Project START: Using a Multiple Intelligences Model in Identifying and Promoting Talent in High-Risk Students. Research Monograph 95136.

ERIC Educational Resources Information Center

Callahan, Carolyn M.; Tomlinson, Carol A.; Moon, Tonya R.; Tomchin, Ellen M.; Plucker, Jonathan A.

This monograph describes Project START (Support To Affirm Rising Talent), a three-year collaborative research effort to develop and apply gifted identification procedures based on Howard Gardner's (1983) theory of multiple intelligences. Specifically, the study attempted to: (1) develop identification procedures; (2) identify high-potential…

Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a Qualitative Study.

PubMed

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2018-03-01

Introduction: Coping with disease is of the main components improving the quality of life in multiple sclerosis patients. Identifying the characteristics of this concept is based on the experiences of patients. Using qualitative research is essential to improve the quality of life. This study was conducted to explore the features of coping with the disease in patients with multiple sclerosis. Method: In this conventional content analysis study, eleven multiple sclerosis patients from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semi structured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and to make codes and categories. Results: Results showed that features of coping with disease in multiple sclerosis patients consists of (a) accepting the current situation, (b) maintenance and development of human interactions, (c) self-regulation and (d) self-efficacy. Each of these categories is composed of sub-categories and codes that showed the perception and experience of patients about the coping with disease. Conclusion: Accordingly, a unique set of features regarding features of coping with the disease were identified among the patients with multiple sclerosis. Therefore, working to ensure the emergence of, and subsequent reinforcement of these features in MS patients can be an important step in improving the adjustment and quality of their lives.

Multiple sensor fault diagnosis for dynamic processes.

PubMed

Li, Cheng-Chih; Jeng, Jyh-Cheng

2010-10-01

Modern industrial plants are usually large scaled and contain a great amount of sensors. Sensor fault diagnosis is crucial and necessary to process safety and optimal operation. This paper proposes a systematic approach to detect, isolate and identify multiple sensor faults for multivariate dynamic systems. The current work first defines deviation vectors for sensor observations, and further defines and derives the basic sensor fault matrix (BSFM), consisting of the normalized basic fault vectors, by several different methods. By projecting a process deviation vector to the space spanned by BSFM, this research uses a vector with the resulted weights on each direction for multiple sensor fault diagnosis. This study also proposes a novel monitoring index and derives corresponding sensor fault detectability. The study also utilizes that vector to isolate and identify multiple sensor faults, and discusses the isolatability and identifiability. Simulation examples and comparison with two conventional PCA-based contribution plots are presented to demonstrate the effectiveness of the proposed methodology. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

How Multiple Interventions Influenced Employee Turnover: A Case Study.

ERIC Educational Resources Information Center

Hatcher, Timothy

1999-01-01

A 3-year study of 46 textile industry workers identified causes of employee turnover (supervision, training, organizational communication) using performance analysis. A study of multiple interventions based on the analysis resulted in changes in orientation procedures, organizational leadership, and climate, reducing turnover by 24%. (SK)

Rare Variant Association Test with Multiple Phenotypes

PubMed Central

Lee, Selyeong; Won, Sungho; Kim, Young Jin; Kim, Yongkang; Kim, Bong-Jo; Park, Taesung

2016-01-01

Although genome-wide association studies (GWAS) have now discovered thousands of genetic variants associated with common traits, such variants cannot explain the large degree of “missing heritability,” likely due to rare variants. The advent of next generation sequencing technology has allowed rare variant detection and association with common traits, often by investigating specific genomic regions for rare variant effects on a trait. Although multiply correlated phenotypes are often concurrently observed in GWAS, most studies analyze only single phenotypes, which may lessen statistical power. To increase power, multivariate analyses, which consider correlations between multiple phenotypes, can be used. However, few existing multi-variant analyses can identify rare variants for assessing multiple phenotypes. Here, we propose Multivariate Association Analysis using Score Statistics (MAAUSS), to identify rare variants associated with multiple phenotypes, based on the widely used Sequence Kernel Association Test (SKAT) for a single phenotype. We applied MAAUSS to Whole Exome Sequencing (WES) data from a Korean population of 1,058 subjects, to discover genes associated with multiple traits of liver function. We then assessed validation of those genes by a replication study, using an independent dataset of 3,445 individuals. Notably, we detected the gene ZNF620 among five significant genes. We then performed a simulation study to compare MAAUSS's performance with existing methods. Overall, MAAUSS successfully conserved type 1 error rates and in many cases, had a higher power than the existing methods. This study illustrates a feasible and straightforward approach for identifying rare variants correlated with multiple phenotypes, with likely relevance to missing heritability. PMID:28039885

A Multiple Identity Approach to Gender: Identification with Women, Identification with Feminists, and Their Interaction

PubMed Central

van Breen, Jolien A.; Spears, Russell; Kuppens, Toon; de Lemus, Soledad

2017-01-01

Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that identification with women reflects attitudes toward the content society gives to group membership: what does it mean to be a woman in terms of group characteristics, interests and values? Identification with feminists, on the other hand, is a politicized identity dimension reflecting attitudes toward the social position of the group: what does it mean to be a woman in terms of disadvantage, inequality, and relative status? We examine the utility of this multiple identity approach in four studies. Study 1 showed that identification with women reflects attitudes toward group characteristics, such as femininity and self-stereotyping, while identification with feminists reflects attitudes toward the group's social position, such as perceived sexism. The two dimensions are shown to be largely independent, and as such provide support for the multiple identity approach. In Studies 2–4, we examine the utility of this multiple identity approach in predicting qualitative differences in gender attitudes. Results show that specific combinations of identification with women and feminists predicted attitudes toward collective action and gender stereotypes. Higher identification with feminists led to endorsement of radical collective action (Study 2) and critical attitudes toward gender stereotypes (Studies 3–4), especially at lower levels of identification with women. The different combinations of high vs. low identification with women and feminists can be thought of as reflecting four theoretical identity “types.” A woman can be (1) strongly identified with neither women nor feminists (“low identifier”), (2) strongly identified with women but less so with feminists (“traditional identifier”), (3) strongly identified with both women and feminists (“dual identifier”), or (4) strongly identified with feminists but less so with women (“distinctive feminist”). In sum, by considering identification with women and identification with feminists as multiple identities we aim to show how the multiple identity approach predicts distinct attitudes to gender issues and offer a new perspective on gender identity. PMID:28713297

Validity of deterministic record linkage using multiple indirect personal identifiers: linking a large registry to claims data.

PubMed

Setoguchi, Soko; Zhu, Ying; Jalbert, Jessica J; Williams, Lauren A; Chen, Chih-Ying

2014-05-01

Linking patient registries with administrative databases can enhance the utility of the databases for epidemiological and comparative effectiveness research. However, registries often lack direct personal identifiers, and the validity of record linkage using multiple indirect personal identifiers is not well understood. Using a large contemporary national cardiovascular device registry and 100% Medicare inpatient data, we linked hospitalization-level records. The main outcomes were the validity measures of several deterministic linkage rules using multiple indirect personal identifiers compared with rules using both direct and indirect personal identifiers. Linkage rules using 2 or 3 indirect, patient-level identifiers (ie, date of birth, sex, admission date) and hospital ID produced linkages with sensitivity of 95% and specificity of 98% compared with a gold standard linkage rule using a combination of both direct and indirect identifiers. Ours is the first large-scale study to validate the performance of deterministic linkage rules without direct personal identifiers. When linking hospitalization-level records in the absence of direct personal identifiers, provider information is necessary for successful linkage. © 2014 American Heart Association, Inc.

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

PubMed Central

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

PubMed Central

Zhang, Shujun

2018-01-01

Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

An Analysis of Student Affairs Professionals' Management of Role Conflict and Multiple Roles in Relation to Work/Life Balance

ERIC Educational Resources Information Center

Mayo, Nicole Lepone

2013-01-01

The purpose of this inquiry is to study how student affairs professionals manage role conflict in relation to work/life balance based on the challenging culture of the field. The underlying goals are to identify the barriers or challenges of managing multiple roles as a student affairs administrator and identify strategies to assist employees in…

Disease-specific molecular events in cortical multiple sclerosis lesions

PubMed Central

Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J.; Krumbholz, Markus; Bauer, Jan; Bradl, Monika

2013-01-01

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen’s encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer’s disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis. PMID:23687122

Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

PubMed

Zhu; Dale

2000-10-01

/ Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

Multiple Trajectories of Successful Aging of Older and Younger Cohorts

ERIC Educational Resources Information Center

Hsu, Hui-Chuan; Jones, Bobby L.

2012-01-01

Purpose: The purpose of this study was to apply group-based trajectory analysis to identify multiple successful aging trajectories by multiple indicators and to examine the factors related to successful aging among the elderly population in Taiwan. Design and Methods: Nation-representative longitudinal data collected from 1993 to 2007 and…

Multiple Intelligences Profiles of Junior Secondary School Students in Indonesia

ERIC Educational Resources Information Center

Emmiyati, Nuri; Rasyid, Muhammad Amin; Rahman, M. Asfah; Arsyad, Azhar; Dirawan, Gufran Darma

2014-01-01

This study aimed to investigate the Multiple Intelligences profiles of the students at junior secondary school in Makassar. The Multiple Intelligences Inventory was used to identify the dominant intelligence among the students. The sample of this research was 302 junior secondary schools students in Makassar Indonesia who willing to participated…

Adherence to Medication Regimens among Low-Income Patients with Multiple Comorbid Chronic Conditions

ERIC Educational Resources Information Center

Mishra, Shiraz I.; Gioia, Deborah; Childress, Saltanat; Barnet, Beth; Webster, Ramothea L.

2011-01-01

This qualitative study sought to explore facilitators and barriers to adherence to multiple medications among low-income patients with comorbid chronic physical and mental health conditions. The 50 focus group participants identified personal/contextual and health system factors as major impediments to adherence to multiple medications. These…

The multiple resource inventory decision-making process

Treesearch

Victor A. Rudis

1993-01-01

A model of the multiple resource inventory decision-making process is presented that identifies steps in conducting inventories, describes the infrastructure, and points out knowledge gaps that are common to many interdisciplinary studies.Successful efforts to date suggest the need to bridge the gaps by sharing elements, maintain dialogue among stakeholders in multiple...

Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

PubMed Central

Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

2014-01-01

Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

A Study of Multiple Intelligences and Higher Education Faculty in the United States

ERIC Educational Resources Information Center

Wilson, Stefanie Denise

2007-01-01

This quantitative research study discovered and identified the degree of relationships between the domains of multiple intelligences: (a) interpersonal, (b) intrapersonal, and (c) linguistic intelligences, and (d) leadership and demographic characteristics such as, (a) age, (b) gender and (c) ethnicity among higher education faculty. Using a…

Psychosocial and Cognitive Functioning of Children with Specific Profiles of Maltreatment

ERIC Educational Resources Information Center

Pears, Katherine C.; Kim, Hyoun K.; Fisher, Philip A.

2008-01-01

Objective: Up to 90% of child welfare system cases involve multiple types of maltreatment; however, studies have rarely incorporated multiple dimensions of maltreatment. The present study employed a latent profile analysis to identify naturally occurring subgroups of children who had experienced maltreatment. Methods: Reports of maltreatment…

Childhood Giftedness, Adolescent Agency: A Systemic Multiple-Case Study

ERIC Educational Resources Information Center

Mudrak, Jiri; Zabrodska, Katerina

2015-01-01

Although considerable research has addressed development from childhood giftedness to adult excellence, subjective perceptions of this development by gifted individuals themselves have remained largely unexplored. This multiple case study examined the ways in which young adults, who in the past had been identified as gifted, made sense of their…

[Quality of life after multiple trauma].

PubMed

Mörsdorf, P; Becker, S C; Holstein, J H; Burkhardt, M; Pohlemann, T

2014-03-01

Multiple trauma is an independent injury pattern which, because of its complexity, is responsible for 25 % of the costs for the treatment of all injured patients. Because of the often long-lasting physical impairment and the high incidence of residual permanent handicaps, it is apparent that multiple trauma can lead to a reduction in patient quality of life. The aim of this study was to give an overview of the known data concerning the change in quality of life for multiple trauma patients. Furthermore, predictors for the reduction of quality of life after multiple trauma will be identified. A MedLine search was performed to identify studies dealing with the outcome after multiple trauma. In addition to functional outcome parameters, the term quality of life has become more important in recent years when it comes to evaluating the outcome following injury. While the mortality after multiple trauma could be significantly reduced over the years, there is no comparable effect on the quality of life. Predictors for a worse quality of life after multiple trauma are female gender, high age, low social status, concomitant head injuries and injury to the lower extremities. The fact that mortality after multiple trauma has decreased but not impairment of the quality of life makes it clear that in addition to the acute medical treatment, a follow-up treatment including not only physiotherapy but also psychotherapy is crucial for multiple trauma patients.

Multiple Intravenous Infusions Phase 2b: Laboratory Study

PubMed Central

Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

2014-01-01

Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

Identifying a Power Elite in a Microcosmic Adult Community.

ERIC Educational Resources Information Center

Roberts, William B.

The study presents the results of testing an original obersvation instrument designed to identify a power elite in multiple sessions of two eight-member adult discussion groups. Two questions guided the development of the study: (1) Can a power elite be identified in participation training groups? (2) Can an effective observation instrument with…

Developing a national dental education research strategy: priorities, barriers and enablers

PubMed Central

Barton, Karen L; Dennis, Ashley A; Rees, Charlotte E

2017-01-01

Objectives This study aimed to identify national dental education research (DER) priorities for the next 3–5 years and to identify barriers and enablers to DER. Setting Scotland. Participants In this two-stage online questionnaire study, we collected data with multiple dental professions (eg, dentistry, dental nursing and dental hygiene) and stakeholder groups (eg, learners, clinicians, educators, managers, researchers and academics). Eighty-five participants completed the Stage 1 qualitative questionnaire and 649 participants the Stage 2 quantitative questionnaire. Results Eight themes were identified at Stage 1. Of the 24 DER priorities identified, the top three were: role of assessments in identifying competence; undergraduate curriculum prepares for practice and promoting teamwork. Following exploratory factor analysis, the 24 items loaded onto four factors: teamwork and professionalism, measuring and enhancing performance, dental workforce issues and curriculum integration and innovation. Barriers and enablers existed at multiple levels: individual, interpersonal, institutional structures and cultures and technology. Conclusions This priority setting exercise provides a necessary first step to developing a national DER strategy capturing multiple perspectives. Promoting DER requires improved resourcing alongside efforts to overcome peer stigma and lack of valuing and motivation. PMID:28360237

Examining Education Leadership Communication Practices around Basic and Advanced Skill Sets: A Multiple Case Study

ERIC Educational Resources Information Center

Minger, Leslie

2017-01-01

The purpose of this multiple case study was to explore and describe the leadership communication practices of school principals in Southern California schools with demonstrated high levels of academic performance in order to identify practices that might be replicated in other schools. Communication practices were studied in relation to two…

Focus on Success: An Explanatory Embedded Multiple-Case Study on How Youth Successfully Navigate Workforce Development Programs in Southern Nevada

ERIC Educational Resources Information Center

Villalobos, Ricardo

2017-01-01

This explanatory qualitative study investigated the perspectives of participant's and practitioner's perceived barriers to success and the necessary navigational expertise for overcoming the identified barriers. This multiple-case study research design examined three WIA out-of-school youth workforce development programs in Southern Nevada, with…

A Multiple Case Study of a Baldrige-Based Peer Review Process in an Urban School District

ERIC Educational Resources Information Center

Ray, Janet L.

2012-01-01

Distinct purposes were identified for this phenomenological multiple-case study. The first purpose of the study was to determine in what ways the BbPRP influenced (a) leadership, (b) strategic planning, and (c) process management among the five selected schools within AISD. The second purpose of this study was to examine administrators'…

Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells.

PubMed

Chen, Junhui; Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

2013-01-01

Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

Learning from the Experiences of Self-Identified Women of Color Activists

ERIC Educational Resources Information Center

Linder, Chris; Rodriguez, Katrina L.

2012-01-01

We studied 7 women of color student activists on a large, predominantly White college campus and employed intersectionality theory and multiple identity development theory to examine how they make meaning of their multiple identities. Findings from this narrative study highlight ways students' identities led them to activism, experiences of…

Reversibility of Thought: An Instance in Multiplicative Tasks

ERIC Educational Resources Information Center

Ramful, Ajay; Olive, John

2008-01-01

In line with current efforts to understand the piece-by-piece structure and articulation of children's mathematical concepts, this case study compares the reversibility schemes of two eighth-grade students. The aim of the study was to identify the mechanism through which students reverse their thought processes in a multiplicative situation. Data…

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies

PubMed Central

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

2016-01-01

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. PMID:27330233

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

PubMed

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

PubMed Central

Westerlind, Helga; Ramanujam, Ryan; Uvehag, Daniel; Kuja-Halkola, Ralf; Boman, Marcus; Bottai, Matteo; Lichtenstein, Paul

2014-01-01

Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42–7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called ‘Carter effect’ could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36–0.76), whereas the shared environmental component was estimated to be 0.01 (0.00–0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported. PMID:24441172

Use of multiple methods to determine factors affecting quality of care of patients with diabetes.

PubMed

Khunti, K

1999-10-01

The process of care of patients with diabetes is complex; however, GPs are playing a greater role in its management. Despite the research evidence, the quality of care of patients with diabetes is variable. In order to improve care, information is required on the obstacles faced by practices in improving care. Qualitative and quantitative methods can be used for formation of hypotheses and the development of survey procedures. However, to date few examples exist in general practice research on the use of multiple methods using both quantitative and qualitative techniques for hypothesis generation. We aimed to determine information on all factors that may be associated with delivery of care to patients with diabetes. Factors for consideration on delivery of diabetes care were generated by multiple qualitative methods including brainstorming with health professionals and patients, a focus group and interviews with key informants which included GPs and practice nurses. Audit data showing variations in care of patients with diabetes were used to stimulate the brainstorming session. A systematic literature search focusing on quality of care of patients with diabetes in primary care was also conducted. Fifty-four potential factors were identified by multiple methods. Twenty (37.0%) were practice-related factors, 14 (25.9%) were patient-related factors and 20 (37.0%) were organizational factors. A combination of brainstorming and the literature review identified 51 (94.4%) factors. Patients did not identify factors in addition to those identified by other methods. The complexity of delivery of care to patients with diabetes is reflected in the large number of potential factors identified in this study. This study shows the feasibility of using multiple methods for hypothesis generation. Each evaluation method provided unique data which could not otherwise be easily obtained. This study highlights a way of combining various traditional methods in an attempt to overcome the deficiencies and bias that may occur when using a single method. Similar methods can also be used to generate hypotheses for other exploratory research. An important responsibility of health authorities and primary care groups will be to assess the health needs of their local populations. Multiple methods could also be used to identify and commission services to meet these needs.

Motivational and Volitional Variables Associated with Stages of Change for Exercise in Multiple Sclerosis: A Multiple Discriminant Analysis

ERIC Educational Resources Information Center

Chiu, Chung-Yi; Fitzgerald, Sandra D.; Strand, David M.; Muller, Veronica; Brooks, Jessica; Chan, Fong

2012-01-01

The main objective of this study was to determine whether motivational and volitional variables identified in the health action process approach (HAPA) model can be used to successfully differentiate people with multiple sclerosis (MS) in different stages of change for exercise and physical activity. Ex-post-facto design using multiple…

Combined use of the Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF): a systematic review.

PubMed

Birken, Sarah A; Powell, Byron J; Presseau, Justin; Kirk, M Alexis; Lorencatto, Fabiana; Gould, Natalie J; Shea, Christopher M; Weiner, Bryan J; Francis, Jill J; Yu, Yan; Haines, Emily; Damschroder, Laura J

2017-01-05

Over 60 implementation frameworks exist. Using multiple frameworks may help researchers to address multiple study purposes, levels, and degrees of theoretical heritage and operationalizability; however, using multiple frameworks may result in unnecessary complexity and redundancy if doing so does not address study needs. The Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF) are both well-operationalized, multi-level implementation determinant frameworks derived from theory. As such, the rationale for using the frameworks in combination (i.e., CFIR + TDF) is unclear. The objective of this systematic review was to elucidate the rationale for using CFIR + TDF by (1) describing studies that have used CFIR + TDF, (2) how they used CFIR + TDF, and (2) their stated rationale for using CFIR + TDF. We undertook a systematic review to identify studies that mentioned both the CFIR and the TDF, were written in English, were peer-reviewed, and reported either a protocol or results of an empirical study in MEDLINE/PubMed, PsycInfo, Web of Science, or Google Scholar. We then abstracted data into a matrix and analyzed it qualitatively, identifying salient themes. We identified five protocols and seven completed studies that used CFIR + TDF. CFIR + TDF was applied to studies in several countries, to a range of healthcare interventions, and at multiple intervention phases; used many designs, methods, and units of analysis; and assessed a variety of outcomes. Three studies indicated that using CFIR + TDF addressed multiple study purposes. Six studies indicated that using CFIR + TDF addressed multiple conceptual levels. Four studies did not explicitly state their rationale for using CFIR + TDF. Differences in the purposes that authors of the CFIR (e.g., comprehensive set of implementation determinants) and the TDF (e.g., intervention development) propose help to justify the use of CFIR + TDF. Given that the CFIR and the TDF are both multi-level frameworks, the rationale that using CFIR + TDF is needed to address multiple conceptual levels may reflect potentially misleading conventional wisdom. On the other hand, using CFIR + TDF may more fully define the multi-level nature of implementation. To avoid concerns about unnecessary complexity and redundancy, scholars who use CFIR + TDF and combinations of other frameworks should specify how the frameworks contribute to their study. PROSPERO CRD42015027615.

ECOTOXICOGENOMICS: EXPOSURE INDICATORS USING ESTS AND SUBTRACTIVE LIBRARIES FOR MULTI-LIFE STAGES OF PIMEPHALES

EPA Science Inventory

Ecotoxicogenomics is research that identifies patterns of gene expression in wildlife and predicts effects of environmental stressors. We are developing a multiple stressor, multiple life stage exposure model using the fathead minnow (Pimephales promelas), initially studying fou...

Renewable Energy Feasibility Study Leading to Development of the Native Spirit Solar Energy Facility

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

Carolyn Stewart; Tracey LeBeau

2008-01-31

DOE-funded renewable energy feasibility study conducted by Red Mountain Tribal Energy on behalf of the Southwest Tribal Energy Consortium (SWTEC). During the course of the study, SWTEC members considered multiple options for the organization structure, selected a proposed organization structure, and drafted a Memorandum of Understanding for the SWTEC organization. High-level resource assessments for SWTEC members were completed; surveys were developed and completed to determine each member’s interest in multiple participation options, including on-reservation projects. With the survey inputs in mind, multiple energy project options were identified and evaluated on a high-level basis. That process led to a narrowing ofmore » the field of technology options to solar generation, specifically, utility-scale Concentrating Solar-Powered Generation projects, with a specific, tentative project location identified at the Fort Mojave Indian Reservation -- the Native Spirit Solar Energy Facility.« less

What Is Successful Writing? An Investigation into the Multiple Ways Writers Can Write Successful Essays

ERIC Educational Resources Information Center

Crossley, Scott A.; Roscoe, Rod; McNamara, Danielle S.

2014-01-01

This study identifies multiple profiles of successful essays via a cluster analysis approach using linguistic features reported by a variety of natural language processing tools. The findings from the study indicate that there are four profiles of successful writers for the samples analyzed. These four profiles are linguistically distinct from one…

Predictors of Employment Status for People with Multiple Sclerosis

ERIC Educational Resources Information Center

Roessler, Richard T.; Rumrill, Phillip D.; Fitzgerald, Shawn M.

2004-01-01

This study examined the relevance of the disease-and-demographics model for explaining the employment outcomes of adults with multiple sclerosis (MS). Participating in a national survey of their employment concerns, 1,310 adults with MS provided data for the study (274 men, 21%; 1,020 women, 78%; 16 participants did not identify their gender).…

Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis.

PubMed

Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung

2009-12-15

The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.

Developing a national dental education research strategy: priorities, barriers and enablers.

PubMed

Ajjawi, Rola; Barton, Karen L; Dennis, Ashley A; Rees, Charlotte E

2017-03-29

This study aimed to identify national dental education research (DER) priorities for the next 3-5 years and to identify barriers and enablers to DER. Scotland. In this two-stage online questionnaire study, we collected data with multiple dental professions (eg, dentistry, dental nursing and dental hygiene) and stakeholder groups (eg, learners, clinicians, educators, managers, researchers and academics). Eighty-five participants completed the Stage 1 qualitative questionnaire and 649 participants the Stage 2 quantitative questionnaire. Eight themes were identified at Stage 1. Of the 24 DER priorities identified, the top three were: role of assessments in identifying competence; undergraduate curriculum prepares for practice and promoting teamwork. Following exploratory factor analysis, the 24 items loaded onto four factors: teamwork and professionalism, measuring and enhancing performance, dental workforce issues and curriculum integration and innovation. Barriers and enablers existed at multiple levels: individual, interpersonal, institutional structures and cultures and technology. This priority setting exercise provides a necessary first step to developing a national DER strategy capturing multiple perspectives. Promoting DER requires improved resourcing alongside efforts to overcome peer stigma and lack of valuing and motivation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholest...

Multiple Intravenous Infusions Phase 1b

PubMed Central

Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

2012-01-01

Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all issues are known in advance, and the frequency of errors is too low to be observed in the time allotted and with the limited sample of observations. Conclusions The administration of multiple IV infusions to a single patient is a complex task with many potential associated patient safety risks. Improvements to infusion and infusion-related technology, education standards, clinical best practice guidelines, hospital policies, and unit work practices are required to reduce the risk potential. This report makes several recommendations to Ontario hospitals so that they can develop an awareness of the issues highlighted in this report and minimize some of the risks. Further investigation of mitigating strategies is required and will be undertaken in Phase 2 of this research. Plain Language Summary Patients, particularly in critical care environments, often require multiple intravenous (IV) medications via large volumetric or syringe infusion pumps. The infusion of multiple IV medications is not without risk; unintended errors during these complex procedures have resulted in patient harm. However, the range of associated risks and the factors contributing to these risks are not well understood. Health Quality Ontario’s Ontario Health Technology Advisory Committee commissioned the Health Technology Safety Research Team at the University Health Network to conduct a multi-phase study to identify and mitigate the risks associated with multiple IV infusions. Some of the questions addressed by the team were as follows: What is needed to reduce the risk of errors for individuals who are receiving a lot of medications? What strategies work best? The initial report, Multiple Intravenous Infusions Phase 1a: Situation Scan Summary Report, summarizes the interim findings based on a literature review, an incident database review, and a technology scan. The Health Technology Safety Research Team worked in close collaboration with the Institute for Safe Medication Practices Canada on an exploratory study to understand the risks associated with multiple IV infusions and the degree to which nurses are educated to help mitigate them. The current report, Multiple Intravenous Infusions Phase 1b: Practice and Training Scan, presents the findings of a field study of 12 hospital clinical units across Ontario, as well as 13 interviews with educators from baccalaureate-level nursing degree programs and postgraduate Critical Care Nursing Certificate programs. It makes 9 recommendations that emphasize best practices for the administration of multiple IV infusions and pertain to secondary infusions, line identification, line set-up and removal, and administering IV bolus medications. The Health Technology Safety Research Team has also produced an associated report for hospitals entitled Mitigating the Risks Associated With Multiple IV Infusions: Recommendations Based on a Field Study of Twelve Ontario Hospitals, which highlights the 9 interim recommendations and provides a brief rationale for each one. PMID:23074426

Mobile multiple access study

NASA Technical Reports Server (NTRS)

1977-01-01

Multiple access techniques (FDMA, CDMA, TDMA) for the mobile user and attempts to identify the current best technique are discussed. Traffic loading is considered as well as voice and data modulation and spacecraft and system design. Emphasis is placed on developing mobile terminal cost estimates for the selected design. In addition, design examples are presented for the alternative techniques of multiple access in order to compare with the selected technique.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Psychiatric disorders in single and multiple sexual murderers.

PubMed

Hill, Andreas; Habermann, Niels; Berner, Wolfgang; Briken, Peer

2007-01-01

Sexual homicides - and particularly offenders with multiple victims - receive much attention in the general public as well as among forensic experts. The aim of this study was to assess psychiatric disorders in a large sample of sexual murderers and to identify disorders related to multiple sexual homicides. Psychiatric court reports from 20 German forensic psychiatrists on 166 men who had committed a sexual homicide were evaluated for psychiatric disorders according to DSM-IV, including standardized instruments for personality disorders (criteria from the Structured Clinical Interview) and psychopathy (Psychopathy Checklist-Revised). Offenders with a single sexual homicide victim (n = 130) were compared to those with multiple victims (n = 36). High lifetime prevalence rates were found for substance abuse or dependence, paraphilias (especially sexual sadism), sexual dysfunctions and personality disorders (especially antisocial, borderline, sadistic and schizoid). In the multiple sexual murderer group sexual sadism, voyeurism, sadistic, antisocial and schizoid personality disorders were more frequent than in the single-victim group; none of the multiple offenders was diagnosed with a mood disorder. Multiple sexual murderers are characterized by disorders in three major psychopathological domains: sexual as well as 'character' sadism, antisociality and schizoid personality. A thorough diagnostic evaluation of Axis I as well as Axis II disorders should be part of risk assessments in sexual homicide perpetrators. Although the study was a retrospective investigation on psychiatric court reports, the size of the sample and consistency with results from previous studies give confidence that the identified group differences are unlikely to be due to methodological limitations.

Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

PubMed

Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

2017-04-01

Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

Identifying the Educationally Influential Physician: A Systematic Review of Approaches

ERIC Educational Resources Information Center

Kronberger, Matthew P.; Bakken, Lori L.

2011-01-01

Introduction: Previous studies have indicated that educationally influential physicians' (EIPs) interactions with peers can lead to practice changes and improved patient outcomes. However, multiple approaches have been used to identify and investigate EIPs' informal or formal influence on practice, which creates study outcomes that are difficult…

Investigating the potential influence of established multiple-choice test-taking cues on item response in a pharmacotherapy board certification examination preparatory manual: a pilot study.

PubMed

Gettig, Jacob P

2006-04-01

To determine the prevalence of established multiple-choice test-taking correct and incorrect answer cues in the American College of Clinical Pharmacy's Updates in Therapeutics: The Pharmacotherapy Preparatory Course, 2005 Edition, as an equal or lesser surrogate indication of the prevalence of such cues in the Pharmacotherapy board certification examination. All self-assessment and patient case question-and-answer sets were assessed individually to determine if they were subject to selected correct and incorrect answer cues commonly seen in multiple-choice question writing. If the question was considered evaluable, correct answer cues-longest answer, mid-range number, one of two similar choices, and one of two opposite choices-were tallied. In addition, incorrect answer cues- inclusionary language and grammatical mismatch-were also tallied. Each cue was counted if it did what was expected or did the opposite of what was expected. Multiple cues could be identified in each question. A total of 237 (47.7%) of 497 questions in the manual were deemed evaluable. A total of 325 correct answer cues and 35 incorrect answer cues were identified in the 237 evaluable questions. Most evaluable questions contained one to two correct and/or incorrect answer cue(s). Longest answer was the most frequently identified correct answer cue; however, it was the least likely to identify the correct answer. Inclusionary language was the most frequently identified incorrect answer cue. Incorrect answer cues were considerably more likely to identify incorrect answer choices than correct answer cues were able to identify correct answer choices. The use of established multiple-choice test-taking cues is unlikely to be of significant help when taking the Pharmacotherapy board certification examination, primarily because of the lack of questions subject to such cues and the inability of correct answer cues to accurately identify correct answers. Incorrect answer cues, especially the use of inclusionary language, almost always will accurately identify an incorrect answer choice. Assuming that questions in the preparatory course manual were equal or lesser surrogates of those in the board certification examination, it is unlikely that intuition alone can replace adequate preparation and studying as the sole determinant of examination success.

Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

PubMed Central

Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R.; Chung, I-Fang

2011-01-01

Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing drug on other diseases as well as designing a single drug for multiple diseases. PMID:21909426

Generalisation of the identity method for determination of high-order moments of multiplicity distributions with a software implementation

NASA Astrophysics Data System (ADS)

Maćkowiak-Pawłowska, Maja; Przybyła, Piotr

2018-05-01

The incomplete particle identification limits the experimentally-available phase space region for identified particle analysis. This problem affects ongoing fluctuation and correlation studies including the search for the critical point of strongly interacting matter performed on SPS and RHIC accelerators. In this paper we provide a procedure to obtain nth order moments of the multiplicity distribution using the identity method, generalising previously published solutions for n=2 and n=3. Moreover, we present an open source software implementation of this computation, called Idhim, that allows one to obtain the true moments of identified particle multiplicity distributions from the measured ones provided the response function of the detector is known.

Using Incremental Rehearsal to Increase Fluency of Single-Digit Multiplication Facts with Children Identified as Learning Disabled in Mathematics Computation

ERIC Educational Resources Information Center

Burns, Matthew K.

2005-01-01

Previous research suggested that Incremental Rehearsal (IR; Tucker, 1989) led to better retention than other drill practices models. However, little research exists in the literature regarding drill models for mathematics and no studies were found that used IR to practice multiplication facts. Therefore, the current study used IR as an…

Student Ownership of Projects in an Upper-Division Optics Laboratory Course: A Multiple Case Study of Successful Experiences

ERIC Educational Resources Information Center

Dounas-Frazer, Dimitri R.; Stanley, Jacob T.; Lewandowski, H. J.

2017-01-01

We investigate students' sense of ownership of multiweek final projects in an upper-division optics lab course. Using a multiple case study approach, we describe three student projects in detail. Within-case analyses focused on identifying key issues in each project, and constructing chronological descriptions of those events. Cross-case analysis…

A discrimination index for selecting markers of tumor growth dynamic across multiple cancer studies with a cure fraction.

PubMed

Rouam, Sigrid; Broët, Philippe

2013-08-01

To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied population is a mixture of cured and uncured patients, like in early-stage cancers. We propose a novel index that quantifies the capability of a genomic marker to separate uncured patients, according to their time-to-event outcomes. It allows to identify genomic markers characterizing tumor growth dynamic across multiple studies. Simulation results show that our index performs better than classical indices based on the Cox model. It is neither affected by the sample size nor the cure rate fraction. In a cross-study of early-stage breast cancers, the index allows to select genomic markers with a potential consistent effect on tumor growth dynamics. Copyright © 2013 Elsevier Inc. All rights reserved.

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

PubMed

Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

2009-07-01

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

Think Tank on Metabolomics and Prospective Cohorts: How to Leverage Resources

Cancer.gov

This Think Tank identified resources that can be used collaboratively across prospective cohorts; developed strategies to leverage resources for advancing the use of metabolomics in prospective cohort studies; identified the best strategies for performing analyses using metabolomics data across multiple studies; and, established a collaborative group that will identify and tackle research projects that cannot be effectively investigated by one independent group.

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

PubMed Central

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

The Association of CD81 Polymorphisms with Alloimmunization in Sickle Cell Disease

PubMed Central

Tatari-Calderone, Zohreh; Tamouza, Ryad; Le Bouder, Gama P.; Dewan, Ramita; Luban, Naomi L. C.; Lasserre, Jacqueline; Maury, Jacqueline; Lionnet, François; Krishnamoorthy, Rajagopal; Girot, Robert

2013-01-01

The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in the CD81, CHRNA10, and ARHG genes in two groups of SCD patients. One group (35) of patients developed alloantibodies, and another (40) had no alloantibodies despite having received multiple transfusions. Two SNPs in the CD81 gene, that encodes molecule involved in the signal modulation of B lymphocytes, show a strong association with alloimmunization. If confirmed in prospective studies with larger cohorts, the two SNPs identified in this retrospective study could serve as predictive biomarkers for alloimmunization. PMID:23762099

Estimating avian population size using Bowden's estimator

USGS Publications Warehouse

Diefenbach, D.R.

2009-01-01

Avian researchers often uniquely mark birds, and multiple estimators could be used to estimate population size using individually identified birds. However, most estimators of population size require that all sightings of marked birds be uniquely identified, and many assume homogeneous detection probabilities. Bowden's estimator can incorporate sightings of marked birds that are not uniquely identified and relax assumptions required of other estimators. I used computer simulation to evaluate the performance of Bowden's estimator for situations likely to be encountered in bird studies. When the assumptions of the estimator were met, abundance and variance estimates and confidence-interval coverage were accurate. However, precision was poor for small population sizes (N < 50) unless a large percentage of the population was marked (>75%) and multiple (≥8) sighting surveys were conducted. If additional birds are marked after sighting surveys begin, it is important to initially mark a large proportion of the population (pm ≥ 0.5 if N ≤ 100 or pm > 0.1 if N ≥ 250) and minimize sightings in which birds are not uniquely identified; otherwise, most population estimates will be overestimated by >10%. Bowden's estimator can be useful for avian studies because birds can be resighted multiple times during a single survey, not all sightings of marked birds have to uniquely identify individuals, detection probabilities among birds can vary, and the complete study area does not have to be surveyed. I provide computer code for use with pilot data to design mark-resight surveys to meet desired precision for abundance estimates.

Risk Profiles of Children Entering Residential Care: A Cluster Analysis

ERIC Educational Resources Information Center

Hagaman, Jessica L.; Trout, Alexandra L.; Chmelka, M. Beth; Thompson, Ronald W.; Reid, Robert

2010-01-01

Children in residential care are a heterogeneous population, presenting various combinations of risks. Existing studies on these children suggest high variability across multiple domains (e.g., academics, behavior). Given this heterogeneity, it is important to begin to identify the combinations and patterns of multiple risks, or risk profiles,…

Adolescent Racial Identity: Self-Identification of Multiple and "Other" Race/Ethnicities

ERIC Educational Resources Information Center

Harris, Bryn; Ravert, Russell D.; Sullivan, Amanda L.

2017-01-01

This mixed methods study focused on adolescents who rejected conventional singular racial/ethnic categorization by selecting multiple race/ethnicities or writing descriptions of "Other" racial/ethnic identities in response to a survey item asking them to identify their race/ethnicity. Written responses reflected eight distinct categories…

Genetic changes associated with testicular cancer susceptibility.

PubMed

Pyle, Louise C; Nathanson, Katherine L

2016-10-01

Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis.

PubMed

Kantor, Daniel; Johnson, Kristen; Vieira, Maria Cecilia; Signorovitch, James; Li, Nanxin; Gao, Wei; Koo, Valerie; Duchesneau, Emilie; Herrera, Vivian

2018-05-15

To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I 2  = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS. Copyright © 2018. Published by Elsevier B.V.

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

PubMed

Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple sclerosis based on their individual responses and perceptions for coping. Implications for rehabilitation Engagement in coping with multiple sclerosis has been associated with individual factors and neuropsychological functions. Considering individual and disease-related factors would allow healthcare professionals to provide more tailored interventions to maintain and master coping with multiple sclerosis. People living with multiple sclerosis should be empowered to appraise and manage ability to cope based on the contextual evidence (individual and clinical condition). Rehabilitation services should move beyond physical management incorporating behavioral aspects for better functioning in living with multiple sclerosis.

Identifying Aspects of Parental Involvement that Affect the Academic Achievement of High School Students

ERIC Educational Resources Information Center

Roulette-McIntyre, Ovella; Bagaka's, Joshua G.; Drake, Daniel D.

