the EDICT error analysis capabilities on a model of the Scalable Processor-Independent Design for Enhanced Reliability (SPIDER) architecture that uses the Reliable Optical Bus (ROBUS). Based on these experiences we draw some initial conclusions about model based design techniques for error modeling and analysis of highly reliable computing architectures.

Service-oriented model-encapsulation strategy for sharing and integrating heterogeneous geo-analysis models in an open web environment

NASA Astrophysics Data System (ADS)

Yue, Songshan; Chen, Min; Wen, Yongning; Lu, Guonian

2016-04-01

Earth environment is extremely complicated and constantly changing; thus, it is widely accepted that the use of a single geo-analysis model cannot accurately represent all details when solving complex geo-problems. Over several years of research, numerous geo-analysis models have been developed. However, a collaborative barrier between model providers and model users still exists. The development of cloud computing has provided a new and promising approach for sharing and integrating geo-analysis models across an open web environment. To share and integrate these heterogeneous models, encapsulation studies should be conducted that are aimed at shielding original execution differences to create services which can be reused in the web environment. Although some model service standards (such as Web Processing Service (WPS) and Geo Processing Workflow (GPW)) have been designed and developed to help researchers construct model services, various problems regarding model encapsulation remain. (1) The descriptions of geo-analysis models are complicated and typically require rich-text descriptions and case-study illustrations, which are difficult to fully represent within a single web request (such as the GetCapabilities and DescribeProcess operations in the WPS standard). (2) Although Web Service technologies can be used to publish model services, model users who want to use a geo-analysis model and copy the model service into another computer still encounter problems (e.g., they cannot access the model deployment dependencies information). This study presents a strategy for encapsulating geo-analysis models to reduce problems encountered when sharing models between model providers and model users and supports the tasks with different web service standards (e.g., the WPS standard). A description method for heterogeneous geo-analysis models is studied. Based on the model description information, the methods for encapsulating the model-execution program to model services and for describing model-service deployment information are also included in the proposed strategy. Hence, the model-description interface, model-execution interface and model-deployment interface are studied to help model providers and model users more easily share, reuse and integrate geo-analysis models in an open web environment. Finally, a prototype system is established, and the WPS standard is employed as an example to verify the capability and practicability of the model-encapsulation strategy. The results show that it is more convenient for modellers to share and integrate heterogeneous geo-analysis models in cloud computing platforms.

Aircraft/Air Traffic Management Functional Analysis Model. Version 2.0; User's Guide

NASA Technical Reports Server (NTRS)

Etheridge, Melvin; Plugge, Joana; Retina, Nusrat

1998-01-01

The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) a National Aeronautics and Space Administration (NASA) contract. This document provides a guide for using the model in analysis. Those interested in making enhancements or modification to the model should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Technical Description.

Illustrating a Model-Game-Model Paradigm for Using Human Wargames in Analysis

DTIC Science & Technology

2017-02-01

Working Paper Illustrating a Model- Game -Model Paradigm for Using Human Wargames in Analysis Paul K. Davis RAND National Security Research...paper proposes and illustrates an analysis-centric paradigm (model- game -model or what might be better called model-exercise-model in some cases) for...to involve stakehold- ers in model development from the outset. The model- game -model paradigm was illustrated in an application to crisis planning

Review: To be or not to be an identifiable model. Is this a relevant question in animal science modelling?

PubMed

Muñoz-Tamayo, R; Puillet, L; Daniel, J B; Sauvant, D; Martin, O; Taghipoor, M; Blavy, P

2018-04-01

What is a good (useful) mathematical model in animal science? For models constructed for prediction purposes, the question of model adequacy (usefulness) has been traditionally tackled by statistical analysis applied to observed experimental data relative to model-predicted variables. However, little attention has been paid to analytic tools that exploit the mathematical properties of the model equations. For example, in the context of model calibration, before attempting a numerical estimation of the model parameters, we might want to know if we have any chance of success in estimating a unique best value of the model parameters from available measurements. This question of uniqueness is referred to as structural identifiability; a mathematical property that is defined on the sole basis of the model structure within a hypothetical ideal experiment determined by a setting of model inputs (stimuli) and observable variables (measurements). Structural identifiability analysis applied to dynamic models described by ordinary differential equations (ODEs) is a common practice in control engineering and system identification. This analysis demands mathematical technicalities that are beyond the academic background of animal science, which might explain the lack of pervasiveness of identifiability analysis in animal science modelling. To fill this gap, in this paper we address the analysis of structural identifiability from a practitioner perspective by capitalizing on the use of dedicated software tools. Our objectives are (i) to provide a comprehensive explanation of the structural identifiability notion for the community of animal science modelling, (ii) to assess the relevance of identifiability analysis in animal science modelling and (iii) to motivate the community to use identifiability analysis in the modelling practice (when the identifiability question is relevant). We focus our study on ODE models. By using illustrative examples that include published mathematical models describing lactation in cattle, we show how structural identifiability analysis can contribute to advancing mathematical modelling in animal science towards the production of useful models and, moreover, highly informative experiments via optimal experiment design. Rather than attempting to impose a systematic identifiability analysis to the modelling community during model developments, we wish to open a window towards the discovery of a powerful tool for model construction and experiment design.

Assessment of Technologies for the Space Shuttle External Tank Thermal Protection System and Recommendations for Technology Improvement. Part 2; Structural Analysis Technologies and Modeling Practices

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.; Nemeth, Michael P.; Hilburger, Mark W.

2004-01-01

A technology review and assessment of modeling and analysis efforts underway in support of a safe return to flight of the thermal protection system (TPS) for the Space Shuttle external tank (ET) are summarized. This review and assessment effort focuses on the structural modeling and analysis practices employed for ET TPS foam design and analysis and on identifying analysis capabilities needed in the short-term and long-term. The current understanding of the relationship between complex flight environments and ET TPS foam failure modes are reviewed as they relate to modeling and analysis. A literature review on modeling and analysis of TPS foam material systems is also presented. Finally, a review of modeling and analysis tools employed in the Space Shuttle Program is presented for the ET TPS acreage and close-out foam regions. This review includes existing simplified engineering analysis tools are well as finite element analysis procedures.

Assessment of current state of the art in modeling techniques and analysis methods for large space structures

NASA Technical Reports Server (NTRS)

Noor, A. K.

1983-01-01

Advances in continuum modeling, progress in reduction methods, and analysis and modeling needs for large space structures are covered with specific attention given to repetitive lattice trusses. As far as continuum modeling is concerned, an effective and verified analysis capability exists for linear thermoelastic stress, birfurcation buckling, and free vibration problems of repetitive lattices. However, application of continuum modeling to nonlinear analysis needs more development. Reduction methods are very effective for bifurcation buckling and static (steady-state) nonlinear analysis. However, more work is needed to realize their full potential for nonlinear dynamic and time-dependent problems. As far as analysis and modeling needs are concerned, three areas are identified: loads determination, modeling and nonclassical behavior characteristics, and computational algorithms. The impact of new advances in computer hardware, software, integrated analysis, CAD/CAM stems, and materials technology is also discussed.

On the Relations among Regular, Equal Unique Variances, and Image Factor Analysis Models.

ERIC Educational Resources Information Center

Hayashi, Kentaro; Bentler, Peter M.

2000-01-01

Investigated the conditions under which the matrix of factor loadings from the factor analysis model with equal unique variances will give a good approximation to the matrix of factor loadings from the regular factor analysis model. Extends the results to the image factor analysis model. Discusses implications for practice. (SLD)

ON IDENTIFIABILITY OF NONLINEAR ODE MODELS AND APPLICATIONS IN VIRAL DYNAMICS

PubMed Central

MIAO, HONGYU; XIA, XIAOHUA; PERELSON, ALAN S.; WU, HULIN

2011-01-01

Ordinary differential equations (ODE) are a powerful tool for modeling dynamic processes with wide applications in a variety of scientific fields. Over the last 2 decades, ODEs have also emerged as a prevailing tool in various biomedical research fields, especially in infectious disease modeling. In practice, it is important and necessary to determine unknown parameters in ODE models based on experimental data. Identifiability analysis is the first step in determing unknown parameters in ODE models and such analysis techniques for nonlinear ODE models are still under development. In this article, we review identifiability analysis methodologies for nonlinear ODE models developed in the past one to two decades, including structural identifiability analysis, practical identifiability analysis and sensitivity-based identifiability analysis. Some advanced topics and ongoing research are also briefly reviewed. Finally, some examples from modeling viral dynamics of HIV, influenza and hepatitis viruses are given to illustrate how to apply these identifiability analysis methods in practice. PMID:21785515

The Use of Object-Oriented Analysis Methods in Surety Analysis

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

Craft, Richard L.; Funkhouser, Donald R.; Wyss, Gregory D.

1999-05-01

Object-oriented analysis methods have been used in the computer science arena for a number of years to model the behavior of computer-based systems. This report documents how such methods can be applied to surety analysis. By embodying the causality and behavior of a system in a common object-oriented analysis model, surety analysts can make the assumptions that underlie their models explicit and thus better communicate with system designers. Furthermore, given minor extensions to traditional object-oriented analysis methods, it is possible to automatically derive a wide variety of traditional risk and reliability analysis methods from a single common object model. Automaticmore » model extraction helps ensure consistency among analyses and enables the surety analyst to examine a system from a wider variety of viewpoints in a shorter period of time. Thus it provides a deeper understanding of a system's behaviors and surety requirements. This report documents the underlying philosophy behind the common object model representation, the methods by which such common object models can be constructed, and the rules required to interrogate the common object model for derivation of traditional risk and reliability analysis models. The methodology is demonstrated in an extensive example problem.« less

Integrated Modeling Activities for the James Webb Space Telescope (JWST): Structural-Thermal-Optical Analysis

NASA Technical Reports Server (NTRS)

Johnston, John D.; Parrish, Keith; Howard, Joseph M.; Mosier, Gary E.; McGinnis, Mark; Bluth, Marcel; Kim, Kevin; Ha, Hong Q.

2004-01-01

This is a continuation of a series of papers on modeling activities for JWST. The structural-thermal- optical, often referred to as "STOP", analysis process is used to predict the effect of thermal distortion on optical performance. The benchmark STOP analysis for JWST assesses the effect of an observatory slew on wavefront error. The paper begins an overview of multi-disciplinary engineering analysis, or integrated modeling, which is a critical element of the JWST mission. The STOP analysis process is then described. This process consists of the following steps: thermal analysis, structural analysis, and optical analysis. Temperatures predicted using geometric and thermal math models are mapped to the structural finite element model in order to predict thermally-induced deformations. Motions and deformations at optical surfaces are input to optical models and optical performance is predicted using either an optical ray trace or WFE estimation techniques based on prior ray traces or first order optics. Following the discussion of the analysis process, results based on models representing the design at the time of the System Requirements Review. In addition to baseline performance predictions, sensitivity studies are performed to assess modeling uncertainties. Of particular interest is the sensitivity of optical performance to uncertainties in temperature predictions and variations in metal properties. The paper concludes with a discussion of modeling uncertainty as it pertains to STOP analysis.

Systems thinking, the Swiss Cheese Model and accident analysis: a comparative systemic analysis of the Grayrigg train derailment using the ATSB, AcciMap and STAMP models.

PubMed

Underwood, Peter; Waterson, Patrick

2014-07-01

The Swiss Cheese Model (SCM) is the most popular accident causation model and is widely used throughout various industries. A debate exists in the research literature over whether the SCM remains a viable tool for accident analysis. Critics of the model suggest that it provides a sequential, oversimplified view of accidents. Conversely, proponents suggest that it embodies the concepts of systems theory, as per the contemporary systemic analysis techniques. The aim of this paper was to consider whether the SCM can provide a systems thinking approach and remain a viable option for accident analysis. To achieve this, the train derailment at Grayrigg was analysed with an SCM-based model (the ATSB accident investigation model) and two systemic accident analysis methods (AcciMap and STAMP). The analysis outputs and usage of the techniques were compared. The findings of the study showed that each model applied the systems thinking approach. However, the ATSB model and AcciMap graphically presented their findings in a more succinct manner, whereas STAMP more clearly embodied the concepts of systems theory. The study suggests that, whilst the selection of an analysis method is subject to trade-offs that practitioners and researchers must make, the SCM remains a viable model for accident analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using Structural Equation Modeling To Fit Models Incorporating Principal Components.

ERIC Educational Resources Information Center

Dolan, Conor; Bechger, Timo; Molenaar, Peter

1999-01-01

Considers models incorporating principal components from the perspectives of structural-equation modeling. These models include the following: (1) the principal-component analysis of patterned matrices; (2) multiple analysis of variance based on principal components; and (3) multigroup principal-components analysis. Discusses fitting these models…

An Analysis Technique/Automated Tool for Comparing and Tracking Analysis Modes of Different Finite Element Models

NASA Technical Reports Server (NTRS)

Towner, Robert L.; Band, Jonathan L.

2012-01-01

An analysis technique was developed to compare and track mode shapes for different Finite Element Models. The technique may be applied to a variety of structural dynamics analyses, including model reduction validation (comparing unreduced and reduced models), mode tracking for various parametric analyses (e.g., launch vehicle model dispersion analysis to identify sensitivities to modal gain for Guidance, Navigation, and Control), comparing models of different mesh fidelity (e.g., a coarse model for a preliminary analysis compared to a higher-fidelity model for a detailed analysis) and mode tracking for a structure with properties that change over time (e.g., a launch vehicle from liftoff through end-of-burn, with propellant being expended during the flight). Mode shapes for different models are compared and tracked using several numerical indicators, including traditional Cross-Orthogonality and Modal Assurance Criteria approaches, as well as numerical indicators obtained by comparing modal strain energy and kinetic energy distributions. This analysis technique has been used to reliably identify correlated mode shapes for complex Finite Element Models that would otherwise be difficult to compare using traditional techniques. This improved approach also utilizes an adaptive mode tracking algorithm that allows for automated tracking when working with complex models and/or comparing a large group of models.

Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

PubMed

Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

2013-05-01

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Copyright © 2012 Wiley Periodicals, Inc.