2005-01-01

This study identified parental practices that relate positively to high school students' academic performance. Parents of 643 high school students participated in the study. Data analysis, using a multiple linear regression model, shows parent-school connection, student gender, and race are significant predictors of student academic performance.…

Identifying Causal Variants at Loci with Multiple Signals of Association

PubMed Central

Hormozdiari, Farhad; Kostem, Emrah; Kang, Eun Yong; Pasaniuc, Bogdan; Eskin, Eleazar

2014-01-01

Although genome-wide association studies have successfully identified thousands of risk loci for complex traits, only a handful of the biologically causal variants, responsible for association at these loci, have been successfully identified. Current statistical methods for identifying causal variants at risk loci either use the strength of the association signal in an iterative conditioning framework or estimate probabilities for variants to be causal. A main drawback of existing methods is that they rely on the simplifying assumption of a single causal variant at each risk locus, which is typically invalid at many risk loci. In this work, we propose a new statistical framework that allows for the possibility of an arbitrary number of causal variants when estimating the posterior probability of a variant being causal. A direct benefit of our approach is that we predict a set of variants for each locus that under reasonable assumptions will contain all of the true causal variants with a high confidence level (e.g., 95%) even when the locus contains multiple causal variants. We use simulations to show that our approach provides 20–50% improvement in our ability to identify the causal variants compared to the existing methods at loci harboring multiple causal variants. We validate our approach using empirical data from an expression QTL study of CHI3L2 to identify new causal variants that affect gene expression at this locus. CAVIAR is publicly available online at http://genetics.cs.ucla.edu/caviar/. PMID:25104515

Identifying causal variants at loci with multiple signals of association.

PubMed

Hormozdiari, Farhad; Kostem, Emrah; Kang, Eun Yong; Pasaniuc, Bogdan; Eskin, Eleazar

2014-10-01

Although genome-wide association studies have successfully identified thousands of risk loci for complex traits, only a handful of the biologically causal variants, responsible for association at these loci, have been successfully identified. Current statistical methods for identifying causal variants at risk loci either use the strength of the association signal in an iterative conditioning framework or estimate probabilities for variants to be causal. A main drawback of existing methods is that they rely on the simplifying assumption of a single causal variant at each risk locus, which is typically invalid at many risk loci. In this work, we propose a new statistical framework that allows for the possibility of an arbitrary number of causal variants when estimating the posterior probability of a variant being causal. A direct benefit of our approach is that we predict a set of variants for each locus that under reasonable assumptions will contain all of the true causal variants with a high confidence level (e.g., 95%) even when the locus contains multiple causal variants. We use simulations to show that our approach provides 20-50% improvement in our ability to identify the causal variants compared to the existing methods at loci harboring multiple causal variants. We validate our approach using empirical data from an expression QTL study of CHI3L2 to identify new causal variants that affect gene expression at this locus. CAVIAR is publicly available online at http://genetics.cs.ucla.edu/caviar/. Copyright © 2014 by the Genetics Society of America.

Training Correctional Educators: A Needs Assessment Study.

ERIC Educational Resources Information Center

Jurich, Sonia; Casper, Marta; Hull, Kim A.

2001-01-01

Focus groups and a training needs survey of Virginia correctional educators identified educational philosophy, communication skills, human behavior, and teaching techniques as topics of interest. Classroom observations identified additional areas: teacher isolation, multiple challenges, absence of grade structure, and safety constraints. (Contains…

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

PubMed

Hillard, Virany H; Shih, Lynn L; Chin, Shing; Moorthy, Chitti R; Benzil, Deborah L

2003-07-01

Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Interpretation and use of evidence in state policymaking: a qualitative analysis

PubMed Central

Apollonio, Dorie E; Bero, Lisa A

2017-01-01

Introduction Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Methods Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Results Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Conclusions Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and researchers can apply to encourage evidence-informed policymaking. PMID:28219958

Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

PubMed

Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E

2006-09-01

To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

Satisfaction with communicative participation as defined by adults with multiple sclerosis: a qualitative study.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn R; Klasner, Estelle R; Deitz, Jean; Dudgeon, Brian J; Eadie, Tanya; Miller, Robert M; Amtmann, Dagmar

2007-01-01

This study examined satisfaction with communicative participation as reported by adults with multiple sclerosis (MS). Eight community-dwelling adults with MS participated in semi-structured interviews. They were asked to discuss their satisfaction with their communication in a variety of situations. Interviews were analyzed using a constant comparative method of qualitative description. Themes derived included: Comfort, consisting of Ease and Confidence; Success of the Outcome, including Function is Achieved and A Connection is Made; and Personal Meaning of Participation, including Personal Preferences, Comparison with the Past, and Thinking about One's Own Communication. Participants described multiple facets of satisfaction with communicative participation. Some of the dimensions were similar to those in existing assessment instruments such as levels of ease or difficulty with performance. Participants did not talk about frequency of activities as a key part of their satisfaction. Implications for identifying intervention targets and treatment outcome measurements are provided. The reader should be able to: 1) define communicative participation and identify key elements of this construct; 2) identify the issues that were most relevant to satisfaction with communicative participation with participants with MS; and 3) identify reasons for greater emphasis on the subjective viewpoint of people with communication disorders in measurement of treatment outcomes.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

Magic Finger Teaching Method in Learning Multiplication Facts among Deaf Students

ERIC Educational Resources Information Center

Thai, Liong; Yasin, Mohd. Hanafi Mohd

2016-01-01

Deaf students face problems in mastering multiplication facts. This study aims to identify the effectiveness of Magic Finger Teaching Method (MFTM) and students' perception towards MFTM. The research employs a quasi experimental with non-equivalent pre-test and post-test control group design. Pre-test, post-test and questionnaires were used. As…

Stress, Behavior, and Children and Youth Who Are Deafblind

ERIC Educational Resources Information Center

Nelson, Catherine; Greenfield, Robin G.; Hyte, Holly A.; Shaffer, Jason P.

2013-01-01

Children and youth who are deafblind with multiple disabilities have several identified risk factors for experiencing toxic levels of stress, and such stress is known to impair physical, mental, and emotional health. This single-case multiple baseline study examined the frequency and duration of behaviors thought to indicate stress, the duration…

Primary Factors Related to Multiple Placements for Children in Out-of-Home Care

ERIC Educational Resources Information Center

Eggertsen, Lars

2008-01-01

Using an ecological framework, this study identified which factors related to out-of-home placements significantly influenced multiple placements for children in Utah during 2000, 2001, and 2002. Multinomial logistic regression statistical procedures and a geographical information system (GIS) were used to analyze the data. The final model…

Multiple Perpetrator Sexual Assault: How Does It Differ from Assault by a Single Perpetrator?

ERIC Educational Resources Information Center

Morgan, Louise; Brittain, Bernadette; Welch, Jan

2012-01-01

Research that attempts to identify characteristic features of multiple perpetrator sexual assault (MPSA) is limited. This study compared demographic and assault related characteristics of 135 cases of MPSA with 139 cases of single perpetrator sexual assault (SPSA) reported to the Haven sexual assault referral centre, Camberwell, London, over a…

OrthoVenn: a web server for genome wide comparison and annotation of orthologous clusters across multiple species

USDA-ARS?s Scientific Manuscript database

Genome wide analysis of orthologous clusters is an important component of comparative genomics studies. Identifying the overlap among orthologous clusters can enable us to elucidate the function and evolution of proteins across multiple species. Here, we report a web platform named OrthoVenn that i...

Next-generation sequencing library preparation method for identification of RNA viruses on the Ion Torrent Sequencing Platform.

PubMed

Chen, Guiqian; Qiu, Yuan; Zhuang, Qingye; Wang, Suchun; Wang, Tong; Chen, Jiming; Wang, Kaicheng

2018-05-09

Next generation sequencing (NGS) is a powerful tool for the characterization, discovery, and molecular identification of RNA viruses. There were multiple NGS library preparation methods published for strand-specific RNA-seq, but some methods are not suitable for identifying and characterizing RNA viruses. In this study, we report a NGS library preparation method to identify RNA viruses using the Ion Torrent PGM platform. The NGS sequencing adapters were directly inserted into the sequencing library through reverse transcription and polymerase chain reaction, without fragmentation and ligation of nucleic acids. The results show that this method is simple to perform, able to identify multiple species of RNA viruses in clinical samples.

Combinations of Multiple Neuroimaging Markers using Logistic Regression for Auxiliary Diagnosis of Alzheimer Disease and Mild Cognitive Impairment.

PubMed

Mao, Nini; Liu, Yunting; Chen, Kewei; Yao, Li; Wu, Xia

2018-06-05

Multiple neuroimaging modalities have been developed providing various aspects of information on the human brain. Used together and properly, these complementary multimodal neuroimaging data integrate multisource information which can facilitate a diagnosis and improve the diagnostic accuracy. In this study, 3 types of brain imaging data (sMRI, FDG-PET, and florbetapir-PET) were fused in the hope to improve diagnostic accuracy, and multivariate methods (logistic regression) were applied to these trimodal neuroimaging indices. Then, the receiver-operating characteristic (ROC) method was used to analyze the outcomes of the logistic classifier, with either each index, multiples from each modality, or all indices from all 3 modalities, to investigate their differential abilities to identify the disease. With increasing numbers of indices within each modality and across modalities, the accuracy of identifying Alzheimer disease (AD) increases to varying degrees. For example, the area under the ROC curve is above 0.98 when all the indices from the 3 imaging data types are combined. Using a combination of different indices, the results confirmed the initial hypothesis that different biomarkers were potentially complementary, and thus the conjoint analysis of multiple information from multiple sources would improve the capability to identify diseases such as AD and mild cognitive impairment. © 2018 S. Karger AG, Basel.

Maltreatment histories of foster youth exiting out-of-home care through emancipation: a latent class analysis.

PubMed

Havlicek, Judy

2014-01-01

Little is known about maltreatment among foster youth transitioning to adulthood. Multiple entries into out-of-home care and unsuccessful attempts at reunification may nevertheless reflect extended exposure to chronic maltreatment and multiple types of victimization. This study used administrative data from the Illinois Department of Children and Family Services to identify all unduplicated allegations of maltreatment in a cohort of 801 foster youth transitioning to adulthood in the state of Illinois. A latent variable modeling approach generated profiles of maltreatment based on substantiated and unsubstantiated reports of maltreatment taken from state administrative data. Four indicators of maltreatment were included in the latent class analysis: multiple types of maltreatment, predominant type of maltreatment, chronicity, and number of different perpetrators. The analysis identified four subpopulations of foster youth in relation to maltreatment. Study findings highlight the heterogeneity of maltreatment in the lives of foster youth transitioning to adulthood and draw attention to a need to raise awareness among service providers to screen for chronic maltreatment and multiple types of victimization. © The Author(s) 2014.

Evaluation of 19,460 Wheat Accessions Conserved in the Indian National Genebank to Identify New Sources of Resistance to Rust and Spot Blotch Diseases.

PubMed

Kumar, Sundeep; Archak, Sunil; Tyagi, R K; Kumar, Jagdish; Vk, Vikas; Jacob, Sherry R; Srinivasan, Kalyani; Radhamani, J; Parimalan, R; Sivaswamy, M; Tyagi, Sandhya; Yadav, Mamata; Kumari, Jyotisna; Deepali; Sharma, Sandeep; Bhagat, Indoo; Meeta, Madhu; Bains, N S; Chowdhury, A K; Saha, B C; Bhattacharya, P M; Kumari, Jyoti; Singh, M C; Gangwar, O P; Prasad, P; Bharadwaj, S C; Gogoi, Robin; Sharma, J B; Gm, Sandeep Kumar; Saharan, M S; Bag, Manas; Roy, Anirban; Prasad, T V; Sharma, R K; Dutta, M; Sharma, Indu; Bansal, K C

2016-01-01

A comprehensive germplasm evaluation study of wheat accessions conserved in the Indian National Genebank was conducted to identify sources of rust and spot blotch resistance. Genebank accessions comprising three species of wheat-Triticum aestivum, T. durum and T. dicoccum were screened sequentially at multiple disease hotspots, during the 2011-14 crop seasons, carrying only resistant accessions to the next step of evaluation. Wheat accessions which were found to be resistant in the field were then assayed for seedling resistance and profiled using molecular markers. In the primary evaluation, 19,460 accessions were screened at Wellington (Tamil Nadu), a hotspot for wheat rusts. We identified 4925 accessions to be resistant and these were further evaluated at Gurdaspur (Punjab), a hotspot for stripe rust and at Cooch Behar (West Bengal), a hotspot for spot blotch. The second round evaluation identified 498 accessions potentially resistant to multiple rusts and 868 accessions potentially resistant to spot blotch. Evaluation of rust resistant accessions for seedling resistance against seven virulent pathotypes of three rusts under artificial epiphytotic conditions identified 137 accessions potentially resistant to multiple rusts. Molecular analysis to identify different combinations of genetic loci imparting resistance to leaf rust, stem rust, stripe rust and spot blotch using linked molecular markers, identified 45 wheat accessions containing known resistance genes against all three rusts as well as a QTL for spot blotch resistance. The resistant germplasm accessions, particularly against stripe rust, identified in this study can be excellent potential candidates to be employed for breeding resistance into the background of high yielding wheat cultivars through conventional or molecular breeding approaches, and are expected to contribute toward food security at national and global levels.

Evaluation of 19,460 Wheat Accessions Conserved in the Indian National Genebank to Identify New Sources of Resistance to Rust and Spot Blotch Diseases

PubMed Central

Jacob, Sherry R.; Srinivasan, Kalyani; Radhamani, J.; Parimalan, R.; Sivaswamy, M.; Tyagi, Sandhya; Yadav, Mamata; Kumari, Jyotisna; Deepali; Sharma, Sandeep; Bhagat, Indoo; Meeta, Madhu; Bains, N. S.; Chowdhury, A. K.; Saha, B. C.; Bhattacharya, P. M.; Kumari, Jyoti; Singh, M. C.; Gangwar, O. P.; Prasad, P.; Bharadwaj, S. C.; Gogoi, Robin; Sharma, J. B.; GM, Sandeep Kumar; Saharan, M. S.; Bag, Manas; Roy, Anirban; Prasad, T. V.; Sharma, R. K.; Dutta, M.; Sharma, Indu; Bansal, K. C.

2016-01-01

A comprehensive germplasm evaluation study of wheat accessions conserved in the Indian National Genebank was conducted to identify sources of rust and spot blotch resistance. Genebank accessions comprising three species of wheat–Triticum aestivum, T. durum and T. dicoccum were screened sequentially at multiple disease hotspots, during the 2011–14 crop seasons, carrying only resistant accessions to the next step of evaluation. Wheat accessions which were found to be resistant in the field were then assayed for seedling resistance and profiled using molecular markers. In the primary evaluation, 19,460 accessions were screened at Wellington (Tamil Nadu), a hotspot for wheat rusts. We identified 4925 accessions to be resistant and these were further evaluated at Gurdaspur (Punjab), a hotspot for stripe rust and at Cooch Behar (West Bengal), a hotspot for spot blotch. The second round evaluation identified 498 accessions potentially resistant to multiple rusts and 868 accessions potentially resistant to spot blotch. Evaluation of rust resistant accessions for seedling resistance against seven virulent pathotypes of three rusts under artificial epiphytotic conditions identified 137 accessions potentially resistant to multiple rusts. Molecular analysis to identify different combinations of genetic loci imparting resistance to leaf rust, stem rust, stripe rust and spot blotch using linked molecular markers, identified 45 wheat accessions containing known resistance genes against all three rusts as well as a QTL for spot blotch resistance. The resistant germplasm accessions, particularly against stripe rust, identified in this study can be excellent potential candidates to be employed for breeding resistance into the background of high yielding wheat cultivars through conventional or molecular breeding approaches, and are expected to contribute toward food security at national and global levels. PMID:27942031

Examination of association to autism of common genetic variationin genes related to dopamine.

PubMed

Anderson, B M; Schnetz-Boutaud, N; Bartlett, J; Wright, H H; Abramson, R K; Cuccaro, M L; Gilbert, J R; Pericak-Vance, M A; Haines, J L

2008-12-01

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals display significant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypic behaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing a rate of one in 150. Although multiple genetic linkage and association studies have yielded multiple suggestive genes or chromosomal regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies have been suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is that multiple genetic variants may be required to significantly increase the risk of developing autism. Thus, we took the alternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28 single nucleotide polymorphisms. Although we did observe a nominally significant association for rs2239535 (P=0.008) on chromosome 20, single-locus analysis did not reveal any results as significant after correction for multiple comparisons. No significant interaction was identified when Multifactor Dimensionality Reduction was employed to test specifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage to various loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to any specific gene or combination of genes within the pathway. These results demonstrate that common genetic variation within the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis.

Techniques for Identifying Cross-Disciplinary and "Hard-to-Detect" Evidence for Systematic Review

ERIC Educational Resources Information Center

O'Mara-Eves, Alison; Brunton, Ginny; McDaid, David; Kavanagh, Josephine; Oliver, Sandy; Thomas, James

2014-01-01

Driven by necessity in our own complex review, we developed alternative systematic ways of identifying relevant evidence where the key concepts are generally not focal to the primary studies' aims and are found across multiple disciplines--that is, hard-to-detect evidence. Specifically, we sought to identify evidence on community engagement in…

Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis

PubMed Central

Elliott, Christina; Lindner, Maren; Arthur, Ariel; Brennan, Kathryn; Jarius, Sven; Hussey, John; Chan, Andrew; Stroet, Anke; Olsson, Tomas; Willison, Hugh; Barnett, Susan C.; Meinl, Edgar

2012-01-01

Pathological and clinical studies implicate antibody-dependent mechanisms in the immunopathogenesis of multiple sclerosis. We tested this hypothesis directly by investigating the ability of patient-derived immunoglobulins to mediate demyelination and axonal injury in vitro. Using a myelinating culture system, we developed a sensitive and reproducible bioassay to detect and quantify these effects and applied this to investigate the pathogenic potential of immunoglobulin G preparations obtained from patients with multiple sclerosis (n = 37), other neurological diseases (n = 10) and healthy control donors (n = 13). This identified complement-dependent demyelinating immunoglobulin G responses in approximately 30% of patients with multiple sclerosis, which in two cases was accompanied by significant complement-dependent antibody mediated axonal loss. No pathogenic immunoglobulin G responses were detected in patients with other neurological disease or healthy controls, indicating that the presence of these demyelinating/axopathic autoantibodies is specific for a subset of patients with multiple sclerosis. Immunofluorescence microscopy revealed immunoglobulin G preparations with demyelinating activity contained antibodies that specifically decorated the surface of myelinating oligodendrocytes and their contiguous myelin sheaths. No other binding was observed indicating that the response is restricted to autoantigens expressed by terminally differentiated myelinating oligodendrocytes. In conclusion, our study identifies axopathic and/or demyelinating autoantibody responses in a subset of patients with multiple sclerosis. This observation underlines the mechanistic heterogeneity of multiple sclerosis and provides a rational explanation why some patients benefit from antibody depleting treatments. PMID:22561643

Identification of limit cycles in multi-nonlinearity, multiple path systems

NASA Technical Reports Server (NTRS)

Mitchell, J. R.; Barron, O. L.

1979-01-01

A method of analysis which identifies limit cycles in autonomous systems with multiple nonlinearities and multiple forward paths is presented. The FORTRAN code for implementing the Harmonic Balance Algorithm is reported. The FORTRAN code is used to identify limit cycles in multiple path and nonlinearity systems while retaining the effects of several harmonic components.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Targeted quantitative analysis of Streptococcus pyogenes virulence factors by multiple reaction monitoring.

PubMed

Lange, Vinzenz; Malmström, Johan A; Didion, John; King, Nichole L; Johansson, Björn P; Schäfer, Juliane; Rameseder, Jonathan; Wong, Chee-Hong; Deutsch, Eric W; Brusniak, Mi-Youn; Bühlmann, Peter; Björck, Lars; Domon, Bruno; Aebersold, Ruedi

2008-08-01

In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples. This approach consists of three steps. First, the proteome is extensively mapped out by multidimensional fractionation and tandem mass spectrometry, and the data generated are assembled in the PeptideAtlas database. Second, based on this proteome map, peptides uniquely identifying the proteins of interest, proteotypic peptides, are selected, and multiple reaction monitoring (MRM) transitions are established and validated by MS2 spectrum acquisition. This process of peptide selection, transition selection, and validation is supported by a suite of software tools, TIQAM (Targeted Identification for Quantitative Analysis by MRM), described in this study. Third, the selected target protein set is quantified in multiple samples by MRM. Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure.

A multiple-dimension liquid chromatography coupled with mass spectrometry data strategy for the rapid discovery and identification of unknown compounds from a Chinese herbal formula (Er-xian decoction).

PubMed

Wang, Caihong; Zhang, Jinlan; Wu, Caisheng; Wang, Zhe

2017-10-06

It is very important to rapidly discover and identify the multiple components of traditional Chinese medicine (TCM) formula. High performance liquid chromatography with high resolution tandem mass spectrometry (HPLC-HRMS/MS) has been widely used to analyze TCM formula and contains multiple-dimension data including retention time (RT), high resolution mass (HRMS), multiple-stage mass spectrometric (MS n ), and isotope intensity distribution (IID) data. So it is very necessary to exploit a useful strategy to utilize multiple-dimension data to rapidly probe structural information and identify chemical compounds. In this study, a new strategy to initiatively use the multiple-dimension LC-MS data has been developed to discover and identify unknown compounds of TCM in many styles. The strategy guarantees the fast discovery of candidate structural information and provides efficient structure clues for identification. The strategy contains four steps in sequence: (1) to discover potential compounds and obtain sub-structure information by the mass spectral tree similarity filter (MTSF) technique, based on HRMS and MS n data; (2) to classify potential compounds into known chemical classes by discriminant analysis (DA) on the basis of RT and HRMS data; (3) to hit the candidate structural information of compounds by intersection sub-structure between MTSF and DA (M,D-INSS); (4) to annotate and confirm candidate structures by IID data. This strategy allowed for the high exclusion efficiency (greater than 41%) of irrelevant ions in er-xian decoction (EXD) while providing accurate structural information of 553 potential compounds and identifying 66 candidates, therefore accelerating and simplifying the discovery and identification of unknown compounds in TCM formula. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

PubMed

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C A; Patsopoulos, Nikolaos A; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E; Edkins, Sarah; Gray, Emma; Booth, David R; Potter, Simon C; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D'alfonso, Sandra; Blackburn, Hannah; Martinelli Boneschi, Filippo; Liddle, Jennifer; Harbo, Hanne F; Perez, Marc L; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J; Barcellos, Lisa F; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P; Brassat, David; Broadley, Simon A; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M; Cavalla, Paola; Celius, Elisabeth G; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B; Cozen, Wendy; Cree, Bruce A C; Cross, Anne H; Cusi, Daniele; Daly, Mark J; Davis, Emma; de Bakker, Paul I W; Debouverie, Marc; D'hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F A; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G; Kilpatrick, Trevor J; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S; Leone, Maurizio A; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R; Link, Jenny; Liu, Jianjun; Lorentzen, Aslaug R; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L; Ramsay, Patricia P; Reunanen, Mauri; Reynolds, Richard; Rioux, John D; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J; Sellebjerg, Finn; Selmaj, Krzysztof W; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M A; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A; Tronczynska, Ewa; Casas, Juan P; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S; Wang, Kai; Mathew, Christopher G; Wason, James; Palmer, Colin N A; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C; Yaouanq, Jacqueline; Viswanathan, Ananth C; Zhang, Haitao; Wood, Nicholas W; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R; Pericak-Vance, Margaret A; Haines, Jonathan L; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J; De Jager, Philip L; Peltonen, Leena; Stewart, Graeme J; Hafler, David A; Hauser, Stephen L; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-08-10

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

PubMed

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

2016-09-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. ©2016 American Association for Cancer Research.

HRCT findings of collagen vascular disease-related interstitial pneumonia (CVD-IP): a comparative study among individual underlying diseases.

PubMed

Tanaka, N; Kunihiro, Y; Kubo, M; Kawano, R; Oishi, K; Ueda, K; Gondo, T

2018-05-29

To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ 2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ 2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ 2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Network-Assisted Investigation of Combined Causal Signals from Genome-Wide Association Studies in Schizophrenia

PubMed Central

Jia, Peilin; Wang, Lily; Fanous, Ayman H.; Pato, Carlos N.; Edwards, Todd L.; Zhao, Zhongming

2012-01-01

With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each single GWAS dataset and then implemented a discovery-evaluation strategy to identify module genes with consistent association signals. We validated the module genes in an independent dataset, and also examined them through meta-analysis of the related SNPs using multiple GWAS datasets. As a result, we identified 205 module genes with a joint effect significantly associated with schizophrenia; these module genes included a number of well-studied candidate genes such as DISC1, GNA12, GNA13, GNAI1, GPR17, and GRIN2B. Further functional analysis suggested these genes are involved in neuronal related processes. Additionally, meta-analysis found that 18 SNPs in 9 module genes had P meta<1×10−4, including the gene HLA-DQA1 located in the MHC region on chromosome 6, which was reported in previous studies using the largest cohort of schizophrenia patients to date. These results demonstrated our bi-directional network-based strategy is efficient for identifying disease-associated genes with modest signals in GWAS datasets. This approach can be applied to any other complex diseases/traits where multiple GWAS datasets are available. PMID:22792057

Design, methodological issues and participation in a multiple sclerosis case-control study.

PubMed

Williamson, D M; Marrie, R A; Ashley-Koch, A; Schiffer, R; Trottier, J; Wagner, L

2012-09-01

This study was conducted to determine whether the risk of developing multiple sclerosis (MS) was associated with certain environmental exposures or genetic factors previously reported to influence MS risk. This paper describes the methodological issues, study design and characteristics of the study population. Individuals with definite MS were identified from a prevalence study conducted in three geographic areas. The target number of cases was not reached, so an additional study area was added. Identifying clinic controls was inefficient, so controls were recruited using random digit dialing. All study participants completed a detailed questionnaire regarding environmental exposures using computer-assisted telephone interviewing, and blood was collected for genetic analysis. In total, 276 cases and 590 controls participated, but participation rates were low, ranging from 28.4% to 38.9%. Only one-third (33.6%) of individuals identified in the prevalence study agreed to participate in the case-control study. Cases were more likely to be non-Hispanic white and older than their source populations as identified in the preceding prevalence study (P < 0.05). Most participants provided a blood sample for genotyping (91%; n = 789). Epidemiological studies play a key role in identifying genetic and environmental factors that are associated with complex diseases like MS. Methodological issues arise in every study, and investigators need to be able to detect, respond to and correct problems in a timely and scientifically valid manner. © 2011 John Wiley & Sons A/S.

Identifying multiple submissions in Internet research: preserving data integrity.

PubMed

Bowen, Anne M; Daniel, Candice M; Williams, Mark L; Baird, Grayson L

2008-11-01

Internet-based sexuality research with hidden populations has become increasingly popular. Respondent anonymity may encourage participation and lower social desirability, but associated disinhibition may promote multiple submissions, especially when incentives are offered. The goal of this study was to identify the usefulness of different variables for detecting multiple submissions from repeat responders and to explore incentive effects. The data included 1,900 submissions from a three-session Internet intervention with a pretest and three post-test questionnaires. Participants were men who have sex with men and incentives were offered to rural participants for completing each questionnaire. The final number of submissions included 1,273 "unique", 132 first submissions by "repeat responders" and 495 additional submissions by the "repeat responders" (N = 1,900). Four categories of repeat responders were identified: "infrequent" (2-5 submissions), "persistent" (6-10 submissions), "very persistent" (11-30 submissions), and "hackers" (more than 30 submissions). Internet Provider (IP) addresses, user names, and passwords were the most useful for identifying "infrequent" repeat responders. "Hackers" often varied their IP address and identifying information to prevent easy identification, but investigating the data for small variations in IP, using reverse telephone look up, and patterns across usernames and passwords were helpful. Incentives appeared to play a role in stimulating multiple submissions, especially from the more sophisticated "hackers". Finally, the web is ever evolving and it will be necessary to have good programmers and staff who evolve as fast as "hackers".

Change Strategies and Associated Implementation Challenges: An Analysis of Online Counselling Sessions.

PubMed

Rodda, Simone N; Hing, Nerilee; Hodgins, David C; Cheetham, Alison; Dickins, Marissa; Lubman, Dan I

2017-09-01

Self-change is the most frequent way people limit or reduce gambling involvement and often the first choice of people experiencing gambling-related problems. Less well known is the range of change strategies gamblers use and how these are selected, initiated or maintained. This study examined change strategies discussed in counselling transcripts from 149 clients who accessed a national online gambling help service in Australia. Using thematic analysis, we identified the presence of six change strategies; cash control and financial management, social support, avoiding or limiting gambling, alternative activities, changing thoughts and beliefs, and self-assessment and monitoring. Four implementation issues were also identified; a mismatch between need and strategy selection or maintenance; importance and readiness versus the cost of implementation; poor or unplanned transitions between strategies; and failure to review the helpfulness of strategies resulting in premature abandonment or unhelpful prolonged application. This study is the first to identify change strategies discussed in online counselling sessions. This study suggests change strategies are frequently discussed in online counselling sessions and we identified multiple new actions associated with change strategies that had not previously been identified. However, multiple implementation issues were identified and further work is required to determine the helpfulness of change strategies in terms of their selection, initiation and maintenance.

Coronary artery analysis: Computer-assisted selection of best-quality segments in multiple-phase coronary CT angiography

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

Zhou, Chuan, E-mail: chuan@umich.edu; Chan, Heang-

Purpose: The authors are developing an automated method to identify the best-quality coronary arterial segment from multiple-phase coronary CT angiography (cCTA) acquisitions, which may be used by either interpreting physicians or computer-aided detection systems to optimally and efficiently utilize the diagnostic information available in multiple-phase cCTA for the detection of coronary artery disease. Methods: After initialization with a manually identified seed point, each coronary artery tree is automatically extracted from multiple cCTA phases using our multiscale coronary artery response enhancement and 3D rolling balloon region growing vessel segmentation and tracking method. The coronary artery trees from multiple phases are thenmore » aligned by a global registration using an affine transformation with quadratic terms and nonlinear simplex optimization, followed by a local registration using a cubic B-spline method with fast localized optimization. The corresponding coronary arteries among the available phases are identified using a recursive coronary segment matching method. Each of the identified vessel segments is transformed by the curved planar reformation (CPR) method. Four features are extracted from each corresponding segment as quality indicators in the original computed tomography volume and the straightened CPR volume, and each quality indicator is used as a voting classifier for the arterial segment. A weighted voting ensemble (WVE) classifier is designed to combine the votes of the four voting classifiers for each corresponding segment. The segment with the highest WVE vote is then selected as the best-quality segment. In this study, the training and test sets consisted of 6 and 20 cCTA cases, respectively, each with 6 phases, containing a total of 156 cCTA volumes and 312 coronary artery trees. An observer preference study was also conducted with one expert cardiothoracic radiologist and four nonradiologist readers to visually rank vessel segment quality. The performance of our automated method was evaluated by comparing the automatically identified best-quality segments identified by the computer to those selected by the observers. Results: For the 20 test cases, 254 groups of corresponding vessel segments were identified after multiple phase registration and recursive matching. The AI-BQ segments agreed with the radiologist’s top 2 ranked segments in 78.3% of the 254 groups (Cohen’s kappa 0.60), and with the 4 nonradiologist observers in 76.8%, 84.3%, 83.9%, and 85.8% of the 254 groups. In addition, 89.4% of the AI-BQ segments agreed with at least two observers’ top 2 rankings, and 96.5% agreed with at least one observer’s top 2 rankings. In comparison, agreement between the four observers’ top ranked segment and the radiologist’s top 2 ranked segments were 79.9%, 80.7%, 82.3%, and 76.8%, respectively, with kappa values ranging from 0.56 to 0.68. Conclusions: The performance of our automated method for selecting the best-quality coronary segments from a multiple-phase cCTA acquisition was comparable to the selection made by human observers. This study demonstrates the potential usefulness of the automated method in clinical practice, enabling interpreting physicians to fully utilize the best available information in cCTA for diagnosis of coronary disease, without requiring manual search through the multiple phases and minimizing the variability in image phase selection for evaluation of coronary artery segments across the diversity of human readers with variations in expertise.« less

In the Context of Multiple Intelligences Theory, Intelligent Data Analysis of Learning Styles Was Based on Rough Set Theory

ERIC Educational Resources Information Center

Narli, Serkan; Ozgen, Kemal; Alkan, Huseyin

2011-01-01

The present study aims to identify the relationship between individuals' multiple intelligence areas and their learning styles with mathematical clarity using the concept of rough sets which is used in areas such as artificial intelligence, data reduction, discovery of dependencies, prediction of data significance, and generating decision…

Study of multiple hologram recording in lithium niobate

NASA Technical Reports Server (NTRS)

Gaylord, T. K.; Callen, W. R.

1974-01-01

The results of detailed experimental and theoretical considerations relating to multiple hologram recording in lithium niobate are reported. The following problem areas are identified and discussed: (1) the angular selectivity of the stored holograms, (2) interference effects due to the crystal surfaces, (3) beam divergence effects, (4) material recording sensitivity, and (5) scattered light from material inhomogeneities.

Singapore Primary Students' Pursuit of Multiple Achievement Goals: A Latent Profile Analysis

ERIC Educational Resources Information Center

Ning, Hoi Kwan

2018-01-01

Based on measures of approach and avoidance mastery and performance goals delineated in the 2 × 2 achievement goal framework, this study utilized a person-centered approach to examine Singapore primary students' (N = 819) multiple goals pursuit in the general school context. Latent profile analysis identified six types of students with distinct…

Historical biogeography and diversification of truffles in the Tuberaceae and their newly identified Southern hemisphere sister lineage

Treesearch

Gregory Bonito; Matthew E. Smith; Michael Nowak; Rosanne A. Healy; Gonzalo Guevara; Efren Cazares; Akihiko Kinoshita; Eduardo R. Nouhra; Laura S. Dominguez; Leho Tedersoo; Claude Murat; Yun Wang; Baldomero Arroyo Moreno; Donald H. Pfister; Kazuhide Nara; Alessandra Zambonelli; James M. Trappe; Rytas Vilgalys

2013-01-01

In this study we reassessed the biogeography and origin of the Tuberaceae and their relatives using multiple loci and a global sampling of taxa. Multiple independent transitions from an aboveground to a belowground truffie fruiting body form have occurred in the Tuberaceae and in its newly recognized sister lineage...

A data-driven multiplicative fault diagnosis approach for automation processes.

PubMed

Hao, Haiyang; Zhang, Kai; Ding, Steven X; Chen, Zhiwen; Lei, Yaguo

2014-09-01

This paper presents a new data-driven method for diagnosing multiplicative key performance degradation in automation processes. Different from the well-established additive fault diagnosis approaches, the proposed method aims at identifying those low-level components which increase the variability of process variables and cause performance degradation. Based on process data, features of multiplicative fault are extracted. To identify the root cause, the impact of fault on each process variable is evaluated in the sense of contribution to performance degradation. Then, a numerical example is used to illustrate the functionalities of the method and Monte-Carlo simulation is performed to demonstrate the effectiveness from the statistical viewpoint. Finally, to show the practical applicability, a case study on the Tennessee Eastman process is presented. Copyright © 2013. Published by Elsevier Ltd.

Identifying Multiple Populations in M71 using CN

NASA Astrophysics Data System (ADS)

Gerber, Jeffrey M.; Friel, Eileen D.; Vesperini, Enrico

2018-01-01

It is now well established that globular clusters (GCs) host multiple stellar populations characterized by differences in several light elements. While these populations have been found in nearly all GCs, we still lack an entirely successful model to explain their formation. A key constraint to these models is the detailed pattern of light element abundances seen among the populations; different techniques for identifying these populations probe different elements and do not always yield the same results. We study a large sample of stars in the GC M71 for light elements C and N, using the CN and CH band strength to identify multiple populations. Our measurements come from low-resolution spectroscopy obtained with the WIYN-3.5m telescope for ~150 stars from the tip of the red-giant branch down to the main-sequence turn-off. The large number of stars and broad spatial coverage of our sample (out to ~3.5 half-light radii) allows us to carry out a comprehensive characterization of the multiple populations in M71. We use a combination of the various spectroscopic and photometric indicators to draw a more complete picture of the properties of the populations and to investigate the consistency of classifications using different techniques.

Surveillance versus Privacy: Considerations for the San Bernardino Community

ERIC Educational Resources Information Center

Price, Robert

2017-01-01

This privacy versus security doctoral research examines existing literature, policies, and perceptions to identify the effects of the 2015 San Bernardino terrorist attack on the San Bernardino community. This study contributes to identifying factors that influence perceptions of governmental surveillance. Multiple articles contribute to the…

Impacts of air pollution and climate change on forest ecosystems - Multiple stressors and ecosystem services

EPA Science Inventory

The nature of scientific investigation involving hypothesis testing dictates the need to conduct controlled experiments, limiting the number of independent variables in order to identify cause and effect relationships. Single or two-factor studies are useful to identify potentia...

Cognitive and Behavioural Correlates of Non-Adherence to HIV Anti-Retroviral Therapy: Theoretical and Practical Insight for Clinical Psychology and Health Psychology

ERIC Educational Resources Information Center

Begley, Kim; McLaws, Mary-Louise; Ross, Michael W.; Gold, Julian

2008-01-01

This cross-sectional study identified variables associated with protease inhibitor (PI) non-adherence in 179 patients taking anti-retroviral therapy. Univariate analyses identified 11 variables associated with PI non-adherence. Multiple logistic regression modelling identified three predictors of PI non-adherence: low adherence self-efficacy and…

Programs to reduce teen pregnancy, sexually transmitted infections, and associated sexual risk behaviors: a systematic review.

PubMed

Goesling, Brian; Colman, Silvie; Trenholm, Christopher; Terzian, Mary; Moore, Kristin

2014-05-01

This systematic review provides a comprehensive, updated assessment of programs with evidence of effectiveness in reducing teen pregnancy, sexually transmitted infections (STIs), or associated sexual risk behaviors. The review was conducted in four steps. First, multiple literature search strategies were used to identify relevant studies released from 1989 through January 2011. Second, identified studies were screened against prespecified eligibility criteria. Third, studies were assessed by teams of two trained reviewers for the quality and execution of their research designs. Fourth, for studies that passed the quality assessment, the review team extracted and analyzed information on the research design, study sample, evaluation setting, and program impacts. A total of 88 studies met the review criteria for study quality and were included in the data extraction and analysis. The studies examined a range of programs delivered in diverse settings. Most studies had mixed-gender and predominately African-American research samples (70% and 51%, respectively). Randomized controlled trials accounted for the large majority (87%) of included studies. Most studies (76%) included multiple follow-ups, with sample sizes ranging from 62 to 5,244. Analysis of the study impact findings identified 31 programs with evidence of effectiveness. Research conducted since the late 1980s has identified more than two dozen teen pregnancy and STI prevention programs with evidence of effectiveness. Key strengths of this research are the large number of randomized controlled trials, the common use of multiple follow-up periods, and attention to a broad range of programs delivered in diverse settings. Two main gaps are a lack of replication studies and the need for more research on Latino youth and other high-risk populations. In addressing these gaps, researchers must overcome common limitations in study design, analysis, and reporting that have negatively affected prior research. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

Multiple loci on 8q24 associated with prostate cancer susceptibility.

PubMed

Al Olama, Ali Amin; Kote-Jarai, Zsofia; Giles, Graham G; Guy, Michelle; Morrison, Jonathan; Severi, Gianluca; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Jhavar, Sameer; Saunders, Ed; Hopper, John L; Southey, Melissa C; Muir, Kenneth R; English, Dallas R; Dearnaley, David P; Ardern-Jones, Audrey T; Hall, Amanda L; O'Brien, Lynne T; Wilkinson, Rosemary A; Sawyer, Emma; Lophatananon, Artitaya; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind A; Easton, Douglas F

2009-10-01

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.

Using Two-Tier Test to Identify Primary Students' Conceptual Understanding and Alternative Conceptions in Acid Base

ERIC Educational Resources Information Center

Bayrak, Beyza Karadeniz

2013-01-01

The purpose of this study was to identify primary students' conceptual understanding and alternative conceptions in acid-base. For this reason, a 15 items two-tier multiple choice test administered 56 eighth grade students in spring semester 2009-2010. Data for this study were collected using a conceptual understanding scale prepared to include…

Critical Success Factors for E-Learning in Developing Countries: A Comparative Analysis between ICT Experts and Faculty

ERIC Educational Resources Information Center

Bhuasiri, Wannasiri; Xaymoungkhoun, Oudone; Zo, Hangjung; Rho, Jae Jeung; Ciganek, Andrew P.

2012-01-01

This study identifies the critical success factors that influence the acceptance of e-learning systems in developing countries. E-learning is a popular mode of delivering educational materials in higher education by universities throughout the world. This study identifies multiple factors that influence the success of e-learning systems from the…

Use of ultrasonic array method for positioning multiple partial discharge sources in transformer oil.

PubMed

Xie, Qing; Tao, Junhan; Wang, Yongqiang; Geng, Jianghai; Cheng, Shuyi; Lü, Fangcheng

2014-08-01

Fast and accurate positioning of partial discharge (PD) sources in transformer oil is very important for the safe, stable operation of power systems because it allows timely elimination of insulation faults. There is usually more than one PD source once an insulation fault occurs in the transformer oil. This study, which has both theoretical and practical significance, proposes a method of identifying multiple PD sources in the transformer oil. The method combines the two-sided correlation transformation algorithm in the broadband signal focusing and the modified Gerschgorin disk estimator. The method of classification of multiple signals is used to determine the directions of arrival of signals from multiple PD sources. The ultrasonic array positioning method is based on the multi-platform direction finding and the global optimization searching. Both the 4 × 4 square planar ultrasonic sensor array and the ultrasonic array detection platform are built to test the method of identifying and positioning multiple PD sources. The obtained results verify the validity and the engineering practicability of this method.

'Normal' and 'failing' mothers: Women's constructions of maternal subjectivity while living with multiple sclerosis.

PubMed

Parton, Chloe; Katz, Terri; Ussher, Jane M

2017-10-01

Multiple sclerosis causes physical and cognitive impairment that can impact women's experiences of motherhood. This study examined how women construct their maternal subjectivities, or sense of self as a mother, drawing on a framework of biographical disruption. A total of 20 mothers with a multiple sclerosis diagnosis took part in semi-structured interviews. Transcripts were analysed using thematic decomposition to identify subject positions that women adopted in relation to cultural discourses of gender, motherhood and illness. Three main subject positions were identified: 'The Failing Mother', 'Fear of Judgement and Burdening Others' and 'The Normal Mother'. Women's sense of self as the 'Failing Mother' was attributed to the impact of multiple sclerosis, contributing to biographical disruption and reinforced through 'Fear of Judgement and Burdening Others' within social interactions. In accounts of the 'Normal Mother', maternal subjectivity was renegotiated by adopting strategies to manage the limitations of multiple sclerosis on mothering practice. This allowed women to self-position as 'good' mothers. Health professionals can assist women by acknowledging the embodied impact of multiple sclerosis on maternal subjectivities, coping strategies that women employ to address potential biographical disruption, and the cultural context of mothering, which contributes to women's experience of subjectivity and well-being when living with multiple sclerosis.

Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.

PubMed

Fröhlich, Kilian; Winder, Klemens; Linker, Ralf A; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Hilz, Max J; Schwab, Stefan; Seifert, Frank

2018-06-01

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.

Quality of search strategies reported in systematic reviews published in stereotactic radiosurgery.

PubMed

Faggion, Clovis M; Wu, Yun-Chun; Tu, Yu-Kang; Wasiak, Jason

2016-06-01

Systematic reviews require comprehensive literature search strategies to avoid publication bias. This study aimed to assess and evaluate the reporting quality of search strategies within systematic reviews published in the field of stereotactic radiosurgery (SRS). Three electronic databases (Ovid MEDLINE(®), Ovid EMBASE(®) and the Cochrane Library) were searched to identify systematic reviews addressing SRS interventions, with the last search performed in October 2014. Manual searches of the reference lists of included systematic reviews were conducted. The search strategies of the included systematic reviews were assessed using a standardized nine-question form based on the Cochrane Collaboration guidelines and Assessment of Multiple Systematic Reviews checklist. Multiple linear regression analyses were performed to identify the important predictors of search quality. A total of 85 systematic reviews were included. The median quality score of search strategies was 2 (interquartile range = 2). Whilst 89% of systematic reviews reported the use of search terms, only 14% of systematic reviews reported searching the grey literature. Multiple linear regression analyses identified publication year (continuous variable), meta-analysis performance and journal impact factor (continuous variable) as predictors of higher mean quality scores. This study identified the urgent need to improve the quality of search strategies within systematic reviews published in the field of SRS. This study is the first to address how authors performed searches to select clinical studies for inclusion in their systematic reviews. Comprehensive and well-implemented search strategies are pivotal to reduce the chance of publication bias and consequently generate more reliable systematic review findings.

Groundwater-quality data associated with abandoned underground coal mine aquifers in West Virginia, 1973-2016: Compilation of existing data from multiple sources

USGS Publications Warehouse

McAdoo, Mitchell A.; Kozar, Mark D.

2017-11-14

This report describes a compilation of existing water-quality data associated with groundwater resources originating from abandoned underground coal mines in West Virginia. Data were compiled from multiple sources for the purpose of understanding the suitability of groundwater from abandoned underground coal mines for public supply, industrial, agricultural, and other uses. This compilation includes data collected for multiple individual studies conducted from July 13, 1973 through September 7, 2016. Analytical methods varied by the time period of data collection and requirements of the independent studies.This project identified 770 water-quality samples from 294 sites that could be attributed to abandoned underground coal mine aquifers originating from multiple coal seams in West Virginia.

Damage detection of structures identified with deterministic-stochastic models using seismic data.

PubMed

Huang, Ming-Chih; Wang, Yen-Po; Chang, Ming-Lian

2014-01-01

A deterministic-stochastic subspace identification method is adopted and experimentally verified in this study to identify the equivalent single-input-multiple-output system parameters of the discrete-time state equation. The method of damage locating vector (DLV) is then considered for damage detection. A series of shaking table tests using a five-storey steel frame has been conducted. Both single and multiple damage conditions at various locations have been considered. In the system identification analysis, either full or partial observation conditions have been taken into account. It has been shown that the damaged stories can be identified from global responses of the structure to earthquakes if sufficiently observed. In addition to detecting damage(s) with respect to the intact structure, identification of new or extended damages of the as-damaged counterpart has also been studied. This study gives further insights into the scheme in terms of effectiveness, robustness, and limitation for damage localization of frame systems.

Large outbreak of salmonella phage type 1 infection with high infection rate and severe illness associated with fast food premises.

PubMed

Giraudon, I; Cathcart, S; Blomqvist, S; Littleton, A; Surman-Lee, S; Mifsud, A; Anaraki, S; Fraser, G

2009-06-01

To describe the epidemiology of an outbreak of Salmonella enteritidis phage type 1 (PT1) infection associated with a fast food premises, and to identify the causative factors leading to an acute outbreak with high attack rate and severe illness including hospital admission. Integrated descriptive study of epidemiology, food and environmental microbiology, and professional environmental health assessment, supplemented by a case-case analytical study. Cases were identified through multiple sources and were interviewed to identify food items consumed. Descriptive epidemiology of all cases and a case-case analytical study of risk factors for severe illness were undertaken. Microbiological investigation included analysis and typing of pathogens from stools, blood and environmental surfaces. Professional environmental heath assessment of the premises was undertaken. S. enteritidis PT1 was recovered from two-thirds of faecal samples. Three cases had dual infection with enterotoxin-producing Clostridium perfringens. S. enteritidis PT1 was isolated from 14 of 40 food samples examined and C. perfringens was isolated from eight food samples. Environmental health inspection of the premises revealed multiple deficiencies, including deficits in food preparation and hygiene consistent with multiple cross-contamination, and time-temperature abuse of sauces widely used across menu items. Severe cases were associated with consumption of chips and salad. Outbreaks from fast food premises have been infrequently described. This outbreak demonstrates the potential for fast food premises, with multiple deficiencies in food preparation and hygiene, to produce large, intense community outbreaks with high attack rates and severe illness, highly confined in space and time.

Scenario Problem Solving: A Measure of the Quality of Gifted Students' Thinking

ERIC Educational Resources Information Center

Munro, John K.

2015-01-01

Teachers continue to face the challenge of identifying efficaciously gifted students' learning capacity in its multiple forms. While most educators acknowledge its multidimensional characteristics, the protocols used to identify it are frequently evaluated as unnecessarily restrictive. This study investigates an assessment tool that could…

DISCOVER in Middle School: Identifying Gifted Minority Students

ERIC Educational Resources Information Center

Sarouphim, Ketty M.

2004-01-01

The purpose of this study was to examine the validity of the grades 6-8 version of DISCOVER, a performance-based assessment, and investigate its effectiveness in identifying gifted minority students. Questions examined the alignment between DISCOVER and Gardner's (1983) theory of multiple intelligences (MI) and assessed gender and ethnic…

Rapid Prototyping in Instructional Design: Creating Competencies

ERIC Educational Resources Information Center

Fulton, Carolyn D.

2010-01-01

Instructional designers working in rapid prototyping environments currently do not have a list of competencies that help to identify the knowledge, skills, and attitudes (KSAs) required in these workplaces. This qualitative case study used multiple cases in an attempt to identify rapid prototyping competencies required in a rapid prototyping…

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis

ERIC Educational Resources Information Center

Gonzalez, Oscar; MacKinnon, David P.

2018-01-01

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to…

Identifying the Key Weaknesses in Network Security at Colleges.

ERIC Educational Resources Information Center

Olsen, Florence

2000-01-01

A new study identifies and ranks the 10 security gaps responsible for most outsider attacks on college computer networks. The list is intended to help campus system administrators establish priorities as they work to increase security. One network security expert urges that institutions utilize multiple security layers. (DB)

The Association Between Stimulant, Opioid, and Multiple Drug Use on Behavioral Health Care Utilization in a Safety-Net Health System.

PubMed

Calcaterra, Susan L; Keniston, Angela; Blum, Joshua; Crume, Tessa; Binswanger, Ingrid A

2015-01-01

Prior studies show an association between drug use and health care utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient, and behavioral health care utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral health care. To assess health care utilization, we conducted a retrospective cohort study of patients who accessed health care at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Health care utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of health care-related visits for inpatient, emergent/urgent, outpatient, and behavioral health care among patients who used drugs, categorized by drug types, compared with patients without identified drug use. Of 95,198 index visits, 4.6% (n=4340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral health care visits than patients without identified drug use (opioid incidence rate ratio [IRR]=7.2; 95% confidence interval [CI]: 3.8-13.8; multiple drug use IRR=5.6, 95% CI: 3.3-9.7). Patients who used stimulants were less likely to use behavioral health services (IRR=1.3, 95% CI: 0.9-2.0) when compared with opioid and multiple drug users, but were more likely to use inpatient (IRR=1.6, 95% CI: 1.4-1.8) and emergent/urgent care (IRR=1.4, 95% CI: 1.3-1.5) services as compared with patients without identified drug use. Integrated medical and mental health care and drug treatment may reduce utilization of costly health care services and improve patient outcomes. How to capture and deliver primary care and behavioral health care to patients who use stimulants needs further investigation.

The confounding effects of hybridization on phylogenetic estimation in the New Zealand cicada genus Kikihia.

PubMed

Banker, Sarah E; Wade, Elizabeth J; Simon, Chris

2017-11-01

Phylogenetic studies of multiple independently inherited nuclear genes considered in combination with patterns of inheritance of organelle DNA have provided considerable insight into the history of species evolution. In particular, investigations of cicadas in the New Zealand genus Kikihia have identified interesting cases where mitochondrial DNA (mtDNA) crosses species boundaries in some species pairs but not others. Previous phylogenetic studies focusing on mtDNA largely corroborated Kikihia species groups identified by song, morphology and ecology with the exception of a unique South Island mitochondrial haplotype clade-the Westlandica group. This newly identified group consists of diverse taxa previously classified as belonging to three different sub-generic clades. We sequenced five nuclear loci from multiple individuals from every species of Kikihia to assess the nuclear gene concordance for this newly-identified mtDNA lineage. Bayes Factor analysis of the constrained phylogeny suggests some support for the mtDNA-based hypotheses, despite the fact that neither concatenation nor multiple species tree methods resolve the Westlandica group as monophyletic. The nuclear analyses suggest a geographic distinction between clearly defined monophyletic North Island clades and unresolved South Island clades. We suggest that more extreme habitat modification on South Island during the Pliocene and Pleistocene resulted in secondary contact and hybridization between species pairs and a series of mitochondrial capture events followed by subsequent lineage evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

PubMed

Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

2015-09-01

High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

PubMed

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H; Yang, Rui; Killela, Patrick J; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Liang, Junbo; Wang, Sizhen; Jiao, Yuchen; Yan, Hai; Tao, Hou-Quan

2015-05-01

Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

PubMed Central

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

2015-01-01

Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

The development and validation of a two-tiered multiple-choice instrument to identify alternative conceptions in earth science

NASA Astrophysics Data System (ADS)

Mangione, Katherine Anna

This study was to determine reliability and validity for a two-tiered, multiple- choice instrument designed to identify alternative conceptions in earth science. Additionally, this study sought to identify alternative conceptions in earth science held by preservice teachers, to investigate relationships between self-reported confidence scores and understanding of earth science concepts, and to describe relationships between content knowledge and alternative conceptions and planning instruction in the science classroom. Eighty-seven preservice teachers enrolled in the MAT program participated in this study. Sixty-eight participants were female, twelve were male, and seven chose not to answer. Forty-seven participants were in the elementary certification program, five were in the middle school certification program, and twenty-nine were pursuing secondary certification. Results indicate that the two-tiered, multiple-choice format can be a reliable and valid method for identifying alternative conceptions. Preservice teachers in all certification areas who participated in this study may possess common alternative conceptions previously identified in the literature. Alternative conceptions included: all rivers flow north to south, the shadow of the Earth covers the Moon causing lunar phases, the Sun is always directly overhead at noon, weather can be predicted by animal coverings, and seasons are caused by the Earth's proximity to the Sun. Statistical analyses indicated differences, however not all of them significant, among all subgroups according to gender and certification area. Generally males outperformed females and preservice teachers pursuing middle school certification had higher scores on the questionnaire followed by those obtaining secondary certification. Elementary preservice teachers scored the lowest. Additionally, self-reported scores of confidence in one's answers and understanding of the earth science concept in question were analyzed. There was a slight positive correlation between overall score and both confidence and understanding. Responses on the questionnaire were investigated with respect to pedagogical choices. Evidence suggests that content knowledge and having alternative conceptions or science fragments may impact a teacher's pedagogical choices. Through careful development of instruments like ACES-Q II-R and other two- tiered, multiple-choice instruments, educators and researchers car not only identify possible alternative conceptions, they can raise an awareness of alternative conceptions held by children and adults.

Reporting Multiple Individual Injuries in Studies of Team Ball Sports: A Systematic Review of Current Practice.

PubMed

Fortington, Lauren V; van der Worp, Henk; van den Akker-Scheek, Inge; Finch, Caroline F

2017-06-01

To identify and prioritise targets for injury prevention efforts, injury incidence studies are widely reported. The accuracy and consistency in calculation and reporting of injury incidence is crucial. Many individuals experience more than one injury but multiple injuries are not consistently reported in sport injury incidence studies. The aim of this systematic review was to evaluate current practice of how multiple injuries within individuals have been defined and reported in prospective, long-term, injury studies in team ball sports. A systematic search of three online databases for articles published before 2016. Publications were included if (1) they collected prospective data on musculoskeletal injuries in individual participants; (2) the study duration was >1 consecutive calendar year/season; and (3) individuals were the unit of analysis. Key study features were summarised, including definitions of injury, how multiple individual injuries were reported and results relating to multiple injuries. Of the 71 publications included, half did not specifically indicate multiple individual injuries; those that did were largely limited to reporting recurrent injuries. Eight studies reported the number/proportion of athletes with more than one injury, and 11 studies presented the mean/number of injuries per athlete. Despite it being relatively common to collect data on individuals across more than one season, the reporting of multiple injuries within individuals is much more limited. Ultimately, better addressing of multiple injuries will improve the accuracy of injury incidence studies and enable more precise targeting and monitoring of the effectiveness of preventive interventions.

An Investigation between Multiple Intelligences and Learning Styles

ERIC Educational Resources Information Center

Sener, Sabriye; Çokçaliskan, Ayten

2018-01-01

Exploring learning style and multiple intelligence type of learners can enable the students to identify their strengths and weaknesses and learn from them. It is also very important for teachers to understand their learners' learning styles and multiple intelligences since they can carefully identify their goals and design activities that can…

Supporting Students in Learning with Multiple Representation to Improve Student Mental Models on Atomic Structure Concepts

ERIC Educational Resources Information Center

Sunyono; Yuanita, L.; Ibrahim, M.

2015-01-01

The aim of this research is identify the effectiveness of a multiple representation-based learning model, which builds a mental model within the concept of atomic structure. The research sample of 108 students in 3 classes is obtained randomly from among students of Mathematics and Science Education Studies using a stratified random sampling…

Conceptual Incoherence as a Result of the Use of Multiple Historical Models in School Textbooks

ERIC Educational Resources Information Center

Gericke, Niklas M.; Hagberg, Mariana

2010-01-01

This paper explores the occurrence of conceptual incoherence in upper secondary school textbooks resulting from the use of multiple historical models. Swedish biology and chemistry textbooks, as well as a selection of books from English speaking countries, were examined. The purpose of the study was to identify which models are used to represent…

Policy, Service Pathways and Mortality: A 10-Year Longitudinal Study of People with Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

Hogg, James; Juhlberg, K.; Lambe, L.

2007-01-01

Background: One hundred and forty-two children and adults with profound intellectual and multiple disabilities were identified in 1993 in a single Scottish region on whom detailed information was collected via a postal questionnaire survey. Methods: They were followed up in 2003. The time spanned represented a period of significant policy change…

Correlates of Adherence to a Telephone-Based Multiple Health Behavior Change Cancer Preventive Intervention for Teens: The Healthy for Life Program (HELP)

ERIC Educational Resources Information Center

Mays, Darren; Peshkin, Beth N.; Sharff, McKane E.; Walker, Leslie R.; Abraham, Anisha A.; Hawkins, Kirsten B.; Tercyak, Kenneth P.

2012-01-01

This study examined factors associated with teens' adherence to a multiple health behavior cancer preventive intervention. Analyses identified predictors of trial enrollment, run-in completion, and adherence (intervention initiation, number of sessions completed). Of 104 teens screened, 73% (n = 76) were trial eligible. White teens were more…

Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension.

PubMed

Zhu, Xiaofeng; Feng, Tao; Tayo, Bamidele O; Liang, Jingjing; Young, J Hunter; Franceschini, Nora; Smith, Jennifer A; Yanek, Lisa R; Sun, Yan V; Edwards, Todd L; Chen, Wei; Nalls, Mike; Fox, Ervin; Sale, Michele; Bottinger, Erwin; Rotimi, Charles; Liu, Yongmei; McKnight, Barbara; Liu, Kiang; Arnett, Donna K; Chakravati, Aravinda; Cooper, Richard S; Redline, Susan

2015-01-08

Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Identification of suitable genes contributes to lung adenocarcinoma clustering by multiple meta-analysis methods.

PubMed

Yang, Ze-Hui; Zheng, Rui; Gao, Yuan; Zhang, Qiang

2016-09-01

With the widespread application of high-throughput technology, numerous meta-analysis methods have been proposed for differential expression profiling across multiple studies. We identified the suitable differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC) clustering based on seven popular multiple meta-analysis methods. Seven microarray expression profiles of ADC and normal controls were extracted from the ArrayExpress database. The Bioconductor was used to perform the data preliminary preprocessing. Then, DE genes across multiple studies were identified. Hierarchical clustering was applied to compare the classification performance for microarray data samples. The classification efficiency was compared based on accuracy, sensitivity and specificity. Across seven datasets, 573 ADC cases and 222 normal controls were collected. After filtering out unexpressed and noninformative genes, 3688 genes were remained for further analysis. The classification efficiency analysis showed that DE genes identified by sum of ranks method separated ADC from normal controls with the best accuracy, sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set with the highest classification accuracy mainly participated in the regulation of response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation of cell proliferation (P = 0.01). Evaluation of DE genes identified by different meta-analysis methods in classification efficiency provided a new perspective to the choice of the suitable method in a given application. Varying meta-analysis methods always present varying abilities, so synthetic consideration should be taken when providing meta-analysis methods for particular research. © 2015 John Wiley & Sons Ltd.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

PubMed Central

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-01-01

Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of in vitro fertilization data with multiple outcomes using discrete time-to-event analysis

PubMed Central

Maity, Arnab; Williams, Paige; Ryan, Louise; Missmer, Stacey; Coull, Brent; Hauser, Russ

2014-01-01

In vitro fertilization (IVF) is an increasingly common method of assisted reproductive technology. Because of the careful observation and followup required as part of the procedure, IVF studies provide an ideal opportunity to identify and assess clinical and demographic factors along with environmental exposures that may impact successful reproduction. A major challenge in analyzing data from IVF studies is handling the complexity and multiplicity of outcome, resulting from both multiple opportunities for pregnancy loss within a single IVF cycle in addition to multiple IVF cycles. To date, most evaluations of IVF studies do not make use of full data due to its complex structure. In this paper, we develop statistical methodology for analysis of IVF data with multiple cycles and possibly multiple failure types observed for each individual. We develop a general analysis framework based on a generalized linear modeling formulation that allows implementation of various types of models including shared frailty models, failure specific frailty models, and transitional models, using standard software. We apply our methodology to data from an IVF study conducted at the Brigham and Women’s Hospital, Massachusetts. We also summarize the performance of our proposed methods based on a simulation study. PMID:24317880

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis

PubMed Central

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

ABSTRACT Background: Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. Methods: This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Results: Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. Conclusions: The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis. PMID:28097178

Using Multiple Types of Studies in Systematic Reviews of Health Care Interventions – A Systematic Review

PubMed Central

Peinemann, Frank; Tushabe, Doreen Allen; Kleijnen, Jos

2013-01-01

Background A systematic review may evaluate different aspects of a health care intervention. To accommodate the evaluation of various research questions, the inclusion of more than one study design may be necessary. One aim of this study is to find and describe articles on methodological issues concerning the incorporation of multiple types of study designs in systematic reviews on health care interventions. Another aim is to evaluate methods studies that have assessed whether reported effects differ by study types. Methods and Findings We searched PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Methodology Register on 31 March 2012 and identified 42 articles that reported on the integration of single or multiple study designs in systematic reviews. We summarized the contents of the articles qualitatively and assessed theoretical and empirical evidence. We found that many examples of reviews incorporating multiple types of studies exist and that every study design can serve a specific purpose. The clinical questions of a systematic review determine the types of design that are necessary or sufficient to provide the best possible answers. In a second independent search, we identified 49 studies, 31 systematic reviews and 18 trials that compared the effect sizes between randomized and nonrandomized controlled trials, which were statistically different in 35%, and not different in 53%. Twelve percent of studies reported both, different and non-different effect sizes. Conclusions Different study designs addressing the same question yielded varying results, with differences in about half of all examples. The risk of presenting uncertain results without knowing for sure the direction and magnitude of the effect holds true for both nonrandomized and randomized controlled trials. The integration of multiple study designs in systematic reviews is required if patients should be informed on the many facets of patient relevant issues of health care interventions. PMID:24416098

Multiplicative Effects of Social and Psychological Risk Factors on College Students' Suicidal Behaviors.

PubMed

Assari, Shervin

2018-05-17

Less is known about the multiplicative effects of social and psychological risk and protective factors of suicidality on college campuses. The current study aimed to investigate the multiplicative effects of social (identifying oneself as gay/lesbian, financial difficulty, violence victimization, and religiosity) and psychological (anxiety, depression, problem alcohol use, drug use) and risk/protective factors on suicidal behaviors among college students in the United States. Using a cross-sectional design, the Healthy Mind Study (HMS; 2016⁻2017), is a national online survey of college students in the United States. Social (identifying oneself as gay/lesbian, violence victimization, financial difficulty, and religiosity) and psychological (anxiety, depression, problem alcohol use, and drug use) risk/protective factors were assessed among 27,961 individuals. Three aspects of suicidality, including ideation, plan, and attempt, were also assessed. Logistic regression models were used for data analysis. Financial difficulty, violence victimization, identifying oneself as gay/lesbian, anxiety, depression, and drug use increased, while religiosity reduced the odds of suicidal behaviors. Multiplicative effects were found between the following social and psychological risk factors: (1) financial difficulty and anxiety; (2) financial difficulty and depression; (3) depression and drug use; (4) problem alcohol use and drug use; and (5) depression and problem alcohol use. There is a considerable overlap in the social and psychological processes, such as financial stress, mood disorders, and substance use problems, on risk of suicide in college students. As social and psychological risk factors do not operate independently, comprehensive suicidal risk evaluations that simultaneously address multiple social and psychological risk factors may be superior to programs that only address a single risk factor.

First evidence of multiple populations along the AGB from Strömgren photometry

NASA Astrophysics Data System (ADS)

Gruyters, Pieter; Casagrande, Luca; Milone, Antonino P.; Hodgkin, Simon T.; Serenelli, Aldo; Feltzing, Sofia

2017-07-01

Spectroscopic studies have demonstrated that nearly all Galactic globular clusters (GCs) harbour multiple stellar populations with different chemical compositions. Moreover, colour-magnitude diagrams based exclusively on Strömgrem photometry have allowed us to identify and characterise multiple populations along the RGB of a large number of clusters. In this paper we show for the first time that Strömgren photometry is also very efficient at identifying multiple populations along the AGB, and demonstrate that the AGB of M 3, M 92, NGC 362, NGC 1851, and NGC 6752 are not consistent with a single stellar population. We also provide a catalogue of RGB and AGB stars photometrically identified in these clusters for further spectroscopic follow-up studies. We combined photometry and elemental abundances from the literature for RGB and AGB stars in NGC 6752 where the presence of multiple populations along the AGB has been widely debated. We find that, while the MS, SGB, and RGB host three stellar populations with different helium and light element abundances, only two populations of AGB stars are present in the cluster. These results are consistent with standard evolutionary theory. Based on observations made with the Isaac Newton Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.Full Tables B.1 and B.2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/603/A37

Identifying Multiple Submissions in Internet Research: Preserving Data Integrity

PubMed Central

Bowen, Anne M.; Daniel, Candice M.; Williams, Mark L.; Baird, Grayson L.

2008-01-01

Internet-based sexuality research with hidden populations has become increasingly popular. Respondent anonymity may encourage participation and lower social desirability, but associated disinhibition may promote multiple submissions, especially when incentives are offered. The goal of this study was to identify the usefulness of different variables for detecting multiple submissions from repeat responders and to explore incentive effects. The data included 1,900 submissions from a three-session Internet intervention with a pretest and three post-test questionnaires. Participants were men who have sex with men and incentives were offered to rural participants for completing each questionnaire. The final number of submissions included 1,273 “unique”, 132 first submissions by “repeat responders” and 495 additional submissions by the “repeat responders” (N = 1,900). Four categories of repeat responders were identified: “infrequent” (2–5 submissions), “persistent” (6–10 submissions), “very persistent” (11–30 submissions), and “hackers” (more than 30 submissions). Internet Provider (IP) addresses, user names, and passwords were the most useful for identifying “infrequent” repeat responders. “Hackers” often varied their IP address and identifying information to prevent easy identification, but investigating the data for small variations in IP, using reverse telephone look up, and patterns across usernames and passwords were helpful. Incentives appeared to play a role in stimulating multiple submissions, especially from the more sophisticated “hackers”. Finally, the web is ever evolving and it will be necessary to have good programmers and staff who evolve as fast as “hackers”. PMID:18240015

Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study.

PubMed

Derancourt, C; Bourdon-Lanoy, E; Grob, J-J; Guillaume, J-C; Bernard, P; Bastuji-Garin, S

2007-01-01

Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. To assess whether these lesions are clinical markers of past severe sunburn. A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

Breaking down the gut microbiome composition in multiple sclerosis.

PubMed

Budhram, Adrian; Parvathy, Seema; Kremenchutzky, Marcelo; Silverman, Michael

2017-04-01

The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review. Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

1996-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

1994-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.

PubMed

Jung, Sungwon

2018-04-20

Obesity and type 2 diabetes (T2D) are two major conditions that are related to metabolic disorders and affect a large population. Although there have been significant efforts to identify their therapeutic targets, few benefits have come from comprehensive molecular profiling. This limited availability of comprehensive molecular profiling of obesity and T2D may be due to multiple challenges, as these conditions involve multiple organs and collecting tissue samples from subjects is more difficult in obesity and T2D than in other diseases, where surgical treatments are popular choices. While there is no repository of comprehensive molecular profiling data for obesity and T2D, multiple existing data resources can be utilized to cover various aspects of these conditions. This review presents studies with available genomic data resources for obesity and T2D and discusses genome-wide association studies (GWAS), a knockout (KO)-based phenotyping study, and gene expression profiles. These studies, based on their assessed coverage and characteristics, can provide insights into how such data can be utilized to identify therapeutic targets for obesity and T2D.

A genotyping protocol for multiple tissue types from the polyploid tree species Sequoia sempervirens (Cupressaceae)1

PubMed Central

Narayan, Lakshmi; Dodd, Richard S.; O’Hara, Kevin L.

2015-01-01

Premise of the study: Identifying clonal lineages in asexually reproducing plants using microsatellite markers is complicated by the possibility of nonidentical genotypes from the same clonal lineage due to somatic mutations, null alleles, and scoring errors. We developed and tested a clonal identification protocol that is robust to these issues for the asexually reproducing hexaploid tree species coast redwood (Sequoia sempervirens). Methods: Microsatellite data from four previously published and two newly developed primers were scored using a modified protocol, and clones were identified using Bruvo genetic distances. The effectiveness of this clonal identification protocol was assessed using simulations and by genotyping a test set of paired samples of different tissue types from the same trees. Results: Data from simulations showed that our protocol allowed us to accurately identify clonal lineages. Multiple test samples from the same trees were identified correctly, although certain tissue type pairs had larger genetic distances on average. Discussion: The methods described in this paper will allow for the accurate identification of coast redwood clones, facilitating future studies of the reproductive ecology of this species. The techniques used in this paper can be applied to studies of other clonal organisms as well. PMID:25798341

Interpretation and use of evidence in state policymaking: a qualitative analysis.

PubMed

Apollonio, Dorie E; Bero, Lisa A

2017-02-20

Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and researchers can apply to encourage evidence-informed policymaking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer

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

Kerns, Sarah L.; Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York; Stock, Richard

2013-01-01

Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. Methods and Materials: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. Results: Twelve SNPs identified in the discovery cohort and validated in themore » replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 Multiplication-Sign 10{sup -5} to 6.2 Multiplication-Sign 10{sup -4}). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 Multiplication-Sign 10{sup -29}). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 Multiplication-Sign 10{sup -19}). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. Conclusions: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.« less

Single- versus Multiple-Pest Infestation Affects Differently the Biochemistry of Tomato (Solanum lycopersicum 'Ailsa Craig').

PubMed

Errard, Audrey; Ulrichs, Christian; Kühne, Stefan; Mewis, Inga; Drungowski, Mario; Schreiner, Monika; Baldermann, Susanne

2015-11-25

Tomato is susceptible to pest infestations by both spider mites and aphids. The effects of each individual pest on plants are known, whereas multiple-pest infestations have received little interest. We studied the effects of single- versus multiple-pest infestation by Tetranychus urticae and Myzus persicae on tomato biochemistry (Solanum lycopersicum) by combining a metabolomic approach and analyses of carotenoids using UHPLC-ToF-MS and volatiles using GC-MS. Plants responded differently to aphids and mites after 3 weeks of infestation, and a multiple infestation induced a specific metabolite composition in plants. In addition, we showed that volatiles emissions differed between the adaxial and abaxial leaf epidermes and identified compounds emitted particularly in response to a multiple infestation (cyclohexadecane, dodecane, aromadendrene, and β-elemene). Finally, the carotenoid concentrations in leaves and stems were more affected by multiple than single infestations. Our study highlights and discusses the interplay of biotic stressors within the terpenoid metabolism.

Gene flow in complex landscapes: Testing multiple hypotheses with causal modeling

Treesearch

Samuel A. Cushman; Kevin S. McKelvey; Jim Hayden; Michael K. Schwartz

2006-01-01

Predicting population-level effects of landscape change depends on identifying factors that influence population connectivity in complex landscapes. However, most putative movement corridors and barriers have not been based on empirical data. In this study, we identify factors that influence connectivity by comparing patterns of genetic similarity among 146 black bears...

Identifying Multiple Levels of Discussion-Based Teaching Strategies for Constructing Scientific Models

ERIC Educational Resources Information Center

Williams, Grant; Clement, John

2015-01-01

This study sought to identify specific types of discussion-based strategies that two successful high school physics teachers using a model-based approach utilized in attempting to foster students' construction of explanatory models for scientific concepts. We found evidence that, in addition to previously documented dialogical strategies that…

Identifying Threshold Concepts in the Careers of Educational Developers

ERIC Educational Resources Information Center

Timmermans, Julie A.

2014-01-01

The purpose of this multiple case study was to identify threshold concepts in the careers of educational developers. Twenty-one common threshold concepts emerged, with one threshold concept common among all participants: Facilitating a change process. The remaining 20 threshold concepts were captured in the following three categories: (1) Ways of…

Forms of Science Capital Mobilized in Adolescents' Engineering Projects

ERIC Educational Resources Information Center

Wilson-Lopez, Amy; Sias, Christina; Smithee, Allen; Hasbún, Indhira María

2018-01-01

The purpose of this multiple case study was to identify the forms of science capital that six groups of adolescents mobilized toward the realization of their self-selected engineering projects during after-school meetings. Research participants were high school students who self-identified as Hispanic, Latina, or Latino; who had received English…

Factors influencing cancer treatment decision-making by indigenous peoples: a systematic review.

PubMed

Tranberg, Rona; Alexander, Susan; Hatcher, Deborah; Mackey, Sandra; Shahid, Shaouli; Holden, Lynda; Kwok, Cannas

2016-02-01

We aim to systematically review studies that identify factors influencing cancer treatment decision-making among indigenous peoples. Following the outline suggested by the Preferred Reporting Items for Systematic Review and Meta-analysis, a rigorous systematic review and meta-synthesis were conducted of factors that influence cancer treatment decision-making by indigenous peoples. A total of 733 articles were retrieved from eight databases and a manual search. After screening the titles and abstracts, the full text of 26 articles were critically appraised, resulting in five articles that met inclusion criteria for the review. Because the five articles to be reviewed were qualitative studies, the Critical Appraisal Skills Program toolkit was used to evaluate the methodological quality. A thematic synthesis was employed to identify common themes across the studies. Multiple socio-economic and cultural factors were identified that all had the potential to influence cancer treatment decision-making by indigenous people. These factors were distilled into four themes: spiritual beliefs, cultural influences, communication and existing healthcare systems and structures. Although existing research identified multiple factors influencing decision-making, this review identified that quality studies in this domain are scarce. There is scope for further investigation, both into decision-making factors and into the subsequent design of culturally appropriate programmes and services that meet the needs of indigenous peoples. Copyright © 2015 John Wiley & Sons, Ltd.

An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

PubMed

Zhao, Suli; Fang, Fang; Tang, Xianfa; Dou, Jinfa; Wang, Wenjun; Zheng, Xiaodong; Sun, Liangdan; Zhang, Anping

2017-10-01

Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10 -3 (0.05/26) was considered statistically significant. The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11-1.31, P=1.20×10 -5 ; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10 -4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12-1.38, P=3.04×10 -5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10 -6 , rs523604: P=4.00×10 -3 , rs638893: P=1.20×10 -5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Multiple sort flow cytometer

DOEpatents

Van den Engh, Ger; Esposito, Richard J.

1996-01-01

A flow cytometer utilizes multiple lasers for excitation and respective fluorescence of identified dyes bonded to specific cells or events to identify and verify multiple events to be sorted from a sheath flow and droplet stream. Once identified, verified and timed in the sheath flow, each event is independently tagged upon separation from the flow by an electrical charge of +60, +120, or +180 volts and passed through oppositely charged deflection plates with ground planes to yield a focused six way deflection of at least six events in a narrow plane.

Computational Identification of Tissue-Specific Splicing Regulatory Elements in Human Genes from RNA-Seq Data.

PubMed

Badr, Eman; ElHefnawi, Mahmoud; Heath, Lenwood S

2016-01-01

Alternative splicing is a vital process for regulating gene expression and promoting proteomic diversity. It plays a key role in tissue-specific expressed genes. This specificity is mainly regulated by splicing factors that bind to specific sequences called splicing regulatory elements (SREs). Here, we report a genome-wide analysis to study alternative splicing on multiple tissues, including brain, heart, liver, and muscle. We propose a pipeline to identify differential exons across tissues and hence tissue-specific SREs. In our pipeline, we utilize the DEXSeq package along with our previously reported algorithms. Utilizing the publicly available RNA-Seq data set from the Human BodyMap project, we identified 28,100 differentially used exons across the four tissues. We identified tissue-specific exonic splicing enhancers that overlap with various previously published experimental and computational databases. A complicated exonic enhancer regulatory network was revealed, where multiple exonic enhancers were found across multiple tissues while some were found only in specific tissues. Putative combinatorial exonic enhancers and silencers were discovered as well, which may be responsible for exon inclusion or exclusion across tissues. Some of the exonic enhancers are found to be co-occurring with multiple exonic silencers and vice versa, which demonstrates a complicated relationship between tissue-specific exonic enhancers and silencers.

Multiple shadows from distorted static black holes

NASA Astrophysics Data System (ADS)

Grover, Jai; Kunz, Jutta; Nedkova, Petya; Wittig, Alexander; Yazadjiev, Stoytcho

2018-04-01

We study the local shadow of the Schwarzschild black hole with a quadrupole distortion and the influence of the external gravitational field on the photon dynamics. The external matter sources modify the light ring structure and lead to the appearance of multiple shadow images. In the case of negative quadrupole moments we identify the most prominent mechanism causing multiple shadow formation. Furthermore, we obtain a condition under which this mechanism can be realized. This condition depends on the quadrupole moment, but also on the position of the observer and the celestial sphere.