Aircraft/Air Traffic Management Functional Analysis Model: Technical Description. 2.0

NASA Technical Reports Server (NTRS)

Etheridge, Melvin; Plugge, Joana; Retina, Nusrat

1998-01-01

The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) under a National Aeronautics and Space Administration (NASA) contract. This document provides a technical description of FAM 2.0 and its computer files to enable the modeler and programmer to make enhancements or modifications to the model. Those interested in a guide for using the model in analysis should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Users Manual.

National Centers for Environmental Prediction

Science.gov Websites

Modeling Mesoscale Modeling Marine Modeling and Analysis Teams Climate Data Assimilation Ensembles and Post Ice group works on sea ice analysis from satellite, sea ice modeling, and ice-atmosphere-ocean / VISION | About EMC Analysis Drift Model KISS Model Numerical Forecast Systems The Polar and Great Lakes

Practical Use of Computationally Frugal Model Analysis Methods

DOE PAGES

Hill, Mary C.; Kavetski, Dmitri; Clark, Martyn; ...

2015-03-21

Computationally frugal methods of model analysis can provide substantial benefits when developing models of groundwater and other environmental systems. Model analysis includes ways to evaluate model adequacy and to perform sensitivity and uncertainty analysis. Frugal methods typically require 10s of parallelizable model runs; their convenience allows for other uses of the computational effort. We suggest that model analysis be posed as a set of questions used to organize methods that range from frugal to expensive (requiring 10,000 model runs or more). This encourages focus on method utility, even when methods have starkly different theoretical backgrounds. We note that many frugalmore » methods are more useful when unrealistic process-model nonlinearities are reduced. Inexpensive diagnostics are identified for determining when frugal methods are advantageous. Examples from the literature are used to demonstrate local methods and the diagnostics. We suggest that the greater use of computationally frugal model analysis methods would allow questions such as those posed in this work to be addressed more routinely, allowing the environmental sciences community to obtain greater scientific insight from the many ongoing and future modeling efforts« less

Differential disease resistance response in the barley necrotic mutant nec1.

PubMed

Keisa, Anete; Kanberga-Silina, Krista; Nakurte, Ilva; Kunga, Laura; Rostoks, Nils

2011-04-15

Although ion fluxes are considered to be an integral part of signal transduction during responses to pathogens, only a few ion channels are known to participate in the plant response to infection. CNGC4 is a disease resistance-related cyclic nucleotide-gated ion channel. Arabidopsis thaliana CNGC4 mutants hlm1 and dnd2 display an impaired hypersensitive response (HR), retarded growth, a constitutively active salicylic acid (SA)-mediated pathogenesis-related response and elevated resistance against bacterial pathogens. Barley CNGC4 shares 67% aa identity with AtCNGC4. The barley mutant nec1 comprising of a frame-shift mutation of CNGC4 displays a necrotic phenotype and constitutively over-expresses PR-1, yet it is not known what effect the nec1 mutation has on barley resistance against different types of pathogens. nec1 mutant accumulated high amount of SA and hydrogen peroxide compared to parental cv. Parkland. Experiments investigating nec1 disease resistance demonstrated positive effect of nec1 mutation on non-host resistance against Pseudomonas syringae pv. tomato (Pst) at high inoculum density, whereas at normal Pst inoculum concentration nec1 resistance did not differ from wt. In contrast to augmented P. syringae resistance, penetration resistance against biotrophic fungus Blumeria graminis f. sp. hordei (Bgh), the causal agent of powdery mildew, was not altered in nec1. The nec1 mutant significantly over-expressed race non-specific Bgh resistance-related genes BI-1 and MLO. Induction of BI-1 and MLO suggested putative involvement of nec1 in race non-specific Bgh resistance, therefore the effect of nec1on mlo-5-mediated Bgh resistance was assessed. The nec1/mlo-5 double mutant was as resistant to Bgh as Nec1/mlo-5 plants, suggesting that nec1 did not impair mlo-5 race non-specific Bgh resistance. Together, the results suggest that nec1 mutation alters activation of systemic acquired resistance-related physiological markers and non-host resistance in barley, while not changing rapid localized response during compatible interaction with host pathogen. Increased resistance of nec1 against non-host pathogen Pst suggests that nec1 mutation may affect certain aspects of barley disease resistance, while it remains to be determined, if the effect on disease resistance is a direct response to changes in SA signaling. © 2011 Keisa et al; licensee BioMed Central Ltd.

Using multiple group modeling to test moderators in meta-analysis.

PubMed

Schoemann, Alexander M

2016-12-01

Meta-analysis is a popular and flexible analysis that can be fit in many modeling frameworks. Two methods of fitting meta-analyses that are growing in popularity are structural equation modeling (SEM) and multilevel modeling (MLM). By using SEM or MLM to fit a meta-analysis researchers have access to powerful techniques associated with SEM and MLM. This paper details how to use one such technique, multiple group analysis, to test categorical moderators in meta-analysis. In a multiple group meta-analysis a model is fit to each level of the moderator simultaneously. By constraining parameters across groups any model parameter can be tested for equality. Using multiple groups to test for moderators is especially relevant in random-effects meta-analysis where both the mean and the between studies variance of the effect size may be compared across groups. A simulation study and the analysis of a real data set are used to illustrate multiple group modeling with both SEM and MLM. Issues related to multiple group meta-analysis and future directions for research are discussed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Integration of design, structural, thermal and optical analysis: And user's guide for structural-to-optical translator (PATCOD)

NASA Technical Reports Server (NTRS)

Amundsen, R. M.; Feldhaus, W. S.; Little, A. D.; Mitchum, M. V.

1995-01-01

Electronic integration of design and analysis processes was achieved and refined at Langley Research Center (LaRC) during the development of an optical bench for a laser-based aerospace experiment. Mechanical design has been integrated with thermal, structural and optical analyses. Electronic import of the model geometry eliminates the repetitive steps of geometry input to develop each analysis model, leading to faster and more accurate analyses. Guidelines for integrated model development are given. This integrated analysis process has been built around software that was already in use by designers and analysis at LaRC. The process as currently implemented used Pro/Engineer for design, Pro/Manufacturing for fabrication, PATRAN for solid modeling, NASTRAN for structural analysis, SINDA-85 and P/Thermal for thermal analysis, and Code V for optical analysis. Currently, the only analysis model to be built manually is the Code V model; all others can be imported for the Pro/E geometry. The translator from PATRAN results to Code V optical analysis (PATCOD) was developed and tested at LaRC. Directions for use of the translator or other models are given.

Global Sensitivity Analysis for Identifying Important Parameters of Nitrogen Nitrification and Denitrification under Model and Scenario Uncertainties

NASA Astrophysics Data System (ADS)

Ye, M.; Chen, Z.; Shi, L.; Zhu, Y.; Yang, J.

2017-12-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. While global sensitivity analysis is a vital tool for identifying the parameters important to nitrogen reactive transport, conventional global sensitivity analysis only considers parametric uncertainty. This may result in inaccurate selection of important parameters, because parameter importance may vary under different models and modeling scenarios. By using a recently developed variance-based global sensitivity analysis method, this paper identifies important parameters with simultaneous consideration of parametric uncertainty, model uncertainty, and scenario uncertainty. In a numerical example of nitrogen reactive transport modeling, a combination of three scenarios of soil temperature and two scenarios of soil moisture leads to a total of six scenarios. Four alternative models are used to evaluate reduction functions used for calculating actual rates of nitrification and denitrification. The model uncertainty is tangled with scenario uncertainty, as the reduction functions depend on soil temperature and moisture content. The results of sensitivity analysis show that parameter importance varies substantially between different models and modeling scenarios, which may lead to inaccurate selection of important parameters if model and scenario uncertainties are not considered. This problem is avoided by using the new method of sensitivity analysis in the context of model averaging and scenario averaging. The new method of sensitivity analysis can be applied to other problems of contaminant transport modeling when model uncertainty and/or scenario uncertainty are present.

Building energy analysis tool

DOEpatents

Brackney, Larry; Parker, Andrew; Long, Nicholas; Metzger, Ian; Dean, Jesse; Lisell, Lars

2016-04-12

A building energy analysis system includes a building component library configured to store a plurality of building components, a modeling tool configured to access the building component library and create a building model of a building under analysis using building spatial data and using selected building components of the plurality of building components stored in the building component library, a building analysis engine configured to operate the building model and generate a baseline energy model of the building under analysis and further configured to apply one or more energy conservation measures to the baseline energy model in order to generate one or more corresponding optimized energy models, and a recommendation tool configured to assess the one or more optimized energy models against the baseline energy model and generate recommendations for substitute building components or modifications.

ModelMate - A graphical user interface for model analysis

USGS Publications Warehouse

Banta, Edward R.

2011-01-01

ModelMate is a graphical user interface designed to facilitate use of model-analysis programs with models. This initial version of ModelMate supports one model-analysis program, UCODE_2005, and one model software program, MODFLOW-2005. ModelMate can be used to prepare input files for UCODE_2005, run UCODE_2005, and display analysis results. A link to the GW_Chart graphing program facilitates visual interpretation of results. ModelMate includes capabilities for organizing directories used with the parallel-processing capabilities of UCODE_2005 and for maintaining files in those directories to be identical to a set of files in a master directory. ModelMate can be used on its own or in conjunction with ModelMuse, a graphical user interface for MODFLOW-2005 and PHAST.

[Model-based biofuels system analysis: a review].

PubMed

Chang, Shiyan; Zhang, Xiliang; Zhao, Lili; Ou, Xunmin

2011-03-01

Model-based system analysis is an important tool for evaluating the potential and impacts of biofuels, and for drafting biofuels technology roadmaps and targets. The broad reach of the biofuels supply chain requires that biofuels system analyses span a range of disciplines, including agriculture/forestry, energy, economics, and the environment. Here we reviewed various models developed for or applied to modeling biofuels, and presented a critical analysis of Agriculture/Forestry System Models, Energy System Models, Integrated Assessment Models, Micro-level Cost, Energy and Emission Calculation Models, and Specific Macro-level Biofuel Models. We focused on the models' strengths, weaknesses, and applicability, facilitating the selection of a suitable type of model for specific issues. Such an analysis was a prerequisite for future biofuels system modeling, and represented a valuable resource for researchers and policy makers.

Model Based Analysis and Test Generation for Flight Software

NASA Technical Reports Server (NTRS)

Pasareanu, Corina S.; Schumann, Johann M.; Mehlitz, Peter C.; Lowry, Mike R.; Karsai, Gabor; Nine, Harmon; Neema, Sandeep

2009-01-01

We describe a framework for model-based analysis and test case generation in the context of a heterogeneous model-based development paradigm that uses and combines Math- Works and UML 2.0 models and the associated code generation tools. This paradigm poses novel challenges to analysis and test case generation that, to the best of our knowledge, have not been addressed before. The framework is based on a common intermediate representation for different modeling formalisms and leverages and extends model checking and symbolic execution tools for model analysis and test case generation, respectively. We discuss the application of our framework to software models for a NASA flight mission.

The application of sensitivity analysis to models of large scale physiological systems

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1974-01-01

A survey of the literature of sensitivity analysis as it applies to biological systems is reported as well as a brief development of sensitivity theory. A simple population model and a more complex thermoregulatory model illustrate the investigatory techniques and interpretation of parameter sensitivity analysis. The role of sensitivity analysis in validating and verifying models, and in identifying relative parameter influence in estimating errors in model behavior due to uncertainty in input data is presented. This analysis is valuable to the simulationist and the experimentalist in allocating resources for data collection. A method for reducing highly complex, nonlinear models to simple linear algebraic models that could be useful for making rapid, first order calculations of system behavior is presented.

Advanced flight design systems subsystem performance models. Sample model: Environmental analysis routine library

NASA Technical Reports Server (NTRS)

Parker, K. C.; Torian, J. G.

1980-01-01

A sample environmental control and life support model performance analysis using the environmental analysis routines library is presented. An example of a complete model set up and execution is provided. The particular model was synthesized to utilize all of the component performance routines and most of the program options.

Airflow and Particle Transport Through Human Airways: A Systematic Review

NASA Astrophysics Data System (ADS)

Kharat, S. B.; Deoghare, A. B.; Pandey, K. M.

2017-08-01

This paper describes review of the relevant literature about two phase analysis of air and particle flow through human airways. An emphasis of the review is placed on elaborating the steps involved in two phase analysis, which are Geometric modelling methods and Mathematical models. The first two parts describes various approaches that are followed for constructing an Airway model upon which analysis are conducted. Broad two categories of geometric modelling viz. Simplified modelling and Accurate modelling using medical scans are discussed briefly. Ease and limitations of simplified models, then examples of CT based models are discussed. In later part of the review different mathematical models implemented by researchers for analysis are briefed. Mathematical models used for Air and Particle phases are elaborated separately.

State Analysis Database Tool

NASA Technical Reports Server (NTRS)

Rasmussen, Robert; Bennett, Matthew

2006-01-01

The State Analysis Database Tool software establishes a productive environment for collaboration among software and system engineers engaged in the development of complex interacting systems. The tool embodies State Analysis, a model-based system engineering methodology founded on a state-based control architecture (see figure). A state represents a momentary condition of an evolving system, and a model may describe how a state evolves and is affected by other states. The State Analysis methodology is a process for capturing system and software requirements in the form of explicit models and states, and defining goal-based operational plans consistent with the models. Requirements, models, and operational concerns have traditionally been documented in a variety of system engineering artifacts that address different aspects of a mission s lifecycle. In State Analysis, requirements, models, and operations information are State Analysis artifacts that are consistent and stored in a State Analysis Database. The tool includes a back-end database, a multi-platform front-end client, and Web-based administrative functions. The tool is structured to prompt an engineer to follow the State Analysis methodology, to encourage state discovery and model description, and to make software requirements and operations plans consistent with model descriptions.

Crash Certification by Analysis - Are We There Yet?

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L.; Lyle, Karen H.

2006-01-01

This paper addresses the issue of crash certification by analysis. This broad topic encompasses many ancillary issues including model validation procedures, uncertainty in test data and analysis models, probabilistic techniques for test-analysis correlation, verification of the mathematical formulation, and establishment of appropriate qualification requirements. This paper will focus on certification requirements for crashworthiness of military helicopters; capabilities of the current analysis codes used for crash modeling and simulation, including some examples of simulations from the literature to illustrate the current approach to model validation; and future directions needed to achieve "crash certification by analysis."

Modeling intelligent adversaries for terrorism risk assessment: some necessary conditions for adversary models.

PubMed

Guikema, Seth

2012-07-01

Intelligent adversary modeling has become increasingly important for risk analysis, and a number of different approaches have been proposed for incorporating intelligent adversaries in risk analysis models. However, these approaches are based on a range of often-implicit assumptions about the desirable properties of intelligent adversary models. This "Perspective" paper aims to further risk analysis for situations involving intelligent adversaries by fostering a discussion of the desirable properties for these models. A set of four basic necessary conditions for intelligent adversary models is proposed and discussed. These are: (1) behavioral accuracy to the degree possible, (2) computational tractability to support decision making, (3) explicit consideration of uncertainty, and (4) ability to gain confidence in the model. It is hoped that these suggested necessary conditions foster discussion about the goals and assumptions underlying intelligent adversary modeling in risk analysis. © 2011 Society for Risk Analysis.

Modeling, Analysis, and Optimization Issues for Large Space Structures

NASA Technical Reports Server (NTRS)

Pinson, L. D. (Compiler); Amos, A. K. (Compiler); Venkayya, V. B. (Compiler)

1983-01-01

Topics concerning the modeling, analysis, and optimization of large space structures are discussed including structure-control interaction, structural and structural dynamics modeling, thermal analysis, testing, and design.

Rasmussen's legacy: A paradigm change in engineering for safety.

PubMed

Leveson, Nancy G

2017-03-01

This paper describes three applications of Rasmussen's idea to systems engineering practice. The first is the application of the abstraction hierarchy to engineering specifications, particularly requirements specification. The second is the use of Rasmussen's ideas in safety modeling and analysis to create a new, more powerful type of accident causation model that extends traditional models to better handle human-operated, software-intensive, sociotechnical systems. Because this new model has a formal, mathematical foundation built on systems theory (as was Rasmussen's original model), new modeling and analysis tools become possible. The third application is to engineering hazard analysis. Engineers have traditionally either omitted human from consideration in system hazard analysis or have treated them rather superficially, for example, that they behave randomly. Applying Rasmussen's model of human error to a powerful new hazard analysis technique allows human behavior to be included in engineering hazard analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

COBRA ATD minefield detection model initial performance analysis

NASA Astrophysics Data System (ADS)

Holmes, V. Todd; Kenton, Arthur C.; Hilton, Russell J.; Witherspoon, Ned H.; Holloway, John H., Jr.

2000-08-01

A statistical performance analysis of the USMC Coastal Battlefield Reconnaissance and Analysis (COBRA) Minefield Detection (MFD) Model has been performed in support of the COBRA ATD Program under execution by the Naval Surface Warfare Center/Dahlgren Division/Coastal Systems Station . This analysis uses the Veridian ERIM International MFD model from the COBRA Sensor Performance Evaluation and Computational Tools for Research Analysis modeling toolbox and a collection of multispectral mine detection algorithm response distributions for mines and minelike clutter objects. These mine detection response distributions were generated form actual COBRA ATD test missions over littoral zone minefields. This analysis serves to validate both the utility and effectiveness of the COBRA MFD Model as a predictive MFD performance too. COBRA ATD minefield detection model algorithm performance results based on a simulate baseline minefield detection scenario are presented, as well as result of a MFD model algorithm parametric sensitivity study.

UNCERTAINTY ANALYSIS IN WATER QUALITY MODELING USING QUAL2E

EPA Science Inventory

A strategy for incorporating uncertainty analysis techniques (sensitivity analysis, first order error analysis, and Monte Carlo simulation) into the mathematical water quality model QUAL2E is described. The model, named QUAL2E-UNCAS, automatically selects the input variables or p...

Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV

PubMed Central

Kahana, Shoshana Y.; Jenkins, Richard A.; Bruce, Douglas; Fernandez, Maria I.; Hightow-Weidman, Lisa B.; Bauermeister, Jose A.

2016-01-01

Background The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. Methods The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer–assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). Results Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent unemployment, and percent of people with less than a high school degree) were less likely to report current ART use (OR: 0.85, 95% CI: 0.72–1.00, p = .05). Among current ART users, living in more disadvantaged areas was associated with greater likelihood of having used ART for ≥6 months. Participants living in counties with greater HIV prevalence among 13–24 year olds were more likely to report current ART use (OR: 1.32, 95% CI: 1.05–1.65, p = .02), ≥6 months ART use (OR: 1.32, 95% CI: 1.05–1.65, p = .02), and to be virally suppressed (OR: 1.50, 95% CI: 1.20–1.87, p = .001); however, youth in these areas were also more likely to report missed medical appointments (OR: 1.32, 95% CI: 1.07–1.63, p = .008). Conclusions The findings underscore the multi-level and structural factors associated with ART use, missed HIV care appointments, and viral suppression for adolescents and young adults in the United States. Consideration of these factors is strongly recommended in future intervention, clinical practice, and policy research that seek to understand the contextual influences on individuals’ health behaviors. PMID:27035905

MMAB Mission Statement

Science.gov Websites

services. Marine Modeling and Analysis Branch Logo Click here to go to the EMC/MMAB homepage MMAB Mission Statement The Marine Modeling and Analysis Branch is part of the Environmental Modeling Center, which is Environmental Prediction Environmental Modeling Center Marine Modeling and Analysis Branch 5830 University

Developing a Learning Progression for Number Sense Based on the Rule Space Model in China

ERIC Educational Resources Information Center

Chen, Fu; Yan, Yue; Xin, Tao

2017-01-01

The current study focuses on developing the learning progression of number sense for primary school students, and it applies a cognitive diagnostic model, the rule space model, to data analysis. The rule space model analysis firstly extracted nine cognitive attributes and their hierarchy model from the analysis of previous research and the…

Model-Based Safety Analysis

NASA Technical Reports Server (NTRS)

Joshi, Anjali; Heimdahl, Mats P. E.; Miller, Steven P.; Whalen, Mike W.

2006-01-01

System safety analysis techniques are well established and are used extensively during the design of safety-critical systems. Despite this, most of the techniques are highly subjective and dependent on the skill of the practitioner. Since these analyses are usually based on an informal system model, it is unlikely that they will be complete, consistent, and error free. In fact, the lack of precise models of the system architecture and its failure modes often forces the safety analysts to devote much of their effort to gathering architectural details about the system behavior from several sources and embedding this information in the safety artifacts such as the fault trees. This report describes Model-Based Safety Analysis, an approach in which the system and safety engineers share a common system model created using a model-based development process. By extending the system model with a fault model as well as relevant portions of the physical system to be controlled, automated support can be provided for much of the safety analysis. We believe that by using a common model for both system and safety engineering and automating parts of the safety analysis, we can both reduce the cost and improve the quality of the safety analysis. Here we present our vision of model-based safety analysis and discuss the advantages and challenges in making this approach practical.

Combining Static Analysis and Model Checking for Software Analysis

NASA Technical Reports Server (NTRS)

Brat, Guillaume; Visser, Willem; Clancy, Daniel (Technical Monitor)

2003-01-01

We present an iterative technique in which model checking and static analysis are combined to verify large software systems. The role of the static analysis is to compute partial order information which the model checker uses to reduce the state space. During exploration, the model checker also computes aliasing information that it gives to the static analyzer which can then refine its analysis. The result of this refined analysis is then fed back to the model checker which updates its partial order reduction. At each step of this iterative process, the static analysis computes optimistic information which results in an unsafe reduction of the state space. However we show that the process converges to a fired point at which time the partial order information is safe and the whole state space is explored.

Modeling and Analysis of Wrinkled Membranes: An Overview

NASA Technical Reports Server (NTRS)

Yang, B.; Ding, H.; Lou, M.; Fang, H.; Broduer, Steve (Technical Monitor)

2001-01-01

Thin-film membranes are basic elements of a variety of space inflatable/deployable structures. Wrinkling degrades the performance and reliability of these membrane structures, and hence has been a topic of continued interest. Wrinkling analysis of membranes for general geometry and arbitrary boundary conditions is quite challenging. The objective of this presentation is two-fold. Firstly, the existing models of wrinkled membranes and related numerical solution methods are reviewed. The important issues to be discussed are the capability of a membrane model to characterize taut, wrinkled and slack states of membranes in a consistent and physically reasonable manner; the ability of a wrinkling analysis method to predict the formation and growth of wrinkled regions, and to determine out-of-plane deformation and wrinkled waves; the convergence of a numerical solution method for wrinkling analysis; and the compatibility of a wrinkling analysis with general-purpose finite element codes. According to this review, several opening issues in modeling and analysis of wrinkled membranes that are to be addressed in future research are summarized, The second objective of this presentation is to discuss a newly developed membrane model of two viable parameters (2-VP model) and associated parametric finite element method (PFEM) for wrinkling analysis are introduced. The innovations and advantages of the proposed membrane model and PFEM-based wrinkling analysis are: (1) Via a unified stress-strain relation; the 2-VP model treat the taut, wrinkled, and slack states of membranes consistently; (2) The PFEM-based wrinkling analysis has guaranteed convergence; (3) The 2-VP model along with PFEM is capable of predicting membrane out-of-plane deformations; and (4) The PFEM can be integrated into any existing finite element code. Preliminary numerical examples are also included in this presentation to demonstrate the 2-VP model and PFEM-based wrinkling analysis approach.

Diagnostic evaluation of distributed physically based model at the REW scale (THREW) using rainfall-runoff event analysis

NASA Astrophysics Data System (ADS)

Tian, F.; Sivapalan, M.; Li, H.; Hu, H.

2007-12-01

The importance of diagnostic analysis of hydrological models is increasingly recognized by the scientific community (M. Sivapalan, et al., 2003; H. V. Gupta, et al., 2007). Model diagnosis refers to model structures and parameters being identified not only by statistical comparison of system state variables and outputs but also by process understanding in a specific watershed. Process understanding can be gained by the analysis of observational data and model results at the specific watershed as well as through regionalization. Although remote sensing technology can provide valuable data about the inputs, state variables, and outputs of the hydrological system, observational rainfall-runoff data still constitute the most accurate, reliable, direct, and thus a basic component of hydrology related database. One critical question in model diagnostic analysis is, therefore, what signature characteristic can we extract from rainfall and runoff data. To this date only a few studies have focused on this question, such as Merz et al. (2006) and Lana-Renault et al. (2007), still none of these studies related event analysis with model diagnosis in an explicit, rigorous, and systematic manner. Our work focuses on the identification of the dominant runoff generation mechanisms from event analysis of rainfall-runoff data, including correlation analysis and analysis of timing pattern. The correlation analysis involves the identification of the complex relationship among rainfall depth, intensity, runoff coefficient, and antecedent conditions, and the timing pattern analysis aims to identify the clustering pattern of runoff events in relation to the patterns of rainfall events. Our diagnostic analysis illustrates the changing pattern of runoff generation mechanisms in the DMIP2 test watersheds located in Oklahoma region, which is also well recognized by numerical simulations based on TsingHua Representative Elementary Watershed (THREW) model. The result suggests the usefulness of rainfall-runoff event analysis for model development as well as model diagnostics.

[How to fit and interpret multilevel models using SPSS].

PubMed

Pardo, Antonio; Ruiz, Miguel A; San Martín, Rafael

2007-05-01

Hierarchic or multilevel models are used to analyse data when cases belong to known groups and sample units are selected both from the individual level and from the group level. In this work, the multilevel models most commonly discussed in the statistic literature are described, explaining how to fit these models using the SPSS program (any version as of the 11 th ) and how to interpret the outcomes of the analysis. Five particular models are described, fitted, and interpreted: (1) one-way analysis of variance with random effects, (2) regression analysis with means-as-outcomes, (3) one-way analysis of covariance with random effects, (4) regression analysis with random coefficients, and (5) regression analysis with means- and slopes-as-outcomes. All models are explained, trying to make them understandable to researchers in health and behaviour sciences.

A menu-driven software package of Bayesian nonparametric (and parametric) mixed models for regression analysis and density estimation.

PubMed

Karabatsos, George

2017-02-01

Most of applied statistics involves regression analysis of data. In practice, it is important to specify a regression model that has minimal assumptions which are not violated by data, to ensure that statistical inferences from the model are informative and not misleading. This paper presents a stand-alone and menu-driven software package, Bayesian Regression: Nonparametric and Parametric Models, constructed from MATLAB Compiler. Currently, this package gives the user a choice from 83 Bayesian models for data analysis. They include 47 Bayesian nonparametric (BNP) infinite-mixture regression models; 5 BNP infinite-mixture models for density estimation; and 31 normal random effects models (HLMs), including normal linear models. Each of the 78 regression models handles either a continuous, binary, or ordinal dependent variable, and can handle multi-level (grouped) data. All 83 Bayesian models can handle the analysis of weighted observations (e.g., for meta-analysis), and the analysis of left-censored, right-censored, and/or interval-censored data. Each BNP infinite-mixture model has a mixture distribution assigned one of various BNP prior distributions, including priors defined by either the Dirichlet process, Pitman-Yor process (including the normalized stable process), beta (two-parameter) process, normalized inverse-Gaussian process, geometric weights prior, dependent Dirichlet process, or the dependent infinite-probits prior. The software user can mouse-click to select a Bayesian model and perform data analysis via Markov chain Monte Carlo (MCMC) sampling. After the sampling completes, the software automatically opens text output that reports MCMC-based estimates of the model's posterior distribution and model predictive fit to the data. Additional text and/or graphical output can be generated by mouse-clicking other menu options. This includes output of MCMC convergence analyses, and estimates of the model's posterior predictive distribution, for selected functionals and values of covariates. The software is illustrated through the BNP regression analysis of real data.

Integrating Cognitive Task Analysis into Instructional Systems Development.