Integrating Multiple Intelligences and Learning Styles on Solving Problems, Achievement in, and Attitudes towards Math in Six Graders with Learning Disabilities in Cooperative Groups

ERIC Educational Resources Information Center

Eissa, Mourad Ali; Mostafa, Amaal Ahmed

2013-01-01

This study investigated the effect of using differentiated instruction by integrating multiple intelligences and learning styles on solving problems, achievement in, and attitudes towards math in six graders with learning disabilities in cooperative groups. A total of 60 students identified with LD were invited to participate. The sample was…

The Effect of Differentiating Instruction Using Multiple Intelligences on Achievement in and Attitudes towards Science in Middle School Students with Learning Disabilities

ERIC Educational Resources Information Center

Gomaa, Omema Mostafa Kamel

2014-01-01

This study investigated the effect of using differentiated instruction using multiple intelligences on achievement in and attitudes towards science in middle school students with learning disabilities. A total of 61 students identified with LD participated. The sample was randomly divided into two groups; experimental (n= 31 boys )and control (n=…

Using an iPad® App to Improve Sight Word Reading Fluency for At-Risk First Graders

ERIC Educational Resources Information Center

Musti-Rao, Shobana; Lo, Ya-yu; Plati, Erin

2015-01-01

We used a multiple baseline across word lists design nested within a multiple baseline across participants design to examine the effects of instruction delivered using an iPad® app on sight word fluency and oral reading fluency of six first graders identified as at risk for reading failure. In Study 1, three students participated in…

Statistical technique for analysing functional connectivity of multiple spike trains.

PubMed

Masud, Mohammad Shahed; Borisyuk, Roman

2011-03-15

A new statistical technique, the Cox method, used for analysing functional connectivity of simultaneously recorded multiple spike trains is presented. This method is based on the theory of modulated renewal processes and it estimates a vector of influence strengths from multiple spike trains (called reference trains) to the selected (target) spike train. Selecting another target spike train and repeating the calculation of the influence strengths from the reference spike trains enables researchers to find all functional connections among multiple spike trains. In order to study functional connectivity an "influence function" is identified. This function recognises the specificity of neuronal interactions and reflects the dynamics of postsynaptic potential. In comparison to existing techniques, the Cox method has the following advantages: it does not use bins (binless method); it is applicable to cases where the sample size is small; it is sufficiently sensitive such that it estimates weak influences; it supports the simultaneous analysis of multiple influences; it is able to identify a correct connectivity scheme in difficult cases of "common source" or "indirect" connectivity. The Cox method has been thoroughly tested using multiple sets of data generated by the neural network model of the leaky integrate and fire neurons with a prescribed architecture of connections. The results suggest that this method is highly successful for analysing functional connectivity of simultaneously recorded multiple spike trains. Copyright © 2011 Elsevier B.V. All rights reserved.

Exploring the boundaries: A study of multiple classroom learning environments

NASA Astrophysics Data System (ADS)

Ritchie, Stephen M.; Tobin, Kenneth; Hook, Karl S.

1995-09-01

The study of learning environments has developed into a productive field of research in science education. Initially, the design and application of classroom perceptual measures of particular dimensions of science classrooms attracted much attention. More recently, such instruments have been used alongside of qualitative techniques to provide a richer understanding of sub-environments. We continue this trend in the present interpretive study by exploring the nature of multiple environments within a middle school classroom from the different perspectives of teacher, student and participant observer. In particular, we examine the activity settings of lectures and group work, as well as the issues of learning and assessment. We conclude by arguing that teachers need to adopt procedures that enable them to identify and plan for multiple environments.

Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

PubMed

Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

2018-07-01

Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p < .0001) and for the reasons they engaged in exercise and physical activity (W = 0.723, p < .0001). The exercise and physical activity practices and the reasons people with multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple sclerosis prioritise and the reasons why they engage in exercise and physical activity as another option for increasing physical activity levels and reducing sedentary behaviours.

Team effectiveness in academic medical libraries: a multiple case study*

PubMed Central

Russo Martin, Elaine

2006-01-01

Objectives: The objective of this study is to apply J. Richard Hackman's framework on team effectiveness to academic medical library settings. Methods: The study uses a qualitative, multiple case study design, employing interviews and focus groups to examine team effectiveness in three academic medical libraries. Another site was selected as a pilot to validate the research design, field procedures, and methods to be used with the cases. In all, three interviews and twelve focus groups, with approximately seventy-five participants, were conducted at the case study libraries. Findings: Hackman identified five conditions leading to team effectiveness and three outcomes dimensions that defined effectiveness. The participants in this study identified additional characteristics of effectiveness that focused on enhanced communication, leadership personality and behavior, and relationship building. The study also revealed an additional outcome dimension related to the evolution of teams. Conclusions: Introducing teams into an organization is not a trivial matter. Hackman's model of effectiveness has implications for designing successful library teams. PMID:16888659

Causal mediation analysis with multiple mediators in the presence of treatment noncompliance.

PubMed

Park, Soojin; Kürüm, Esra

2018-05-20

Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention-to-treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals. Copyright © 2018 John Wiley & Sons, Ltd.

Do Multiple Concussions Lead to Cumulative Cognitive Deficits? A Literature Review.

PubMed

Yumul, Joy Noelle; McKinlay, Audrey

2016-11-01

A concussion is an important health concern for children and adolescents, particularly in the context of sporting injuries. Some research suggests a cumulative effect from multiple concussions (also referred to as mild traumatic brain injury), which creates a dilemma when considering how to manage children and young persons who may experience multiple concussive events within a sporting season. However, there is very little research regarding the outcomes of multiple concussions and their optimal management. The purpose of this review is to evaluate the evidence regarding the cognitive outcomes of multiple concussions. After assessing the eligibility of the articles from the literature search, 7 studies were identified and included in the review. In most of the available literature, the cognitive outcomes related to multiple concussions are measured during the same developmental age as when the injuries happened. Moreover, most studies that investigated multiple concussions are focused on sports-related injuries, and only some are conducted in children and adolescents in the general population. The current evidence is inconclusive; whereas some studies reported adverse outcomes, others reported null findings. The studies that reported adverse or cumulative effects based their findings on worse cognitive outcomes, more subjective symptoms, and prolonged recovery postinjury. II. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Multiple Access Schemes for Lunar Missions

NASA Technical Reports Server (NTRS)

Deutsch, Leslie; Hamkins, Jon; Stocklin, Frank J.

2010-01-01

Two years ago, the NASA Coding, Modulation, and Link Protocol (CMLP) study was completed. The study, led by the authors of this paper, recommended codes, modulation schemes, and desired attributes of link protocols for all space communication links in NASA's future space architecture. Portions of the NASA CMLP team were reassembled to resolve one open issue: the use of multiple access (MA) communication from the lunar surface. The CMLP-MA team analyzed and simulated two candidate multiple access schemes that were identified in the original CMLP study: Code Division MA (CDMA) and Frequency Division MA (FDMA) based on a bandwidth-efficient Continuous Phase Modulation (CPM) with a superimposed Pseudo-Noise (PN) ranging signal (CPM/PN). This paper summarizes the results of the analysis and simulation of the CMLP-MA study and describes the final recommendations.

Using Module Analysis for Multiple Choice Responses: A New Method Applied to Force Concept Inventory Data

ERIC Educational Resources Information Center

Brewe, Eric; Bruun, Jesper; Bearden, Ian G.

2016-01-01

We describe "Module Analysis for Multiple Choice Responses" (MAMCR), a new methodology for carrying out network analysis on responses to multiple choice assessments. This method is used to identify modules of non-normative responses which can then be interpreted as an alternative to factor analysis. MAMCR allows us to identify conceptual…

Circular RNA expression in basal cell carcinoma.

PubMed

Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

2016-05-01

Circular RNAs (circRNAs), are nonprotein coding RNAs consisting of a circular loop with multiple miRNA, binding sites called miRNA response elements (MREs), functioning as miRNA sponges. This study was performed to identify differentially expressed circRNAs and their MREs in basal cell carcinoma (BCC). Microarray circRNA expression profiles were acquired from BCC and control followed by qRT-PCR validation. Bioinformatical target prediction revealed multiple MREs. Sequence analysis was performed concerning MRE interaction potential with the BCC miRNome. We identified 23 upregulated and 48 downregulated circRNAs with 354 miRNA response elements capable of sequestering miRNA target sequences of the BCC miRNome. The present study describes a variety of circRNAs that are potentially involved in the molecular pathogenesis of BCC.

Identification of treatment responders based on multiple longitudinal outcomes with applications to multiple sclerosis patients.

PubMed

Kondo, Yumi; Zhao, Yinshan; Petkau, John

2017-05-30

Identification of treatment responders is a challenge in comparative studies where treatment efficacy is measured by multiple longitudinally collected continuous and count outcomes. Existing procedures often identify responders on the basis of only a single outcome. We propose a novel multiple longitudinal outcome mixture model that assumes that, conditionally on a cluster label, each longitudinal outcome is from a generalized linear mixed effect model. We utilize a Monte Carlo expectation-maximization algorithm to obtain the maximum likelihood estimates of our high-dimensional model and classify patients according to their estimated posterior probability of being a responder. We demonstrate the flexibility of our novel procedure on two multiple sclerosis clinical trial datasets with distinct data structures. Our simulation study shows that incorporating multiple outcomes improves the responder identification performance; this can occur even if some of the outcomes are ineffective. Our general procedure facilitates the identification of responders who are comprehensively defined by multiple outcomes from various distributions. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Clinical and genetic spectrum of Birt–Hogg–Dubé syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature

PubMed Central

Kunogi, Makiko; Kurihara, Masatoshi; Ikegami, Takako Shigihara; Kobayashi, Toshiyuki; Shindo, Noriko; Kumasaka, Toshio; Gunji, Yoko; Kikkawa, Mika; Iwakami, Shin-ichiro; Hino, Okio; Takahashi, Kazuhisa

2010-01-01

Background Birt–Hogg–Dubé syndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. Objectives BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. Methods This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. Results An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3′-end of the FLCN gene including exons 12 and 13 (13/25=52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. Conclusions BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations. PMID:20413710

Overexpression of the Cytokine BAFF and Autoimmunity Risk.

PubMed

Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

2017-04-27

Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks.

PubMed

Clerc, Frédéric; Bertrand, Nicolas Jean Hyacinthe; La Rocca, Bénédicte

2017-12-15

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Child Maltreatment Among Singletons and Multiple Births in Japan: A Population-Based Study.

PubMed

Yokoyama, Yoshie; Oda, Terumi; Nagai, Noriyo; Sugimoto, Masako; Mizukami, Kenji

2015-12-01

The occurrence of multiple births has been recognized as a risk factor for child maltreatment. However, few population-based studies have examined the relationship between multiple births and child maltreatment. This study aimed to evaluate the degree of risk of child maltreatment among singletons and multiple births in Japan and to identify factors associated with increased risk. Using population-based data, we analyzed the database of records on child maltreatment and medical checkups for infants aged 1.5 years filed at Nishinomiya City Public Health Center between April 2007 and March 2011. To protect personal information, the data were transferred to anonymized electronic files for analysis. After adjusting by logistic regression for each associated factor and gestation number, multiples themselves were not associated with the risk of child maltreatment. However, compared with singletons, multiples had a significantly higher rate of risk factors for child maltreatment, including low birth weight and neural abnormality. Moreover, compared with mothers of singleton, mothers of twins had a significantly higher rate of poor health, which is a risk factor of child maltreatment. Multiples were not associated with the risk of child maltreatment. However, compared with singletons, multiples and their mothers had a significantly higher rate of risk factors of child maltreatment.

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing.

PubMed

Balci, T B; Hartley, T; Xi, Y; Dyment, D A; Beaulieu, C L; Bernier, F P; Dupuis, L; Horvath, G A; Mendoza-Londono, R; Prasad, C; Richer, J; Yang, X-R; Armour, C M; Bareke, E; Fernandez, B A; McMillan, H J; Lamont, R E; Majewski, J; Parboosingh, J S; Prasad, A N; Rupar, C A; Schwartzentruber, J; Smith, A C; Tétreault, M; Innes, A M; Boycott, K M

2017-09-01

Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of multiple perturbations in multi-omics biological networks.

PubMed

Griffin, Paula J; Zhang, Yuqing; Johnson, William Evan; Kolaczyk, Eric D

2018-05-17

Cellular mechanism-of-action is of fundamental concern in many biological studies. It is of particular interest for identifying the cause of disease and learning the way in which treatments act against disease. However, pinpointing such mechanisms is difficult, due to the fact that small perturbations to the cell can have wide-ranging downstream effects. Given a snapshot of cellular activity, it can be challenging to tell where a disturbance originated. The presence of an ever-greater variety of high-throughput biological data offers an opportunity to examine cellular behavior from multiple angles, but also presents the statistical challenge of how to effectively analyze data from multiple sources. In this setting, we propose a method for mechanism-of-action inference by extending network filtering to multi-attribute data. We first estimate a joint Gaussian graphical model across multiple data types using penalized regression and filter for network effects. We then apply a set of likelihood ratio tests to identify the most likely site of the original perturbation. In addition, we propose a conditional testing procedure to allow for detection of multiple perturbations. We demonstrate this methodology on paired gene expression and methylation data from The Cancer Genome Atlas (TCGA). © 2018, The International Biometric Society.

Prognostic factors for early severity in a childhood multiple sclerosis cohort.

PubMed

Mikaeloff, Yann; Caridade, Guillaume; Assi, Saada; Suissa, Samy; Tardieu, Marc

2006-09-01

The goal was to identify prognostic factors for an early severe course in a cohort of patients with childhood-onset multiple sclerosis, for the construction of a predictive tool. The cohort consisted of 197 children from the French Kid Sclérose en Plaques neuropediatric cohort with relapsing/remitting multiple sclerosis beginning before the age of 16 years. Patients were included from 1990 to 2003. We used multivariate survival analysis (Cox model) to evaluate the prognostic value of clinical, MRI, and biological covariates at onset for the occurrence of a third attack or severe disability ("severity" outcome). The cohort was monitored for a mean of 5.5 +/- 3.6 years. The "severity" outcome was recorded for 144 patients (73%). The risk of severity was higher for girls, for a time between the first and second attacks of < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an absence of severe mental state changes at onset, and for a progressive course. A derived childhood-onset multiple sclerosis potential index for early severity was found to have a positive predictive value for severity of > 35% for the upper 2 quartiles. The clinical and MRI prognostic factors for early severity that were identified were used as the basis of a predictive tool, which will be validated in another cohort. This tool should make it possible to identify subgroups at risk of early severe disease and should facilitate therapeutic studies.

Citation searching: a systematic review case study of multiple risk behaviour interventions

PubMed Central

2014-01-01

Background The value of citation searches as part of the systematic review process is currently unknown. While the major guides to conducting systematic reviews state that citation searching should be carried out in addition to searching bibliographic databases there are still few studies in the literature that support this view. Rather than using a predefined search strategy to retrieve studies, citation searching uses known relevant papers to identify further papers. Methods We describe a case study about the effectiveness of using the citation sources Google Scholar, Scopus, Web of Science and OVIDSP MEDLINE to identify records for inclusion in a systematic review. We used the 40 included studies identified by traditional database searches from one systematic review of interventions for multiple risk behaviours. We searched for each of the included studies in the four citation sources to retrieve the details of all papers that have cited these studies. We carried out two analyses; the first was to examine the overlap between the four citation sources to identify which citation tool was the most useful; the second was to investigate whether the citation searches identified any relevant records in addition to those retrieved by the original database searches. Results The highest number of citations was retrieved from Google Scholar (1680), followed by Scopus (1173), then Web of Science (1095) and lastly OVIDSP (213). To retrieve all the records identified by the citation tracking searching all four resources was required. Google Scholar identified the highest number of unique citations. The citation tracking identified 9 studies that met the review’s inclusion criteria. Eight of these had already been identified by the traditional databases searches and identified in the screening process while the ninth was not available in any of the databases when the original searches were carried out. It would, however, have been identified by two of the database search strategies if searches had been carried out later. Conclusions Based on the results from this investigation, citation searching as a supplementary search method for systematic reviews may not be the best use of valuable time and resources. It would be useful to verify these findings in other reviews. PMID:24893958

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

PubMed Central

Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Schwander, Karen; McKenzie, Colin A.; Fox, Ervin; Nalls, Michael A.; Young, J. Hunter; Lane, Jacqueline M.; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K.; Wang, Heming; Forrester, Terrence; Chu, Pei-Lun; Evans, Michele K.; Morrison, Alanna C.; Martin, Lisa W.; Wiggins, Kerri L.; Hui, Qin; Zhao, Wei; Jackson, Rebecca D.; Faul, Jessica D.; Reiner, Alex P.; Bray, Michael; Denny, Joshua C.; Mosley, Thomas H.; Palmas, Walter; Guo, Xiuqing; Polak, Joseph F.; Taylor, Ken D.; Boerwinkle, Eric; Bottinger, Erwin P.; Liu, Kiang; Risch, Neil; Hunt, Steven C.; Kooperberg, Charles; Zonderman, Alan B.; Becker, Diane M.; Cai, Jianwen; Loos, Ruth J. F.; Psaty, Bruce M.; Weir, David R.; Kardia, Sharon L. R.; Arnett, Donna K.; Won, Sungho; Edwards, Todd L.; Redline, Susan; Cooper, Richard S.; Rao, D. C.; Rotimi, Charles; Levy, Daniel; Chakravarti, Aravinda

2017-01-01

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension. PMID:28498854

Congenital multiple cranial neuropathies: Relevance of orofacial electromyography in infants.

PubMed

Renault, Francis; Flores-Guevara, Roberto; Baudon, Jean-Jacques; Vazquez, Marie-Paule

2015-11-01

The aim of this study was to assess diagnoses and outcomes of infants with 2 or more cranial neuropathies identified using orofacial electromyography (EMG). This retrospective study involved 90 patients. Diagnoses took into account clinical, radiological, and genetic data. EMG examined the orbicularis oculi, genioglossus, and levator veli palatini muscles, and blink responses. To evaluate outcome, neurological disability, respiratory complications, and feeding difficulties were recorded. The patients had malformation syndromes (59), encephalopathies (29), or no underlying disorders (2). Neurogenic EMG signs were detected in a mean of 4 muscles, reflecting a mean of 3 affected nerves. EMG identified a higher number of neuropathies than clinical examination alone (82 vs. 31, facial; 56 vs. 2, pharyngeal; 25 vs. 3, hypoglossal). Poor outcome and death were more frequent when EMG identified ≥4 affected nerves (P = 0.02). EMG highlights multiple cranial neuropathies that can be clinically silent in infants with malformation syndromes or encephalopathies. © 2015 Wiley Periodicals, Inc.

A new multiple regression model to identify multi-family houses with a high prevalence of sick building symptoms "SBS", within the healthy sustainable house study in Stockholm (3H).

PubMed

Engvall, Karin; Hult, M; Corner, R; Lampa, E; Norbäck, D; Emenius, G

2010-01-01

The aim was to develop a new model to identify residential buildings with higher frequencies of "SBS" than expected, "risk buildings". In 2005, 481 multi-family buildings with 10,506 dwellings in Stockholm were studied by a new stratified random sampling. A standardised self-administered questionnaire was used to assess "SBS", atopy and personal factors. The response rate was 73%. Statistical analysis was performed by multiple logistic regressions. Dwellers owning their building reported less "SBS" than those renting. There was a strong relationship between socio-economic factors and ownership. The regression model, ended up with high explanatory values for age, gender, atopy and ownership. Applying our model, 9% of all residential buildings in Stockholm were classified as "risk buildings" with the highest proportion in houses built 1961-1975 (26%) and lowest in houses built 1985-1990 (4%). To identify "risk buildings", it is necessary to adjust for ownership and population characteristics.

Limited Agreement of Independent RNAi Screens for Virus-Required Host Genes Owes More to False-Negative than False-Positive Factors

PubMed Central

Wang, Zhishi; Craven, Mark; Newton, Michael A.; Ahlquist, Paul

2013-01-01

Systematic, genome-wide RNA interference (RNAi) analysis is a powerful approach to identify gene functions that support or modulate selected biological processes. An emerging challenge shared with some other genome-wide approaches is that independent RNAi studies often show limited agreement in their lists of implicated genes. To better understand this, we analyzed four genome-wide RNAi studies that identified host genes involved in influenza virus replication. These studies collectively identified and validated the roles of 614 cell genes, but pair-wise overlap among the four gene lists was only 3% to 15% (average 6.7%). However, a number of functional categories were overrepresented in multiple studies. The pair-wise overlap of these enriched-category lists was high, ∼19%, implying more agreement among studies than apparent at the gene level. Probing this further, we found that the gene lists implicated by independent studies were highly connected in interacting networks by independent functional measures such as protein-protein interactions, at rates significantly higher than predicted by chance. We also developed a general, model-based approach to gauge the effects of false-positive and false-negative factors and to estimate, from a limited number of studies, the total number of genes involved in a process. For influenza virus replication, this novel statistical approach estimates the total number of cell genes involved to be ∼2,800. This and multiple other aspects of our experimental and computational results imply that, when following good quality control practices, the low overlap between studies is primarily due to false negatives rather than false-positive gene identifications. These results and methods have implications for and applications to multiple forms of genome-wide analysis. PMID:24068911

Association of Cancer Susceptibility Variants with Risk of Multiple Primary Cancers: the Population Architecture using Genomics and Epidemiology Study

PubMed Central

Park, S. Lani; Caberto, Christian P.; Lin, Yi; Goodloe, Robert J.; Dumitrescu, Logan; Love, Shelly-Ann; Matise, Tara C.; Hindorff, Lucia A.; Fowke, Jay H.; Schumacher, Fredrick R.; Beebe-Dimmer, Jennifer; Chen, Chu; Hou, Lifang; Thomas, Fridtjof; Deelman, Ewa; Han, Ying; Peters, Ulrike; North, Kari E.; Heiss, Gerardo; Crawford, Dana C.; Haiman, Christopher A.; Wilkens, Lynne R.; Bush, William S.; Kooperberg, Charles; Cheng, Iona; Le Marchand, Loïc

2014-01-01

Background Multiple primary cancers account for ~16% of all incident cancers in the U.S.. While genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). Methods As part of the NHGRI Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort and Women’s Health Initiative. Incident MPC (IMPC) cases (n=1,385) were defined as participants diagnosed with >1 incident cancers after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n= 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the association between cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false positive report probability (FPRP) to determine statistical significance. Results A nicotine dependence-associated and lung cancer variant, CHRNA3 rs578776 (OR=1.16, 95% CI=1.05–1.26; p=0.004) and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR=1.16, 95% CI=1.04–1.28; p=0.005 and OR=1.13, 95% CI=1.03–1.23; p=0.006) were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (p<0.05) after removing subjects who had lung or breast cancers, respectively (p-values≤0.046). These associations did not show significant heterogeneity by smoking status (p-heterogeneity≥0.53). Conclusions Our study has identified rs578776 and rs11249433 as risk variants for IMPC. Impact These findings may help to identify genetic regions associated with IMPC risk. PMID:25139936

Comparison of learning preferences of Turkish children who had been applied cochlear implantation in Turkey and Germany according to theory of multiple intelligence.

PubMed

Sahli, Sanem; Laszig, Roland; Aschendorff, Antje; Kroeger, Stefanie; Wesarg, Thomas; Belgin, Erol

2011-12-01

The aim of the study is to determinate the using dominant multiple intelligence types and compare the learning preferences of Turkish cochlear implanted children aged four to ten in Turkey and Germany according to Theory of multiple intelligence. The study has been conducted on a total of 80 children and four groups in Freiburg/Germany and Ankara/Turkey. The applications have been done in University of Freiburg, Cochlear Implant Center in Germany, and University of Hacettepe, ENT Department, Audiology and Speech Pathology Section in Turkey. In this study, the data have been collected by means of General Information Form and Cochlear Implant Information Form applied to parents. To determine the dominant multiple intelligence types of children, the TIMI (Teele Inventory of Multiple Intelligences) which was developed by Sue Teele have been used. The study results exposed that there was not a statistically significant difference on dominant intelligence areas and averages of scores of multiple intelligence types in control groups (p>0.05). Although, the dominant intelligence areas were different (except for first dominant intelligence) in cochlear implanted children in Turkey and Germany, there was not a statistically significant difference on averages of scores of dominant multiple intelligence types. Every hearing impaired child who started training, should be evaluated in terms of multiple intelligence areas and identified strengths and weaknesses. Multiple intelligence activities should be used in their educational programs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Missing data treatments matter: an analysis of multiple imputation for anterior cervical discectomy and fusion procedures.

PubMed

Ondeck, Nathaniel T; Fu, Michael C; Skrip, Laura A; McLynn, Ryan P; Cui, Jonathan J; Basques, Bryce A; Albert, Todd J; Grauer, Jonathan N

2018-04-09

The presence of missing data is a limitation of large datasets, including the National Surgical Quality Improvement Program (NSQIP). In addressing this issue, most studies use complete case analysis, which excludes cases with missing data, thus potentially introducing selection bias. Multiple imputation, a statistically rigorous approach that approximates missing data and preserves sample size, may be an improvement over complete case analysis. The present study aims to evaluate the impact of using multiple imputation in comparison with complete case analysis for assessing the associations between preoperative laboratory values and adverse outcomes following anterior cervical discectomy and fusion (ACDF) procedures. This is a retrospective review of prospectively collected data. Patients undergoing one-level ACDF were identified in NSQIP 2012-2015. Perioperative adverse outcome variables assessed included the occurrence of any adverse event, severe adverse events, and hospital readmission. Missing preoperative albumin and hematocrit values were handled using complete case analysis and multiple imputation. These preoperative laboratory levels were then tested for associations with 30-day postoperative outcomes using logistic regression. A total of 11,999 patients were included. Of this cohort, 63.5% of patients had missing preoperative albumin and 9.9% had missing preoperative hematocrit. When using complete case analysis, only 4,311 patients were studied. The removed patients were significantly younger, healthier, of a common body mass index, and male. Logistic regression analysis failed to identify either preoperative hypoalbuminemia or preoperative anemia as significantly associated with adverse outcomes. When employing multiple imputation, all 11,999 patients were included. Preoperative hypoalbuminemia was significantly associated with the occurrence of any adverse event and severe adverse events. Preoperative anemia was significantly associated with the occurrence of any adverse event, severe adverse events, and hospital readmission. Multiple imputation is a rigorous statistical procedure that is being increasingly used to address missing values in large datasets. Using this technique for ACDF avoided the loss of cases that may have affected the representativeness and power of the study and led to different results than complete case analysis. Multiple imputation should be considered for future spine studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling Human Cancers in Drosophila.

PubMed

Sonoshita, M; Cagan, R L

2017-01-01

Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

Is anybody listening? A phenomenological study of pain in hospitalized persons with AIDS.

PubMed

Newshan, G

1998-01-01

Pain is a common problem among hospitalized persons with AIDS (PWAs), yet it has not been well studied. The purpose of this study was to understand, using the phenomenological method, the experience of pain in hospitalized PWAs. Multiple sources of data, including interviews with 11 hospitalized PWAs, literature, poetry, and film, were used to investigate the phenomenon. Five broad themes emerged: knowing pain, battling pain, having AIDS, pain's influence, and being a drug user. Multiple barriers to effective pain management were identified. Although there were commonalities in the experience of pain in chemically dependent and nonchemically dependent PWAs, unique challenges for the chemically dependent PWAs were identified. The findings indicate the importance of listening to and believing reports of pain. In addition, the findings underscore the delicate balance that exists between pain relief and relapse in PWAs with a history of chemical dependency.

Identifying the Factors Affecting Science and Mathematics Achievement Using Data Mining Methods

ERIC Educational Resources Information Center

Kiray, S. Ahmet; Gok, Bilge; Bozkir, A. Selman

2015-01-01

The purpose of this article is to identify the order of significance of the variables that affect science and mathematics achievement in middle school students. For this aim, the study deals with the relationship between science and math in terms of different angles using the perspectives of multiple causes-single effect and of multiple…

"I Just Want to Be Myself": Adolescents with Disabilities Who Identify as a Sexual or Gender Minority

ERIC Educational Resources Information Center

Kahn, Laurie Gutmann; Lindstrom, Lauren

2015-01-01

Adolescents with disabilities who identify as a sexual or gender minority are at high risk for negative school experiences and poor outcomes, including peer rejection, bullying, and dropping out. Using an intersectionality framework, this study examined how multiple marginalized identities influence sense of self and school experience for this…

A Comparison of Multiple Facets of Self-Concept in Gifted vs. Non-Identified Israeli Students

ERIC Educational Resources Information Center

Zeidner, Moshe; Shani-Zinovich, Inbal

2015-01-01

This study compares facets of self-concept in gifted and non-identified Israeli adolescent students. The self-concept mean score profile of gifted vs. non-selected Israeli students was significantly different, with gifted students reporting higher mean levels of academic self-concept, but lower mean levels of social, personal, and physical…

Close the Gap: A Multiple Case Study about the Decision-Making Process of Administrators in Ohio Districts

ERIC Educational Resources Information Center

Guthrie, Tammy Reutzel

2017-01-01

Research has identified evidenced-based practices and programs that are successful for increasing the learning outcomes of students with disabilities which in turn helps narrow the achievement gap between the student subgroup and non-disabled peers. Employing the identified practices has produced inconsistent results and led to a closer…

Importance of multi-P450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude and prediction from in vitro data

PubMed Central

Isoherranen, Nina; Lutz, Justin D; Chung, Sophie P; Hachad, Houda; Levy, Rene H; Ragueneau-Majlessi, Isabelle

2012-01-01

Drugs that are mainly cleared by a single enzyme are considered more sensitive to drug-drug interactions (DDIs) than drugs cleared by multiple pathways. However, whether this is true when a drug cleared by multiple pathways is co-administered with an inhibitor of multiple P450 enzymes (multi-P450 inhibition) is not known. Mathematically, simultaneous equipotent inhibition of two elimination pathways that each contributes half of the drug clearance is equal to equipotent inhibition of a single pathway that clears the drug. However, simultaneous strong or moderate inhibition of two pathways by a single inhibitor is perceived as an unlikely scenario. The aim of this study was (i) to identify P450 inhibitors currently in clinical use that can inhibit more than one clearance pathway of an object drug in vivo, and (ii) to evaluate the magnitude and predictability of DDIs caused by these multi-P450 inhibitors. Multi-P450 inhibitors were identified using the Metabolism and Transport Drug Interaction Database™. A total of 38 multi-P450 inhibitors, defined as inhibitors that increased the AUC or decreased the clearance of probes of two or more P450’s, were identified. Seventeen (45 %) multi-P450 inhibitors were strong inhibitors of at least one P450 and an additional 12 (32 %) were moderate inhibitors of one or more P450s. Only one inhibitor (fluvoxamine) was a strong inhibitor of more than one enzyme. Fifteen of the multi-P450 inhibitors also inhibit drug transporters in vivo, but such data are lacking on many of the inhibitors. Inhibition of multiple P450 enzymes by a single inhibitor resulted in significant (>2-fold) clinical DDIs with drugs that are cleared by multiple pathways such as imipramine and diazepam while strong P450 inhibitors resulted in only weak DDIs with these object drugs. The magnitude of the DDIs between multi-P450 inhibitors and diazepam, imipramine and omeprazole could be predicted using in vitro data with similar accuracy as probe substrate studies with the same inhibitors. The results of this study suggest that inhibition of multiple clearance pathways in vivo is clinically relevant and the risk of DDIs with object drugs may be best evaluated in studies using multi-P450 inhibitors. PMID:22823924

Trends and Characteristics of Pediatric Dentistry Patients Treated under General Anesthesia.

PubMed

Rudie, Maxwell N; Milano, Michael M; Roberts, Michael W; Divaris, Kimon

2018-05-11

The aims of this study were to describe the demographic characteristics of pediatric dentistry patients undergoing dental rehabilitation under general anesthesia (DRGA) at UNC-Chapel Hill during the last 13 years and identify factors associated with multiple (1 versus 2 or more) DRGA visits during that timeframe. Administrative claims data were used to identify children and adolescents (age <18 years) who underwent DRGA between 1/1/2002 and 12/31/2014 at the UNC Hospitals system. Information on children's age, sex and all treatment-associated CDT codes were collected. Descriptive statistics and bivariate tests of association were used for data analyses. There were 4,413 DRGAs among 3,973 children (median age=4 years 8 months, males=55%) during the study period. The annual rate of DRGAs increased over time, peaking (n=447) in 2013. Overall, 9% of children had ≥2 visits with repeat rates up to 18%. There was no association between children's sex and receipt of one versus multiple DRGAs; however, craniofacial cases were more likely (p<0.0005) to have multiple DRGAs compared to non-craniofacial ones. DRGAs are on the increase-with the exception of craniofacial and special health care needs patients, multiple DRGAs may be reflective of sub-optimal adherence to preventive and continuing care recommendations.

Integrative prescreening in analysis of multiple cancer genomic studies

PubMed Central

2012-01-01

Background In high throughput cancer genomic studies, results from the analysis of single datasets often suffer from a lack of reproducibility because of small sample sizes. Integrative analysis can effectively pool and analyze multiple datasets and provides a cost effective way to improve reproducibility. In integrative analysis, simultaneously analyzing all genes profiled may incur high computational cost. A computationally affordable remedy is prescreening, which fits marginal models, can be conducted in a parallel manner, and has low computational cost. Results An integrative prescreening approach is developed for the analysis of multiple cancer genomic datasets. Simulation shows that the proposed integrative prescreening has better performance than alternatives, particularly including prescreening with individual datasets, an intensity approach and meta-analysis. We also analyze multiple microarray gene profiling studies on liver and pancreatic cancers using the proposed approach. Conclusions The proposed integrative prescreening provides an effective way to reduce the dimensionality in cancer genomic studies. It can be coupled with existing analysis methods to identify cancer markers. PMID:22799431

Identification of interacting proteins of the TaFVE protein involved in spike development in bread wheat.

PubMed

Zheng, Yong-Sheng; Lu, Yu-Qing; Meng, Ying-Ying; Zhang, Rong-Zhi; Zhang, Han; Sun, Jia-Mei; Wang, Mu-Mu; Li, Li-Hui; Li, Ru-Yu

2017-05-01

WD-40 repeat-containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin-remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin-remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple sort flow cytometer

DOEpatents

Engh, G. van den; Esposito, R.J.

1996-01-09

A flow cytometer utilizes multiple lasers for excitation and respective fluorescence of identified dyes bonded to specific cells or events to identify and verify multiple events to be sorted from a sheath flow and droplet stream. Once identified, verified and timed in the sheath flow, each event is independently tagged upon separation from the flow by an electrical charge of +60, +120, or +180 volts and passed through oppositely charged deflection plates with ground planes to yield a focused six way deflection of at least six events in a narrow plane. 8 figs.

Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

NASA Astrophysics Data System (ADS)

Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

2016-12-01

Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

Multiple independent identification decisions: a method of calibrating eyewitness identifications.

PubMed

Pryke, Sean; Lindsay, R C L; Dysart, Jennifer E; Dupuis, Paul

2004-02-01

Two experiments (N = 147 and N = 90) explored the use of multiple independent lineups to identify a target seen live. In Experiment 1, simultaneous face, body, and sequential voice lineups were used. In Experiment 2, sequential face, body, voice, and clothing lineups were used. Both studies demonstrated that multiple identifications (by the same witness) from independent lineups of different features are highly diagnostic of suspect guilt (G. L. Wells & R. C. L. Lindsay, 1980). The number of suspect and foil selections from multiple independent lineups provides a powerful method of calibrating the accuracy of eyewitness identification. Implications for use of current methods are discussed. ((c) 2004 APA, all rights reserved)

Resonance transition periodic orbits in the circular restricted three-body problem

NASA Astrophysics Data System (ADS)

Lei, Hanlun; Xu, Bo

2018-04-01

This work studies a special type of cislunar periodic orbits in the circular restricted three-body problem called resonance transition periodic orbits, which switch between different resonances and revolve about the secondary with multiple loops during one period. In the practical computation, families of multiple periodic orbits are identified first, and then the invariant manifolds emanating from the unstable multiple periodic orbits are taken to generate resonant homoclinic connections, which are used to determine the initial guesses for computing the desired periodic orbits by means of multiple-shooting scheme. The obtained periodic orbits have potential applications for the missions requiring long-term continuous observation of the secondary and tour missions in a multi-body environment.

Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells.

PubMed

Yu, Zhenlong; Li, Tao; Wang, Chao; Deng, Sa; Zhang, Baojing; Huo, Xiaokui; Zhang, Bo; Wang, Xiaobo; Zhong, Yuping; Ma, Xiaochi

2016-03-29

Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM.

Software forecasting as it is really done: A study of JPL software engineers

NASA Technical Reports Server (NTRS)

Griesel, Martha Ann; Hihn, Jairus M.; Bruno, Kristin J.; Fouser, Thomas J.; Tausworthe, Robert C.

1993-01-01

This paper presents a summary of the results to date of a Jet Propulsion Laboratory internally funded research task to study the costing process and parameters used by internally recognized software cost estimating experts. Protocol Analysis and Markov process modeling were used to capture software engineer's forecasting mental models. While there is significant variation between the mental models that were studied, it was nevertheless possible to identify a core set of cost forecasting activities, and it was also found that the mental models cluster around three forecasting techniques. Further partitioning of the mental models revealed clustering of activities, that is very suggestive of a forecasting lifecycle. The different forecasting methods identified were based on the use of multiple-decomposition steps or multiple forecasting steps. The multiple forecasting steps involved either forecasting software size or an additional effort forecast. Virtually no subject used risk reduction steps in combination. The results of the analysis include: the identification of a core set of well defined costing activities, a proposed software forecasting life cycle, and the identification of several basic software forecasting mental models. The paper concludes with a discussion of the implications of the results for current individual and institutional practices.

Patient characteristics associated with multiple pharmacy use in the U.S. population: Findings from the Medical Expenditure Panel Survey.

PubMed

Look, Kevin A

2015-01-01

Multiple pharmacy use (MPU) is an important safety and quality issue, as it results in fragmented patient care. However, few studies have examined patient characteristics predicting the use of multiple pharmacies, and the findings have been inconsistent. To identify patient characteristics associated with MPU using national data. Data were obtained from the 2011 U.S. Medical Expenditure Panel Survey. The dependent variable was MPU, or the use of more than one pharmacy. The Andersen Behavioral Model of Health Service Use was used to guide the selection of independent variables, which were categorized as predisposing, enabling, and medical need related characteristics. Multivariable logistic regression analysis was conducted to identify the relationships between predisposing, enabling, and need variables and MPU in a hierarchical fashion. Point estimates were weighted to the U.S. non-institutionalized population, and to adjust standard errors to account for the complex survey design. MPU was common, with a national prevalence of 41.3%. Individuals aged 40-64 and adults 65 and older were significantly less likely to use multiple pharmacies as patients aged 18-39 years (40-64 years OR: 0.67, CI: 0.58-0.77; ≥65 years OR: 0.49, CI: 0.41-0.58). Females were significantly more likely to use multiple pharmacies than males (OR: 1.16, CI: 1.05-1.29). Individuals lacking health insurance were more likely to use multiple pharmacies as individuals with private health insurance (OR: 1.42, CI: 1.16-1.73); in contrast, individuals having drug insurance were more likely to use multiple pharmacies (OR: 1.25, CI: 1.06-1.47) relative to those without drug insurance. Any mail order use was the strongest predictor of MPU (OR: 6.94, CI: 5.90-8.18). Pharmacists and other health care providers need to be aware that their patients may be using multiple pharmacies, especially younger patients, those lacking access to health insurance, or those using mail order pharmacies. The findings from this study can be used to identify patients that may need additional monitoring to ensure safe and appropriate drug therapy, and has important implications as health care continues to shift toward performance-based reimbursement and quality ratings. Copyright © 2015 Elsevier Inc. All rights reserved.

Exploring undergraduates' understanding of photosynthesis using diagnostic question clusters.