ERIC Educational Resources Information Center

Ryder, Joan M.; Redding, Richard E.

1993-01-01

Discussion of instructional systems development (ISD) focuses on recent developments in cognitive task analysis and describes the Integrated Task Analysis Model, a framework for integrating cognitive and behavioral task analysis methods within the ISD model. Three components of expertise are analyzed: skills, knowledge, and mental models. (96…

NCEP SST Analysis

Science.gov Websites

Branches Global Climate & Weather Modeling Mesoscale Modeling Marine Modeling and Analysis Contact EMC , state and local government Web resources and services. Real-time, global, sea surface temperature (RTG_SST_HR) analysis For a regional map, click the desired area in the global SST analysis and anomaly maps

SMP: A solid modeling program version 2.0

NASA Technical Reports Server (NTRS)

Randall, D. P.; Jones, K. H.; Vonofenheim, W. H.; Gates, R. L.; Matthews, C. G.

1986-01-01

The Solid Modeling Program (SMP) provides the capability to model complex solid objects through the composition of primitive geometric entities. In addition to the construction of solid models, SMP has extensive facilities for model editing, display, and analysis. The geometric model produced by the software system can be output in a format compatible with existing analysis programs such as PATRAN-G. The present version of the SMP software supports six primitives: boxes, cones, spheres, paraboloids, tori, and trusses. The details for creating each of the major primitive types is presented. The analysis capabilities of SMP, including interfaces to existing analysis programs, are discussed.

Analytic uncertainty and sensitivity analysis of models with input correlations

NASA Astrophysics Data System (ADS)

Zhu, Yueying; Wang, Qiuping A.; Li, Wei; Cai, Xu

2018-03-01

Probabilistic uncertainty analysis is a common means of evaluating mathematical models. In mathematical modeling, the uncertainty in input variables is specified through distribution laws. Its contribution to the uncertainty in model response is usually analyzed by assuming that input variables are independent of each other. However, correlated parameters are often happened in practical applications. In the present paper, an analytic method is built for the uncertainty and sensitivity analysis of models in the presence of input correlations. With the method, it is straightforward to identify the importance of the independence and correlations of input variables in determining the model response. This allows one to decide whether or not the input correlations should be considered in practice. Numerical examples suggest the effectiveness and validation of our analytic method in the analysis of general models. A practical application of the method is also proposed to the uncertainty and sensitivity analysis of a deterministic HIV model.

Integrating model behavior, optimization, and sensitivity/uncertainty analysis: overview and application of the MOUSE software toolbox

USDA-ARS?s Scientific Manuscript database

This paper provides an overview of the Model Optimization, Uncertainty, and SEnsitivity Analysis (MOUSE) software application, an open-source, Java-based toolbox of visual and numerical analysis components for the evaluation of environmental models. MOUSE is based on the OPTAS model calibration syst...

SBKF Modeling and Analysis Plan: Buckling Analysis of Compression-Loaded Orthogrid and Isogrid Cylinders

NASA Technical Reports Server (NTRS)

Lovejoy, Andrew E.; Hilburger, Mark W.

2013-01-01

This document outlines a Modeling and Analysis Plan (MAP) to be followed by the SBKF analysts. It includes instructions on modeling and analysis formulation and execution, model verification and validation, identifying sources of error and uncertainty, and documentation. The goal of this MAP is to provide a standardized procedure that ensures uniformity and quality of the results produced by the project and corresponding documentation.

Requirements analysis, domain knowledge, and design

NASA Technical Reports Server (NTRS)

Potts, Colin

1988-01-01

Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

Model Performance Evaluation and Scenario Analysis (MPESA) Tutorial

EPA Science Inventory

This tool consists of two parts: model performance evaluation and scenario analysis (MPESA). The model performance evaluation consists of two components: model performance evaluation metrics and model diagnostics. These metrics provides modelers with statistical goodness-of-fit m...

Performance analysis and dynamic modeling of a single-spool turbojet engine

NASA Astrophysics Data System (ADS)

Andrei, Irina-Carmen; Toader, Adrian; Stroe, Gabriela; Frunzulica, Florin

2017-01-01

The purposes of modeling and simulation of a turbojet engine are the steady state analysis and transient analysis. From the steady state analysis, which consists in the investigation of the operating, equilibrium regimes and it is based on appropriate modeling describing the operation of a turbojet engine at design and off-design regimes, results the performance analysis, concluded by the engine's operational maps (i.e. the altitude map, velocity map and speed map) and the engine's universal map. The mathematical model that allows the calculation of the design and off-design performances, in case of a single spool turbojet is detailed. An in house code was developed, its calibration was done for the J85 turbojet engine as the test case. The dynamic modeling of the turbojet engine is obtained from the energy balance equations for compressor, combustor and turbine, as the engine's main parts. The transient analysis, which is based on appropriate modeling of engine and its main parts, expresses the dynamic behavior of the turbojet engine, and further, provides details regarding the engine's control. The aim of the dynamic analysis is to determine a control program for the turbojet, based on the results provided by performance analysis. In case of the single-spool turbojet engine, with fixed nozzle geometry, the thrust is controlled by one parameter, which is the fuel flow rate. The design and management of the aircraft engine controls are based on the results of the transient analysis. The construction of the design model is complex, since it is based on both steady-state and transient analysis, further allowing the flight path cycle analysis and optimizations. This paper presents numerical simulations for a single-spool turbojet engine (J85 as test case), with appropriate modeling for steady-state and dynamic analysis.

Comparison of Response Surface and Kriging Models in the Multidisciplinary Design of an Aerospike Nozzle

NASA Technical Reports Server (NTRS)

Simpson, Timothy W.

1998-01-01

The use of response surface models and kriging models are compared for approximating non-random, deterministic computer analyses. After discussing the traditional response surface approach for constructing polynomial models for approximation, kriging is presented as an alternative statistical-based approximation method for the design and analysis of computer experiments. Both approximation methods are applied to the multidisciplinary design and analysis of an aerospike nozzle which consists of a computational fluid dynamics model and a finite element analysis model. Error analysis of the response surface and kriging models is performed along with a graphical comparison of the approximations. Four optimization problems are formulated and solved using both approximation models. While neither approximation technique consistently outperforms the other in this example, the kriging models using only a constant for the underlying global model and a Gaussian correlation function perform as well as the second order polynomial response surface models.

Finite element modeling and analysis of tires

NASA Technical Reports Server (NTRS)

Noor, A. K.; Andersen, C. M.

1983-01-01

Predicting the response of tires under various loading conditions using finite element technology is addressed. Some of the recent advances in finite element technology which have high potential for application to tire modeling problems are reviewed. The analysis and modeling needs for tires are identified. Reduction methods for large-scale nonlinear analysis, with particular emphasis on treatment of combined loads, displacement-dependent and nonconservative loadings; development of simple and efficient mixed finite element models for shell analysis, identification of equivalent mixed and purely displacement models, and determination of the advantages of using mixed models; and effective computational models for large-rotation nonlinear problems, based on a total Lagrangian description of the deformation are included.

Design and Analysis Tools for Supersonic Inlets

NASA Technical Reports Server (NTRS)

Slater, John W.; Folk, Thomas C.

2009-01-01

Computational tools are being developed for the design and analysis of supersonic inlets. The objective is to update existing tools and provide design and low-order aerodynamic analysis capability for advanced inlet concepts. The Inlet Tools effort includes aspects of creating an electronic database of inlet design information, a document describing inlet design and analysis methods, a geometry model for describing the shape of inlets, and computer tools that implement the geometry model and methods. The geometry model has a set of basic inlet shapes that include pitot, two-dimensional, axisymmetric, and stream-traced inlet shapes. The inlet model divides the inlet flow field into parts that facilitate the design and analysis methods. The inlet geometry model constructs the inlet surfaces through the generation and transformation of planar entities based on key inlet design factors. Future efforts will focus on developing the inlet geometry model, the inlet design and analysis methods, a Fortran 95 code to implement the model and methods. Other computational platforms, such as Java, will also be explored.

Global sensitivity analysis of DRAINMOD-FOREST, an integrated forest ecosystem model

Treesearch

Shiying Tian; Mohamed A. Youssef; Devendra M. Amatya; Eric D. Vance

2014-01-01

Global sensitivity analysis is a useful tool to understand process-based ecosystem models by identifying key parameters and processes controlling model predictions. This study reported a comprehensive global sensitivity analysis for DRAINMOD-FOREST, an integrated model for simulating water, carbon (C), and nitrogen (N) cycles and plant growth in lowland forests. The...

NCEP SST Analysis

Science.gov Websites

Branches Global Climate & Weather Modeling Mesoscale Modeling Marine Modeling and Analysis Contact EMC Weather Service NWS logo - Click to go to the NWS homepage Environmental Modeling Center Home News Organization Search Go Search Polar Go MMAB SST Analysis Main page About MMAB Our Mission Our Personnel EMC

Information Flow in an Atmospheric Model and Data Assimilation

ERIC Educational Resources Information Center

Yoon, Young-noh

2011-01-01

Weather forecasting consists of two processes, model integration and analysis (data assimilation). During the model integration, the state estimate produced by the analysis evolves to the next cycle time according to the atmospheric model to become the background estimate. The analysis then produces a new state estimate by combining the background…

Meta-analysis of Gaussian individual patient data: Two-stage or not two-stage?

PubMed

Morris, Tim P; Fisher, David J; Kenward, Michael G; Carpenter, James R

2018-04-30

Quantitative evidence synthesis through meta-analysis is central to evidence-based medicine. For well-documented reasons, the meta-analysis of individual patient data is held in higher regard than aggregate data. With access to individual patient data, the analysis is not restricted to a "two-stage" approach (combining estimates and standard errors) but can estimate parameters of interest by fitting a single model to all of the data, a so-called "one-stage" analysis. There has been debate about the merits of one- and two-stage analysis. Arguments for one-stage analysis have typically noted that a wider range of models can be fitted and overall estimates may be more precise. The two-stage side has emphasised that the models that can be fitted in two stages are sufficient to answer the relevant questions, with less scope for mistakes because there are fewer modelling choices to be made in the two-stage approach. For Gaussian data, we consider the statistical arguments for flexibility and precision in small-sample settings. Regarding flexibility, several of the models that can be fitted only in one stage may not be of serious interest to most meta-analysis practitioners. Regarding precision, we consider fixed- and random-effects meta-analysis and see that, for a model making certain assumptions, the number of stages used to fit this model is irrelevant; the precision will be approximately equal. Meta-analysts should choose modelling assumptions carefully. Sometimes relevant models can only be fitted in one stage. Otherwise, meta-analysts are free to use whichever procedure is most convenient to fit the identified model. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

ADAM: analysis of discrete models of biological systems using computer algebra.

PubMed

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.

Rapid State Space Modeling Tool for Rectangular Wing Aeroservoelastic Studies

NASA Technical Reports Server (NTRS)

Suh, Peter M.; Conyers, Howard J.; Mavris, Dimitri N.

2014-01-01

This paper introduces a modeling and simulation tool for aeroservoelastic analysis of rectangular wings with trailing edge control surfaces. The inputs to the code are planform design parameters such as wing span, aspect ratio and number of control surfaces. A doublet lattice approach is taken to compute generalized forces. A rational function approximation is computed. The output, computed in a few seconds, is a state space aeroservoelastic model which can be used for analysis and control design. The tool is fully parameterized with default information so there is little required interaction with the model developer. Although, all parameters can be easily modified if desired.The focus of this paper is on tool presentation, verification and validation. This process is carried out in stages throughout the paper. The rational function approximation is verified against computed generalized forces for a plate model. A model composed of finite element plates is compared to a modal analysis from commercial software and an independently conducted experimental ground vibration test analysis. Aeroservoelastic analysis is the ultimate goal of this tool. Therefore the flutter speed and frequency for a clamped plate are computed using V-g and V-f analysis. The computational results are compared to a previously published computational analysis and wind tunnel results for the same structure. Finally a case study of a generic wing model with a single control surface is presented. Verification of the state space model is presented in comparison to V-g and V-f analysis. This also includes the analysis of the model in response to a 1-cos gust.

Rapid State Space Modeling Tool for Rectangular Wing Aeroservoelastic Studies

NASA Technical Reports Server (NTRS)

Suh, Peter M.; Conyers, Howard J.; Mavris, Dimitri N.

2015-01-01

This paper introduces a modeling and simulation tool for aeroservoelastic analysis of rectangular wings with trailing-edge control surfaces. The inputs to the code are planform design parameters such as wing span, aspect ratio, and number of control surfaces. Using this information, the generalized forces are computed using the doublet-lattice method. Using Roger's approximation, a rational function approximation is computed. The output, computed in a few seconds, is a state space aeroservoelastic model which can be used for analysis and control design. The tool is fully parameterized with default information so there is little required interaction with the model developer. All parameters can be easily modified if desired. The focus of this paper is on tool presentation, verification, and validation. These processes are carried out in stages throughout the paper. The rational function approximation is verified against computed generalized forces for a plate model. A model composed of finite element plates is compared to a modal analysis from commercial software and an independently conducted experimental ground vibration test analysis. Aeroservoelastic analysis is the ultimate goal of this tool, therefore, the flutter speed and frequency for a clamped plate are computed using damping-versus-velocity and frequency-versus-velocity analysis. The computational results are compared to a previously published computational analysis and wind-tunnel results for the same structure. A case study of a generic wing model with a single control surface is presented. Verification of the state space model is presented in comparison to damping-versus-velocity and frequency-versus-velocity analysis, including the analysis of the model in response to a 1-cos gust.

Rapid State Space Modeling Tool for Rectangular Wing Aeroservoelastic Studies

NASA Technical Reports Server (NTRS)

Suh, Peter M.; Conyers, Howard Jason; Mavris, Dimitri N.

2015-01-01

This report introduces a modeling and simulation tool for aeroservoelastic analysis of rectangular wings with trailing-edge control surfaces. The inputs to the code are planform design parameters such as wing span, aspect ratio, and number of control surfaces. Using this information, the generalized forces are computed using the doublet-lattice method. Using Roger's approximation, a rational function approximation is computed. The output, computed in a few seconds, is a state space aeroservoelastic model which can be used for analysis and control design. The tool is fully parameterized with default information so there is little required interaction with the model developer. All parameters can be easily modified if desired. The focus of this report is on tool presentation, verification, and validation. These processes are carried out in stages throughout the report. The rational function approximation is verified against computed generalized forces for a plate model. A model composed of finite element plates is compared to a modal analysis from commercial software and an independently conducted experimental ground vibration test analysis. Aeroservoelastic analysis is the ultimate goal of this tool, therefore, the flutter speed and frequency for a clamped plate are computed using damping-versus-velocity and frequency-versus-velocity analysis. The computational results are compared to a previously published computational analysis and wind-tunnel results for the same structure. A case study of a generic wing model with a single control surface is presented. Verification of the state space model is presented in comparison to damping-versus-velocity and frequency-versus-velocity analysis, including the analysis of the model in response to a 1-cos gust.

Image analysis and modeling in medical image computing. Recent developments and advances.

PubMed

Handels, H; Deserno, T M; Meinzer, H-P; Tolxdorff, T

2012-01-01

Medical image computing is of growing importance in medical diagnostics and image-guided therapy. Nowadays, image analysis systems integrating advanced image computing methods are used in practice e.g. to extract quantitative image parameters or to support the surgeon during a navigated intervention. However, the grade of automation, accuracy, reproducibility and robustness of medical image computing methods has to be increased to meet the requirements in clinical routine. In the focus theme, recent developments and advances in the field of modeling and model-based image analysis are described. The introduction of models in the image analysis process enables improvements of image analysis algorithms in terms of automation, accuracy, reproducibility and robustness. Furthermore, model-based image computing techniques open up new perspectives for prediction of organ changes and risk analysis of patients. Selected contributions are assembled to present latest advances in the field. The authors were invited to present their recent work and results based on their outstanding contributions to the Conference on Medical Image Computing BVM 2011 held at the University of Lübeck, Germany. All manuscripts had to pass a comprehensive peer review. Modeling approaches and model-based image analysis methods showing new trends and perspectives in model-based medical image computing are described. Complex models are used in different medical applications and medical images like radiographic images, dual-energy CT images, MR images, diffusion tensor images as well as microscopic images are analyzed. The applications emphasize the high potential and the wide application range of these methods. The use of model-based image analysis methods can improve segmentation quality as well as the accuracy and reproducibility of quantitative image analysis. Furthermore, image-based models enable new insights and can lead to a deeper understanding of complex dynamic mechanisms in the human body. Hence, model-based image computing methods are important tools to improve medical diagnostics and patient treatment in future.

Using structural equation modeling for network meta-analysis.

PubMed

Tu, Yu-Kang; Wu, Yun-Chun

2017-07-14

Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison. SEM provides a very flexible framework for univariate and multivariate meta-analysis, and its potential as a powerful tool for advanced meta-analysis is still to be explored.

Underground Test Area Subproject Phase I Data Analysis Task. Volume VII - Tritium Transport Model Documentation Package

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

None

Volume VII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the tritium transport model documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

Box truss analysis and technology development. Task 1: Mesh analysis and control

NASA Technical Reports Server (NTRS)

Bachtell, E. E.; Bettadapur, S. S.; Coyner, J. V.

1985-01-01

An analytical tool was developed to model, analyze and predict RF performance of box truss antennas with reflective mesh surfaces. The analysis system is unique in that it integrates custom written programs for cord tied mesh surfaces, thereby drastically reducing the cost of analysis. The analysis system is capable of determining the RF performance of antennas under any type of manufacturing or operating environment by integrating together the various disciplines of design, finite element analysis, surface best fit analysis and RF analysis. The Integrated Mesh Analysis System consists of six separate programs: The Mesh Tie System Model Generator, The Loadcase Generator, The Model Optimizer, The Model Solver, The Surface Topography Solver and The RF Performance Solver. Additionally, a study using the mesh analysis system was performed to determine the effect of on orbit calibration, i.e., surface adjustment, on a typical box truss antenna.

Theoretical and software considerations for nonlinear dynamic analysis

NASA Technical Reports Server (NTRS)

Schmidt, R. J.; Dodds, R. H., Jr.

1983-01-01

In the finite element method for structural analysis, it is generally necessary to discretize the structural model into a very large number of elements to accurately evaluate displacements, strains, and stresses. As the complexity of the model increases, the number of degrees of freedom can easily exceed the capacity of present-day software system. Improvements of structural analysis software including more efficient use of existing hardware and improved structural modeling techniques are discussed. One modeling technique that is used successfully in static linear and nonlinear analysis is multilevel substructuring. This research extends the use of multilevel substructure modeling to include dynamic analysis and defines the requirements for a general purpose software system capable of efficient nonlinear dynamic analysis. The multilevel substructuring technique is presented, the analytical formulations and computational procedures for dynamic analysis and nonlinear mechanics are reviewed, and an approach to the design and implementation of a general purpose structural software system is presented.

Beauty and the beast: Some perspectives on efficient model analysis, surrogate models, and the future of modeling

NASA Astrophysics Data System (ADS)

Hill, M. C.; Jakeman, J.; Razavi, S.; Tolson, B.

2015-12-01

For many environmental systems model runtimes have remained very long as more capable computers have been used to add more processes and more time and space discretization. Scientists have also added more parameters and kinds of observations, and many model runs are needed to explore the models. Computational demand equals run time multiplied by number of model runs divided by parallelization opportunities. Model exploration is conducted using sensitivity analysis, optimization, and uncertainty quantification. Sensitivity analysis is used to reveal consequences of what may be very complex simulated relations, optimization is used to identify parameter values that fit the data best, or at least better, and uncertainty quantification is used to evaluate the precision of simulated results. The long execution times make such analyses a challenge. Methods for addressing this challenges include computationally frugal analysis of the demanding original model and a number of ingenious surrogate modeling methods. Both commonly use about 50-100 runs of the demanding original model. In this talk we consider the tradeoffs between (1) original model development decisions, (2) computationally frugal analysis of the original model, and (3) using many model runs of the fast surrogate model. Some questions of interest are as follows. If the added processes and discretization invested in (1) are compared with the restrictions and approximations in model analysis produced by long model execution times, is there a net benefit related of the goals of the model? Are there changes to the numerical methods that could reduce the computational demands while giving up less fidelity than is compromised by using computationally frugal methods or surrogate models for model analysis? Both the computationally frugal methods and surrogate models require that the solution of interest be a smooth function of the parameters or interest. How does the information obtained from the local methods typical of (2) and the global averaged methods typical of (3) compare for typical systems? The discussion will use examples of response of the Greenland glacier to global warming and surface and groundwater modeling.

Beyond the scope of Free-Wilson analysis: building interpretable QSAR models with machine learning algorithms.

PubMed

Chen, Hongming; Carlsson, Lars; Eriksson, Mats; Varkonyi, Peter; Norinder, Ulf; Nilsson, Ingemar

2013-06-24

A novel methodology was developed to build Free-Wilson like local QSAR models by combining R-group signatures and the SVM algorithm. Unlike Free-Wilson analysis this method is able to make predictions for compounds with R-groups not present in a training set. Eleven public data sets were chosen as test cases for comparing the performance of our new method with several other traditional modeling strategies, including Free-Wilson analysis. Our results show that the R-group signature SVM models achieve better prediction accuracy compared with Free-Wilson analysis in general. Moreover, the predictions of R-group signature models are also comparable to the models using ECFP6 fingerprints and signatures for the whole compound. Most importantly, R-group contributions to the SVM model can be obtained by calculating the gradient for R-group signatures. For most of the studied data sets, a significant correlation with that of a corresponding Free-Wilson analysis is shown. These results suggest that the R-group contribution can be used to interpret bioactivity data and highlight that the R-group signature based SVM modeling method is as interpretable as Free-Wilson analysis. Hence the signature SVM model can be a useful modeling tool for any drug discovery project.

Educational and Scientific Applications of Climate Model Diagnostic Analyzer

NASA Astrophysics Data System (ADS)

Lee, S.; Pan, L.; Zhai, C.; Tang, B.; Kubar, T. L.; Zhang, J.; Bao, Q.

2016-12-01

Climate Model Diagnostic Analyzer (CMDA) is a web-based information system designed for the climate modeling and model analysis community to analyze climate data from models and observations. CMDA provides tools to diagnostically analyze climate data for model validation and improvement, and to systematically manage analysis provenance for sharing results with other investigators. CMDA utilizes cloud computing resources, multi-threading computing, machine-learning algorithms, web service technologies, and provenance-supporting technologies to address technical challenges that the Earth science modeling and model analysis community faces in evaluating and diagnosing climate models. As CMDA infrastructure and technology have matured, we have developed the educational and scientific applications of CMDA. Educationally, CMDA supported the summer school of the JPL Center for Climate Sciences for three years since 2014. In the summer school, the students work on group research projects where CMDA provide datasets and analysis tools. Each student is assigned to a virtual machine with CMDA installed in Amazon Web Services. A provenance management system for CMDA is developed to keep track of students' usages of CMDA, and to recommend datasets and analysis tools for their research topic. The provenance system also allows students to revisit their analysis results and share them with their group. Scientifically, we have developed several science use cases of CMDA covering various topics, datasets, and analysis types. Each use case developed is described and listed in terms of a scientific goal, datasets used, the analysis tools used, scientific results discovered from the use case, an analysis result such as output plots and data files, and a link to the exact analysis service call with all the input arguments filled. For example, one science use case is the evaluation of NCAR CAM5 model with MODIS total cloud fraction. The analysis service used is Difference Plot Service of Two Variables, and the datasets used are NCAR CAM total cloud fraction and MODIS total cloud fraction. The scientific highlight of the use case is that the CAM5 model overall does a fairly decent job at simulating total cloud cover, though simulates too few clouds especially near and offshore of the eastern ocean basins where low clouds are dominant.

An NCME Instructional Module on Latent DIF Analysis Using Mixture Item Response Models

ERIC Educational Resources Information Center

Cho, Sun-Joo; Suh, Youngsuk; Lee, Woo-yeol

2016-01-01

The purpose of this ITEMS module is to provide an introduction to differential item functioning (DIF) analysis using mixture item response models. The mixture item response models for DIF analysis involve comparing item profiles across latent groups, instead of manifest groups. First, an overview of DIF analysis based on latent groups, called…

Latent Transition Analysis of Pre-Service Teachers' Efficacy in Mathematics and Science

ERIC Educational Resources Information Center

Ward, Elizabeth Kennedy

2009-01-01

This study modeled changes in pre-service teacher efficacy in mathematics and science over the course of the final year of teacher preparation using latent transition analysis (LTA), a longitudinal form of analysis that builds on two modeling traditions (latent class analysis (LCA) and auto-regressive modeling). Data were collected using the…

Null Models for Everyone: A Two-Step Approach to Teaching Null Model Analysis of Biological Community Structure

ERIC Educational Resources Information Center

McCabe, Declan J.; Knight, Evelyn J.

2016-01-01

Since being introduced by Connor and Simberloff in response to Diamond's assembly rules, null model analysis has been a controversial tool in community ecology. Despite being commonly used in the primary literature, null model analysis has not featured prominently in general textbooks. Complexity of approaches along with difficulty in interpreting…

Effect Sizes for Growth-Modeling Analysis for Controlled Clinical Trials in the Same Metric as for Classical Analysis

ERIC Educational Resources Information Center

Feingold, Alan

2009-01-01

The use of growth-modeling analysis (GMA)--including hierarchical linear models, latent growth models, and general estimating equations--to evaluate interventions in psychology, psychiatry, and prevention science has grown rapidly over the last decade. However, an effect size associated with the difference between the trajectories of the…

Updating the Behavior Engineering Model.

ERIC Educational Resources Information Center

Chevalier, Roger

2003-01-01

Considers Thomas Gilbert's Behavior Engineering Model as a tool for systematically identifying barriers to individual and organizational performance. Includes a detailed case study and a performance aid that incorporates gap analysis, cause analysis, and force field analysis to update the original model. (Author/LRW)

2012 National Park visitor spending effects: economic contributions to local communities, states, and the nation

USGS Publications Warehouse

Cullinane Thomas, Catherine; Huber, Christopher C.; Koontz, Lynne

2014-01-01

This 2012 analysis marks a major revision to the NPS visitor spending effects analyses, with the development of a new visitor spending effects model (VSE model) that replaces the former Money Generation Model (MGM2). Many of the hallmarks and processes of the MGM2 model are preserved in the new VSE model, but the new model makes significant strides in improving the accuracy and transparency of the analysis. Because of this change from the MGM2 model to the VSE model, estimates from this year’s analysis are not directly comparable to previous analyses.

Model-Based Linkage Analysis of a Quantitative Trait.

PubMed

Song, Yeunjoo E; Song, Sunah; Schnell, Audrey H

2017-01-01

Linkage Analysis is a family-based method of analysis to examine whether any typed genetic markers cosegregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single-marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model-based linkage analysis the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it also includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single-marker analysis, and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait.

Modeling and simulation of satellite subsystems for end-to-end spacecraft modeling

NASA Astrophysics Data System (ADS)

Schum, William K.; Doolittle, Christina M.; Boyarko, George A.

2006-05-01

During the past ten years, the Air Force Research Laboratory (AFRL) has been simultaneously developing high-fidelity spacecraft payload models as well as a robust distributed simulation environment for modeling spacecraft subsystems. Much of this research has occurred in the Distributed Architecture Simulation Laboratory (DASL). AFRL developers working in the DASL have effectively combined satellite power, attitude pointing, and communication link analysis subsystem models with robust satellite sensor models to create a first-order end-to-end satellite simulation capability. The merging of these two simulation areas has advanced the field of spacecraft simulation, design, and analysis, and enabled more in-depth mission and satellite utility analyses. A core capability of the DASL is the support of a variety of modeling and analysis efforts, ranging from physics and engineering-level modeling to mission and campaign-level analysis. The flexibility and agility of this simulation architecture will be used to support space mission analysis, military utility analysis, and various integrated exercises with other military and space organizations via direct integration, or through DOD standards such as Distributed Interaction Simulation. This paper discusses the results and lessons learned in modeling satellite communication link analysis, power, and attitude control subsystems for an end-to-end satellite simulation. It also discusses how these spacecraft subsystem simulations feed into and support military utility and space mission analyses.