PubMed

Parker, Joyce M; Anderson, Charles W; Heidemann, Merle; Merrill, John; Merritt, Brett; Richmond, Gail; Urban-Lurain, Mark

2012-01-01

We present a diagnostic question cluster (DQC) that assesses undergraduates' thinking about photosynthesis. This assessment tool is not designed to identify individual misconceptions. Rather, it is focused on students' abilities to apply basic concepts about photosynthesis by reasoning with a coordinated set of practices based on a few scientific principles: conservation of matter, conservation of energy, and the hierarchical nature of biological systems. Data on students' responses to the cluster items and uses of some of the questions in multiple-choice, multiple-true/false, and essay formats are compared. A cross-over study indicates that the multiple-true/false format shows promise as a machine-gradable format that identifies students who have a mixture of accurate and inaccurate ideas. In addition, interviews with students about their choices on three multiple-choice questions reveal the fragility of students' understanding. Collectively, the data show that many undergraduates lack both a basic understanding of the role of photosynthesis in plant metabolism and the ability to reason with scientific principles when learning new content. Implications for instruction are discussed.

Exploring Undergraduates' Understanding of Photosynthesis Using Diagnostic Question Clusters

PubMed Central

Parker, Joyce M.; Anderson, Charles W.; Heidemann, Merle; Merrill, John; Merritt, Brett; Richmond, Gail; Urban-Lurain, Mark

2012-01-01

We present a diagnostic question cluster (DQC) that assesses undergraduates' thinking about photosynthesis. This assessment tool is not designed to identify individual misconceptions. Rather, it is focused on students' abilities to apply basic concepts about photosynthesis by reasoning with a coordinated set of practices based on a few scientific principles: conservation of matter, conservation of energy, and the hierarchical nature of biological systems. Data on students' responses to the cluster items and uses of some of the questions in multiple-choice, multiple-true/false, and essay formats are compared. A cross-over study indicates that the multiple-true/false format shows promise as a machine-gradable format that identifies students who have a mixture of accurate and inaccurate ideas. In addition, interviews with students about their choices on three multiple-choice questions reveal the fragility of students' understanding. Collectively, the data show that many undergraduates lack both a basic understanding of the role of photosynthesis in plant metabolism and the ability to reason with scientific principles when learning new content. Implications for instruction are discussed. PMID:22383617

Tracking Multiple Topics for Finding Interesting Articles

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

Pon, R K; Cardenas, A F; Buttler, D J

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on only interesting topics enables iScore to discard useless profiles to address changes in user interests and to achieve a balance between resource consumption and classification accuracy. iScore is able to achieve higher quality results than traditional methods such as themore » Rocchio algorithm. We identify several operating parameters that work well for MTT. Using the same parameters, we show that MTT alone yields high quality results for recommending interesting articles from several corpora. The inclusion of MTT improves iScore's performance by 25% in recommending news articles from the Yahoo! News RSS feeds and the TREC11 adaptive filter article collection. And through a small user study, we show that iScore can still perform well when only provided with little user feedback.« less

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed

Stout, N; Bell, C

1991-06-01

The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems.

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed Central

Stout, N; Bell, C

1991-01-01

BACKGROUND: The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. METHODS: At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. RESULTS: The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. CONCLUSIONS: This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems. PMID:1827569

A vector space model approach to identify genetically related diseases.

PubMed

Sarkar, Indra Neil

2012-01-01

The relationship between diseases and their causative genes can be complex, especially in the case of polygenic diseases. Further exacerbating the challenges in their study is that many genes may be causally related to multiple diseases. This study explored the relationship between diseases through the adaptation of an approach pioneered in the context of information retrieval: vector space models. A vector space model approach was developed that bridges gene disease knowledge inferred across three knowledge bases: Online Mendelian Inheritance in Man, GenBank, and Medline. The approach was then used to identify potentially related diseases for two target diseases: Alzheimer disease and Prader-Willi Syndrome. In the case of both Alzheimer Disease and Prader-Willi Syndrome, a set of plausible diseases were identified that may warrant further exploration. This study furthers seminal work by Swanson, et al. that demonstrated the potential for mining literature for putative correlations. Using a vector space modeling approach, information from both biomedical literature and genomic resources (like GenBank) can be combined towards identification of putative correlations of interest. To this end, the relevance of the predicted diseases of interest in this study using the vector space modeling approach were validated based on supporting literature. The results of this study suggest that a vector space model approach may be a useful means to identify potential relationships between complex diseases, and thereby enable the coordination of gene-based findings across multiple complex diseases.

A Multiple-Tracer Approach for Identifying Sewage Sources to an Urban Stream System

USGS Publications Warehouse

Hyer, Kenneth Edward

2007-01-01

The presence of human-derived fecal coliform bacteria (sewage) in streams and rivers is recognized as a human health hazard. The source of these human-derived bacteria, however, is often difficult to identify and eliminate, because sewage can be delivered to streams through a variety of mechanisms, such as leaking sanitary sewers or private lateral lines, cross-connected pipes, straight pipes, sewer-line overflows, illicit dumping of septic waste, and vagrancy. A multiple-tracer study was conducted to identify site-specific sources of sewage in Accotink Creek, an urban stream in Fairfax County, Virginia, that is listed on the Commonwealth's priority list of impaired streams for violations of the fecal coliform bacteria standard. Beyond developing this multiple-tracer approach for locating sources of sewage inputs to Accotink Creek, the second objective of the study was to demonstrate how the multiple-tracer approach can be applied to other streams affected by sewage sources. The tracers used in this study were separated into indicator tracers, which are relatively simple and inexpensive to apply, and confirmatory tracers, which are relatively difficult and expensive to analyze. Indicator tracers include fecal coliform bacteria, surfactants, boron, chloride, chloride/bromide ratio, specific conductance, dissolved oxygen, turbidity, and water temperature. Confirmatory tracers include 13 organic compounds that are associated with human waste, including caffeine, cotinine, triclosan, a number of detergent metabolites, several fragrances, and several plasticizers. To identify sources of sewage to Accotink Creek, a detailed investigation of the Accotink Creek main channel, tributaries, and flowing storm drains was undertaken from 2001 to 2004. Sampling was conducted in a series of eight synoptic sampling events, each of which began at the most downstream site and extended upstream through the watershed and into the headwaters of each tributary. Using the synoptic sampling approach, 149 sites were sampled at least one time for indicator tracers; 52 of these sites also were sampled for confirmatory tracers at least one time. Through the analysis of multiple-tracer levels in the synoptic samples, three major sewage sources to the Accotink Creek stream network were identified, and several other minor sewage sources to the Accotink Creek system likely deserve additional investigation. Near the end of the synoptic sampling activities, three additional sampling methods were used to gain better understanding of the potential for sewage sources to the watershed. These additional sampling methods included optical brightener monitoring, intensive stream sampling using automated samplers, and additional sampling of several storm-drain networks. The samples obtained by these methods provided further understanding of possible sewage sources to the streams and a better understanding of the variability in the tracer concentrations at a given sampling site. Collectively, these additional sampling methods were a valuable complement to the synoptic sampling approach that was used for the bulk of this study. The study results provide an approach for local authorities to use in applying a relatively simple and inexpensive collection of tracers to locate sewage sources to streams. Although this multiple-tracer approach is effective in detecting sewage sources to streams, additional research is needed to better detect extremely low-volume sewage sources and better enable local authorities to identify the specific sources of the sewage once it is detected in a stream reach.

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

PubMed Central

Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

2015-01-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants. PMID:25616667

Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.

PubMed

Taylor, Robert W; Pyle, Angela; Griffin, Helen; Blakely, Emma L; Duff, Jennifer; He, Langping; Smertenko, Tania; Alston, Charlotte L; Neeve, Vivienne C; Best, Andrew; Yarham, John W; Kirschner, Janbernd; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Baric, Ivo; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Kleinle, Stephanie; Morris, Andrew A M; Vassallo, Grace; Gorman, Grainne S; Ramesh, Venkateswaran; Turnbull, Douglass M; Santibanez-Koref, Mauro; McFarland, Robert; Horvath, Rita; Chinnery, Patrick F

2014-07-02

Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease. To determine the molecular basis of multiple respiratory chain complex deficiencies. We studied 53 patients referred to 2 national centers in the United Kingdom and Germany between 2005 and 2012. All had biochemical evidence of multiple respiratory chain complex defects but no primary pathogenic mitochondrial DNA mutation. Whole-exome sequencing was performed using 62-Mb exome enrichment, followed by variant prioritization using bioinformatic prediction tools, variant validation by Sanger sequencing, and segregation of the variant with the disease phenotype in the family. Presumptive causal variants were identified in 28 patients (53%; 95% CI, 39%-67%) and possible causal variants were identified in 4 (8%; 95% CI, 2%-18%). Together these accounted for 32 patients (60% 95% CI, 46%-74%) and involved 18 different genes. These included recurrent mutations in RMND1, AARS2, and MTO1, each on a haplotype background consistent with a shared founder allele, and potential novel mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and PTCD1). Distinguishing clinical features included deafness and renal involvement associated with RMND1 and cardiomyopathy with AARS2 and MTO1. However, atypical clinical features were present in some patients, including normal liver function and Leigh syndrome (subacute necrotizing encephalomyelopathy) seen in association with TRMU mutations and no cardiomyopathy with founder SCO2 mutations. It was not possible to confidently identify the underlying genetic basis in 21 patients (40%; 95% CI, 26%-54%). Exome sequencing enhances the ability to identify potential nuclear gene mutations in patients with biochemically defined defects affecting multiple mitochondrial respiratory chain complexes. Additional study is required in independent patient populations to determine the utility of this approach in comparison with traditional diagnostic methods.

Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

PubMed Central

2013-01-01

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome. PMID:24267946

Prediction of pediatric unipolar depression using multiple neuromorphometric measurements: a pattern classification approach.

PubMed

Wu, Mon-Ju; Wu, Hanjing Emily; Mwangi, Benson; Sanches, Marsal; Selvaraj, Sudhakar; Zunta-Soares, Giovana B; Soares, Jair C

2015-03-01

Diagnosis of pediatric neuropsychiatric disorders such as unipolar depression is largely based on clinical judgment - without objective biomarkers to guide diagnostic process and subsequent therapeutic interventions. Neuroimaging studies have previously reported average group-level neuroanatomical differences between patients with pediatric unipolar depression and healthy controls. In the present study, we investigated the utility of multiple neuromorphometric indices in distinguishing pediatric unipolar depression patients from healthy controls at an individual subject level. We acquired structural T1-weighted scans from 25 pediatric unipolar depression patients and 26 demographically matched healthy controls. Multiple neuromorphometric indices such as cortical thickness, volume, and cortical folding patterns were obtained. A support vector machine pattern classification model was 'trained' to distinguish individual subjects with pediatric unipolar depression from healthy controls based on multiple neuromorphometric indices and model predictive validity (sensitivity and specificity) calculated. The model correctly identified 40 out of 51 subjects translating to 78.4% accuracy, 76.0% sensitivity and 80.8% specificity, chi-square p-value = 0.000049. Volumetric and cortical folding abnormalities in the right thalamus and right temporal pole respectively were most central in distinguishing individual patients with pediatric unipolar depression from healthy controls. These findings provide evidence that a support vector machine pattern classification model using multiple neuromorphometric indices may qualify as diagnostic marker for pediatric unipolar depression. In addition, our results identified the most relevant neuromorphometric features in distinguishing PUD patients from healthy controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

Multiple-Purpose Subsonic Naval Aircraft (MPSNA): Multiple Application Propfan Study (MAPS)

NASA Technical Reports Server (NTRS)

Engelbeck, R. M.; Havey, C. T.; Klamka, A.; Mcneil, C. L.; Paige, M. A.

1986-01-01

Study requirements, assumptions and guidelines were identified regarding carrier suitability, aircraft missions, technology availability, and propulsion considerations. Conceptual designs were executed for two missions, a full multimission aircraft and a minimum mission aircraft using three different propulsion systems, the UnDucted Fan (UDF), the Propfan and an advanced Turbofan. Detailed aircraft optimization was completed on those configurations yielding gross weight performance and carrier spot factors. Propfan STOVL conceptual designs were exercised also to show the effects of STOVL on gross weight, spot factor and cost. An advanced technology research plan was generated to identify additional investigation opportunities from an airframe contractors standpoint. Life cycle cost analysis was accomplished yielding a comparison of the UDF and propfan configurations against each other as well as against a turbofan with equivalent state of the art turbo-machinery.

Multiple tuning of magnetic biskyrmions using in situ L-TEM in centrosymmetric MnNiGa alloy

NASA Astrophysics Data System (ADS)

Peng, Licong; Zhang, Ying; He, Min; Ding, Bei; Wang, Wenhong; Li, Jianqi; Cai, Jianwang; Wang, Shouguo; Wu, Guangheng; Shen, Baogen

2018-02-01

Magnetic skyrmions are topologically protected spin configurations and have recently received growingly attention in magnetic materials. The existence of biskyrmions within a broad temperature range has been identified in our newly-discovered MnNiGa material, promising for potential application in physics and technological study. Here, the biskyrmion microscopic origination from the spin configuration evolution of stripe ground state is experimentally identified. The biskyrmion manipulations based on the influences of the basic microstructures and external factors such as grain boundary confinement, sample thickness, electric current, magnetic field and temperature have been systematically studied by using real-space Lorentz transmission electron microscopy. These multiple tuning options help to understand the essential properties of MnNiGa and predict a significant step forward for the realization of skyrmion-based spintronic devices.

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

PubMed

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-05-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

Examination of Association to Autism of Common Genetic Variation in Genes Related to Dopamine

PubMed Central

Anderson, B.M.; Schnetz-Boutaud, N.; Bartlett, J.; Wright, H.H.; Abramson, R.K.; Cuccaro, M.L.; Gilbert, J.R.; Pericak-Vance, M.A.; Haines, J.L.

2010-01-01

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals display significant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypic behaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing a rate of one in 150. Although this genomic approach has yielded multiple suggestive regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies have been suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is that multiple genetic variants may be required to significantly increase the risk of developing autism. Thus we took the alternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28 SNPs. Although we did observe a nominally significant association for rs2239535 (p=.008) on chromosome 20, single locus analysis did not reveal any results as significant after correction for multiple comparisons. No significant interaction was identified when Multifactor Dimensionality Reduction (MDR) was employed to test specifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage to various loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to any specific gene or combination of genes within the pathway. These results demonstrate that common genetic variation within the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis. PMID:19360691

Defining Success in Adult Basic Education Settings: Multiple Stakeholders, Multiple Perspectives

PubMed Central

Tighe, Elizabeth L.; Barnes, Adrienne E.; Connor, Carol M.; Steadman, Sharilyn C.

2015-01-01

This study employed quantitative and qualitative research approaches to investigate what constitutes “success” in Adult Basic Education (ABE) programs from the perspectives of multiple educational stakeholders: the state funding agency, the teachers, and the students. Success was defined in multiple ways. In the quantitative section of the study, we computed classroom value-added scores (used as a metric of the state’s definition of success) to identify more and less effective ABE classrooms in two Florida counties. In the qualitative section of the study, we observed and conducted interviews with teachers and students in the selected classrooms to investigate how these stakeholders defined success in ABE. Iterative consideration of the qualitative data revealed three principal markers of success: (a) instructional strategies and teacher-student interactions; (b) views on standardized testing; and (c) student motivational factors. In general, classrooms with higher value-added scores were characterized by multiple instructional approaches, positive and collaborative teacher-student interactions, and students engaging in goal setting and citing motivational factors such as family and personal fulfillment. The implications for ABE programs are discussed. PMID:26279590

Horizontal Dissemination of Antimicrobial Resistance Determinants in Multiple Salmonella Serotypes following Isolation from the Commercial Swine Operation Environment after Manure Application.

PubMed

Pornsukarom, Suchawan; Thakur, Siddhartha

2017-10-15

The aim of this study was to characterize the plasmids carrying antimicrobial resistance (AMR) determinants in multiple Salmonella serotypes recovered from the commercial swine farm environment after manure application on land. Manure and soil samples were collected on day 0 before and after manure application on six farms in North Carolina, and sequential soil samples were recollected on days 7, 14, and 21 from the same plots. All environmental samples were processed for Salmonella , and their plasmid contents were further characterized. A total of 14 isolates including Salmonella enterica serotypes Johannesburg ( n = 2), Ohio ( n = 2), Rissen ( n = 1), Typhimurium var5- ( n = 5), Worthington ( n = 3), and 4,12:i:- ( n = 1), representing different farms, were selected for plasmid analysis. Antimicrobial susceptibility testing was done by broth microdilution against a panel of 14 antimicrobials on the 14 confirmed transconjugants after conjugation assays. The plasmids were isolated by modified alkaline lysis, and PCRs were performed on purified plasmid DNA to identify the AMR determinants and the plasmid replicon types. The plasmids were sequenced for further analysis and to compare profiles and create phylogenetic trees. A class 1 integron with an ANT(2″)-Ia- aadA2 cassette was detected in the 50-kb IncN plasmids identified in S Worthington isolates. We identified 100-kb and 90-kb IncI1 plasmids in S Johannesburg and S Rissen isolates carrying the bla CMY-2 and tet (A) genes, respectively. An identical 95-kb IncF plasmid was widely disseminated among the different serotypes and across different farms. Our study provides evidence on the importance of horizontal dissemination of resistance determinants through plasmids of multiple Salmonella serotypes distributed across commercial swine farms after manure application. IMPORTANCE The horizontal gene transfer of antimicrobial resistance (AMR) determinants located on plasmids is considered to be the main reason for the rapid proliferation and spread of drug resistance. The deposition of manure generated in swine production systems into the environment is identified as a potential source of AMR dissemination. In this study, AMR gene-carrying plasmids were detected in multiple Salmonella serotypes across different commercial swine farms in North Carolina. The plasmid profiles were characterized based on Salmonella serotype donors and incompatibility (Inc) groups. We found that different Inc plasmids showed evidence of AMR gene transfer in multiple Salmonella serotypes. We detected an identical 95-kb plasmid that was widely distributed across swine farms in North Carolina. These conjugable resistance plasmids were able to persist on land after swine manure application. Our study provides strong evidence of AMR determinant dissemination present in plasmids of multiple Salmonella serotypes in the environment after manure application. Copyright © 2017 American Society for Microbiology.

Prevalence, clinical features and management of pediatric magnetic foreign body ingestions.

PubMed

Tavarez, Melissa M; Saladino, Richard A; Gaines, Barbara A; Manole, Mioara D

2013-01-01

Foreign body (FB) ingestions are frequent in children. Whereas the majority of FBs pass spontaneously through the gastrointestinal tract, ingestion of magnetic FBs pose a particular risk for obstruction due to proximate attraction through the intestinal wall. We aimed to identify the prevalence, clinical presentation, and management of magnetic FB ingestions at our tertiary care institution. We performed a retrospective chart review of medical records of patients presenting to the pediatric Emergency Department (ED) or admitted to the hospital with FB ingestions from June 2003-July 2009. From those cases, patients with magnetic FB ingestions were identified. During the study period, 337,839 patients presented to the ED; 38 cases of magnetic FB ingestion were identified (prevalence 0.01%). Abdominal radiography was obtained in all cases. Ingestion of a single magnet occurred in 30 of 38 cases (79%). Of those, 4 patients underwent endoscopic removal due to signs of FB impaction in the esophagus or pylorus; no complications were noted. Ingestion of multiple magnets (range 2-6) occurred in 8 of 38 cases. Four of the 8 patients with multiple magnetic FBs (50%) presented with signs of peritonitis and required operative repair of multiple intestinal perforations. No deaths were identified. Although ingestion of a single magnetic FB may, in most cases, be managed as a simple FB ingestion, the ingestion of multiple magnetic FB is associated with a high risk of complication and requires aggressive management. We propose an algorithm for management of children with magnetic FB ingestions. Copyright © 2013 Elsevier Inc. All rights reserved.

Comprehensive Characterization of Cancer Driver Genes and Mutations.

PubMed

Bailey, Matthew H; Tokheim, Collin; Porta-Pardo, Eduard; Sengupta, Sohini; Bertrand, Denis; Weerasinghe, Amila; Colaprico, Antonio; Wendl, Michael C; Kim, Jaegil; Reardon, Brendan; Ng, Patrick Kwok-Shing; Jeong, Kang Jin; Cao, Song; Wang, Zixing; Gao, Jianjiong; Gao, Qingsong; Wang, Fang; Liu, Eric Minwei; Mularoni, Loris; Rubio-Perez, Carlota; Nagarajan, Niranjan; Cortés-Ciriano, Isidro; Zhou, Daniel Cui; Liang, Wen-Wei; Hess, Julian M; Yellapantula, Venkata D; Tamborero, David; Gonzalez-Perez, Abel; Suphavilai, Chayaporn; Ko, Jia Yu; Khurana, Ekta; Park, Peter J; Van Allen, Eliezer M; Liang, Han; Lawrence, Michael S; Godzik, Adam; Lopez-Bigas, Nuria; Stuart, Josh; Wheeler, David; Getz, Gad; Chen, Ken; Lazar, Alexander J; Mills, Gordon B; Karchin, Rachel; Ding, Li

2018-04-05

Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors. Published by Elsevier Inc.

Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans.

PubMed

He, Kan; Zhou, Tao; Shao, Jiaofang; Ren, Xiaoliang; Zhao, Zhongying; Liu, Dahai

2014-03-01

Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.

Classification and Clustering Methods for Multiple Environmental Factors in Gene-Environment Interaction: Application to the Multi-Ethnic Study of Atherosclerosis.

PubMed

Ko, Yi-An; Mukherjee, Bhramar; Smith, Jennifer A; Kardia, Sharon L R; Allison, Matthew; Diez Roux, Ana V

2016-11-01

There has been an increased interest in identifying gene-environment interaction (G × E) in the context of multiple environmental exposures. Most G × E studies analyze one exposure at a time, but we are exposed to multiple exposures in reality. Efficient analysis strategies for complex G × E with multiple environmental factors in a single model are still lacking. Using the data from the Multiethnic Study of Atherosclerosis, we illustrate a two-step approach for modeling G × E with multiple environmental factors. First, we utilize common clustering and classification strategies (e.g., k-means, latent class analysis, classification and regression trees, Bayesian clustering using Dirichlet Process) to define subgroups corresponding to distinct environmental exposure profiles. Second, we illustrate the use of an additive main effects and multiplicative interaction model, instead of the conventional saturated interaction model using product terms of factors, to study G × E with the data-driven exposure subgroups defined in the first step. We demonstrate useful analytical approaches to translate multiple environmental exposures into one summary class. These tools not only allow researchers to consider several environmental exposures in G × E analysis but also provide some insight into how genes modify the effect of a comprehensive exposure profile instead of examining effect modification for each exposure in isolation.

Neuromuscular orthotics in the treatment of craniomandibular dysfunction and the effects on patients with multiple sclerosis: a pilot study.

PubMed

Heit, Tammarie

2011-01-01

The purpose of this pilot study was to identify, measure and document an effect on the subjective multiple sclerosis symptoms and compare it to any objective data changes in the neuromuscular system of the head and neck, following the correction of the jaw position using a neuromuscular orthotic. The hope is to provide clinical evidence of improvement in the disease long-term without relying on the subjective evidence of remissions and exacerbations reported by the patient. The evidence found in the current pilot study measured improvement of head position, jaw position, jaw function, and airway in the neuromuscular bite position, which correlated with the improvement of subjective symptoms of craniomandibular dysfunction and multiple sclerosis. Studies show that the bite affects blood flow in the brain, which may explain the improvement of the patients in the current study.

SZDB: A Database for Schizophrenia Genetic Research

PubMed Central

Wu, Yong; Yao, Yong-Gang

2017-01-01

Abstract Schizophrenia (SZ) is a debilitating brain disorder with a complex genetic architecture. Genetic studies, especially recent genome-wide association studies (GWAS), have identified multiple variants (loci) conferring risk to SZ. However, how to efficiently extract meaningful biological information from bulk genetic findings of SZ remains a major challenge. There is a pressing need to integrate multiple layers of data from various sources, eg, genetic findings from GWAS, copy number variations (CNVs), association and linkage studies, gene expression, protein–protein interaction (PPI), co-expression, expression quantitative trait loci (eQTL), and Encyclopedia of DNA Elements (ENCODE) data, to provide a comprehensive resource to facilitate the translation of genetic findings into SZ molecular diagnosis and mechanism study. Here we developed the SZDB database (http://www.szdb.org/), a comprehensive resource for SZ research. SZ genetic data, gene expression data, network-based data, brain eQTL data, and SNP function annotation information were systematically extracted, curated and deposited in SZDB. In-depth analyses and systematic integration were performed to identify top prioritized SZ genes and enriched pathways. Multiple types of data from various layers of SZ research were systematically integrated and deposited in SZDB. In-depth data analyses and integration identified top prioritized SZ genes and enriched pathways. We further showed that genes implicated in SZ are highly co-expressed in human brain and proteins encoded by the prioritized SZ risk genes are significantly interacted. The user-friendly SZDB provides high-confidence candidate variants and genes for further functional characterization. More important, SZDB provides convenient online tools for data search and browse, data integration, and customized data analyses. PMID:27451428

Preschoolers' Use of Morphosyntactic Cues to Identify Generic Sentences: Indefinite Singular Noun Phrases, Tense, and Aspect

ERIC Educational Resources Information Center

Cimpian, Andrei; Meltzer, Trent J.; Markman, Ellen M.

2011-01-01

Generic sentences (e.g., "Birds lay eggs") convey generalizations about entire categories and may thus be an important source of knowledge for children. However, these sentences cannot be identified by a simple rule, requiring instead the integration of multiple cues. The present studies focused on 3- to 5-year-olds' (N = 91) use of…

A genotyping protocol for multiple tissue types from the polyploid tree species Sequoia sempervirens (Cupressaceae).

PubMed

Narayan, Lakshmi; Dodd, Richard S; O'Hara, Kevin L

2015-03-01

Identifying clonal lineages in asexually reproducing plants using microsatellite markers is complicated by the possibility of nonidentical genotypes from the same clonal lineage due to somatic mutations, null alleles, and scoring errors. We developed and tested a clonal identification protocol that is robust to these issues for the asexually reproducing hexaploid tree species coast redwood (Sequoia sempervirens). Microsatellite data from four previously published and two newly developed primers were scored using a modified protocol, and clones were identified using Bruvo genetic distances. The effectiveness of this clonal identification protocol was assessed using simulations and by genotyping a test set of paired samples of different tissue types from the same trees. Data from simulations showed that our protocol allowed us to accurately identify clonal lineages. Multiple test samples from the same trees were identified correctly, although certain tissue type pairs had larger genetic distances on average. The methods described in this paper will allow for the accurate identification of coast redwood clones, facilitating future studies of the reproductive ecology of this species. The techniques used in this paper can be applied to studies of other clonal organisms as well.

Graduate medical education competencies for international health electives: A qualitative study.

PubMed

Nordhues, Hannah C; Bashir, M Usmaan; Merry, Stephen P; Sawatsky, Adam P

2017-11-01

Residency programs offer international health electives (IHEs), providing multiple educational benefits. This study aimed to identify how IHEs fulfill the Accreditation Council for Graduate Medical Education (ACGME) core competencies. We conducted a thematic analysis of post-rotation reflective reports from residents who participated in IHEs through the Mayo International Health Program. We coded reports using a codebook created from the ACGME competencies. Using a constant comparative method, we identified significant themes within each competency. Residents from 40 specialties participated in 377 IHEs in 56 countries from 2001 to 2014. Multiple themes were identified within each of the six ACGME core competencies: Patient Care and Procedural Skills (4), Medical Knowledge (5), Practice-Based Learning and Improvement (3), Interpersonal and Communication Skills (5), Professionalism (4), and Systems-Based Practice and Improvement (3). Themes included improving physical exam and procedural skills, providing care in resource-limited setting, gaining knowledge of tropical and non-tropical diseases, identifying socioeconomic determinants of health, engaging in the education of others, and increasing communication across cultures and multidisciplinary teams. Through IHEs, residents advanced their knowledge, skills, and attitudes in each of the six ACGME competencies. These data can be used for development of IHE competencies and milestones for resident assessment.

Anti-inflammatory genes associated with multiple sclerosis: a gene expression study.

PubMed

Perga, S; Montarolo, F; Martire, S; Berchialla, P; Malucchi, S; Bertolotto, A

2015-02-15

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system caused by a complex interaction between multiple genes and environmental factors. HLA region is the strongest susceptibility locus, but recent huge genome-wide association studies identified new susceptibility genes. Among these, BACH2, PTGER4, RGS1 and ZFP36L1 were highlighted. Here, a gene expression analysis revealed that three of them, namely BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients' blood cells compared to healthy subjects. Interestingly, all these genes are involved in the immune system regulation with predominant anti-inflammatory role and their reduction could predispose to MS development. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

Workplace accident-related finger-fracture at the Mexican Institute of Social Security. Resolution time, economic impact and sequelae.

PubMed

Salinas-Tovar, Santiago; Hernández-Leyva, Blanca E; Marín-Cotoñieto, Irma Araceli; Santos-Celis, Rafael; Luna-Pizarro, Daniel; López-Rojas, Pablo

2007-01-01

To identify resolution time and economic impact of occupational finger fracture with permanent disability. A cross-sectional study was conducted in 2004; the main variables were age; sex; disability days and sequelae. The International Classification of Diseases (ICD 10) was used for the study. The analysis included frequency, exceeded disability days and estimation of cost of disabilities, pensions and direct costs. Chi square test was used to identify the differences. 13,410 Fractures occurred nationwide: multiple finger fractures (803); thumb fractures (1982) and other finger fractures (10,625). Days of resolution time were: 70.5 days for multiple finger fractures and 51.1 days for another finger fractures. Permanent disability partial rate of thumb fracture was 5.3/100, 15.8/100 multiple finger fractures and 5.9 fractures of other finger. The estimated cost by temporary disability in the Instituto Mexicano del Seguro Social was on $10,669,000 U.S., while permanent disability costs in cases of settlements and annual pension payments were $758,536 U.S. Finger-fracture is a prevalent pathology whichever needs that medical procedures are review, also identify factors that decrease resolution time and establish improve actions that create boundaries on the workers damage health. It must be considered that this condition affects enterprise' productivity and decrease the quality of life from workers.

Creating a Common Table: Using Peer Mediated Intervention to Promote Social Communication Skills with At-Risk and Autism Spectrum Disorder Populations

ERIC Educational Resources Information Center

Craig-Unkefer, Lesley; Loncola Walberg, Jennifer

2015-01-01

Identifying an intervention that is effective for multiple populations can be a challenge. Given the potential range of students in an inclusive setting, the need to identify common strategies that promote skill development for multiple populations is essential. Professionals need to identify those strategies that promote skill development that…

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

PubMed Central

Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

2017-01-01

Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

Screening of differentially expressed genes between multiple trauma patients with and without sepsis.

PubMed

Ji, S C; Pan, Y T; Lu, Q Y; Sun, Z Y; Liu, Y Z

2014-03-17

The purpose of this study was to identify critical genes associated with septic multiple trauma by comparing peripheral whole blood samples from multiple trauma patients with and without sepsis. A microarray data set was downloaded from the Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36 from multiple trauma patients with sepsis and 34 from multiple trauma patients without sepsis (as a control set). The data were preprocessed, and differentially expressed genes (DEGs) were then screened for using packages of the R language. Functional analysis of DEGs was performed with DAVID. Interaction networks were then established for the most up- and down-regulated genes using HitPredict. Pathway-enrichment analysis was conducted for genes in the networks using WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down-regulated) and MMP8 (up-regulated) presented the largest fold-changes, and interaction networks were established for these genes. Further analysis revealed that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase inhibitor, clade F, member 2), which interact with PLAU, play important roles in the pathway of the component and coagulation cascade. We hypothesize that PLAU is a major regulator of the component and coagulation cascade, and down-regulation of PLAU results in dysfunction of the pathway, causing sepsis.

Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies

PubMed Central

Liu, Zhonghua; Lin, Xihong

2017-01-01

Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391

Multiple phenotype association tests using summary statistics in genome-wide association studies.

PubMed

Liu, Zhonghua; Lin, Xihong

2018-03-01

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.

MixGF: spectral probabilities for mixture spectra from more than one peptide.

PubMed

Wang, Jian; Bourne, Philip E; Bandeira, Nuno

2014-12-01

In large-scale proteomic experiments, multiple peptide precursors are often cofragmented simultaneously in the same mixture tandem mass (MS/MS) spectrum. These spectra tend to elude current computational tools because of the ubiquitous assumption that each spectrum is generated from only one peptide. Therefore, tools that consider multiple peptide matches to each MS/MS spectrum can potentially improve the relatively low spectrum identification rate often observed in proteomics experiments. More importantly, data independent acquisition protocols promoting the cofragmentation of multiple precursors are emerging as alternative methods that can greatly improve the throughput of peptide identifications but their success also depends on the availability of algorithms to identify multiple peptides from each MS/MS spectrum. Here we address a fundamental question in the identification of mixture MS/MS spectra: determining the statistical significance of multiple peptides matched to a given MS/MS spectrum. We propose the MixGF generating function model to rigorously compute the statistical significance of peptide identifications for mixture spectra and show that this approach improves the sensitivity of current mixture spectra database search tools by a ≈30-390%. Analysis of multiple data sets with MixGF reveals that in complex biological samples the number of identified mixture spectra can be as high as 20% of all the identified spectra and the number of unique peptides identified only in mixture spectra can be up to 35.4% of those identified in single-peptide spectra. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MixGF: Spectral Probabilities for Mixture Spectra from more than One Peptide*

PubMed Central

Wang, Jian; Bourne, Philip E.; Bandeira, Nuno

2014-01-01

In large-scale proteomic experiments, multiple peptide precursors are often cofragmented simultaneously in the same mixture tandem mass (MS/MS) spectrum. These spectra tend to elude current computational tools because of the ubiquitous assumption that each spectrum is generated from only one peptide. Therefore, tools that consider multiple peptide matches to each MS/MS spectrum can potentially improve the relatively low spectrum identification rate often observed in proteomics experiments. More importantly, data independent acquisition protocols promoting the cofragmentation of multiple precursors are emerging as alternative methods that can greatly improve the throughput of peptide identifications but their success also depends on the availability of algorithms to identify multiple peptides from each MS/MS spectrum. Here we address a fundamental question in the identification of mixture MS/MS spectra: determining the statistical significance of multiple peptides matched to a given MS/MS spectrum. We propose the MixGF generating function model to rigorously compute the statistical significance of peptide identifications for mixture spectra and show that this approach improves the sensitivity of current mixture spectra database search tools by a ≈30–390%. Analysis of multiple data sets with MixGF reveals that in complex biological samples the number of identified mixture spectra can be as high as 20% of all the identified spectra and the number of unique peptides identified only in mixture spectra can be up to 35.4% of those identified in single-peptide spectra. PMID:25225354

Student experiences across multiple flipped courses in a single curriculum.

PubMed

Khanova, Julia; Roth, Mary T; Rodgers, Jo Ellen; McLaughlin, Jacqueline E

2015-10-01

The flipped classroom approach has garnered significant attention in health professions education, which has resulted in calls for curriculum-wide implementations of the model. However, research to support the development of evidence-based guidelines for large-scale flipped classroom implementations is lacking. This study was designed to examine how students experience the flipped classroom model of learning in multiple courses within a single curriculum, as well as to identify specific elements of flipped learning that students perceive as beneficial or challenging. A qualitative analysis of students' comments (n = 6010) from mid-course and end-of-course evaluations of 10 flipped courses (in 2012-2014) was conducted. Common and recurring themes were identified through systematic iterative coding and sorting using the constant comparison method. Multiple coders, agreement through consensus and member checking were utilised to ensure the trustworthiness of findings. Several themes emerged from the analysis: (i) the perceived advantages of flipped learning coupled with concerns about implementation; (ii) the benefits of pre-class learning and factors that negatively affect these benefits, such as quality and quantity of learning materials, as well as overall increase in workload, especially in the context of multiple concurrent flipped courses; (iii) the role of the instructor in the flipped learning environment, particularly in engaging students in active learning and ensuring instructional alignment, and (iv) the need for assessments that emphasise the application of knowledge and critical thinking skills. Analysis of data from 10 flipped courses provided insight into common patterns of student learning experiences specific to the flipped learning model within a single curriculum. The study points to the challenges associated with scaling the implementation of the flipped classroom across multiple courses. Several core elements critical to the effective design and implementation of the flipped classroom model are identified. © 2015 John Wiley & Sons Ltd.

Risk factors of suicide mortality among multiple attempters: A national registry study in Taiwan.

PubMed

Chen, I-Ming; Liao, Shih-Cheng; Lee, Ming-Been; Wu, Chia-Yi; Lin, Po-Hsien; Chen, Wei J

2016-05-01

Little is known about the risk factors of suicide mortality among multiple attempters. This study aims to investigate the predictors of suicidal mortality in a prospective cohort of attempters in Taiwan, focusing on the time interval and suicide method change between the last two nonfatal attempts. The representative data retrieved from the National Suicide Surveillance System (NSSS) was linked with National Mortality Database to identify the causes of death in multiple attempters during 2006-2008. Cox-proportional hazard models were applied to calculate the hazard ratios for the predictors of suicide. Among the 55,560 attempters, 6485 (11.7%) had survived attempts ranging from one to 11 times; 861 (1.5%) eventually died by suicide. Multiple attempters were characterized by female (OR = 1.56, p < 0.0001), nonrecipient of national aftercare service (OR = 1.62, p < 0.0001), and current contact with mental health services (OR = 3.17, p < 0.0001). Most multiple attempters who survived from hanging (68.1%) and gas poisoning (61.9%) chose the same method in the following fatal episode. Predictors of suicidal death were identified as male, older age (≥ 45 years), shorter interval and not maintaining methods of low lethality in the last two nonfatal attempts. Receipt of nationwide aftercare was associated with lower risk of suicide but the effect was insignificant. The time interval of the last two nonfatal attempts and alteration in the lethality of suicide method were significant factors for completed suicide. Risk assessment involving these two factors may be necessary for multiple attempters in different clinical settings. Effective strategies for suicide prevention emphasizing this high risk population should be developed in the future. Copyright © 2015. Published by Elsevier B.V.

Genome-Wide Association Studies of Drug-Resistance Determinants.

PubMed

Volkman, Sarah K; Herman, Jonathan; Lukens, Amanda K; Hartl, Daniel L

2017-03-01

Population genetic strategies that leverage association, selection, and linkage have identified drug-resistant loci. However, challenges and limitations persist in identifying drug-resistance loci in malaria. In this review we discuss the genetic basis of drug resistance and the use of genome-wide association studies, complemented by selection and linkage studies, to identify and understand mechanisms of drug resistance and response. We also discuss the implications of nongenetic mechanisms of drug resistance recently reported in the literature, and present models of the interplay between nongenetic and genetic processes that contribute to the emergence of drug resistance. Throughout, we examine artemisinin resistance as an example to emphasize challenges in identifying phenotypes suitable for population genetic studies as well as complications due to multiple-factor drug resistance. Copyright © 2016. Published by Elsevier Ltd.

Identifying potential conflict associated with oil and gas exploration in Texas state coastal waters: A multicriteria spatial analysis.