Combining multiple imputation and meta-analysis with individual participant data

PubMed Central

Burgess, Stephen; White, Ian R; Resche-Rigon, Matthieu; Wood, Angela M

2013-01-01

Multiple imputation is a strategy for the analysis of incomplete data such that the impact of the missingness on the power and bias of estimates is mitigated. When data from multiple studies are collated, we can propose both within-study and multilevel imputation models to impute missing data on covariates. It is not clear how to choose between imputation models or how to combine imputation and inverse-variance weighted meta-analysis methods. This is especially important as often different studies measure data on different variables, meaning that we may need to impute data on a variable which is systematically missing in a particular study. In this paper, we consider a simulation analysis of sporadically missing data in a single covariate with a linear analysis model and discuss how the results would be applicable to the case of systematically missing data. We find in this context that ensuring the congeniality of the imputation and analysis models is important to give correct standard errors and confidence intervals. For example, if the analysis model allows between-study heterogeneity of a parameter, then we should incorporate this heterogeneity into the imputation model to maintain the congeniality of the two models. In an inverse-variance weighted meta-analysis, we should impute missing data and apply Rubin's rules at the study level prior to meta-analysis, rather than meta-analyzing each of the multiple imputations and then combining the meta-analysis estimates using Rubin's rules. We illustrate the results using data from the Emerging Risk Factors Collaboration. PMID:23703895

Bayesian structural equation modeling: a more flexible representation of substantive theory.

PubMed

Muthén, Bengt; Asparouhov, Tihomir

2012-09-01

This article proposes a new approach to factor analysis and structural equation modeling using Bayesian analysis. The new approach replaces parameter specifications of exact zeros with approximate zeros based on informative, small-variance priors. It is argued that this produces an analysis that better reflects substantive theories. The proposed Bayesian approach is particularly beneficial in applications where parameters are added to a conventional model such that a nonidentified model is obtained if maximum-likelihood estimation is applied. This approach is useful for measurement aspects of latent variable modeling, such as with confirmatory factor analysis, and the measurement part of structural equation modeling. Two application areas are studied, cross-loadings and residual correlations in confirmatory factor analysis. An example using a full structural equation model is also presented, showing an efficient way to find model misspecification. The approach encompasses 3 elements: model testing using posterior predictive checking, model estimation, and model modification. Monte Carlo simulations and real data are analyzed using Mplus. The real-data analyses use data from Holzinger and Swineford's (1939) classic mental abilities study, Big Five personality factor data from a British survey, and science achievement data from the National Educational Longitudinal Study of 1988.

SensA: web-based sensitivity analysis of SBML models.

PubMed

Floettmann, Max; Uhlendorf, Jannis; Scharp, Till; Klipp, Edda; Spiesser, Thomas W

2014-10-01

SensA is a web-based application for sensitivity analysis of mathematical models. The sensitivity analysis is based on metabolic control analysis, computing the local, global and time-dependent properties of model components. Interactive visualization facilitates interpretation of usually complex results. SensA can contribute to the analysis, adjustment and understanding of mathematical models for dynamic systems. SensA is available at http://gofid.biologie.hu-berlin.de/ and can be used with any modern browser. The source code can be found at https://bitbucket.org/floettma/sensa/ (MIT license) © The Author 2014. Published by Oxford University Press.

Gait characterization in golden retriever muscular dystrophy dogs using linear discriminant analysis.

PubMed

Fraysse, Bodvaël; Barthélémy, Inès; Qannari, El Mostafa; Rouger, Karl; Thorin, Chantal; Blot, Stéphane; Le Guiner, Caroline; Chérel, Yan; Hogrel, Jean-Yves

2017-04-12

Accelerometric analysis of gait abnormalities in golden retriever muscular dystrophy (GRMD) dogs is of limited sensitivity, and produces highly complex data. The use of discriminant analysis may enable simpler and more sensitive evaluation of treatment benefits in this important preclinical model. Accelerometry was performed twice monthly between the ages of 2 and 12 months on 8 healthy and 20 GRMD dogs. Seven accelerometric parameters were analysed using linear discriminant analysis (LDA). Manipulation of the dependent and independent variables produced three distinct models. The ability of each model to detect gait alterations and their pattern change with age was tested using a leave-one-out cross-validation approach. Selecting genotype (healthy or GRMD) as the dependent variable resulted in a model (Model 1) allowing a good discrimination between the gait phenotype of GRMD and healthy dogs. However, this model was not sufficiently representative of the disease progression. In Model 2, age in months was added as a supplementary dependent variable (GRMD_2 to GRMD_12 and Healthy_2 to Healthy_9.5), resulting in a high overall misclassification rate (83.2%). To improve accuracy, a third model (Model 3) was created in which age was also included as an explanatory variable. This resulted in an overall misclassification rate lower than 12%. Model 3 was evaluated using blinded data pertaining to 81 healthy and GRMD dogs. In all but one case, the model correctly matched gait phenotype to the actual genotype. Finally, we used Model 3 to reanalyse data from a previous study regarding the effects of immunosuppressive treatments on muscular dystrophy in GRMD dogs. Our model identified significant effect of immunosuppressive treatments on gait quality, corroborating the original findings, with the added advantages of direct statistical analysis with greater sensitivity and more comprehensible data representation. Gait analysis using LDA allows for improved analysis of accelerometry data by applying a decision-making analysis approach to the evaluation of preclinical treatment benefits in GRMD dogs.

Factor analysis and multiple regression between topography and precipitation on Jeju Island, Korea

NASA Astrophysics Data System (ADS)

Um, Myoung-Jin; Yun, Hyeseon; Jeong, Chang-Sam; Heo, Jun-Haeng

2011-11-01

SummaryIn this study, new factors that influence precipitation were extracted from geographic variables using factor analysis, which allow for an accurate estimation of orographic precipitation. Correlation analysis was also used to examine the relationship between nine topographic variables from digital elevation models (DEMs) and the precipitation in Jeju Island. In addition, a spatial analysis was performed in order to verify the validity of the regression model. From the results of the correlation analysis, it was found that all of the topographic variables had a positive correlation with the precipitation. The relations between the variables also changed in accordance with a change in the precipitation duration. However, upon examining the correlation matrix, no significant relationship between the latitude and the aspect was found. According to the factor analysis, eight topographic variables (latitude being the exception) were found to have a direct influence on the precipitation. Three factors were then extracted from the eight topographic variables. By directly comparing the multiple regression model with the factors (model 1) to the multiple regression model with the topographic variables (model 3), it was found that model 1 did not violate the limits of statistical significance and multicollinearity. As such, model 1 was considered to be appropriate for estimating the precipitation when taking into account the topography. In the study of model 1, the multiple regression model using factor analysis was found to be the best method for estimating the orographic precipitation on Jeju Island.

A Hierarchical Visualization Analysis Model of Power Big Data

NASA Astrophysics Data System (ADS)

Li, Yongjie; Wang, Zheng; Hao, Yang

2018-01-01

Based on the conception of integrating VR scene and power big data analysis, a hierarchical visualization analysis model of power big data is proposed, in which levels are designed, targeting at different abstract modules like transaction, engine, computation, control and store. The regularly departed modules of power data storing, data mining and analysis, data visualization are integrated into one platform by this model. It provides a visual analysis solution for the power big data.

Integrated Modeling for the James Webb Space Telescope (JWST) Project: Structural Analysis Activities

NASA Technical Reports Server (NTRS)

Johnston, John; Mosier, Mark; Howard, Joe; Hyde, Tupper; Parrish, Keith; Ha, Kong; Liu, Frank; McGinnis, Mark

2004-01-01

This paper presents viewgraphs about structural analysis activities and integrated modeling for the James Webb Space Telescope (JWST). The topics include: 1) JWST Overview; 2) Observatory Structural Models; 3) Integrated Performance Analysis; and 4) Future Work and Challenges.

Transient three-dimensional thermal-hydraulic analysis of nuclear reactor fuel rod arrays: general equations and numerical scheme

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

Wnek, W.J.; Ramshaw, J.D.; Trapp, J.A.

1975-11-01

A mathematical model and a numerical solution scheme for thermal- hydraulic analysis of fuel rod arrays are given. The model alleviates the two major deficiencies associated with existing rod array analysis models, that of a correct transverse momentum equation and the capability of handling reversing and circulatory flows. Possible applications of the model include steady state and transient subchannel calculations as well as analysis of flows in heat exchangers, other engineering equipment, and porous media. (auth)

Computer-aided-engineering system for modeling and analysis of ECLSS integration testing

NASA Technical Reports Server (NTRS)

Sepahban, Sonbol

1987-01-01

The accurate modeling and analysis of two-phase fluid networks found in environmental control and life support systems is presently undertaken by computer-aided engineering (CAE) techniques whose generalized fluid dynamics package can solve arbitrary flow networks. The CAE system for integrated test bed modeling and analysis will also furnish interfaces and subsystem/test-article mathematical models. Three-dimensional diagrams of the test bed are generated by the system after performing the requisite simulation and analysis.

Model Performance Evaluation and Scenario Analysis (MPESA)

EPA Pesticide Factsheets

Model Performance Evaluation and Scenario Analysis (MPESA) assesses the performance with which models predict time series data. The tool was developed Hydrological Simulation Program-Fortran (HSPF) and the Stormwater Management Model (SWMM)

A quantitative analysis of the F18 flight control system

NASA Technical Reports Server (NTRS)

Doyle, Stacy A.; Dugan, Joanne B.; Patterson-Hine, Ann

1993-01-01

This paper presents an informal quantitative analysis of the F18 flight control system (FCS). The analysis technique combines a coverage model with a fault tree model. To demonstrate the method's extensive capabilities, we replace the fault tree with a digraph model of the F18 FCS, the only model available to us. The substitution shows that while digraphs have primarily been used for qualitative analysis, they can also be used for quantitative analysis. Based on our assumptions and the particular failure rates assigned to the F18 FCS components, we show that coverage does have a significant effect on the system's reliability and thus it is important to include coverage in the reliability analysis.

A comprehensive probabilistic analysis model of oil pipelines network based on Bayesian network

NASA Astrophysics Data System (ADS)

Zhang, C.; Qin, T. X.; Jiang, B.; Huang, C.

2018-02-01

Oil pipelines network is one of the most important facilities of energy transportation. But oil pipelines network accident may result in serious disasters. Some analysis models for these accidents have been established mainly based on three methods, including event-tree, accident simulation and Bayesian network. Among these methods, Bayesian network is suitable for probabilistic analysis. But not all the important influencing factors are considered and the deployment rule of the factors has not been established. This paper proposed a probabilistic analysis model of oil pipelines network based on Bayesian network. Most of the important influencing factors, including the key environment condition and emergency response are considered in this model. Moreover, the paper also introduces a deployment rule for these factors. The model can be used in probabilistic analysis and sensitive analysis of oil pipelines network accident.

Simulation skill of APCC set of global climate models for Asian summer monsoon rainfall variability

NASA Astrophysics Data System (ADS)

Singh, U. K.; Singh, G. P.; Singh, Vikas

2015-04-01

The performance of 11 Asia-Pacific Economic Cooperation Climate Center (APCC) global climate models (coupled and uncoupled both) in simulating the seasonal summer (June-August) monsoon rainfall variability over Asia (especially over India and East Asia) has been evaluated in detail using hind-cast data (3 months advance) generated from APCC which provides the regional climate information product services based on multi-model ensemble dynamical seasonal prediction systems. The skill of each global climate model over Asia was tested separately in detail for the period of 21 years (1983-2003), and simulated Asian summer monsoon rainfall (ASMR) has been verified using various statistical measures for Indian and East Asian land masses separately. The analysis found a large variation in spatial ASMR simulated with uncoupled model compared to coupled models (like Predictive Ocean Atmosphere Model for Australia, National Centers for Environmental Prediction and Japan Meteorological Agency). The simulated ASMR in coupled model was closer to Climate Prediction Centre Merged Analysis of Precipitation (CMAP) compared to uncoupled models although the amount of ASMR was underestimated in both models. Analysis also found a high spread in simulated ASMR among the ensemble members (suggesting that the model's performance is highly dependent on its initial conditions). The correlation analysis between sea surface temperature (SST) and ASMR shows that that the coupled models are strongly associated with ASMR compared to the uncoupled models (suggesting that air-sea interaction is well cared in coupled models). The analysis of rainfall using various statistical measures suggests that the multi-model ensemble (MME) performed better compared to individual model and also separate study indicate that Indian and East Asian land masses are more useful compared to Asia monsoon rainfall as a whole. The results of various statistical measures like skill of multi-model ensemble, large spread among the ensemble members of individual model, strong teleconnection (correlation analysis) with SST, coefficient of variation, inter-annual variability, analysis of Taylor diagram, etc. suggest that there is a need to improve coupled model instead of uncoupled model for the development of a better dynamical seasonal forecast system.

Separate-channel analysis of two-channel microarrays: recovering inter-spot information.

PubMed

Smyth, Gordon K; Altman, Naomi S

2013-05-26

Two-channel (or two-color) microarrays are cost-effective platforms for comparative analysis of gene expression. They are traditionally analysed in terms of the log-ratios (M-values) of the two channel intensities at each spot, but this analysis does not use all the information available in the separate channel observations. Mixed models have been proposed to analyse intensities from the two channels as separate observations, but such models can be complex to use and the gain in efficiency over the log-ratio analysis is difficult to quantify. Mixed models yield test statistics for the null distributions can be specified only approximately, and some approaches do not borrow strength between genes. This article reformulates the mixed model to clarify the relationship with the traditional log-ratio analysis, to facilitate information borrowing between genes, and to obtain an exact distributional theory for the resulting test statistics. The mixed model is transformed to operate on the M-values and A-values (average log-expression for each spot) instead of on the log-expression values. The log-ratio analysis is shown to ignore information contained in the A-values. The relative efficiency of the log-ratio analysis is shown to depend on the size of the intraspot correlation. A new separate channel analysis method is proposed that assumes a constant intra-spot correlation coefficient across all genes. This approach permits the mixed model to be transformed into an ordinary linear model, allowing the data analysis to use a well-understood empirical Bayes analysis pipeline for linear modeling of microarray data. This yields statistically powerful test statistics that have an exact distributional theory. The log-ratio, mixed model and common correlation methods are compared using three case studies. The results show that separate channel analyses that borrow strength between genes are more powerful than log-ratio analyses. The common correlation analysis is the most powerful of all. The common correlation method proposed in this article for separate-channel analysis of two-channel microarray data is no more difficult to apply in practice than the traditional log-ratio analysis. It provides an intuitive and powerful means to conduct analyses and make comparisons that might otherwise not be possible.

Determination of Uncertainties for the New SSME Model

NASA Technical Reports Server (NTRS)

Coleman, Hugh W.; Hawk, Clark W.

1996-01-01

This report discusses the uncertainty analysis performed in support of a new test analysis and performance prediction model for the Space Shuttle Main Engine. The new model utilizes uncertainty estimates for experimental data and for the analytical model to obtain the most plausible operating condition for the engine system. This report discusses the development of the data sets and uncertainty estimates to be used in the development of the new model. It also presents the application of uncertainty analysis to analytical models and the uncertainty analysis for the conservation of mass and energy balance relations is presented. A new methodology for the assessment of the uncertainty associated with linear regressions is presented.

Multiscale hidden Markov models for photon-limited imaging

NASA Astrophysics Data System (ADS)

Nowak, Robert D.

1999-06-01

Photon-limited image analysis is often hindered by low signal-to-noise ratios. A novel Bayesian multiscale modeling and analysis method is developed in this paper to assist in these challenging situations. In addition to providing a very natural and useful framework for modeling an d processing images, Bayesian multiscale analysis is often much less computationally demanding compared to classical Markov random field models. This paper focuses on a probabilistic graph model called the multiscale hidden Markov model (MHMM), which captures the key inter-scale dependencies present in natural image intensities. The MHMM framework presented here is specifically designed for photon-limited imagin applications involving Poisson statistics, and applications to image intensity analysis are examined.

Precursor Analysis for Flight- and Ground-Based Anomaly Risk Significance Determination

NASA Technical Reports Server (NTRS)

Groen, Frank

2010-01-01

This slide presentation reviews the precursor analysis for flight and ground based anomaly risk significance. It includes information on accident precursor analysis, real models vs. models, and probabilistic analysis.

Practical Application of Model-based Programming and State-based Architecture to Space Missions

NASA Technical Reports Server (NTRS)

Horvath, Gregory; Ingham, Michel; Chung, Seung; Martin, Oliver; Williams, Brian

2006-01-01

A viewgraph presentation to develop models from systems engineers that accomplish mission objectives and manage the health of the system is shown. The topics include: 1) Overview; 2) Motivation; 3) Objective/Vision; 4) Approach; 5) Background: The Mission Data System; 6) Background: State-based Control Architecture System; 7) Background: State Analysis; 8) Overview of State Analysis; 9) Background: MDS Software Frameworks; 10) Background: Model-based Programming; 10) Background: Titan Model-based Executive; 11) Model-based Execution Architecture; 12) Compatibility Analysis of MDS and Titan Architectures; 13) Integrating Model-based Programming and Execution into the Architecture; 14) State Analysis and Modeling; 15) IMU Subsystem State Effects Diagram; 16) Titan Subsystem Model: IMU Health; 17) Integrating Model-based Programming and Execution into the Software IMU; 18) Testing Program; 19) Computationally Tractable State Estimation & Fault Diagnosis; 20) Diagnostic Algorithm Performance; 21) Integration and Test Issues; 22) Demonstrated Benefits; and 23) Next Steps

The HIV Cure Research Agenda: The Role of Mathematical Modelling and Cost-Effectiveness Analysis.

PubMed

Freedberg, Kenneth A; Possas, Cristina; Deeks, Steven; Ross, Anna Laura; Rosettie, Katherine L; Di Mascio, Michele; Collins, Chris; Walensky, Rochelle P; Yazdanpanah, Yazdan

The research agenda towards an HIV cure is building rapidly. In this article, we discuss the reasons for and methodological approach to using mathematical modeling and cost-effectiveness analysis in this agenda. We provide a brief description of the proof of concept for cure and the current directions of cure research. We then review the types of clinical economic evaluations, including cost analysis, cost-benefit analysis, and cost-effectiveness analysis. We describe the use of mathematical modeling and cost-effectiveness analysis early in the HIV epidemic as well as in the era of combination antiretroviral therapy. We then highlight the novel methodology of Value of Information analysis and its potential role in the planning of clinical trials. We close with recommendations for modeling and cost-effectiveness analysis in the HIV cure agenda.

Problem Solving Model for Science Learning

NASA Astrophysics Data System (ADS)

Alberida, H.; Lufri; Festiyed; Barlian, E.

2018-04-01

This research aims to develop problem solving model for science learning in junior high school. The learning model was developed using the ADDIE model. An analysis phase includes curriculum analysis, analysis of students of SMP Kota Padang, analysis of SMP science teachers, learning analysis, as well as the literature review. The design phase includes product planning a science-learning problem-solving model, which consists of syntax, reaction principle, social system, support system, instructional impact and support. Implementation of problem-solving model in science learning to improve students' science process skills. The development stage consists of three steps: a) designing a prototype, b) performing a formative evaluation and c) a prototype revision. Implementation stage is done through a limited trial. A limited trial was conducted on 24 and 26 August 2015 in Class VII 2 SMPN 12 Padang. The evaluation phase was conducted in the form of experiments at SMPN 1 Padang, SMPN 12 Padang and SMP National Padang. Based on the development research done, the syntax model problem solving for science learning at junior high school consists of the introduction, observation, initial problems, data collection, data organization, data analysis/generalization, and communicating.

Evaluation of RCAS Inflow Models for Wind Turbine Analysis

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

Tangler, J.; Bir, G.

The finite element structural modeling in the Rotorcraft Comprehensive Analysis System (RCAS) provides a state-of-the-art approach to aeroelastic analysis. This, coupled with its ability to model all turbine components, results in a methodology that can simulate complex system interactions characteristic of large wind. In addition, RCAS is uniquely capable of modeling advanced control algorithms and the resulting dynamic responses.

Applying Model Analysis to a Resource-Based Analysis of the Force and Motion Conceptual Evaluation

ERIC Educational Resources Information Center

Smith, Trevor I.; Wittmann, Michael C.; Carter, Tom

2014-01-01

Previously, we analyzed the Force and Motion Conceptual Evaluation in terms of a resources-based model that allows for clustering of questions so as to provide useful information on how students correctly or incorrectly reason about physics. In this paper, we apply model analysis to show that the associated model plots provide more information…

A LISREL Model for the Analysis of Repeated Measures with a Patterned Covariance Matrix.

ERIC Educational Resources Information Center

Rovine, Michael J.; Molenaar, Peter C. M.

1998-01-01

Presents a LISREL model for the estimation of the repeated measures analysis of variance (ANOVA) with a patterned covariance matrix. The model is demonstrated for a 5 x 2 (Time x Group) ANOVA in which the data are assumed to be serially correlated. Similarities with the Statistical Analysis System PROC MIXED model are discussed. (SLD)

Organization Domain Modeling. Volume 1. Conceptual Foundations, Process and Workproduct Description

DTIC Science & Technology

1993-07-31

J.A. Hess, W.E. Novak, and A.S. Peterson. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study. Technical Report CMU/SEI-90-TR-21, Software...domain analysis (DA) and modeling, including a structured set of workproducts, a tailorable process model and a set of modeling techniques and guidelines...23 5.3.1 U sability Analysis (Rescoping) ..................................................... 24

Methodology for object-oriented real-time systems analysis and design: Software engineering

NASA Technical Reports Server (NTRS)

Schoeffler, James D.

1991-01-01

Successful application of software engineering methodologies requires an integrated analysis and design life-cycle in which the various phases flow smoothly 'seamlessly' from analysis through design to implementation. Furthermore, different analysis methodologies often lead to different structuring of the system so that the transition from analysis to design may be awkward depending on the design methodology to be used. This is especially important when object-oriented programming is to be used for implementation when the original specification and perhaps high-level design is non-object oriented. Two approaches to real-time systems analysis which can lead to an object-oriented design are contrasted: (1) modeling the system using structured analysis with real-time extensions which emphasizes data and control flows followed by the abstraction of objects where the operations or methods of the objects correspond to processes in the data flow diagrams and then design in terms of these objects; and (2) modeling the system from the beginning as a set of naturally occurring concurrent entities (objects) each having its own time-behavior defined by a set of states and state-transition rules and seamlessly transforming the analysis models into high-level design models. A new concept of a 'real-time systems-analysis object' is introduced and becomes the basic building block of a series of seamlessly-connected models which progress from the object-oriented real-time systems analysis and design system analysis logical models through the physical architectural models and the high-level design stages. The methodology is appropriate to the overall specification including hardware and software modules. In software modules, the systems analysis objects are transformed into software objects.

Modeling time-to-event (survival) data using classification tree analysis.

PubMed

Linden, Ariel; Yarnold, Paul R

2017-12-01

Time to the occurrence of an event is often studied in health research. Survival analysis differs from other designs in that follow-up times for individuals who do not experience the event by the end of the study (called censored) are accounted for in the analysis. Cox regression is the standard method for analysing censored data, but the assumptions required of these models are easily violated. In this paper, we introduce classification tree analysis (CTA) as a flexible alternative for modelling censored data. Classification tree analysis is a "decision-tree"-like classification model that provides parsimonious, transparent (ie, easy to visually display and interpret) decision rules that maximize predictive accuracy, derives exact P values via permutation tests, and evaluates model cross-generalizability. Using empirical data, we identify all statistically valid, reproducible, longitudinally consistent, and cross-generalizable CTA survival models and then compare their predictive accuracy to estimates derived via Cox regression and an unadjusted naïve model. Model performance is assessed using integrated Brier scores and a comparison between estimated survival curves. The Cox regression model best predicts average incidence of the outcome over time, whereas CTA survival models best predict either relatively high, or low, incidence of the outcome over time. Classification tree analysis survival models offer many advantages over Cox regression, such as explicit maximization of predictive accuracy, parsimony, statistical robustness, and transparency. Therefore, researchers interested in accurate prognoses and clear decision rules should consider developing models using the CTA-survival framework. © 2017 John Wiley & Sons, Ltd.

A global sensitivity analysis approach for morphogenesis models.

PubMed

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Hierarchical model analysis of the Atlantic Flyway Breeding Waterfowl Survey

USGS Publications Warehouse

Sauer, John R.; Zimmerman, Guthrie S.; Klimstra, Jon D.; Link, William A.

2014-01-01

We used log-linear hierarchical models to analyze data from the Atlantic Flyway Breeding Waterfowl Survey. The survey has been conducted by state biologists each year since 1989 in the northeastern United States from Virginia north to New Hampshire and Vermont. Although yearly population estimates from the survey are used by the United States Fish and Wildlife Service for estimating regional waterfowl population status for mallards (Anas platyrhynchos), black ducks (Anas rubripes), wood ducks (Aix sponsa), and Canada geese (Branta canadensis), they are not routinely adjusted to control for time of day effects and other survey design issues. The hierarchical model analysis permits estimation of year effects and population change while accommodating the repeated sampling of plots and controlling for time of day effects in counting. We compared population estimates from the current stratified random sample analysis to population estimates from hierarchical models with alternative model structures that describe year to year changes as random year effects, a trend with random year effects, or year effects modeled as 1-year differences. Patterns of population change from the hierarchical model results generally were similar to the patterns described by stratified random sample estimates, but significant visibility differences occurred between twilight to midday counts in all species. Controlling for the effects of time of day resulted in larger population estimates for all species in the hierarchical model analysis relative to the stratified random sample analysis. The hierarchical models also provided a convenient means of estimating population trend as derived statistics from the analysis. We detected significant declines in mallard and American black ducks and significant increases in wood ducks and Canada geese, a trend that had not been significant for 3 of these 4 species in the prior analysis. We recommend using hierarchical models for analysis of the Atlantic Flyway Breeding Waterfowl Survey.

Entrance and exit region friction factor models for annular seal analysis. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Elrod, David Alan

1988-01-01

The Mach number definition and boundary conditions in Nelson's nominally-centered, annular gas seal analysis are revised. A method is described for determining the wall shear stress characteristics of an annular gas seal experimentally. Two friction factor models are developed for annular seal analysis; one model is based on flat-plate flow theory; the other uses empirical entrance and exit region friction factors. The friction factor predictions of the models are compared to experimental results. Each friction model is used in an annular gas seal analysis. The seal characteristics predicted by the two seal analyses are compared to experimental results and to the predictions of Nelson's analysis. The comparisons are for smooth-rotor seals with smooth and honeycomb stators. The comparisons show that the analysis which uses empirical entrance and exit region shear stress models predicts the static and stability characteristics of annular gas seals better than the other analyses. The analyses predict direct stiffness poorly.

Regression Model Optimization for the Analysis of Experimental Data

NASA Technical Reports Server (NTRS)

Ulbrich, N.

2009-01-01

A candidate math model search algorithm was developed at Ames Research Center that determines a recommended math model for the multivariate regression analysis of experimental data. The search algorithm is applicable to classical regression analysis problems as well as wind tunnel strain gage balance calibration analysis applications. The algorithm compares the predictive capability of different regression models using the standard deviation of the PRESS residuals of the responses as a search metric. This search metric is minimized during the search. Singular value decomposition is used during the search to reject math models that lead to a singular solution of the regression analysis problem. Two threshold dependent constraints are also applied. The first constraint rejects math models with insignificant terms. The second constraint rejects math models with near-linear dependencies between terms. The math term hierarchy rule may also be applied as an optional constraint during or after the candidate math model search. The final term selection of the recommended math model depends on the regressor and response values of the data set, the user s function class combination choice, the user s constraint selections, and the result of the search metric minimization. A frequently used regression analysis example from the literature is used to illustrate the application of the search algorithm to experimental data.