PubMed

Brody, Samuel D; Grover, Himanshu; Bernhardt, Sarah; Tang, Zhenghong; Whitaker, Bianca; Spence, Colin

2006-10-01

Recent interest in expanding offshore oil production within waters of the United States has been met with opposition by groups concerned with recreational, environmental, and aesthetic values associated with the coastal zone. Although the proposition of new oil platforms off the coast has generated conflict over how coastal resources should be utilized, little research has been conducted on where these user conflicts might be most intense and which sites might be most suitable for locating oil production facilities in light of the multiple, and often times, competing interests. In this article, we develop a multiple-criteria spatial decision support tool that identifies the potential degree of conflict associated with oil and gas production activities for existing lease tracts in the coastal margin of Texas. We use geographic information systems to measure and map a range of potentially competing representative values impacted by establishing energy extraction infrastructure and then spatially identify which leased tracts are the least contentious sites for oil and gas production in Texas state waters. Visual and statistical results indicate that oil and gas lease blocks within the study area vary in their potential to generate conflict among multiple stakeholders.

Complete genomic screen in Parkinson disease: evidence for multiple genes.

PubMed

Scott, W K; Nance, M A; Watts, R L; Hubble, J P; Koller, W C; Lyons, K; Pahwa, R; Stern, M B; Colcher, A; Hiner, B C; Jankovic, J; Ondo, W G; Allen, F H; Goetz, C G; Small, G W; Masterman, D; Mastaglia, F; Laing, N G; Stajich, J M; Slotterbeck, B; Booze, M W; Ribble, R C; Rampersaud, E; West, S G; Gibson, R A; Middleton, L T; Roses, A D; Haines, J L; Scott, B L; Vance, J M; Pericak-Vance, M A

2001-11-14

The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. To identify genetic risk factors for idiopathic PD. Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades.

PubMed

Kyle, Robert A; Therneau, Terry M; Rajkumar, S Vincent; Larson, Dirk R; Plevak, Matthew F; Melton, L Joseph

2004-12-01

Previous studies have indicated that the incidence and mortality rates for multiple myeloma have increased in the United States. The authors reported on the incidence of multiple myeloma in Olmsted County, Minnesota, between 1991 and 2001 and on trends in multiple myeloma incidence over the last 56 years. Using the files of the Mayo Clinic and the Olmsted Medical Center (Rochester, MN), the authors identified all residents of Olmsted County who had multiple myeloma, suspected myeloma, or a related disorder. Reports of all laboratory determinations, in addition to autopsy findings and death certificates, were obtained. The criteria for the diagnosis of multiple myeloma have not changed during the last 6 decades. All but 1 of the 47 residents with multiple myeloma first diagnosed between 1991 and 2001 were recognized antemortem. Fifty-five percent had a previous monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma before multiple myeloma was diagnosed. From 1991 to 2001, the overall annual incidence rate, age-adjusted to the 2000 U.S. population, was 4.3 per 100,000 (95% confidence interval, 3.0-5.5 per 100,000). Poisson regression analysis showed no statistically significant trend in Olmsted County incidence rates over 56 years. In similar fashion, the authors adjusted multiple myeloma incidence rates from nine other studies worldwide for which adequate data were available and documented similar findings in each case, except for one study that included patients with smoldering multiple myeloma. The overall incidence of multiple myeloma in Olmsted County, Minnesota, has not changed in almost 6 decades. The apparent increase in incidence elsewhere is unexplained but probably is attributable to improvements in diagnostic techniques, particularly in older patients. (c) 2004 American Cancer Society

Case studies of transportation investment to identify the impacts on the local and state economy.

DOT National Transportation Integrated Search

2013-01-01

This project provides case studies of the impact of transportation investments on local economies. We use multiple : approaches to measure impacts since the effects of transportation projects can vary according to the size of a : project and the size...

Investigating Students' Understanding of the Dissolving Process

ERIC Educational Resources Information Center

Naah, Basil M.; Sanger, Michael J.

2013-01-01

In a previous study, the authors identified several student misconceptions regarding the process of dissolving ionic compounds in water. The present study used multiple-choice questions whose distractors were derived from these misconceptions to assess students' understanding of the dissolving process at the symbolic and particulate levels. The…

A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

PubMed

Wang, Nani; Zhao, Guizhi; Zhang, Yang; Wang, Xuping; Zhao, Lisha; Xu, Pingcui; Shou, Dan

2017-10-27

BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

What is the extent of research on the characteristics, behaviors, and impacts of health information technology champions? A scoping review.

PubMed

Shea, Christopher Michael; Belden, Charles M

2016-01-12

Although champions are commonly employed in health information technology (HIT) implementations, the state of empirical literature on HIT champions' is unclear. The purpose of our review was to synthesize quantitative and qualitative studies to identify the extent of research on the characteristics, behaviors, and impacts of HIT champions. Ultimately, our goal was to identify gaps in the literature and inform implementation science. Our review employed a broad search strategy using multiple databases-Embase, Pubmed, Cinahl, PsychInfo, Web of Science, and the Cochrane library. We identified 1728 candidate articles, of which 42 were retained for full-text review. Of the 42 studies included, fourteen studies employed a multiple-case study design (33 %), 12 additional articles employed a single-case study design (29 %), five used quantitative methods (12 %), two used mixed-methods (5 %), and one used a Delphi methodology (2 %). Our review revealed multiple categories and characteristics of champions as well as influence tactics they used to promote an HIT project. Furthermore, studies have assessed three general types of HIT champion impacts: (1) impacts on the implementation process of a specific HIT; (2) impacts on usage behavior or overall success of a specific HIT; and (3) impacts on general organizational-level innovativeness. However the extent to which HIT projects fail even with a champion and why such failures occur is not clear. Also unclear is whether all organizations require a champion for successful HIT project implementation. In other words, we currently do not know enough about the conditions under which (1) a health IT champion is needed, (2) multiple champions are needed, and (3) an appointed champion-as opposed to an emergent champion-can be successful. Although champions appear to have contributed to successful implementation of HIT projects, simply measuring the presence or absence of a champion is not sufficient for assessing impacts. Future research should aim for answers to questions about who champions should be, when they should be engaged, what they should do, how management can support their efforts, and what their impact is given the organizational context.

Tehran Survey of Potential Risk Factors for Multiple Births.

PubMed

Omani Samani, Reza; Almasi-Hashiani, Amir; Vesali, Samira; Shokri, Fatemeh; Cheraghi, Rezvaneh; Torkestani, Farahnaz; Sepidarkish, Mahdi

2017-10-01

The multiple pregnancy incidence is increasing worldwide. This increased incidence is concerning to the health care system. This study aims to determine the frequency of multiple pregnancy and identify factors that affect this frequency in Tehran, Iran. This cross-sectional study included 5170 mothers in labor between July 6-21, 2015 from 103 hospitals with Obstetrics and Gynecology Wards. The questionnaire used in this study consisted of five parts: demographic characteristics; information related to pregnancy; information related to the infant; information regarding the multiple pregnancy; and information associated with infertility. We recruited 103 trained midwives to collect data related to the questionnaire from eligible participants through an interview and medical records review. Frequencies and odds ratios (OR) for the association between multiple pregnancy and the selected characteristics (maternal age, economic status, history of multiple pregnancy in first-degree relatives, and reproductive history) were computed by multiple logistic regression. Stata software, version 13 (Stata Corp, College Station, TX, USA) was used for all statistical analyses. Multiple pregnancy had a prevalence of 1.48% [95% confidence interval (CI): 1.19-1.85]. After controlling for confounding variables, we observed a significant association between frequency of multiple pregnancy and mother's age (OR=1.04, 95% CI: 1.001-1.09, P=0.044), assisted reproductive technique (ART, OR=6.11, 95% CI: 1.7- 21.97, P=0.006), and history of multiple pregnancy in the mother's family (OR=5.49, 95% CI: 3.55-9.93, P=0.001). The frequency of multiple pregnancy approximated results reported in previous studies in Iran. Based on the results, we observed significantly greater frequency of multiple pregnancy in older women, those with a history of ART, and a history of multiple pregnancy in the mother's family compared to the other variables. Copyright© by Royan Institute. All rights reserved.

Strategies for Promoting Autonomous Reading Motivation: A Multiple Case Study Research in Primary Education

ERIC Educational Resources Information Center

De Naeghel, Jessie; Van Keer, Hilde; Vanderlinde, Ruben

2014-01-01

It is important to reveal strategies which foster students' reading motivation in order to break through the declining trend in reading motivation throughout children's educational careers. Consequently, the present study advances an underexposed field in reading motivation research by studying and identifying the strategies of teachers excellent…

Conceptualizing Social Integration among Formerly Homeless Adults with Severe Mental Illness

ERIC Educational Resources Information Center

Tsai, Jack; Rosenheck, Robert A.

2012-01-01

The multiple dimensions of social integration among formerly homeless adults with severe mental illness have not been well-studied. Previous studies have focused on clinical measures or narrow components of social integration. We used a multisite study of chronically homeless adults who were provided housing to (a) identify the main factors…

A Qualitative Study of Undergraduate Instrumentalists Teaching Elementary General Music Education

ERIC Educational Resources Information Center

Corfield-Adams, Maggie Beth

2012-01-01

The central purpose of this multiple-case study was to describe the professional identities of six general music teachers who identified as instrumentalists as undergraduates. The study builds upon research addressing why students choose music education (Bergee, et al., 2001; Bright, 2006; Gillespie & Hamann, 1999; Lee, 2003; Madsen &…

Successful Leadership in Three High-Poverty Urban Elementary Schools

ERIC Educational Resources Information Center

Jacobson, Stephen L.; Brooks, Sharon; Giles, Corrie; Johnson, Lauri; Ylimaki, Rose

2007-01-01

This study examined the beliefs and practices of three principals during whose tenure their high-poverty urban elementary schools experienced improved student achievement. A two-stage, multiple case-study methodology was employed. First, New York State Education Department (NYSED) school report card data were analyzed to identify case-study sites.…

Principals' Instructional Leadership within a Teacher Performance Appraisal System: Enhancing Students' Academic Success

ERIC Educational Resources Information Center

Ovando, Martha N.; Ramirez, Alfredo, Jr.

2007-01-01

The purpose of this study was to identify principals' instructional leadership actions within a comprehensive teacher evaluation system in successful schools rated as recognized or exemplary by the accountability measures in place. The study followed a multiple case study approach. Participants included six school administrators within the same…

Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: A prospective observational study.

PubMed

Takaesu, Yoshikazu; Kishimoto, Taishiro; Murakoshi, Akiko; Takahashi, Nobutada; Inoue, Yuichi

2016-02-28

The purpose of the study was to identify factors associated with discontinuation of aripiprazole after switching from other antipsychotics in patients with schizophrenia in real world clinical settings. From January 2011 to December 2012, a prospective, 48-week open-label study was undertaken. Thirty-eight subjects on antipsychotic monotherapy were switched to aripiprazole. Patients who discontinued aripiprazole were compared to those who continued with regards to demographic characteristics as well as treatment factors. Multiple regression analysis was conducted to identify predictors for aripiprazole discontinuation. Thirteen out of 38 patients (34.2%) discontinued aripiprazole during the follow up period. Nine patients (23.7%) discontinued aripiprazole due to worsening of psychotic symptoms. Multiple logistic regression analysis revealed that only the duration of previous antipsychotic treatment was associated with aripiprazole discontinuation after switching to aripiprazole. The receiver operating curve (ROC) analysis identified that the cut-off length for duration of illness to predict aripiprazole discontinuation was 10.5 years. Longer duration of illness was associated with aripiprazole discontinuation. Greater caution may be required when treating such patients with aripiprazole. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetic association of impulsivity in young adults: a multivariate study

PubMed Central

Khadka, S; Narayanan, B; Meda, S A; Gelernter, J; Han, S; Sawyer, B; Aslanzadeh, F; Stevens, M C; Hawkins, K A; Anticevic, A; Potenza, M N; Pearlson, G D

2014-01-01

Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype–phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors. PMID:25268255

Hydrometric, Hydrochemical, and Hydrogeophysical Runoff Characterization Across Multiple Land Covers in the Agua Salud Project, Panama

NASA Astrophysics Data System (ADS)

Litt, Guy Finley

As the Panama Canal Authority faces sensitivity to water shortages, managing water resources becomes crucial for the global shipping industry's security. These studies address knowledge gaps in tropical water resources to aid hydrological model development and validation. Field-based hydrological investigations in the Agua Salud Project within the Panama Canal Watershed employed multiple tools across a variety of land covers to investigate hydrological processes. Geochemical tracers informed where storm runoff in a stream comes from and identified electrical conductivity (EC) as an economical, high sample frequency tracer during small storms. EC-based hydrograph separation coupled with hydrograph recession rate analyses identified shallow and deep groundwater storage-discharge relationships that varied by season and land cover. A series of plot-scale electrical resistivity imaging geophysical experiments coupled with rainfall simulation characterized subsurface flow pathway behavior and quantified respectively increasing infiltration rates across pasture, 10 year old secondary succession forest, teak (tectona grandis), and 30 year old secondary succession forest land covers. Additional soil water, groundwater, and geochemical studies informed conceptual model development in subsurface flow pathways and groundwater, and identified future research needs.

Genetic variation in heat tolerance-related traits in a population of wheat multiple synthetic derivatives

PubMed Central

Elbashir, Awad A. E.; Gorafi, Yasir S. A.; Tahir, Izzat S. A.; Elhashimi, Ashraf. M. A.; Abdalla, Modather G. A.; Tsujimoto, Hisashi

2017-01-01

In wheat (Triticum aestivum L.) high temperature (≥30°C) during grain filling leads to considerable reduction in grain yield. We studied 400 multiple synthetic derivatives (MSD) lines to examine the genetic variability of heat stress–adaptive traits and to identify new sources of heat tolerance to be used in wheat breeding programs. The experiment was arranged in an augmented randomized complete block design in four environments in Sudan. A wide range of genetic variability was found in most of the traits in all environments. For all traits examined, we found MSD lines that showed better performance than their parent ‘Norin 61’ and two adapted Sudanese cultivars. Using the heat tolerance efficiency, we identified 13 highly heat-tolerant lines and several lines with intermediate heat tolerance and good yield potential. We also identified lines with alleles that can be used to increase wheat yield potential. Our study revealed that the use of the MSD population is an efficient way to explore the genetic variation in Ae. tauschii for wheat breeding and improvement. PMID:29398942

Use of nondestructive evaluation to detect moisture in flexible pavements.

DOT National Transportation Integrated Search

2006-01-01

The purpose of this study was to identify the currently available nondestructive evaluation technology that holds the greatest potential to detect moisture in flexible pavements and then apply the technology in multiple locations throughout Virginia....

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

PubMed

Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

2013-08-13

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

PubMed Central

Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

2013-01-01

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis. PMID:23904484

Use of radar in urban studies

NASA Technical Reports Server (NTRS)

Bryan, M. L.

1976-01-01

The use of side-looking airborne radar for urban studies is reviewed with attention given to the work of Moore (1969) and Lewis (1968) which may be summarized as follows: (1) linear elements of the transportation net were easily defined, (2) gross patterns of industry, residential and open space land were identified, but it was not possible to map the land use boundaries in great detail, (3) commercial land areas were often difficult to identify, and (4) multiple polarized imagery was helpful in correctly interpreting the total scene. It is found that the sensitivity of radar to surface roughness and the availability of multiple wavelength data allow the discrimination of variations in the surface roughness of intra-urban areas. An L-band imaging radar (25 cm; 1215-1225 GHz) of 25 m resolution will be operating from satellite altitudes in 1978 and will increase the availability of radar data.

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data

PubMed Central

Hu, Bo; Xu, Yaomin

2013-01-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach. PMID:23710259

The Image of Women in the National Education Text Books in Jordan

ERIC Educational Resources Information Center

Al-Khalidi, Nasiema Mustafa Sadeq

2016-01-01

The study aimed to identify the image of women and how it was dealt with in the National Education books in Jordan, where the content of the National Education books analyzed and for multiple age stages, also it addressed the content analysis of images, concepts and fees, activities and evaluation to identify the image of women in the family, at…

Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks.

PubMed

Calhoun, Vince D; Kiehl, Kent A; Pearlson, Godfrey D

2008-07-01

Brain regions which exhibit temporally coherent fluctuations, have been increasingly studied using functional magnetic resonance imaging (fMRI). Such networks are often identified in the context of an fMRI scan collected during rest (and thus are called "resting state networks"); however, they are also present during (and modulated by) the performance of a cognitive task. In this article, we will refer to such networks as temporally coherent networks (TCNs). Although there is still some debate over the physiological source of these fluctuations, TCNs are being studied in a variety of ways. Recent studies have examined ways TCNs can be used to identify patterns associated with various brain disorders (e.g. schizophrenia, autism or Alzheimer's disease). Independent component analysis (ICA) is one method being used to identify TCNs. ICA is a data driven approach which is especially useful for decomposing activation during complex cognitive tasks where multiple operations occur simultaneously. In this article we review recent TCN studies with emphasis on those that use ICA. We also present new results showing that TCNs are robust, and can be consistently identified at rest and during performance of a cognitive task in healthy individuals and in patients with schizophrenia. In addition, multiple TCNs show temporal and spatial modulation during the cognitive task versus rest. In summary, TCNs show considerable promise as potential imaging biological markers of brain diseases, though each network needs to be studied in more detail. (c) 2008 Wiley-Liss, Inc.

Modulation of Temporally Coherent Brain Networks Estimated Using ICA at Rest and During Cognitive Tasks

PubMed Central

Calhoun, Vince D.; Kiehl, Kent A.; Pearlson, Godfrey D.

2009-01-01

Brain regions which exhibit temporally coherent fluctuations, have been increasingly studied using functional magnetic resonance imaging (fMRI). Such networks are often identified in the context of an fMRI scan collected during rest (and thus are called “resting state networks”); however, they are also present during (and modulated by) the performance of a cognitive task. In this article, we will refer to such networks as temporally coherent networks (TCNs). Although there is still some debate over the physiological source of these fluctuations, TCNs are being studied in a variety of ways. Recent studies have examined ways TCNs can be used to identify patterns associated with various brain disorders (e.g. schizophrenia, autism or Alzheimer’s disease). Independent component analysis (ICA) is one method being used to identify TCNs. ICA is a data driven approach which is especially useful for decomposing activation during complex cognitive tasks where multiple operations occur simultaneously. In this article we review recent TCN studies with emphasis on those that use ICA. We also present new results showing that TCNs are robust, and can be consistently identified at rest and during performance of a cognitive task in healthy individuals and in patients with schizophrenia. In addition, multiple TCNs show temporal and spatial modulation during the cognitive task versus rest. In summary, TCNs show considerable promise as potential imaging biological markers of brain diseases, though each network needs to be studied in more detail. PMID:18438867

Joint Identification of Genetic Variants for Physical Activity in Korean Population

PubMed Central

Kim, Jayoun; Kim, Jaehee; Min, Haesook; Oh, Sohee; Kim, Yeonjung; Lee, Andy H.; Park, Taesung

2014-01-01

There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA. PMID:25026172

A New Look at Multiple Goal Pursuit: The Promise of a Person-Centered Approach

ERIC Educational Resources Information Center

Wormington, Stephanie Virgine; Linnenbrink-Garcia, Lisa

2017-01-01

The current study reviewed and synthesized studies employing a person-centered approach to studying achievement goals. Towards this end, a common labeling scheme was developed for goal profiles. Ten profile types were identified across studies and compared via meta-analytic techniques in terms of academic motivation, social/emotional well-being,…

Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease.

PubMed

Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

2017-01-01

Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz - neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach's coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses.

Genetic stability of Brucella abortus isolates from an outbreak by multiple-locus variable-number tandem repeat analysis (MLVA16)

PubMed Central

2014-01-01

Background Brucellosis caused by Brucella abortus is one of the most important zoonoses in the world. Multiple-locus variable-number tandem repeat analysis (MLVA16) has been shown be a useful tool to epidemiological traceback studies in B. abortus infection. Thus, the present study aimed (i) to evaluate the genetic diversity of B. abortus isolates from a brucellosis outbreak, and (ii) to investigate the in vivo stability of the MLVA16 markers. Results Three-hundred and seventy-five clinical samples, including 275 vaginal swabs and 100 milk samples, were cultured from a brucellosis outbreak in a cattle herd, which adopted RB51 vaccination and test-and-slaughter policies. Thirty-seven B. abortus isolates were obtained, eight from milk and twenty-nine from post-partum/abortion vaginal swabs, which were submitted to biotyping and genotyping by MLVA16. Twelve B. abortus isolates obtained from vaginal swabs were identified as RB51. Twenty four isolates, seven obtained from milk samples and seventeen from vaginal swabs, were identified as B. abortus biovar 3, while one isolate from vaginal swabs was identified as B. abortus biovar 1. Three distinct genotypes were observed during the brucellosis outbreak: RB observed in all isolates identified as RB51; W observed in all B. abortus biovar 3 isolates; and Z observed in the single B. abortus biovar 1 isolate. Epidemiological and molecular data show that the B. abortus biovar 1 genotype Z strain is not related to the B. abortus biovar 3 genotype W isolates, and represents a new introduction B. abortus during the outbreak. Conclusions The results of the present study on typing of multiple clinical B. abortus isolates from the same outbreak over a sixteen month period indicate the in vivo stability of MLVA16 markers, a low genetic diversity among B. abortus isolates and the usefulness of MLVA16 for epidemiological studies of bovine brucellosis. PMID:25015840

Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease

PubMed Central

Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

2017-01-01

Purpose Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Methods Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Results Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz – neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach’s coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. Discussion The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses. PMID:28919803

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

PubMed

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

Identification of multiple mRNA and DNA sequences from small tissue samples isolated by laser-assisted microdissection.

PubMed

Bernsen, M R; Dijkman, H B; de Vries, E; Figdor, C G; Ruiter, D J; Adema, G J; van Muijen, G N

1998-10-01

Molecular analysis of small tissue samples has become increasingly important in biomedical studies. Using a laser dissection microscope and modified nucleic acid isolation protocols, we demonstrate that multiple mRNA as well as DNA sequences can be identified from a single-cell sample. In addition, we show that the specificity of procurement of tissue samples is not compromised by smear contamination resulting from scraping of the microtome knife during sectioning of lesions. The procedures described herein thus allow for efficient RT-PCR or PCR analysis of multiple nucleic acid sequences from small tissue samples obtained by laser-assisted microdissection.

MicroRNAs in urine are not biomarkers of multiple myeloma.

PubMed

Sedlaříková, Lenka; Bešše, Lenka; Novosadová, Soňa; Kubaczková, Veronika; Radová, Lenka; Staník, Michal; Krejčí, Marta; Hájek, Roman; Ševčíková, Sabina

2015-09-23

In this study, we aimed to identify microRNA from urine of multiple myeloma patients that could serve as a biomarker for the disease. Analysis of urine samples was performed using Serum/Plasma Focus PCR MicroRNA Panel (Exiqon) and verified using individual TaqMan miRNA assays for qPCR. We found 20 deregulated microRNA (p < 0.05); for further validation, we chose 8 of them. Nevertheless, only differences in expression levels of miR-22-3p remained close to statistical significance. Our preliminary results did not confirm urine microRNA as a potential biomarker for multiple myeloma.

Nonlinear Predictive Models for Multiple Mediation Analysis: With an Application to Explore Ethnic Disparities in Anxiety and Depression Among Cancer Survivors.

PubMed

Yu, Qingzhao; Medeiros, Kaelen L; Wu, Xiaocheng; Jensen, Roxanne E

2018-04-02

Mediation analysis allows the examination of effects of a third variable (mediator/confounder) in the causal pathway between an exposure and an outcome. The general multiple mediation analysis method (MMA), proposed by Yu et al., improves traditional methods (e.g., estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. Previous studies find that compared with non-Hispanic cancer survivors, Hispanic survivors are more likely to endure anxiety and depression after cancer diagnoses. In this paper, we applied MMA on MY-Health study to identify mediators/confounders and quantify the indirect effect of each identified mediator/confounder in explaining ethnic disparities in anxiety and depression among cancer survivors who enrolled in the study. We considered a number of socio-demographic variables, tumor characteristics, and treatment factors as potential mediators/confounders and found that most of the ethnic differences in anxiety or depression between Hispanic and non-Hispanic white cancer survivors were explained by younger diagnosis age, lower education level, lower proportions of employment, less likely of being born in the USA, less insurance, and less social support among Hispanic patients.

Multiple congenital PSS in a dog: case report and literature review.

PubMed

Leeman, Jessica J; Kim, Stanley E; Reese, David J; Risselada, Marije; Ellison, Gary W

2013-01-01

A 4 yr old spayed female mixed-breed dog presented with a 2 yr history of recurring increases in liver enzymes. Two congenital portosystemic shunts (PSSs) were identified using computed tomography (CT) angiography, which included a portoazygous and portorenal extrahepatic shunt. Double right renal veins were also identified. The shunts were successfully identified and attenuated with cellophane banding. Multiple congenital PSS is a rare phenomenon, but should be considered during exploratory laparotomy for PSS and in dogs with poor response to surgical attenuation of a single PSS. CT proved to be a crucial part of accurate diagnosis and surgical planning for this dog with multiple congenital PSS.

Older age, higher perceived disability and depressive symptoms predict the amount and severity of work-related difficulties in persons with multiple sclerosis.

PubMed

Raggi, Alberto; Giovannetti, Ambra Mara; Schiavolin, Silvia; Brambilla, Laura; Brenna, Greta; Confalonieri, Paolo Agostino; Cortese, Francesca; Frangiamore, Rita; Leonardi, Matilde; Mantegazza, Renato Emilio; Moscatelli, Marco; Ponzio, Michela; Torri Clerici, Valentina; Zaratin, Paola; De Torres, Laura

2018-04-16

This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire's overall score and its six subscales. A total of 177 participants (108 females, aged 21-63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire's subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis. Implications for rehabilitation Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

Physical activity and cognitive function in adults with multiple sclerosis: an integrative review.

PubMed

Morrison, Janet D; Mayer, Lori

2017-09-01

To identify and synthesize the research evidence concerning (1) the relationship between physical activity and cognitive performance in persons with multiple sclerosis (MS) and (2) to review the reported effects of physical activity interventions on neurocognitive performance conducted in this population. Relevant peer-reviewed journal articles were identified by searching PubMed, PsychINFO, and SPORTDiscus through May 2016. Full-text articles meeting the inclusion criteria were evaluated for quality using tools developed by the National Institutes of Health. Studies deemed to be of poor quality were excluded from the review. Nineteen studies meeting the inclusion/exclusion criteria were analyzed. Nine studies reported significant relationships between higher levels of physical activity or cardiorespiratory fitness and measures of cognitive function. Data extracted from 10 physical activity intervention studies reported mixed results on the effectiveness of physical activity to improve selected domains of cognitive function in persons with MS. Although correlational studies provide evidence to support a linkage between physical activity and cognitive function in persons with MS, this linkage is confounded by factors that may have influenced the studies' results. Evidence derived from intervention studies that could support a positive effect of physical activity on cognition in persons with MS is equivocal. Implications for Rehabilitation Physical activity has numerous benefits for persons with multiple sclerosis (MS) including improvements in balance, ambulation, depression, fatigue, and quality of life. Structured physical activity programs may contribute to cognitive function stability or improvement in persons with MS.

Tracking Multiple Topics for Finding Interesting Articles

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

Pon, R K; Cardenas, A F; Buttler, D J

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on only interesting topics enables iScore to discard useless profiles to address changes in user interests and to achieve a balance between resource consumption and classification accuracy. Also by relating a topic's interestingness to an article's interestingness, iScore is able tomore » achieve higher quality results than traditional methods such as the Rocchio algorithm. We identify several operating parameters that work well for MTT. Using the same parameters, we show that MTT alone yields high quality results for recommending interesting articles from several corpora. The inclusion of MTT improves iScore's performance by 9% to 14% in recommending news articles from the Yahoo! News RSS feeds and the TREC11 adaptive filter article collection. And through a small user study, we show that iScore can still perform well when only provided with little user feedback.« less

Studying Parental Involvement and University Access and Choice: An "Interacting Multiple Capitals" Model

ERIC Educational Resources Information Center

Gao, Fang; Ng, Jacky Chi Kit

2017-01-01

Capital-embedded parental involvement in education is essential in enhancing university enrolment and maximising the educational potentials for equality and excellence. Previous studies in this field have mainly utilised Perna's (2000, 2006) model, which defines parental involvement as social capital and identifies the additive influences of…

Multiple Images, Common Threads. Case Studies of Good Practice in Adult Community Education.

ERIC Educational Resources Information Center

Bradshaw, Delia

This document presents 10 case studies of adult community education programs (ACE) in the state of Victoria, Australia, in the mid 1990s, that were identified as exemplifying the following principles of good practice in ACE: expansiveness, integration, responsiveness, innovation, belonging, explicitness, autonomy, accessibility, synthesis, and…

Investigating the Relationship of Library Usage to Student Outcomes

ERIC Educational Resources Information Center

Stemmer, John K.; Mahan, David M.

2016-01-01

This study connects library user surveys, a common library assessment technique, to institutional data to demonstrate the value an academic library brings to student learning and student outcomes. Using regression techniques, the study identifies multiple significant correlations, both positive and negative, between student use of the library and…

Personal Agency Inspired by Hardship: Bilingual Latinas as Liberatory Educators

ERIC Educational Resources Information Center

Morales, Amanda R.; Shroyer, M. Gail

2016-01-01

This qualitative multiple case study focused on eleven non-traditional, bilingual, Latinas within a teacher education program. The study explored various factors that influenced participants' desire to pursue and ability to persist as pre-service teachers. The overarching theme identified among participant discourse was personal agency inspired by…

Authentically Engaged Learning through Live Supervision: A Phenomenological Study

ERIC Educational Resources Information Center

Moody, Steven; Kostohryz, Katie; Vereen, Linwood

2014-01-01

This phenomenological study explored the experiential learning of 5 master's-level counseling students undergoing live supervision in a group techniques course. Multiple themes were identified to provide a textural-structural description of how students authentically engaged in the learning process. Implications for counselor education and…

Evolving Approaches to the Study of Childhood Poverty and Education

ERIC Educational Resources Information Center

Hannum, Emily; Liu, Ran; Alvarado-Urbina, Andrea

2017-01-01

Social scientists have conceptualised poverty in multiple ways, with measurement approaches that seek to identify absolute, relative, subjective, and multi-dimensional poverty. The concept of poverty is central in the comparative education field, but has been empirically elusive in many large, international educational surveys: these studies have…

Nitrogen mineralization in riparian soils along a river continuum within a multi-landuse basin

EPA Science Inventory

Nitrogen dynamics in riparian systems are often addressed within one landuse type and are rarely studied on watershed scales involving multiple land uses. This study tested for both temporal trends and watershed-wide spatial patterns in N mineralization and identified site fact...

Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users

PubMed Central

Jönsson, Anna K.; Lesén, Eva; Mårdby, Ann-Charlotte; Sundell, Karolina Andersson

2016-01-01

Objective Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. Study Design and Setting New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. Results The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. Conclusion The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications. PMID:27192203

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.

PubMed

Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

2016-01-01

Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

PubMed Central

Dunning, Mark D.; Brownlie, Serena

2016-01-01

Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH. PMID:28070514

Challenges of self-management when living with multiple chronic conditions

PubMed Central

Liddy, Clare; Blazkho, Valerie; Mill, Karina

2014-01-01

Abstract Objective To explore the perspectives of patients who live with multiple chronic conditions as they relate to the challenges of self-management. Data sources On September 30, 2013, we searched MEDLINE, EMBASE, and CINAHL using relevant key words including chronic disease, comorbidity, multimorbidity, multiple chronic conditions, self-care, self-management, perspective, and perception. Study selection Three reviewers assessed and extracted the data from the included studies after study quality was rated. Qualitative thematic synthesis method was then used to identify common themes. Twenty-three articles met the inclusion criteria, with most coming from the United States. Synthesis Important themes raised by people living with multiple chronic conditions related to their ability to self-manage included living with undesirable physical and emotional symptoms, with pain and depression highlighted. Issues with conflicting knowledge, access to care, and communication with health care providers were raised. The use of cognitive strategies, including reframing, prioritizing, and changing beliefs, was reported to improve people’s ability to self-manage their multiple chronic conditions. Conclusion This study provides a unique view into patients’ perspectives of living with multiple chronic conditions, which are clearly linked to common functional challenges as opposed to specific diseases. Future policy and programming in self-management support should be better aligned with patients’ perspectives on living with multiple chronic conditions. This might be achieved by ensuring a more patient-centred approach is adopted by providers and health service organizations. PMID:25642490

Biopsychosocial Predictors of Fall Events among Older African Americans

PubMed Central

Nicklett, Emily Joy; Taylor, Robert Joseph; Rostant, Ola; Johnson, Kimson E.; Evans, Linnea

2016-01-01

This study identifies risk and protective factors for falls among older, community-dwelling African Americans. Drawing upon the biopsychosocial perspective (Engel, 1997), we conducted a series of sex- and age-adjusted multinomial logistic regression analyses to identify the correlates of fall events among older African Americans. Our sample consisted of 1,442 community-dwelling African Americans aged 65 and older, participating in the 2010-12 rounds of the Health and Retirement Study. Biophysical characteristics associated with greater relative risk of experiencing single and/or multiple falls included greater functional limitations, poorer self-rated health, poorer self-rated vision, chronic illnesses (high blood pressure, diabetes, cancer, lung disease, heart problems, stroke, and arthritis), greater chronic illness comorbidity, older age, and female sex. Physical activity was negatively associated with recurrent falls. Among the examined psychosocial characteristics, greater depressive symptoms were associated with greater relative risk of experiencing single and multiple fall events. Implications for clinicians and future studies are discussed. PMID:28285579

Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

PubMed Central

Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

2015-01-01

The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

PubMed

Werling, Donna M; Brand, Harrison; An, Joon-Yong; Stone, Matthew R; Zhu, Lingxue; Glessner, Joseph T; Collins, Ryan L; Dong, Shan; Layer, Ryan M; Markenscoff-Papadimitriou, Eirene; Farrell, Andrew; Schwartz, Grace B; Wang, Harold Z; Currall, Benjamin B; Zhao, Xuefang; Dea, Jeanselle; Duhn, Clif; Erdman, Carolyn A; Gilson, Michael C; Yadav, Rachita; Handsaker, Robert E; Kashin, Seva; Klei, Lambertus; Mandell, Jeffrey D; Nowakowski, Tomasz J; Liu, Yuwen; Pochareddy, Sirisha; Smith, Louw; Walker, Michael F; Waterman, Matthew J; He, Xin; Kriegstein, Arnold R; Rubenstein, John L; Sestan, Nenad; McCarroll, Steven A; Neale, Benjamin M; Coon, Hilary; Willsey, A Jeremy; Buxbaum, Joseph D; Daly, Mark J; State, Matthew W; Quinlan, Aaron R; Marth, Gabor T; Roeder, Kathryn; Devlin, Bernie; Talkowski, Michael E; Sanders, Stephan J

2018-05-01

Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutations, coding regions still exhibited the strongest associations. Thus, in autism, the contribution of de novo noncoding variation is probably modest in comparison to that of de novo coding variants. Robust results from future WGS studies will require large cohorts and comprehensive analytical strategies that consider the substantial multiple-testing burden.

Whole transcriptome analysis using next-generation sequencing of model species Setaria viridis to support C4 photosynthesis research.

PubMed

Xu, Jiajia; Li, Yuanyuan; Ma, Xiuling; Ding, Jianfeng; Wang, Kai; Wang, Sisi; Tian, Ye; Zhang, Hui; Zhu, Xin-Guang

2013-09-01

Setaria viridis is an emerging model species for genetic studies of C4 photosynthesis. Many basic molecular resources need to be developed to support for this species. In this paper, we performed a comprehensive transcriptome analysis from multiple developmental stages and tissues of S. viridis using next-generation sequencing technologies. Sequencing of the transcriptome from multiple tissues across three developmental stages (seed germination, vegetative growth, and reproduction) yielded a total of 71 million single end 100 bp long reads. Reference-based assembly using Setaria italica genome as a reference generated 42,754 transcripts. De novo assembly generated 60,751 transcripts. In addition, 9,576 and 7,056 potential simple sequence repeats (SSRs) covering S. viridis genome were identified when using the reference based assembled transcripts and the de novo assembled transcripts, respectively. This identified transcripts and SSR provided by this study can be used for both reverse and forward genetic studies based on S. viridis.

Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

PubMed Central

Wong, Vanessa K.; Holt, Kathryn E.; Okoro, Chinyere; Baker, Stephen; Pickard, Derek J.; Marks, Florian; Page, Andrew J.; Olanipekun, Grace; Munir, Huda; Alter, Roxanne; Fey, Paul D.; Feasey, Nicholas A.; Weill, Francois-Xavier; Le Hello, Simon; Hart, Peter J.; Kariuki, Samuel; Breiman, Robert F.; Gordon, Melita A.; Heyderman, Robert S.; Jacobs, Jan; Lunguya, Octavie; Msefula, Chisomo; MacLennan, Calman A.; Keddy, Karen H.; Smith, Anthony M.; Onsare, Robert S.; De Pinna, Elizabeth; Nair, Satheesh; Amos, Ben; Dougan, Gordon; Obaro, Stephen

2016-01-01

Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. PMID:27657909

Polygenic sex determination in the cichlid fish Astatotilapia burtoni.

PubMed

Roberts, Natalie B; Juntti, Scott A; Coyle, Kaitlin P; Dumont, Bethany L; Stanley, M Kaitlyn; Ryan, Allyson Q; Fernald, Russell D; Roberts, Reade B

2016-10-26

The East African riverine cichlid species Astatotilapia burtoni serves as an important laboratory model for sexually dimorphic physiology and behavior, and also serves as an outgroup species for the explosive adaptive radiations of cichlid species in Lake Malawi and Lake Victoria. An astounding diversity of genetic sex determination systems have been revealed within the adaptive radiation of East African cichlids thus far, including polygenic sex determination systems involving the epistatic interaction of multiple, independently segregating sex determination alleles. However, sex determination has remained unmapped in A. burtoni. Here we present mapping results supporting the presence of multiple, novel sex determination alleles, and thus the presence of polygenic sex determination in A. burtoni. Using mapping in small families in conjunction with restriction-site associated DNA sequencing strategies, we identify associations with sex at loci on linkage group 13 and linkage group 5-14. Inheritance patterns support an XY sex determination system on linkage group 5-14 (a chromosome fusion relative to other cichlids studied), and an XYW system on linkage group 13, and these associations are replicated in multiple families. Additionally, combining our genetic data with comparative genomic analysis identifies another fusion that is unassociated with sex, with linkage group 8-24 and linkage group 16-21 fused in A. burtoni relative to other East African cichlid species. We identify genetic signals supporting the presence of three previously unidentified sex determination alleles at two loci in the species A. burtoni, strongly supporting the presence of polygenic sex determination system in the species. These results provide a foundation for future mapping of multiple sex determination genes and their interactions. A better understanding of sex determination in A. burtoni provides important context for their use in behavioral studies, as well as studies of the evolution of genetic sex determination and sexual conflicts in East African cichlids.

Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing.

PubMed

Ryland, Georgina L; Jones, Kate; Chin, Melody; Markham, John; Aydogan, Elle; Kankanige, Yamuna; Caruso, Marisa; Guinto, Jerick; Dickinson, Michael; Prince, H Miles; Yong, Kwee; Blombery, Piers

2018-05-14

Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline. At least one mutation was found in 69 (80%) patients. Frequently mutated genes included TP53 (36%), KRAS (22.1%), NRAS (15.1%), FAM46C/DIS3 (8.1%) and TET2/FGFR3 (5.8%), including multiple mutations not previously described in myeloma. Importantly we observed TP53 mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed. Our results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density.