The shallow water equations as a hybrid flow model for the numerical and experimental analysis of hydro power stations

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

Ostermann, Lars; Seidel, Christian

2015-03-10

The numerical analysis of hydro power stations is an important method of the hydraulic design and is used for the development and optimisation of hydro power stations in addition to the experiments with the physical submodel of a full model in the hydraulic laboratory. For the numerical analysis, 2D and 3D models are appropriate and commonly used.The 2D models refer mainly to the shallow water equations (SWE), since for this flow model a large experience on a wide field of applications for the flow analysis of numerous problems in hydraulic engineering already exists. Often, the flow model is verified bymore » in situ measurements. In order to consider 3D flow phenomena close to singularities like weirs, hydro power stations etc. the development of a hybrid fluid model is advantageous to improve the quality and significance of the global model. Here, an extended hybrid flow model based on the principle of the SWE is presented. The hybrid flow model directly links the numerical model with the experimental data, which may originate from physical full models, physical submodels and in-situ measurements. Hence a wide field of application of the hybrid model emerges including the improvement of numerical models and the strong coupling of numerical and experimental analysis.« less

Uncertainty Analysis and Parameter Estimation For Nearshore Hydrodynamic Models

NASA Astrophysics Data System (ADS)

Ardani, S.; Kaihatu, J. M.

2012-12-01

Numerical models represent deterministic approaches used for the relevant physical processes in the nearshore. Complexity of the physics of the model and uncertainty involved in the model inputs compel us to apply a stochastic approach to analyze the robustness of the model. The Bayesian inverse problem is one powerful way to estimate the important input model parameters (determined by apriori sensitivity analysis) and can be used for uncertainty analysis of the outputs. Bayesian techniques can be used to find the range of most probable parameters based on the probability of the observed data and the residual errors. In this study, the effect of input data involving lateral (Neumann) boundary conditions, bathymetry and off-shore wave conditions on nearshore numerical models are considered. Monte Carlo simulation is applied to a deterministic numerical model (the Delft3D modeling suite for coupled waves and flow) for the resulting uncertainty analysis of the outputs (wave height, flow velocity, mean sea level and etc.). Uncertainty analysis of outputs is performed by random sampling from the input probability distribution functions and running the model as required until convergence to the consistent results is achieved. The case study used in this analysis is the Duck94 experiment, which was conducted at the U.S. Army Field Research Facility at Duck, North Carolina, USA in the fall of 1994. The joint probability of model parameters relevant for the Duck94 experiments will be found using the Bayesian approach. We will further show that, by using Bayesian techniques to estimate the optimized model parameters as inputs and applying them for uncertainty analysis, we can obtain more consistent results than using the prior information for input data which means that the variation of the uncertain parameter will be decreased and the probability of the observed data will improve as well. Keywords: Monte Carlo Simulation, Delft3D, uncertainty analysis, Bayesian techniques, MCMC

A Model-Based Systems Engineering Methodology for Employing Architecture In System Analysis: Developing Simulation Models Using Systems Modeling Language Products to Link Architecture and Analysis

DTIC Science & Technology

2016-06-01

characteristics, experimental design techniques, and analysis methodologies that distinguish each phase of the MBSE MEASA. To ensure consistency... methodology . Experimental design selection, simulation analysis, and trade space analysis support the final two stages. Figure 27 segments the MBSE MEASA...rounding has the potential to increase the correlation between columns of the experimental design matrix. The design methodology presented in Vieira

The CICT Earth Science Systems Analysis Model

NASA Technical Reports Server (NTRS)

Pell, Barney; Coughlan, Joe; Biegel, Bryan; Stevens, Ken; Hansson, Othar; Hayes, Jordan

2004-01-01

Contents include the following: Computing Information and Communications Technology (CICT) Systems Analysis. Our modeling approach: a 3-part schematic investment model of technology change, impact assessment and prioritization. A whirlwind tour of our model. Lessons learned.

Advanced Modeling, Simulation and Analysis (AMSA) Capability Roadmap Progress Review

NASA Technical Reports Server (NTRS)

Antonsson, Erik; Gombosi, Tamas

2005-01-01

Contents include the following: NASA capability roadmap activity. Advanced modeling, simulation, and analysis overview. Scientific modeling and simulation. Operations modeling. Multi-special sensing (UV-gamma). System integration. M and S Environments and Infrastructure.

A brief review of models of DC-DC power electronic converters for analysis of their stability

NASA Astrophysics Data System (ADS)

Siewniak, Piotr; Grzesik, Bogusław

2014-10-01

A brief review of models of DC-DC power electronic converters (PECs) is presented in this paper. It contains the most popular, continuous-time and discrete-time models used for PEC simulation, design, stability analysis and other applications. Both large-signal and small-signal models are considered. Special attention is paid to models that are used in practice for the analysis of the global and local stability of PECs.

Computational models for the nonlinear analysis of reinforced concrete plates

NASA Technical Reports Server (NTRS)

Hinton, E.; Rahman, H. H. A.; Huq, M. M.

1980-01-01

A finite element computational model for the nonlinear analysis of reinforced concrete solid, stiffened and cellular plates is briefly outlined. Typically, Mindlin elements are used to model the plates whereas eccentric Timoshenko elements are adopted to represent the beams. The layering technique, common in the analysis of reinforced concrete flexural systems, is incorporated in the model. The proposed model provides an inexpensive and reasonably accurate approach which can be extended for use with voided plates.

Dynamic Chest Image Analysis: Evaluation of Model-Based Pulmonary Perfusion Analysis With Pyramid Images

DTIC Science & Technology

2001-10-25

Image Analysis aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the Dynamic Pulmonary Imaging technique 18,5,17,6. We have proposed and evaluated a multiresolutional method with an explicit ventilation model based on pyramid images for ventilation analysis. We have further extended the method for ventilation analysis to pulmonary perfusion. This paper focuses on the clinical evaluation of our method for

Modeling and analysis needs and resources for small metropolitan area transportation planning : report on a peer exchange.

DOT National Transportation Integrated Search

2012-09-01

A peer exchange on Modeling and Analysis Needs and Resources for Small Metropolitan Area Transportation Planning was convened on August 28 and 29, 2011, to explore the state of transportation modeling and analysis practice in communities with populat...

ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

PubMed Central

2011-01-01

Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics. PMID:21774817

Structural mode significance using INCA. [Interactive Controls Analysis computer program

NASA Technical Reports Server (NTRS)

Bauer, Frank H.; Downing, John P.; Thorpe, Christopher J.

1990-01-01

Structural finite element models are often too large to be used in the design and analysis of control systems. Model reduction techniques must be applied to reduce the structural model to manageable size. In the past, engineers either performed the model order reduction by hand or used distinct computer programs to retrieve the data, to perform the significance analysis and to reduce the order of the model. To expedite this process, the latest version of INCA has been expanded to include an interactive graphical structural mode significance and model order reduction capability.

Models for residential-and commercial-sector energy conservation analysis: Applications, limitations, and future potential

NASA Astrophysics Data System (ADS)

Cole, H. E.; Fuller, R. E.

1980-09-01

Four of the major models used by DOE for energy conservation analyses in the residential and commercial building sectors are reviewed and critically analyzed to determine how these models can serve as tools for DOE and its Conservation Policy Office in evaluating and quantifying their policy and program requirements. The most effective role for each model in addressing future issues of buildings energy conservation policy and analysis is assessed. The four models covered are: Oak Ridge Residential Energy Model; Micro Analysis of Transfers to Households/Comprehensive Human Resources Data System (MATH/CHRDS) Model; Oak Ridge Commercial Energy Model; and Brookhaven Buildings Energy Conservation Optimization Model (BECOM).

Automation for System Safety Analysis

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Fleming, Land; Throop, David; Thronesbery, Carroll; Flores, Joshua; Bennett, Ted; Wennberg, Paul

2009-01-01

This presentation describes work to integrate a set of tools to support early model-based analysis of failures and hazards due to system-software interactions. The tools perform and assist analysts in the following tasks: 1) extract model parts from text for architecture and safety/hazard models; 2) combine the parts with library information to develop the models for visualization and analysis; 3) perform graph analysis and simulation to identify and evaluate possible paths from hazard sources to vulnerable entities and functions, in nominal and anomalous system-software configurations and scenarios; and 4) identify resulting candidate scenarios for software integration testing. There has been significant technical progress in model extraction from Orion program text sources, architecture model derivation (components and connections) and documentation of extraction sources. Models have been derived from Internal Interface Requirements Documents (IIRDs) and FMEA documents. Linguistic text processing is used to extract model parts and relationships, and the Aerospace Ontology also aids automated model development from the extracted information. Visualizations of these models assist analysts in requirements overview and in checking consistency and completeness.

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

PubMed Central

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-01-01

Background It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. Results This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. Conclusion SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes. PMID:18706080

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

PubMed

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-08-15

It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

Dynamical System Analysis of Reynolds Stress Closure Equations

NASA Technical Reports Server (NTRS)

Girimaji, Sharath S.

1997-01-01

In this paper, we establish the causality between the model coefficients in the standard pressure-strain correlation model and the predicted equilibrium states for homogeneous turbulence. We accomplish this by performing a comprehensive fixed point analysis of the modeled Reynolds stress and dissipation rate equations. The results from this analysis will be very useful for developing improved pressure-strain correlation models to yield observed equilibrium behavior.

Fusing modeling techniques to support domain analysis for reuse opportunities identification

NASA Technical Reports Server (NTRS)

Hall, Susan Main; Mcguire, Eileen

1993-01-01

Functional modeling techniques or object-oriented graphical representations, which are more useful to someone trying to understand the general design or high level requirements of a system? For a recent domain analysis effort, the answer was a fusion of popular modeling techniques of both types. By using both functional and object-oriented techniques, the analysts involved were able to lean on their experience in function oriented software development, while taking advantage of the descriptive power available in object oriented models. In addition, a base of familiar modeling methods permitted the group of mostly new domain analysts to learn the details of the domain analysis process while producing a quality product. This paper describes the background of this project and then provides a high level definition of domain analysis. The majority of this paper focuses on the modeling method developed and utilized during this analysis effort.

Factors Influencing Progressive Failure Analysis Predictions for Laminated Composite Structure

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.

2008-01-01

Progressive failure material modeling methods used for structural analysis including failure initiation and material degradation are presented. Different failure initiation criteria and material degradation models are described that define progressive failure formulations. These progressive failure formulations are implemented in a user-defined material model for use with a nonlinear finite element analysis tool. The failure initiation criteria include the maximum stress criteria, maximum strain criteria, the Tsai-Wu failure polynomial, and the Hashin criteria. The material degradation model is based on the ply-discounting approach where the local material constitutive coefficients are degraded. Applications and extensions of the progressive failure analysis material model address two-dimensional plate and shell finite elements and three-dimensional solid finite elements. Implementation details are described in the present paper. Parametric studies for laminated composite structures are discussed to illustrate the features of the progressive failure modeling methods that have been implemented and to demonstrate their influence on progressive failure analysis predictions.

ROCKETSHIP: a flexible and modular software tool for the planning, processing and analysis of dynamic MRI studies.

PubMed

Barnes, Samuel R; Ng, Thomas S C; Santa-Maria, Naomi; Montagne, Axel; Zlokovic, Berislav V; Jacobs, Russell E

2015-06-16

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising technique to characterize pathology and evaluate treatment response. However, analysis of DCE-MRI data is complex and benefits from concurrent analysis of multiple kinetic models and parameters. Few software tools are currently available that specifically focuses on DCE-MRI analysis with multiple kinetic models. Here, we developed ROCKETSHIP, an open-source, flexible and modular software for DCE-MRI analysis. ROCKETSHIP incorporates analyses with multiple kinetic models, including data-driven nested model analysis. ROCKETSHIP was implemented using the MATLAB programming language. Robustness of the software to provide reliable fits using multiple kinetic models is demonstrated using simulated data. Simulations also demonstrate the utility of the data-driven nested model analysis. Applicability of ROCKETSHIP for both preclinical and clinical studies is shown using DCE-MRI studies of the human brain and a murine tumor model. A DCE-MRI software suite was implemented and tested using simulations. Its applicability to both preclinical and clinical datasets is shown. ROCKETSHIP was designed to be easily accessible for the beginner, but flexible enough for changes or additions to be made by the advanced user as well. The availability of a flexible analysis tool will aid future studies using DCE-MRI. A public release of ROCKETSHIP is available at https://github.com/petmri/ROCKETSHIP .

Sparse Group Penalized Integrative Analysis of Multiple Cancer Prognosis Datasets

PubMed Central

Liu, Jin; Huang, Jian; Xie, Yang; Ma, Shuangge

2014-01-01

SUMMARY In cancer research, high-throughput profiling studies have been extensively conducted, searching for markers associated with prognosis. Because of the “large d, small n” characteristic, results generated from the analysis of a single dataset can be unsatisfactory. Recent studies have shown that integrative analysis, which simultaneously analyzes multiple datasets, can be more effective than single-dataset analysis and classic meta-analysis. In most of existing integrative analysis, the homogeneity model has been assumed, which postulates that different datasets share the same set of markers. Several approaches have been designed to reinforce this assumption. In practice, different datasets may differ in terms of patient selection criteria, profiling techniques, and many other aspects. Such differences may make the homogeneity model too restricted. In this study, we assume the heterogeneity model, under which different datasets are allowed to have different sets of markers. With multiple cancer prognosis datasets, we adopt the AFT (accelerated failure time) model to describe survival. This model may have the lowest computational cost among popular semiparametric survival models. For marker selection, we adopt a sparse group MCP (minimax concave penalty) approach. This approach has an intuitive formulation and can be computed using an effective group coordinate descent algorithm. Simulation study shows that it outperforms the existing approaches under both the homogeneity and heterogeneity models. Data analysis further demonstrates the merit of heterogeneity model and proposed approach. PMID:23938111