PubMed

Wang, W; Huang, S; Hou, W; Liu, Y; Fan, Q; He, A; Wen, Y; Hao, J; Guo, X; Zhang, F

2017-10-01

Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data METHOD: We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients' BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10 -4 for LS and 2.7 × 10 -2 for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10 -4 for femoral necks and 2.6 × 10 -2 for lumbar spines BMD in meQTLs-based GSEA). Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article : W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572-576. © 2017 Wang et al.

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis.

PubMed

Snook, Erin M; Motl, Robert W

2009-02-01

The study used meta-analytic procedures to examine the overall effect of exercise training interventions on walking mobility among individuals with multiple sclerosis. A search was conducted for published exercise training studies from 1960 to November 2007 using MEDLINE, PsychINFO, CINAHL, and Current Contents Plus. Studies were selected if they measured walking mobility, using instruments identified as acceptable walking mobility constructs and outcome measures for individuals with neurologic disorders, before and after an intervention that included exercise training. Forty-two published articles were located and reviewed, and 22 provided enough data to compute effect sizes expressed as Cohen's d. Sixty-six effect sizes were retrieved from the 22 publications with 600 multiple sclerosis participants and yielded a weighted mean effect size of g = 0.19 (95% confidence interval, 0.09-0.28). There were larger effects associated with supervised exercise training ( g = 0.32), exercise programs that were less than 3 months in duration (g = 0.28), and mixed samples of relapsing-remitting and progressive multiple sclerosis (g = 0.52). The cumulative evidence supports that exercise training is associated with a small improvement in walking mobility among individuals with multiple sclerosis.

Predictors of postoperative outcomes of cubital tunnel syndrome treatments using multiple logistic regression analysis.

PubMed

Suzuki, Taku; Iwamoto, Takuji; Shizu, Kanae; Suzuki, Katsuji; Yamada, Harumoto; Sato, Kazuki

2017-05-01

This retrospective study was designed to investigate prognostic factors for postoperative outcomes for cubital tunnel syndrome (CubTS) using multiple logistic regression analysis with a large number of patients. Eighty-three patients with CubTS who underwent surgeries were enrolled. The following potential prognostic factors for disease severity were selected according to previous reports: sex, age, type of surgery, disease duration, body mass index, cervical lesion, presence of diabetes mellitus, Workers' Compensation status, preoperative severity, and preoperative electrodiagnostic testing. Postoperative severity of disease was assessed 2 years after surgery by Messina's criteria which is an outcome measure specifically for CubTS. Bivariate analysis was performed to select candidate prognostic factors for multiple linear regression analyses. Multiple logistic regression analysis was conducted to identify the association between postoperative severity and selected prognostic factors. Both bivariate and multiple linear regression analysis revealed only preoperative severity as an independent risk factor for poor prognosis, while other factors did not show any significant association. Although conflicting results exist regarding prognosis of CubTS, this study supports evidence from previous studies and concludes early surgical intervention portends the most favorable prognosis. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Nutrition-based interventions to address metabolic syndrome in the Navajo: a systematic review.

PubMed

Nava, Lorenzo T; Zambrano, Jenelle M; Arviso, Karen P; Brochetti, Denise; Becker, Kathleen L

2015-11-01

The objective of this systematic review is to identify nutrition-based interventions that may be effective for the prevention and treatment of metabolic syndrome in the Navajo. Metabolic syndrome, a major risk factor for cardiovascular disease, affects almost half of the Navajo population. The diet of the Navajo, heavy in fat and refined carbohydrates, has been identified as an important contributing factor to the high rates of metabolic syndrome in this population. A search was conducted on PubMed, EMBASE and CINAHL to identify studies published before October, 2013, involving nutrition-based interventions in adult populations similar to the Navajo targeting at least one measure of metabolic syndrome. Data on efficacy and participation were gathered and synthesised qualitatively. Out of 19 studies included in this systematic review, 11 interventions were identified to be effective at improving at least one measure of metabolic syndrome. Level of exposure to the intervention, frequency of intervention activities, family and social support, cultural adaptation and case management were identified as factors that may improve the efficacy of an intervention. Multiple nutrition-based interventions have been found to be effective in populations similar to the Navajo. Development of a strategy to address metabolic syndrome in the Navajo may involve aspects from multiple interventions to increase efficacy and maximise participation. © 2015 John Wiley & Sons Ltd.

Identifying applicants suitable to a career in nursing: a value-based approach to undergraduate selection.

PubMed

Traynor, Marian; Galanouli, Despina; Roberts, Martin; Leonard, Lawrence; Gale, Thomas

2017-06-01

The aim of this study was to complement existing evidence on the suitability of Multiple Mini Interviews as a potential tool for the selection of nursing candidates on to a BSc (Hons) nursing programme. This study aimed to trial the Multiple Mini Interview approach to recruitment with a group of first year nursing students (already selected using traditional interviews). Cross-sectional validation study. This paper reports on the evaluation of the participants' detailed scores from the Multiple Mini Interview stations; their original interview scores and their end of year results. This study took place in March 2015. Scores from the seven Multiple Mini Interview stations were analysed to show the internal structure, reliability and generalizability of the stations. Original selection scores from interviews and in-course assessment were correlated with the MMI scores and variation by students' age, gender and disability status was explored. Reliability of the Multiple Mini Interview score was moderate (G = 0·52). The Multiple Mini Interview score provided better differentiation between more able students than did the original interview score but neither score was correlated with the module results. Multiple Mini Interview scores were positively associated with students' age but not their gender or disability status. The Multiple Mini Interview reported in this study offers a selection process that is based on the values and personal attributes regarded as desirable for a career in nursing and does not necessarily predict academic success. Its moderate reliability indicates the need for further improvement but it is capable of discriminating between candidates and shows little evidence of bias. © 2016 John Wiley & Sons Ltd.

Joint Radioisotope Electric Propulsion Studies - Neptune System Explorer

NASA Technical Reports Server (NTRS)

Khan, M. Omair; Amini, Rashied; Ervin, Joan; Lang, Jared; Landau, Damon; Oleson, Steven; Spilker, Thomas; Strange, Nathan

2011-01-01

The Neptune System Explorer (NSE) mission concept study assessed opportunities to conduct Cassini-like science at Neptune with a radioisotope electric propulsion (REP) based spacecraft. REP is based on powering an electric propulsion (EP) engine with a radioisotope power source (RPS). The NSE study was commissioned under the Joint Radioisotope Electric Propulsion Studies (JREPS) project, which sought to determine the technical feasibility of flagship class REP applications. Within JREPS, special emphasis was given toward identifying tall technology tent poles, as well as recommending any new RPS technology developments that would be required for complicated REP missions. Based on the goals of JREPS, multiple RPS (e.g. thermoelectric and Stirling based RPS) and EP (e.g. Hall and ion engines) technology combinations were traded during the NSE study to determine the most favorable REP design architecture. Among the findings from the study was the need for >400We RPS systems, which was driven by EP operating powers and the requirement for a long-lived mission in the deep solar system. Additionally multiple development and implementation risks were identified for the NSE concept, as well as REP missions in general. Among the strengths of the NSE mission would be the benefits associated with RPS and EP use, such as long-term power (approx. 2-3kW) at Neptune and flexible trajectory options for achieving orbit or tours of the Neptune system. Although there are still multiple issues to mitigate, the NSE concept demonstrated distinct advantages associated with using REP for deep space flagship-class missions.

A regulation probability model-based meta-analysis of multiple transcriptomics data sets for cancer biomarker identification.

PubMed

Xie, Xin-Ping; Xie, Yu-Feng; Wang, Hong-Qiang

2017-08-23

Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal. This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis. Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.

Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations of Kentucky.

PubMed

Pravosud, Vira; Huang, Bin; Tucker, Thomas; Vanderford, Nathan L

2017-12-01

The aim of this study was to investigate whether patients with lung cancer in Appalachian Kentucky are more likely to develop multiple primary cancers than patients in non-Appalachian Kentucky. Additional analyses were conducted to identify other factors that may be associated with an increased hazard of developing multiple primary cancers in patients with lung cancer. The data for this retrospective, population-based cohort study of 26,456 primary lung cancer patients were drawn from the Kentucky Cancer Registry. For inclusion in the study, patients must have been diagnosed between January 1, 2000 and December 31, 2013 and they must either have continually resided in Appalachian Kentucky or continually resided in non-Appalachian Kentucky. Cases were excluded if the patient was diagnosed as having additional primary cancers within 3 months of the initial diagnosis of primary lung cancer. The medical records for each case were examined to determine whether the patient was subsequently diagnosed as having additional primary cancers. The Cox proportional hazards model was then used to assess whether there was an association between the region in which the patients live and the likelihood of developing multiple primary cancers. Time to event was considered as the time from diagnosis to either death or development of a second primary cancer. The results presented here indicate that the risk of developing multiple primary cancers is the same for patients with lung cancer throughout Kentucky (hazard ratio [HR] 1.002, P = 0.9713). We found no evidence for a greater hazard in patients from Appalachia; however, additional analyses revealed several high-risk groups. Male patients and older patients had a significantly greater hazard of developing multiple primary cancers (HR 1.169, P = 0.012 and 1.015, P = 0.0001, respectively). In addition, patients who underwent surgery and those who were diagnosed initially as having an earlier stage of cancer also were more likely to develop multiple primary cancers (HR 1.446, P = 0.0003 and 0.684, P = 0.0015, respectively). This is a negative study. Patients with primary lung cancer living in Appalachian Kentucky are not at a greater risk of developing multiple primary cancers than those residing in non-Appalachian Kentucky. High-risk groups identified in this study are male patients and older patients. The increased hazard seen in patients who underwent surgery or those who were diagnosed as having earlier stages of lung cancer are likely an artifact of these patients living longer and, therefore, having more time to develop additional primary cancers.

Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

PubMed

Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

2017-08-01

Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan. Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline. Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes. Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR . ©2017 American Association for Cancer Research.

Assessing Adult Exposure to Community Violence: A Review of Definitions and Measures.

PubMed

DeCou, Christopher R; Lynch, Shannon M

2017-01-01

Although experiences of community violence are linked with negative outcomes for adults and children, few standardized measures assessing community violence exist, and available measures lack consistency concerning the definition of community violence. Further, most measures currently utilized to assess adult exposure to community violence were designed for use with children and adolescents. To address these identified concerns and make recommendations for future research, this article reviews contemporary definitions of community violence, identifies the outcomes of exposure to community violence for adults, and evaluates measures of exposure to community violence with published psychometric data employing adult samples. A systematic review of the literature was conducted to identify studies that (1) included a self-report of community violence exposure, (2) included primarily adult respondents, and (3) reported psychometric data. Seventeen studies met the inclusion criteria. Measures employed in these studies were reviewed and basic psychometric properties discussed. Notably, the Survey of Exposure to Community Violence was the most commonly used measure among these studies. Although multiple measures demonstrated limited but acceptable psychometric performance in select studies, few in-depth psychometric analyses exist for measures of adult exposure to community violence. Also, it is difficult to compare studies due to variations in definitions of community violence and multiple versions of each measure. Recommendations for future research include provision of explicit definitions of community violence and reporting psychometric data for measures. © The Author(s) 2015.

A regenerative approach to the treatment of multiple sclerosis.

PubMed

Deshmukh, Vishal A; Tardif, Virginie; Lyssiotis, Costas A; Green, Chelsea C; Kerman, Bilal; Kim, Hyung Joon; Padmanabhan, Krishnan; Swoboda, Jonathan G; Ahmad, Insha; Kondo, Toru; Gage, Fred H; Theofilopoulos, Argyrios N; Lawson, Brian R; Schultz, Peter G; Lairson, Luke L

2013-10-17

Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Individuals with Single Versus Multiple Suicide Attempts Over 10 Years of Prospective Follow-Up

PubMed Central

Boisseau, Christina L.; Yen, Shirley; Markowitz, John C.; Grilo, Carlos M.; Sanislow, Charles A.; Shea, M. Tracie; Zanarini, Mary C.; Skodol, Andrew E.; Gunderson, John G.; Morey, Leslie C.; McGlashan, Thomas H.

2012-01-01

Background The study attempted to identify characteristics that differentiate multiple suicide attempters from single attempters in individuals with personality disorders (PDs) and/or major depression. Method Participants were 431 participants enrolled in the Collaborative Longitudinal Study of Personality Disorders from July 1996 to June 2008. Suicide attempts were assessed with the Longitudinal Interval Follow-up Evaluation at 6 and 12 months, then yearly through 10 years. Logistic regression was used to compare single attempters to multiple attempters on Axis I and II psychiatric disorders and personality trait variables. Results Twenty-one percent of participants attempted suicide during the 10 years of observation, with 39 (9.0%) reporting a single suicide attempt and 54 (12.5%) reporting multiple suicide attempts. Although no significant differences in were found in baseline Axis I disorders, multiple attempters were significantly more likely to meet criteria for borderline personality disorder and to have higher impulsivity scores than single attempters. Conclusion These results underscore the importance of considering both personality disorders and traits in the assessment of suicidality. PMID:22995448

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

PubMed Central

Damschroder, Laura J; Aron, David C; Keith, Rosalind E; Kirsh, Susan R; Alexander, Jeffery A; Lowery, Julie C

2009-01-01

Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings. PMID:19664226

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.

PubMed

Amin Al Olama, Ali; Dadaev, Tokhir; Hazelett, Dennis J; Li, Qiuyan; Leongamornlert, Daniel; Saunders, Edward J; Stephens, Sarah; Cieza-Borrella, Clara; Whitmore, Ian; Benlloch Garcia, Sara; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; Mcdonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokołorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Govindasami, Koveela; Guy, Michelle; Lophatonanon, Artitaya; Muir, Kenneth; Viñuela, Ana; Brown, Andrew A; Freedman, Mathew; Conti, David V; Easton, Douglas; Coetzee, Gerhard A; Eeles, Rosalind A; Kote-Jarai, Zsofia

2015-10-01

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. © The Author 2015. Published by Oxford University Press.

Evaluation of multiple emission point facilities

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

Miltenberger, R.P.; Hull, A.P.; Strachan, S.

In 1970, the New York State Department of Environmental Conservation (NYSDEC) assumed responsibility for the environmental aspect of the state's regulatory program for by-product, source, and special nuclear material. The major objective of this study was to provide consultation to NYSDEC and the US NRC to assist NYSDEC in determining if broad-based licensed facilities with multiple emission points were in compliance with NYCRR Part 380. Under this contract, BNL would evaluate a multiple emission point facility, identified by NYSDEC, as a case study. The review would be a nonbinding evaluation of the facility to determine likely dispersion characteristics, compliance withmore » specified release limits, and implementation of the ALARA philosophy regarding effluent release practices. From the data collected, guidance as to areas of future investigation and the impact of new federal regulations were to be developed. Reported here is the case study for the University of Rochester, Strong Memorial Medical Center and Riverside Campus.« less

High multiplicity α-particle breakup measurements to study α-condensate states

NASA Astrophysics Data System (ADS)

Bishop, J.; Kokalova, Tz; Freer, M.; Assie, M.; Acosta, L.; Bailey, S.; Cardella, G.; Curtis, N.; De Filippo, E.; Dell'Aquila, D.; De Luca, S.; Francalanza, L.; Gnoffo, B.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Rizzo, F.; Russotto, P.; Quattrocchi, L.; Smith, R.; Stefan, I.; Trifirò, A.; Trimarchì, M.; Verde, G.; Vigilante, M.; Wheldon, C.

2017-06-01

An experiment was performed to investigate α-condensate states via high α-particle multiplicity breakup. The nucleus of interest was 28Si therefore to measure multiplicity 7 particle breakup events, a highly granular detector with a high solid angle coverage was required. For this purpose, the CHIMERA and FARCOS detectors at INFN LNS were employed. Particle identification was achieved through ΔE-E energy loss. The α-particle multiplicity was measured at three beam energies to investigate different excitation regimes in 28Si. At a beam energy where the energy is sufficient to provide the 7 α-particles with enough energy to be identified using the ΔE-E method, multiplicity 7 events can be seen. Given these high multiplicity events, the particles can be reconstructed to investigate the breakup of α-condensate states. Analysing the decay paths of these states can elucidate whether the state of interest corresponds to a non-cluster, clustered or condensed state.

Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome

PubMed Central

Vodopiutz, Julia; Zoller, Heinz; Fenwick, Aimée L.; Arnhold, Richard; Schmid, Max; Prayer, Daniela; Müller, Thomas; Repa, Andreas; Pollak, Arnold; Aufricht, Christoph; Wilkie, Andrew O.M.; Janecke, Andreas R.

2013-01-01

Objective To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. Study design Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. Results We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. Conclusion Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations. PMID:23069192

Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens

PubMed Central

Chasman, Deborah; Walters, Kevin B.; Lopes, Tiago J. S.; Eisfeld, Amie J.; Kawaoka, Yoshihiro; Roy, Sushmita

2016-01-01

Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID:27403523

Automated identification of best-quality coronary artery segments from multiple-phase coronary CT angiography (cCTA) for vessel analysis

NASA Astrophysics Data System (ADS)

Zhou, Chuan; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Chughtai, Aamer; Wei, Jun; Kazerooni, Ella A.

2016-03-01

We are developing an automated method to identify the best quality segment among the corresponding segments in multiple-phase cCTA. The coronary artery trees are automatically extracted from different cCTA phases using our multi-scale vessel segmentation and tracking method. An automated registration method is then used to align the multiple-phase artery trees. The corresponding coronary artery segments are identified in the registered vessel trees and are straightened by curved planar reformation (CPR). Four features are extracted from each segment in each phase as quality indicators in the original CT volume and the straightened CPR volume. Each quality indicator is used as a voting classifier to vote the corresponding segments. A newly designed weighted voting ensemble (WVE) classifier is finally used to determine the best-quality coronary segment. An observer preference study is conducted with three readers to visually rate the quality of the vessels in 1 to 6 rankings. Six and 10 cCTA cases are used as training and test set in this preliminary study. For the 10 test cases, the agreement between automatically identified best-quality (AI-BQ) segments and radiologist's top 2 rankings is 79.7%, and between AI-BQ and the other two readers are 74.8% and 83.7%, respectively. The results demonstrated that the performance of our automated method was comparable to those of experienced readers for identification of the best-quality coronary segments.

Field Scale Optimization for Long-Term Sustainability of Best Management Practices in Watersheds

NASA Astrophysics Data System (ADS)

Samuels, A.; Babbar-Sebens, M.

2012-12-01

Agricultural and urban land use changes have led to disruption of natural hydrologic processes and impairment of streams and rivers. Multiple previous studies have evaluated Best Management Practices (BMPs) as means for restoring existing hydrologic conditions and reducing impairment of water resources. However, planning of these practices have relied on watershed scale hydrologic models for identifying locations and types of practices at scales much coarser than the actual field scale, where landowners have to plan, design and implement the practices. Field scale hydrologic modeling provides means for identifying relationships between BMP type, spatial location, and the interaction between BMPs at a finer farm/field scale that is usually more relevant to the decision maker (i.e. the landowner). This study focuses on development of a simulation-optimization approach for field-scale planning of BMPs in the School Branch stream system of Eagle Creek Watershed, Indiana, USA. The Agricultural Policy Environmental Extender (APEX) tool is used as the field scale hydrologic model, and a multi-objective optimization algorithm is used to search for optimal alternatives. Multiple climate scenarios downscaled to the watershed-scale are used to test the long term performance of these alternatives and under extreme weather conditions. The effectiveness of these BMPs under multiple weather conditions are included within the simulation-optimization approach as a criteria/goal to assist landowners in identifying sustainable design of practices. The results from these scenarios will further enable efficient BMP planning for current and future usage.

Characteristics of Effective Pedagogy of Third Grade English Learners in Language Arts: An Exploratory Case Study

ERIC Educational Resources Information Center

Merwin, Gregory J.

2012-01-01

The purpose of this study was to identify pedagogical and non-pedagogical factors that affect the academic achievement of English Learner (EL) students in the area of language arts at Dr. Albert Schweitzer Elementary School in Anaheim, California. The researcher conducted an exploratory multiple case study to develop a comprehensive, contextual…

Identifying Instructor's Experiences Who Teach Using the Individual Education Approach at an Elementary School

ERIC Educational Resources Information Center

Lopez, Alexandra

2017-01-01

This study focused on discovering what instructors' experiences help elementary school students develop not only academically but also socially. This qualitative multiple case study method was guided by Yin, and the purpose of the study was to investigate effective instruction strategies from the perspective of instructors who worked in an…

The Heart of School Improvement: A Multi-Site Case Study of Leadership for Teacher Learning in Vietnam

ERIC Educational Resources Information Center

Tran, Ngoc H.; Hallinger, Philip; Truong, Thang

2018-01-01

This study addressed the research question: How do Vietnamese principals lead the professional learning of teachers? The research was comprised of a multiple-site case study of leadership and teacher learning in four Vietnamese schools. Qualitative data analysis aimed at identifying modal practices adopted by these Vietnamese principals to lead…

Lessons for Co-Innovation in Agricultural Innovation Systems: A Multiple Case Study Analysis and a Conceptual Model

ERIC Educational Resources Information Center

Fielke, Simon J.; Botha, Neels; Reid, Janet; Gray, David; Blackett, Paula; Park, Nicola; Williams, Tracy

2018-01-01

Purpose: This paper highlights important lessons for co-innovation drawn from three ex-post case study innovation projects implemented within three sub-sectors of the primary industry sector in New Zealand. Design/methodology/approach: The characteristics that fostered co-innovation in each innovation project case study were identified from…

Progressing from Identification and Functional Analysis of Precursor Behavior to Treatment of Self-Injurious Behavior

ERIC Educational Resources Information Center

Dracobly, Joseph D.; Smith, Richard G.

2012-01-01

This multiple-study experiment evaluated the utility of assessing and treating severe self-injurious behavior (SIB) based on the outcomes of a functional analysis of precursor behavior. In Study 1, a precursor to SIB was identified using descriptive assessment and conditional probability analyses. In Study 2, a functional analysis of precursor…

Meaning in Life: One Link in the Chain from Religiousness to Well-Being

ERIC Educational Resources Information Center

Steger, Michael F.; Frazier, Patricia

2005-01-01

Meaning in life has been identified as a potential mediator of the link between religiousness and psychological health. The authors tested this hypothesis in 2 studies, using multiple methods and measures of religiousness and well-being. In the studies, meaning in life mediated the relation between religiousness and life satisfaction (Study 1A),…

Action Research of an Error Self-Correction Intervention: Examining the Effects on the Spelling Accuracy Behaviors of Fifth-Grade Students Identified as At-Risk

ERIC Educational Resources Information Center

Turner, Jill; Rafferty, Lisa A.; Sullivan, Ray; Blake, Amy

2017-01-01

In this action research case study, the researchers used a multiple baseline across two student pairs design to investigate the effects of the error self-correction method on the spelling accuracy behaviors for four fifth-grade students who were identified as being at risk for learning disabilities. The dependent variable was the participants'…

High Prescription Drug Utilization and Associated Costs among Medicaid-eligible Children with Autism Spectrum Disorders Identified by a Population-based Surveillance Network

PubMed Central

Logan, Sarah L.; Nicholas, Joyce S.; Carpenter, Laura A.; King, Lydia B.; Garrett-Mayer, Elizabeth; Charles, Jane M.

2011-01-01

Purpose This study assessed medication use and associated costs among 8- and 15-yearold children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network. Methods All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n=263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder- not otherwise specified (PDD-NOS) were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data. Results All 263 SCADDM-identified children had Medicaid data available; 56% (n=147) had a prescription of any type, 40% (n=105) used psychotropic medication, and 20% (n=52) used multiple psychotropic classes over the study period. Common combinations were (1) attention deficit hyperactivity disorder (ADHD) medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age. Conclusions Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age. PMID:22153288

Systems and Methods for Imaging of Falling Objects

NASA Technical Reports Server (NTRS)

Fallgatter, Cale (Inventor); Garrett, Tim (Inventor)

2014-01-01

Imaging of falling objects is described. Multiple images of a falling object can be captured substantially simultaneously using multiple cameras located at multiple angles around the falling object. An epipolar geometry of the captured images can be determined. The images can be rectified to parallelize epipolar lines of the epipolar geometry. Correspondence points between the images can be identified. At least a portion of the falling object can be digitally reconstructed using the identified correspondence points to create a digital reconstruction.

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

PubMed

Parker, Nicole R; Hudson, Amanda L; Khong, Peter; Parkinson, Jonathon F; Dwight, Trisha; Ikin, Rowan J; Zhu, Ying; Cheng, Zhangkai Jason; Vafaee, Fatemeh; Chen, Jason; Wheeler, Helen R; Howell, Viive M

2016-03-04

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response. This may be due to intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion. Aberrations in other DNA repair mechanisms may also contribute. This study investigated intratumoral heterogeneity in multiple glioblastoma tumors with a particular focus on the DNA repair pathways. Transcriptional intratumoral heterogeneity was identified in 40% of cases with variability in MGMT methylation status found in 14% of cases. As well as identifying intratumoral heterogeneity at the transcriptional and epigenetic levels, targeted next generation sequencing identified between 1 and 37 unique sequence variants per specimen. In-silico tools were then able to identify deleterious variants in both the base excision repair and the mismatch repair pathways that may contribute to therapeutic response. As these pathways have roles in temozolomide response, these findings may confound patient management and highlight the importance of assessing multiple tumor biopsies.

Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

PubMed

Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

2017-12-01

Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

PubMed

Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

2017-02-28

Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Translation of lifestyle modification programs focused on physical activity and dietary habits delivered in community settings.

PubMed

Stoutenberg, Mark; Stanzilis, Katie; Falcon, Ashley

2015-06-01

Lifestyle modification programs (LMPs) can provide individuals with behavioral skills to sustain long-term changes to their physical activity (PA) levels and dietary habits. Yet, there is much work to be done in the translation of these programs to community settings. This review identified LMPs that focused on changing both PA and dietary behaviors and examined common features and barriers faced in their translation to community settings. A search of multiple online databases was conducted to identify LMPs that included participants over the age of 18 who enrolled in LMPs, offered in community settings, and had the goal of improving both PA and dietary behaviors. Data were extracted on participant demographics, study design characteristics, and study outcome variables including changes in PA, dietary habits, body weight, and clinical outcomes. We identified 27 studies that met inclusion criteria. Despite high levels of retention and adherence to the interventions, varying levels of success were observed in increasing PA levels, improving dietary habits, reducing body weight, and improving clinic outcomes. LMPs addressing issues of PA and dietary habits can be successfully implemented in a community setting. However, inconsistent reporting of key components in the translation of these studies (participant recruitment, utilization of behavioral strategies) may limit their replication and advancement of future programs. Future efforts should better address issues such as identifying barriers to participation and program implementation, utilization of community resources, and evaluating changes across multiple health behaviors.

Patterns of Exposure to Multiple Metals and Associations with Neurodevelopment of Preschool Children from Montevideo, Uruguay

PubMed Central

Kordas, Katarzyna; Ardoino, Graciela; Coffman, Donna L.; Queirolo, Elena I.; Ciccariello, Daniela; Mañay, Nelly; Ettinger, Adrienne S.

2015-01-01

While it is known that toxic metals contribute individually to child cognitive and behavioral deficits, we still know little about the effects of exposure to multiple metals, particularly when exposures are low. We studied the association between children's blood lead and hair arsenic, cadmium, and manganese and their performance on the Bayley Scales of Infant Development III. Ninety-two preschool children (age 13–42 months) from Montevideo, Uruguay, provided a hair sample and 78 had a blood lead level (BLL) measurement. Using latent class analysis (LCA), we identified four groups of exposure based on metal concentrations: (1) low metals, (2) low-to-moderate metals, (3) high lead and cadmium, and (4) high metals. Using the four-group exposure variable as the main predictor, and fitting raw scores on the cognitive, receptive vocabulary, and expressive vocabulary scales as dependent variables, both complete-case and multiple imputation (MI) analyses were conducted. We found no association between multiple-metal exposures and neurodevelopment in covariate-adjusted models. This study demonstrates the use of LCA together with MI to determine patterns of exposure to multiple toxic metals and relate these to child neurodevelopment. However, because the overall study population was small, other studies with larger sample sizes are needed to investigate these associations. PMID:25694786

The use of intelligent database systems in acute pancreatitis--a systematic review.

PubMed

van den Heever, Marc; Mittal, Anubhav; Haydock, Matthew; Windsor, John

2014-01-01

Acute pancreatitis (AP) is a complex disease with multiple aetiological factors, wide ranging severity, and multiple challenges to effective triage and management. Databases, data mining and machine learning algorithms (MLAs), including artificial neural networks (ANNs), may assist by storing and interpreting data from multiple sources, potentially improving clinical decision-making. 1) Identify database technologies used to store AP data, 2) collate and categorise variables stored in AP databases, 3) identify the MLA technologies, including ANNs, used to analyse AP data, and 4) identify clinical and non-clinical benefits and obstacles in establishing a national or international AP database. Comprehensive systematic search of online reference databases. The predetermined inclusion criteria were all papers discussing 1) databases, 2) data mining or 3) MLAs, pertaining to AP, independently assessed by two reviewers with conflicts resolved by a third author. Forty-three papers were included. Three data mining technologies and five ANN methodologies were reported in the literature. There were 187 collected variables identified. ANNs increase accuracy of severity prediction, one study showed ANNs had a sensitivity of 0.89 and specificity of 0.96 six hours after admission--compare APACHE II (cutoff score ≥8) with 0.80 and 0.85 respectively. Problems with databases were incomplete data, lack of clinical data, diagnostic reliability and missing clinical data. This is the first systematic review examining the use of databases, MLAs and ANNs in the management of AP. The clinical benefits these technologies have over current systems and other advantages to adopting them are identified. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Multidisciplinary approaches to managing osteoarthritis in multiple joint sites: a systematic review.

PubMed

Finney, Andrew; Healey, Emma; Jordan, Joanne L; Ryan, Sarah; Dziedzic, Krysia S

2016-07-08

The National Institute for Health and Care Excellence's Osteoarthritis (OA) guidelines recommended that future research should consider the benefits of combination therapies in people with OA across multiple joint sites. However, the clinical effectiveness of such approaches to OA management is unknown. This systematic review therefore aimed to identify the clinical and cost effectiveness of multidisciplinary approaches targeting multiple joint sites for OA in primary care. A systematic review of randomised controlled trials. Computerised bibliographic databases were searched (MEDLINE, EMBASE, CINAHL, PsychINFO, BNI, HBE, HMIC, AMED, Web of Science and Cochrane). Studies were included if they met the following criteria; a randomised controlled trial (RCT), a primary care population with OA across at least two different peripheral joint sites (multiple joint sites), and interventions undertaken by at least two different health disciplines (multidisciplinary). The Cochrane 'Risk of Bias' tool and PEDro were used for quality assessment of eligible studies. Clinical and cost effectiveness was determined by extracting and examining self-reported outcomes for pain, function, quality of life (QoL) and health care utilisation. The date range for the search was from database inception until August 2015. The search identified 1148 individual titles of which four were included in the review. A narrative review was conducted due to the heterogeneity of the included trials. Each of the four trials used either educational or exercise interventions facilitated by a range of different health disciplines. Moderate clinical benefits on pain, function and QoL were reported across the studies. The beneficial effects of exercise generally decreased over time within all studies. Two studies were able to show a reduction in healthcare utilisation due to a reduction in visits to a physiotherapist or a reduction in x-rays and orthopaedic referrals. The intervention that showed the most promise used educational interventions delivered by GPs with reinforcement by practice nurses. There are currently very few studies that target multidisciplinary approaches suitable for OA across multiple joint sites, in primary care. A more consistent approach to outcome measurement in future studies of this nature should be considered to allow for better comparison.

Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

PubMed

Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

2014-01-01

This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

OSD CALS Architecture Master Plan Study. Concept Paper. Indexing. Volume 30

DOT National Transportation Integrated Search

1989-06-01

An index identifies and reference information which is exchanged between multiple users and systems. The increased automation that will take place as CALS evolves will dictate an increased use of indexes for the successful exchange of information. Th...

Occupational Health Promotion Programs to Reduce Cardiovascular Risk.

ERIC Educational Resources Information Center

Glasgow, Russell E.; Terborg, James R.

1988-01-01

Surveys literature on worksite health promotion programs targeting cardiovascular risk factors. Reviews findings on health-risk appraisal, hypertension control, smoking cessation, weight reduction, exercise, and programs addressing multiple risk factors. Discusses current knowledge, highlights exemplary studies, and identifies problems and…

Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

EPA Science Inventory

The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.

PubMed

Kang, Eun Yong; Han, Buhm; Furlotte, Nicholas; Joo, Jong Wha J; Shih, Diana; Davis, Richard C; Lusis, Aldons J; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study.

Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

PubMed Central

Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study. PMID:24415945

Epidemiology of multiple childhood traumatic events: child abuse, parental psychopathology, and other family-level stressors.

PubMed

Menard, C B; Bandeen-Roche, K J; Chilcoat, H D

2004-11-01

Multiple family-level childhood stressors are common and are correlated. It is unknown if clusters of commonly co-occurring stressors are identifiable. The study was designed to explore family-level stressor clustering in the general population, to estimate the prevalence of exposure classes, and to examine the correlation of sociodemographic characteristics with class prevalence. Data were collected from an epidemiological sample and analyzed using latent class regression. A six-class solution was identified. Classes were characterized by low risk (prevalence=23%), universal high risk (7 %), family conflict (11 %), household substance problems (22 %), non-nuclear family structure (24 %), parent's mental illness (13 %). Class prevalence varied with race and welfare status, not gender. Interventions for childhood stressors are person-focused; the analytic approach may uniquely inform resource allocation.

Identifying a maximum tolerated contour in two-dimensional dose-finding

PubMed Central

Wages, Nolan A.

2016-01-01

The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

Trajectories of Annual Number of Sexual Partners from Adolescence to Emerging Adulthood: Individual and Family Predictors.

PubMed

Rossi, Erika; Poulin, François; Boislard, Marie-Aude

2017-05-01

Adolescent sexual development is not the same across the board, and can be seen as both normative as well as risky behavior, depending on factors such as age of onset and number of partners. This longitudinal study identified developmental trajectories of annual number of sexual partners from adolescence to emerging adulthood and their antecedents. From the ages of 16-22, 332 participants (60.8 % females) annually reported their number of sexual partners. Measures of adolescent and family characteristics taken at ages 13-15 were used as predictors. Group-based modeling identified four trajectory groups: the abstainers group (9.1 %), low-increasing group (30.6 %), medium-increasing group (53.0 %), and multiple-partners group (7.3 %). Multinomial logistical regressions indicated that better social competence increased chances of belonging to the multiple-partners group as compared to the abstainers and low-increasing groups, and more substance use predicted membership in the multiple-partners group as compared to the abstainers group. Moreover, females were overrepresented in the low-increasing and medium-increasing groups. These results imply a greater diversity in sexual development than proposed in the literature and highlight the importance of identifying the strengths and competencies associated with healthy sexual development along with the early risk factors.

MultiP-Apo: A Multilabel Predictor for Identifying Subcellular Locations of Apoptosis Proteins

PubMed Central

Li, Hui; Wang, Rong; Gan, Yong

2017-01-01

Apoptosis proteins play an important role in the mechanism of programmed cell death. Predicting subcellular localization of apoptosis proteins is an essential step to understand their functions and identify drugs target. Many computational prediction methods have been developed for apoptosis protein subcellular localization. However, these existing works only focus on the proteins that have one location; proteins with multiple locations are either not considered or assumed as not existing when constructing prediction models, so that they cannot completely predict all the locations of the apoptosis proteins with multiple locations. To address this problem, this paper proposes a novel multilabel predictor named MultiP-Apo, which can predict not only apoptosis proteins with single subcellular location but also those with multiple subcellular locations. Specifically, given a query protein, GO-based feature extraction method is used to extract its feature vector. Subsequently, the GO feature vector is classified by a new multilabel classifier based on the label-specific features. It is the first multilabel predictor ever established for identifying subcellular locations of multilocation apoptosis proteins. As an initial study, MultiP-Apo achieves an overall accuracy of 58.49% by jackknife test, which indicates that our proposed predictor may become a very useful high-throughput tool in this area. PMID:28744305

Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors Among Overweight/Obese Latino Smokers

PubMed Central

Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Robles, Eden Hernandez; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

2015-01-01

More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social cognitive theory and principles of motivational interviewing originally developed for smoking cessation to also address physical activity and fruit/vegetable consumption among Latinos exhibiting multiple health risk behaviors. Literature reviews, focus groups, expert consultation, pretesting, and pilot testing were used to inform adaptation decisions. We identified common mechanisms underlying change in smoking, physical activity, and diet used as treatment targets; identified practical models of patient-centered cross-cultural service provision; and identified that family preferences and support as particularly strong concerns among the priority population. Adaptations made to the original intervention are described. The current study is a practical example of how an intervention can be adapted to maximize relevance and acceptability and also maintain the core elements of the original evidence-based intervention. The intervention has significant potential to influence cancer prevention efforts among Latinos in the United States and is being evaluated in a sample of 400 Latino overweight/obese smokers. PMID:25527143

Emergence of antibiotic-resistant extremophiles (AREs).

PubMed

Gabani, Prashant; Prakash, Dhan; Singh, Om V

2012-09-01

Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.

An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species.

PubMed

Rybaczyk, Leszek A; Bashaw, Meredith J; Pathak, Dorothy R; Huang, Kun

2008-03-20

Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types. Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls. These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.

MultiP-Apo: A Multilabel Predictor for Identifying Subcellular Locations of Apoptosis Proteins.

PubMed

Wang, Xiao; Li, Hui; Wang, Rong; Zhang, Qiuwen; Zhang, Weiwei; Gan, Yong

2017-01-01

Apoptosis proteins play an important role in the mechanism of programmed cell death. Predicting subcellular localization of apoptosis proteins is an essential step to understand their functions and identify drugs target. Many computational prediction methods have been developed for apoptosis protein subcellular localization. However, these existing works only focus on the proteins that have one location; proteins with multiple locations are either not considered or assumed as not existing when constructing prediction models, so that they cannot completely predict all the locations of the apoptosis proteins with multiple locations. To address this problem, this paper proposes a novel multilabel predictor named MultiP-Apo, which can predict not only apoptosis proteins with single subcellular location but also those with multiple subcellular locations. Specifically, given a query protein, GO-based feature extraction method is used to extract its feature vector. Subsequently, the GO feature vector is classified by a new multilabel classifier based on the label-specific features. It is the first multilabel predictor ever established for identifying subcellular locations of multilocation apoptosis proteins. As an initial study, MultiP-Apo achieves an overall accuracy of 58.49% by jackknife test, which indicates that our proposed predictor may become a very useful high-throughput tool in this area.

Note-Taking Interventions for College Students: A Synthesis and Meta-Analysis of the Literature

ERIC Educational Resources Information Center

Reed, Deborah K.; Rimel, Hillary; Hallett, Abigail

2016-01-01

Although note taking is frequently described as an important skill for postsecondary success, there have been few note-taking intervention studies involving multiple sessions spanning more than one week. In a systematic search, we identified seven peer-reviewed articles reporting 10 intervention studies published from 1990-2014. The only…

ePortfolios in the Workplace for Human Capital Management: A Multiple Case Study

ERIC Educational Resources Information Center

Lievens, Ronald

2015-01-01

This study researches whether the ePortfolio is a suitable instrument for human capital management in the business environment. The implementation of ePortfolio systems in five different organizations is analyzed. It considers whether ePortfolio implementations were successful, and relevant critical success factors were identified. For the latter…

Why College Students Cheat: A Conceptual Model of Five Factors

ERIC Educational Resources Information Center

Yu, Hongwei; Glanzer, Perry L.; Johnson, Byron R.; Sriram, Rishi; Moore, Brandon

2018-01-01

Though numerous studies have identified factors associated with academic misconduct, few have proposed conceptual models that could make sense of multiple factors. In this study, we used structural equation modeling (SEM) to test a conceptual model of five factors using data from a relatively large sample of 2,503 college students. The results…

Job Satisfaction in Mexican Faculty: An Analysis of its Predictor Variables. ASHE Annual Meeting Paper.

ERIC Educational Resources Information Center

Galaz-Fontes, Jesus Francisco; Gil-Anton, Manuel

This study examined overall job satisfaction among college faculty in Mexico. The study used data from a 1992-93 Carnegie International Faculty Survey. Secondary multiple regression analysis identified predictor variables for several faculty subgroups. Results were interpreted by differentiating between work-related and intrinsic factors, as well…

The human dimensions of urban greenways: planning for recreation and related experiences

Treesearch

Paul H. Gobster; Lynne M. Westpahl

2004-01-01

In this paper, we summarize findings from a series of interrelated studies that examine an urban greenway, the 150 mile Chicago River corridor in Chicago, USA, from multiple perspectives, stakeholder viewpoints, and methodological techniques. Six interdependent "human dimensions" of greenways are identified in the studies: cleanliness, naturalness, aesthetics...

A Social Judgment Analysis of Information Source Preference Profiles: An Exploratory Study to Empirically Represent Media Selection Patterns.

ERIC Educational Resources Information Center

Stefl-Mabry, Joette

2003-01-01

Describes a study that empirically identified individual preferences profiles to understand information-seeking behavior among professional groups for six selected information sources. Highlights include Social Judgment Analysis; the development of the survey used, a copy of which is appended; hypotheses tested; results of multiple regression…

The Invisible Student: Benefits and Challenges of Part-Time Doctoral Studies

ERIC Educational Resources Information Center

Bates, Peter; Goff, Lori

2012-01-01

This autoethnographic study explores the experiences of two part-time doctoral students as we document our journey of balancing our multiple competing roles. As we reflected and consulted the literature, we began to identify many benefits and challenges that part-time candidature brings to students, universities and employers. Through our…

Formal Service Practitioners' Views of Family Caregivers' Responsibilities and Difficulties

ERIC Educational Resources Information Center

Guberman, Nancy; Lavoie, Jean-Pierre; Pepin, Jacinthe; Lauzon, Sylvie; Montejo, Maria-Elisa

2006-01-01

This article identifies home care practitioners' perceptions of the responsibilities, difficulties, and needs for support of caregivers. It is based on a study undertaken in Quebec with 55 practitioners and 10 administrators from 10 CLSCs located in rural, urban, and metropolitan areas. The study had a qualitative, multiple-case design and used…

Rich in vitamin C or just a convenient snack? Multiple-category reasoning with cross-classified foods.

PubMed

Hayes, Brett K; Kurniawan, Hendy; Newell, Ben R

2011-01-01

Two studies examined multiple category reasoning in property induction with cross-classified foods. Pilot tests identified foods that were more typical of a taxonomic category (e.g., "fruit"; termed 'taxonomic primary') or a script based category (e.g., "snack foods"; termed 'script primary'). They also confirmed that taxonomic categories were perceived as more coherent than script categories. In Experiment 1 participants completed an induction task in which information from multiple categories could be searched and combined to generate a property prediction about a target food. Multiple categories were more often consulted and used in prediction for script primary than for taxonomic primary foods. Experiment 2 replicated this finding across a range of property types but found that multiple category reasoning was reduced in the presence of a concurrent cognitive load. Property type affected which categories were consulted first and how information from multiple categories was weighted. The results show that multiple categories are more likely to be used for property predictions about cross-classified objects when an object is primarily associated with a category that has low coherence.

Suitability of public use secondary data sets to study multiple activities.

PubMed

Putnam, Michelle; Morrow-Howell, Nancy; Inoue, Megumi; Greenfield, Jennifer C; Chen, Huajuan; Lee, YungSoo

2014-10-01

The aims of this study were to inventory activity items within and across U.S. public use data sets, to identify gaps in represented activity domains and challenges in interpreting domains, and to assess the potential for studying multiple activity engagement among older adults using existing data. We engaged in content analysis of activity measures of 5U.S. public use data sets with nationally representative samples of older adults. Data sets included the Health & Retirement Survey (HRS), Americans' Changing Lives Survey (ACL), Midlife in the United States Survey (MIDUS), the National Health Interview Survey (NHIS), and the Panel Study of Income Dynamics survey (PSID). Two waves of each data set were analyzed. We identified 13 distinct activity domains across the 5 data sets, with substantial differences in representation of those domains among the data sets, and variance in the number and type of activity measures included in each. Our findings indicate that although it is possible to study multiple activity engagement within existing data sets, fuller sets of activity measures need to be developed in order to evaluate the portfolio of activities older adults engage in and the relationship of these portfolios to health and wellness outcomes. Importantly, clearer conceptual models of activity broadly conceived are required to guide this work. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effects of Tai Chi on physical and psychosocial function among persons with multiple sclerosis: A systematic review.

PubMed

Taylor, Emily; Taylor-Piliae, Ruth E

2017-04-01

Conduct a systematic review to evaluate the effects of Tai Chi on physical and psychosocial function among individuals with Multiple Sclerosis. An electronic literature search of 12 databases using controlled vocabulary function and keywords from inception through August 2016. All Tai Chi intervention studies assessing physical and psychosocial function among persons with Multiple Sclerosis were included. Study quality was scored using an established tool examining 16 study elements (range=0-32). A total of 91 articles were retrieved, with 3 additional articles identified through reviewing bibliographies of relevant articles. A total of 8 studies (randomized controlled trials, n=3; quasi-experimental, n=5) enrolled 193 participants with Multiple Sclerosis. Studies were conducted in the USA (n=3), Europe (n=3), Iran, (n=1), and India (n=1). A total of 3 studies reported using the Yang style of Tai Chi (not specified, n=5 studies). The Tai Chi intervention averaged 27 sessions over 11 weeks. Study quality scores for the randomized controlled trials had a mean score of 23 (range 19-26), while quality scores for quasi-experimental studies had a mean score of 20 (range 13-26). Overall, participants enrolled in Tai Chi had better balance, gait and flexibility, less fatigue and depression, and better quality of life after the intervention; though mixed results were reported. The results indicate that Tai Chi is likely safe and may provide physical and psychosocial benefits in individuals with Multiple Sclerosis. Further research is needed using more rigorous study designs to assess the benefits of Tai Chi for individuals with Multiple Sclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Construct validity and frequency of euphoria sclerotica in multiple sclerosis.

PubMed

Fishman, Inna; Benedict, Ralph H B; Bakshi, Rohit; Priore, Roger; Weinstock-Guttman, Bianca

2004-01-01

Using the Neuropsychiatric Inventory (NPI), we studied euphoria and other behavioral changes in 75 consecutive, unselected multiple sclerosis (MS) patients and 25 healthy controls. We also assessed disease duration, clinical course, physical disability, personality, depression, insight, cognition, and caregiver distress. Factor analysis identified a cluster of symptoms--labeled euphoria/disinhibition--similar to the euphoria sclerotica syndrome originally described by Charcot and others. The euphoria/disinhibition factor score was elevated in 9% of patients and associated with secondary-progressive course, low agreeableness, poor insight, impaired cognition, and high caregiver distress. Thus, we used the NPI to validate the euphoria syndrome in multiple sclerosis (MS) and determined its frequency, and its neurological and psychological correlates.

Comparative transcript profiling of fertile and sterile flower buds from multiple-allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp. pekinensis).

PubMed

Zhou, Xue; Liu, Zhiyong; Ji, Ruiqin; Feng, Hui

2017-10-01

We studied the underlying causes of multiple-allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp. pekinensis) by identifying differentially expressed genes (DEGs) related to pollen sterility between fertile and sterile flower buds. In this work, we verified the stages of sterility microscopically and then performed transcriptome analysis of mRNA isolated from fertile and sterile buds using Illumina HiSeq 2000 platform sequencing. Approximately 80% of ~229 million high-quality paired-end reads were uniquely mapped to the reference genome. In sterile buds, 699 genes were significantly up-regulated and 4096 genes were down-regulated. Among the DEGs, 28 pollen cell wall-related genes, 54 transcription factor genes, 45 phytohormone-related genes, 20 anther and pollen-related genes, 212 specifically expressed transcripts, and 417 DEGs located on linkage group A07 were identified. Six transcription factor genes BrAMS, BrMS1, BrbHLH089, BrbHLH091, BrAtMYB103, and BrANAC025 were identified as putative sterility-related genes. The weak auxin signal that is regulated by BrABP1 may be one of the key factors causing pollen sterility observed here. Moreover, several significantly enriched GO terms such as "cell wall organization or biogenesis" (GO:0071554), "intrinsic to membrane" (GO:0031224), "integral to membrane" (GO:0016021), "hydrolase activity, acting on ester bonds" (GO:0016788), and one significantly enriched pathway "starch and sucrose metabolism" (ath00500) were identified in this work. qRT-PCR, PCR, and in situ hybridization experiments validated our RNA-seq transcriptome analysis as accurate and reliable. This study will lay the foundation for elucidating the molecular mechanism(s) that underly sterility and provide valuable information for studying multiple-allele-inherited male sterility in the Chinese cabbage line 'AB01'.

Multivariate trajectories across multiple domains of health-related quality of life in children with new-onset epilepsy.

PubMed

Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel

2017-10-01

The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified for each pattern can help clinicians provide more targeted care to these children and their families. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple fault separation and detection by joint subspace learning for the health assessment of wind turbine gearboxes

NASA Astrophysics Data System (ADS)

Du, Zhaohui; Chen, Xuefeng; Zhang, Han; Zi, Yanyang; Yan, Ruqiang

2017-09-01

The gearbox of a wind turbine (WT) has dominant failure rates and highest downtime loss among all WT subsystems. Thus, gearbox health assessment for maintenance cost reduction is of paramount importance. The concurrence of multiple faults in gearbox components is a common phenomenon due to fault induction mechanism. This problem should be considered before planning to replace the components of the WT gearbox. Therefore, the key fault patterns should be reliably identified from noisy observation data for the development of an effective maintenance strategy. However, most of the existing studies focusing on multiple fault diagnosis always suffer from inappropriate division of fault information in order to satisfy various rigorous decomposition principles or statistical assumptions, such as the smooth envelope principle of ensemble empirical mode decomposition and the mutual independence assumption of independent component analysis. Thus, this paper presents a joint subspace learning-based multiple fault detection (JSL-MFD) technique to construct different subspaces adaptively for different fault patterns. Its main advantage is its capability to learn multiple fault subspaces directly from the observation signal itself. It can also sparsely concentrate the feature information into a few dominant subspace coefficients. Furthermore, it can eliminate noise by simply performing coefficient shrinkage operations. Consequently, multiple fault patterns are reliably identified by utilizing the maximum fault information criterion. The superiority of JSL-MFD in multiple fault separation and detection is comprehensively investigated and verified by the analysis of a data set of a 750 kW WT gearbox. Results show that JSL-MFD is superior to a state-of-the-art technique in detecting hidden fault patterns and enhancing detection accuracy.

Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

PubMed

Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

2017-09-01

Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (p<0.05). The Timed Up and Go test was independently predicted by the severity of the neurological lesion, Body Mass Index, ataxia, and tactile sensation (R2=0.58), whereas the Functional Reach test was predicted by the severity of the neurological lesion, lower limb strength, and vibration sense (R2=0.49). Somatosensory impairments are very common in people with multiple sclerosis. These impairments are independent predictors of balance limitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Physical disability, life stress, and psychosocial adjustment in multiple sclerosis.

PubMed

Zeldow, P B; Pavlou, M

1984-02-01

Eighty-one outpatients with diagnosed multiple sclerosis were studied in an effort to examine the relative contributions of physical health status, life stress, duration of illness, age, sex, marital status, and social class on various aspects of personal and interpersonal functioning. Stepwise multiple regression analyses were performed to identify the most significant discriminators of the seven psychosocial measures. Physical health status exerted the broadest influence, affecting personal efficiency and well-being, capacity for independent thought and action, self-confidence, self-reliance, and number of meaningful social contacts. Life stress was associated with lowered personal efficiency and sense of well-being. Duration of illness and the demographic variables had few or no effects on psychosocial adjustment. Discussion contrasts the present findings with others in the rehabilitation literature and specifies certain limitations of the study's design.

Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.

PubMed

Low, Siew-Kee; Chung, Suyoun; Takahashi, Atsushi; Zembutsu, Hitoshi; Mushiroda, Taisei; Kubo, Michiaki; Nakamura, Yusuke

2013-08-01

Chemotherapeutic agents are notoriously known to have a narrow therapeutic range that often results in life-threatening toxicity. Hence, it is clinically important to identify the patients who are at high risk for severe toxicity to certain chemotherapy through a pharmacogenomics approach. In this study, we carried out multiple genome-wide association studies (GWAS) of 13 122 cancer patients who received different chemotherapy regimens, including cyclophosphamide- and platinum-based (cisplatin and carboplatin), anthracycline-based (doxorubicin and epirubicin), and antimetabolite-based (5-fluorouracil and gemcitabine) treatment, antimicrotubule agents (paclitaxel and docetaxel), and topoisomerase inhibitors (camptothecin and etoposide), as well as combination therapy with paclitaxel and carboplatin, to identify genetic variants that are associated with the risk of severe neutropenia/leucopenia in the Japanese population. In addition, we used a weighted genetic risk scoring system to evaluate the cumulative effects of the suggestive genetic variants identified from GWAS in order to predict the risk levels of individuals who carry multiple risk alleles. Although we failed to identify genetic variants that surpassed the genome-wide significance level (P < 5.0 × 10(-8) ) through GWAS, probably due to insufficient statistical power and complex clinical features, we were able to shortlist some of the suggestive associated loci. The current study is at the relatively preliminary stage, but does highlight the complexity and problematic issues associated with retrospective pharmacogenomics studies. However, we hope that verification of these genetic variants through local and international collaborations could improve the clinical outcome for cancer patients. © 2013 Japanese Cancer Association.

Combining Computational Modeling and Neuroimaging to Examine Multiple Category Learning Systems in the Brain

PubMed Central

Nomura, Emi M.; Reber, Paul J.

2012-01-01

Considerable evidence has argued in favor of multiple neural systems supporting human category learning, one based on conscious rule inference and one based on implicit information integration. However, there have been few attempts to study potential system interactions during category learning. The PINNACLE (Parallel Interactive Neural Networks Active in Category Learning) model incorporates multiple categorization systems that compete to provide categorization judgments about visual stimuli. Incorporating competing systems requires inclusion of cognitive mechanisms associated with resolving this competition and creates a potential credit assignment problem in handling feedback. The hypothesized mechanisms make predictions about internal mental states that are not always reflected in choice behavior, but may be reflected in neural activity. Two prior functional magnetic resonance imaging (fMRI) studies of category learning were re-analyzed using PINNACLE to identify neural correlates of internal cognitive states on each trial. These analyses identified additional brain regions supporting the two types of category learning, regions particularly active when the systems are hypothesized to be in maximal competition, and found evidence of covert learning activity in the “off system” (the category learning system not currently driving behavior). These results suggest that PINNACLE provides a plausible framework for how competing multiple category learning systems are organized in the brain and shows how computational modeling approaches and fMRI can be used synergistically to gain access to cognitive processes that support complex decision-making machinery. PMID:24962771

The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle

PubMed Central

Zhou, Bo; Schrader, Jared M.; Kalogeraki, Virginia S.; Abeliuk, Eduardo; Dinh, Cong B.; Pham, James Q.; Cui, Zhongying Z.; Dill, David L.; McAdams, Harley H.; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. PMID:25569173

WebMOTIFS: automated discovery, filtering and scoring of DNA sequence motifs using multiple programs and Bayesian approaches

PubMed Central

Romer, Katherine A.; Kayombya, Guy-Richard; Fraenkel, Ernest

2007-01-01

WebMOTIFS provides a web interface that facilitates the discovery and analysis of DNA-sequence motifs. Several studies have shown that the accuracy of motif discovery can be significantly improved by using multiple de novo motif discovery programs and using randomized control calculations to identify the most significant motifs or by using Bayesian approaches. WebMOTIFS makes it easy to apply these strategies. Using a single submission form, users can run several motif discovery programs and score, cluster and visualize the results. In addition, the Bayesian motif discovery program THEME can be used to determine the class of transcription factors that is most likely to regulate a set of sequences. Input can be provided as a list of gene or probe identifiers. Used with the default settings, WebMOTIFS accurately identifies biologically relevant motifs from diverse data in several species. WebMOTIFS is freely available at http://fraenkel.mit.edu/webmotifs. PMID:17584794

The global regulatory architecture of transcription during the Caulobacter cell cycle.

PubMed

Zhou, Bo; Schrader, Jared M; Kalogeraki, Virginia S; Abeliuk, Eduardo; Dinh, Cong B; Pham, James Q; Cui, Zhongying Z; Dill, David L; McAdams, Harley H; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle.

Development of a systematic strategy for the global identification and classification of the chemical constituents and metabolites of Kai-Xin-San based on liquid chromatography with quadrupole time-of-flight mass spectrometry combined with multiple data-processing approaches.

PubMed

Wang, Xiaotong; Liu, Jing; Yang, Xiaomei; Zhang, Qian; Zhang, Yiwen; Li, Qing; Bi, Kaishun

2018-03-30

To rapidly identify and classify complicated components and metabolites for traditional Chinese medicines, a liquid chromatography with quadrupole time-of-flight mass spectrometry method combined with multiple data-processing approaches was established. In this process, Kai-Xin-San, a widely used classic traditional Chinese medicine preparation, was chosen as a model prescription. Initially, the fragmentation patterns, diagnostic product ions and neutral loss of each category of compounds were summarized by collision-induced dissociation analysis of representative standards. In vitro, the multiple product ions filtering technique was utilized to identify the chemical constituents for globally covering trace components. With this strategy, 108 constituents were identified, and compounds database was successfully established. In vivo, the prototype compounds were extracted based on the established database, and the neutral loss filtering technique combined with the drug metabolism reaction rules was employed to identify metabolites. Overall, 69 constituents including prototype and metabolites were characterized in rat plasma and nine constituents were firstly characterized in rat brain, which may be the potential active constituents resulting in curative effects by synergistic interaction. In conclusion, this study provides a generally applicable strategy to global metabolite identification for the complicated components in complex matrix and a chemical basis for further pharmacological research of Kai-Xin-San. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic control and comparative genomic analysis of flowering time in Setaria (Poaceae).

PubMed

Mauro-Herrera, Margarita; Wang, Xuewen; Barbier, Hugues; Brutnell, Thomas P; Devos, Katrien M; Doust, Andrew N

2013-02-01

We report the first study on the genetic control of flowering in Setaria, a panicoid grass closely related to switchgrass, and in the same subfamily as maize and sorghum. A recombinant inbred line mapping population derived from a cross between domesticated Setaria italica (foxtail millet) and its wild relative Setaria viridis (green millet), was grown in eight trials with varying environmental conditions to identify a small number of quantitative trait loci (QTL) that control differences in flowering time. Many of the QTL across trials colocalize, suggesting that the genetic control of flowering in Setaria is robust across a range of photoperiod and other environmental factors. A detailed comparison of QTL for flowering in Setaria, sorghum, and maize indicates that several of the major QTL regions identified in maize and sorghum are syntenic orthologs with Setaria QTL, although the maize large effect QTL on chromosome 10 is not. Several Setaria QTL intervals had multiple LOD peaks and were composed of multiple syntenic blocks, suggesting that observed QTL represent multiple tightly linked loci. Candidate genes from flowering time pathways identified in rice and Arabidopsis were identified in Setaria QTL intervals, including those involved in the CONSTANS photoperiod pathway. However, only three of the approximately seven genes cloned for flowering time in maize colocalized with Setaria QTL. This suggests that variation in flowering time in separate grass lineages is controlled by a combination of conserved and lineage specific genes.

Genetic Control and Comparative Genomic Analysis of Flowering Time in Setaria (Poaceae)

PubMed Central

Mauro-Herrera, Margarita; Wang, Xuewen; Barbier, Hugues; Brutnell, Thomas P.; Devos, Katrien M.; Doust, Andrew N.

2013-01-01

We report the first study on the genetic control of flowering in Setaria, a panicoid grass closely related to switchgrass, and in the same subfamily as maize and sorghum. A recombinant inbred line mapping population derived from a cross between domesticated Setaria italica (foxtail millet) and its wild relative Setaria viridis (green millet), was grown in eight trials with varying environmental conditions to identify a small number of quantitative trait loci (QTL) that control differences in flowering time. Many of the QTL across trials colocalize, suggesting that the genetic control of flowering in Setaria is robust across a range of photoperiod and other environmental factors. A detailed comparison of QTL for flowering in Setaria, sorghum, and maize indicates that several of the major QTL regions identified in maize and sorghum are syntenic orthologs with Setaria QTL, although the maize large effect QTL on chromosome 10 is not. Several Setaria QTL intervals had multiple LOD peaks and were composed of multiple syntenic blocks, suggesting that observed QTL represent multiple tightly linked loci. Candidate genes from flowering time pathways identified in rice and Arabidopsis were identified in Setaria QTL intervals, including those involved in the CONSTANS photoperiod pathway. However, only three of the approximately seven genes cloned for flowering time in maize colocalized with Setaria QTL. This suggests that variation in flowering time in separate grass lineages is controlled by a combination of conserved and lineage specific genes. PMID:23390604

Molecular study on some antibiotic resistant genes in Salmonella spp. isolates

NASA Astrophysics Data System (ADS)

Nabi, Ari Q.

2017-09-01

Studying the genes related with antimicrobial resistance in Salmonella spp. is a crucial step toward a correct and faster treatment of infections caused by the pathogen. In this work Integron mediated antibiotic resistant gene IntI1 (Class I Integrase IntI1) and some plasmid mediated antibiotic resistance genes (Qnr) were scanned among the isolated non-Typhoid Salmonellae strains with known resistance to some important antimicrobial drugs using Sybr Green real time PCR. The aim of the study was to correlate the multiple antibiotics and antimicrobial resistance of Salmonella spp. with the presence of integrase (IntI1) gene and plasmid mediated quinolone resistant genes. Results revealed the presence of Class I Integrase gene in 76% of the isolates with confirmed multiple antibiotic resistances. Moreover, about 32% of the multiple antibiotic resistant serotypes showed a positive R-PCR for plasmid mediated qnrA gene encoding for nalidixic acid and ciprofloxacin resistance. No positive results could be revealed form R-PCRs targeting qnrB or qnrS. In light of these results we can conclude that the presence of at least one of the qnr genes and/or the presence of Integrase Class I gene were responsible for the multiple antibiotic resistance to for nalidixic acid and ciprofloxacin from the studied Salmonella spp. and further studies required to identify the genes related with multiple antibiotic resistance of the pathogen.

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

PubMed

Owen, Rhiannon K; Cooper, Nicola J; Quinn, Terence J; Lees, Rosalind; Sutton, Alex J

2018-07-01

Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whereas MMSE at threshold <25/30 appeared to have the best true negative rate. The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Health care administrators' perspectives on the role of absorptive capacity for strategic change initiatives: a qualitative study.

PubMed

Kash, Bita A; Spaulding, Aaron; Gamm, Larry; Johnson, Christopher E

2013-01-01

The dimensions of absorptive capacity (ACAP) are defined, and the importance of ACAP is established in the management literature, but the concept has not been applied to health care organizations attempting to implement multiple strategic initiatives. The aim of this study was to test the utility of ACAP by analyzing health care administrators' experiences with multiple strategic initiatives within two health systems. Results are drawn from administrators' assessments of multiple initiatives within two health systems using in-depth personal interviews with a total of 61 health care administrators. Data analysis was performed following deductive qualitative analysis guidelines. Interview transcripts were coded based on the four dimensions of ACAP: acquiring, assimilating, internalizing/transforming, and exploiting knowledge. Furthermore, we link results related to utilization of management resources, including number of key personnel involved and time consumption, to dimensions of ACAP. Participants' description of multiple strategic change initiatives confirmed the importance of the four ACAP dimensions. ACAP can be a useful framework to assess organizational capacity with respect to the organization's ability to concurrently implement multiple strategic initiatives. This capacity specifically revolves around human capital requirements from upper management based on the initiatives' location or stage within the ACAP framework. Strategic change initiatives in health care can be usefully viewed from an ACAP perspective. There is a tendency for those strategic initiatives ranking higher in priority and time consumption to reflect more advanced dimensions of ACAP (assimilate and transform), whereas few initiatives were identified in the ACAP "exploit" dimension. This may suggest that health care leaders tend to no longer identify as strategic initiatives those innovations that have moved to the exploitation stage or that less attention is given to the exploitation elements of a strategic initiative than to the earlier stages.

Toxicogenomic identification of biomarkers of acute respiratory exposure sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

Toxicogenomic identification of biomarkers of acute respiratory expsoure to sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

Why Study Music?

ERIC Educational Resources Information Center

Hodges, Donald A.

2005-01-01

Cognitive neuroscience is identifying neural networks in the brain that support multiple ways of knowing. This notion is also supported by evidence from psychology, anthropology, sociology, and other related disciplines. These human knowledge systems provide a means for sharing, expressing, understanding, knowing, and gaining insights into one's…

Emergency nursing management of the multiple trauma patient.

PubMed

Kosmos, C A

1989-01-01

This case study reinforces key principles in caring for multiply injured trauma victims. The Primary Survey is a tool developed to allow those caring for trauma patients to prioritize injuries. Those injuries identified in the Primary Survey will be the most life threatening.

Success factors for strategic change initiatives: a qualitative study of healthcare administrators' perspectives.

PubMed

Kash, Bita Arbab; Spaulding, Aaron; Johnson, Christopher E; Gamm, Larry

2014-01-01

Success factors related to the implementation of change initiatives are well documented and discussed in the management literature, but they are seldom studied in healthcare organizations engaged in multiple strategic change initiatives. The purpose of this study was to identify key success factors related to implementation of change initiatives based on rich qualitative data gathered from health leader interviews at two large health systems implementing multiple change initiatives. In-depth personal interviews with 61 healthcare leaders in the two large systems were conducted and inductive qualitative analysis was employed to identify success factors associated with 13 change initiatives. Results from this analysis were compared to success factors identified in the literature, and generalizations were drawn that add significantly to the management literature, especially to that in the healthcare sector. Ten specific success factors were identified for the implementation of change initiatives. The top three success factors were (1) culture and values, (2) business processes, and (3) people and engagement. Two of the identified success factors are unique to the healthcare sector and not found in the literature on change models: service quality and client satisfaction (ranked fourth of 10) and access to information (ranked ninth). Results demonstrate the importance of human resource functions, alignment of culture and values with change, and business processes that facilitate effective communication and access to information to achieve many change initiatives. The responses also suggest opportunities for leaders of healthcare organizations to more formally recognize the degree to which various change initiatives are dependent on one another.

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

ERIC Educational Resources Information Center

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

Adaptive human immunity drives remyelination in a mouse model of demyelination

PubMed Central

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand

2017-01-01

Abstract One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. PMID:28334918

Adaptive human immunity drives remyelination in a mouse model of demyelination.

PubMed

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Zujovic, Violetta

2017-04-01

One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

How the Adoption of the Big-Data Paradigm Affects the Key Factors That Influence the Effectiveness of an Information Assurance (IA) Framework: A Multiple-Case Study

ERIC Educational Resources Information Center

Apple, Benjamin G.

2017-01-01

This qualitative study identified those factors that influence the perceived effectiveness of traditional IA control frameworks. The key factors examined in this study are risk management, governance, access control, privacy protection, integrity, availability, reliability, and usability. The researcher endeavored to determine how the…

Developing an Exemplary Fine Arts Program: A Multiple Case-Study of Three Private Institutions of Higher Education

ERIC Educational Resources Information Center

Filippelli, James Anthony

2014-01-01

This study intended to identify commonalities of fine arts programs at selected private liberal arts colleges and universities in order to ultimately develop an exemplary fine arts program in a similar setting. This study searched for answers to three research questions within the context of art, music, dance, and theatre. The first research…

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

Capturing the experiences of patients across multiple complex interventions: a meta-qualitative approach

PubMed Central

Webster, Fiona; Christian, Jennifer; Mansfield, Elizabeth; Bhattacharyya, Onil; Hawker, Gillian; Levinson, Wendy; Naglie, Gary; Pham, Thuy-Nga; Rose, Louise; Schull, Michael; Sinha, Samir; Stergiopoulos, Vicky; Upshur, Ross; Wilson, Lynn

2015-01-01

Objectives The perspectives, needs and preferences of individuals with complex health and social needs can be overlooked in the design of healthcare interventions. This study was designed to provide new insights on patient perspectives drawing from the qualitative evaluation of 5 complex healthcare interventions. Setting Patients and their caregivers were recruited from 5 interventions based in primary, hospital and community care in Ontario, Canada. Participants We included 62 interviews from 44 patients and 18 non-clinical caregivers. Intervention Our team analysed the transcripts from 5 distinct projects. This approach to qualitative meta-evaluation identifies common issues described by a diverse group of patients, therefore providing potential insights into systems issues. Outcome measures This study is a secondary analysis of qualitative data; therefore, no outcome measures were identified. Results We identified 5 broad themes that capture the patients’ experience and highlight issues that might not be adequately addressed in complex interventions. In our study, we found that: (1) the emergency department is the unavoidable point of care; (2) patients and caregivers are part of complex and variable family systems; (3) non-medical issues mediate patients’ experiences of health and healthcare delivery; (4) the unanticipated consequences of complex healthcare interventions are often the most valuable; and (5) patient experiences are shaped by the healthcare discourses on medically complex patients. Conclusions Our findings suggest that key assumptions about patients that inform intervention design need to be made explicit in order to build capacity to better understand and support patients with multiple chronic diseases. Across many health systems internationally, multiple models are being implemented simultaneously that may have shared features and target similar patients, and a qualitative meta-evaluation approach, thus offers an opportunity for cumulative learning at a system level in addition to informing intervention design and modification. PMID:26351182

Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

PubMed

Lebelo, Ramokone L; Thys, Sofie; Benoy, Ina; Depuydt, Christophe E; Bogers, John-Paul; Bida, Meshack N; Mphahlele, M Jeffrey

2015-10-01

The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections. © 2015 Wiley Periodicals, Inc.

In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

PubMed

Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

2017-01-01

Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

The Multiple Correspondence Analysis Method and Brain Functional Connectivity: Its Application to the Study of the Non-linear Relationships of Motor Cortex and Basal Ganglia.

PubMed

Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Rodriguez, Manuel

2017-01-01

The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods. The multiple correspondence analysis (MCA), an unsupervised multivariable procedure which can identify non-linear interactions, was used to study the functional connectivity of BG when subjects were at rest. Linear methods showed different functional interactions expected according to current BG models. MCA showed additional functional interactions which were not evident when using lineal methods. Seven functional configurations of BG were identified with MCA, two involving the primary motor and somatosensory cortex, one involving the deepest BG (external-internal globus pallidum, subthalamic nucleus and substantia nigral), one with the input-output BG centers (putamen and motor thalamus), two linking the input-output centers with other BG (external pallidum and subthalamic nucleus), and one linking the external pallidum and the substantia nigral. The results provide evidence that the non-linear MCA and linear methods are complementary and should be best used in conjunction to more fully understand the nature of functional connectivity of brain centers.

Use of Multiple Imputation Method to Improve Estimation of Missing Baseline Serum Creatinine in Acute Kidney Injury Research

PubMed Central

Peterson, Josh F.; Eden, Svetlana K.; Moons, Karel G.; Ikizler, T. Alp; Matheny, Michael E.

2013-01-01

Summary Background and objectives Baseline creatinine (BCr) is frequently missing in AKI studies. Common surrogate estimates can misclassify AKI and adversely affect the study of related outcomes. This study examined whether multiple imputation improved accuracy of estimating missing BCr beyond current recommendations to apply assumed estimated GFR (eGFR) of 75 ml/min per 1.73 m2 (eGFR 75). Design, setting, participants, & measurements From 41,114 unique adult admissions (13,003 with and 28,111 without BCr data) at Vanderbilt University Hospital between 2006 and 2008, a propensity score model was developed to predict likelihood of missing BCr. Propensity scoring identified 6502 patients with highest likelihood of missing BCr among 13,003 patients with known BCr to simulate a “missing” data scenario while preserving actual reference BCr. Within this cohort (n=6502), the ability of various multiple-imputation approaches to estimate BCr and classify AKI were compared with that of eGFR 75. Results All multiple-imputation methods except the basic one more closely approximated actual BCr than did eGFR 75. Total AKI misclassification was lower with multiple imputation (full multiple imputation + serum creatinine) (9.0%) than with eGFR 75 (12.3%; P<0.001). Improvements in misclassification were greater in patients with impaired kidney function (full multiple imputation + serum creatinine) (15.3%) versus eGFR 75 (40.5%; P<0.001). Multiple imputation improved specificity and positive predictive value for detecting AKI at the expense of modestly decreasing sensitivity relative to eGFR 75. Conclusions Multiple imputation can improve accuracy in estimating missing BCr and reduce misclassification of AKI beyond currently proposed methods. PMID:23037980

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology: implications for microbicide development☆

PubMed Central

Mahan, Ellen D.; Morrow, Kathleen M.; Hayes, John E.

2015-01-01

Background Increasing prevalence of HIV infection among women worldwide has motivated the development of female-initiated prevention methods, including gel-based microbicides. User acceptability is vital for microbicide success; however, varying cultural vaginal practices indicate multiple formulations must be developed to appeal to different populations. Perceptual attributes of microbicides have been identified as primary drivers of acceptability; however, previous studies do not allow for direct comparison of these qualities between multiple formulations. Study Design Six vaginal products were analyzed ex vivo using descriptive analysis. Perceptual attributes of samples were identified by trained participants (n=10) and rated quantitatively using scales based on a panel-developed lexicon. Data were analyzed using two-way ANOVAs for each attribute; product differences were assessed via Tukey’s honestly significant difference test. Results Significant differences were found between products for multiple attributes. Patterns were also seen for attributes across intended product usage (i.e., contraceptive, moisturizer or lubricant). For example, Options© Gynol II® (Caldwell Consumer Health, LLC) was significantly stickier and grainier than other products. Conclusions Descriptive analysis, a quantitative approach that is based on consensus lexicon usage among participants, successfully quantified perceptual differences among vaginal products. Since perceptual attributes of products can be directly compared quantitatively, this study represents a novel approach that could be used to inform rational design of microbicides. PMID:21757061

Stress and Multiple Substance Use Behaviors Among Hispanic Adolescents.

PubMed

Cardoso, Jodi Berger; Goldbach, Jeremy T; Cervantes, Richard C; Swank, Paul

2016-02-01

Hispanic adolescents reported a higher annual prevalence of use of nearly all major drugs compared to non-Hispanic White and African American adolescents. Cultural or minority stressors, such as those related to the acculturation process, discrimination, immigration, poverty, and community violence, have been implicated in these outcomes. Unfortunately, few studies have examined how these stressors may have a differential or additive effect when considered simultaneously. The current study examined the relation between stress and multiple substance use behaviors in a sample of Hispanic adolescents (n = 1036), age 11-19 years old. Latent class analysis identified subgroups of Hispanic adolescents based on combinations of substance use behaviors. General linear models were used to examine mean differences by class among the eight domains of stress. Fit statistics revealed a six-class structure: no substance use risk, predominately alcohol use, low polysubstance use, high polysubstance use, illicit drug use, and predominately marijuana use. Differences in stress across the six classes were identified for four of the eight domains: family economic, acculturation gap, community and gang, and family and drug stress. The effect sizes revealed the largest mean differences in stress between the no substance use group and the two polysubstance use groups and between the no risk group and alcohol use group. The findings from this study support the use of interventions that target stress to affect multiple substance use behaviors in Hispanic adolescents.

Participant perceptions of a novel physiotherapy approach ("Blue Prescription") for increasing levels of physical activity in people with multiple sclerosis: a qualitative study following intervention.

PubMed

Smith, Catherine M; Hale, Leigh A; Mulligan, Hilda F; Treharne, Gareth J

2013-07-01

The aim of this study was to investigate experiences of participating in a feasibility trial of a novel physiotherapy intervention (Blue Prescription). The trial was designed to increase participation in physical activity for people with multiple sclerosis living in the community. We individually interviewed 27 volunteers from two New Zealand metropolitan areas at the conclusion of their participation in Blue Prescription. We asked volunteers about what participation in Blue Prescription had meant to them; how participants intended to continue with their physical activity; how the approach differed from previous experiences of physiotherapy encounters; and how Blue Prescription could be improved. Interviews were semi-structured, audio-recorded, transcribed verbatim, and analysed using a General Inductive Approach. 'Support' was identified as a key theme with three sub-themes: 'The therapeutic relationship'; 'The Blue Prescription approach'; and 'Supporting themselves'. We identified two additional themes 'Motivation to participate' and 'Improving the Blue Prescription approach'. A novel approach (Blue Prescription) which facilitates engagement in higher levels of desirable physical activity was perceived by participants to be supportive, motivating and enabling. This approach might be particularly useful for people with multiple sclerosis ready to adopt new health-related behaviours. For future studies, this approach requires further refinement, particularly with regards to methods of communication and evaluation.

Performance of stochastic approaches for forecasting river water quality.

PubMed

Ahmad, S; Khan, I H; Parida, B P

2001-12-01

This study analysed water quality data collected from the river Ganges in India from 1981 to 1990 for forecasting using stochastic models. Initially the box and whisker plots and Kendall's tau test were used to identify the trends during the study period. For detecting the possible intervention in the data the time series plots and cusum charts were used. The three approaches of stochastic modelling which account for the effect of seasonality in different ways. i.e. multiplicative autoregressive integrated moving average (ARIMA) model. deseasonalised model and Thomas-Fiering model were used to model the observed pattern in water quality. The multiplicative ARIMA model having both nonseasonal and seasonal components were, in general, identified as appropriate models. In the deseasonalised modelling approach, the lower order ARIMA models were found appropriate for the stochastic component. The set of Thomas-Fiering models were formed for each month for all water quality parameters. These models were then used to forecast the future values. The error estimates of forecasts from the three approaches were compared to identify the most suitable approach for the reliable forecast. The deseasonalised modelling approach was recommended for forecasting of water quality parameters of a river.

Simultaneous use of camera and probe diagnostics to unambiguously identify and study the dynamics of multiple underlying instabilities during the route to plasma turbulence.

PubMed

Thakur, S C; Brandt, C; Light, A; Cui, L; Gosselin, J J; Tynan, G R

2014-11-01

We use multiple-tip Langmuir probes and fast imaging to unambiguously identify and study the dynamics of underlying instabilities during the controlled route to fully-developed plasma turbulence in a linear magnetized helicon plasma device. Langmuir probes measure radial profiles of electron temperature, plasma density and potential; from which we compute linear growth rates of instabilities, cross-phase between density and potential fluctuations, Reynold's stress, particle flux, vorticity, time-delay estimated velocity, etc. Fast imaging complements the 1D probe measurements by providing temporally and spatially resolved 2D details of plasma structures associated with the instabilities. We find that three radially separated plasma instabilities exist simultaneously. Density gradient driven resistive drift waves propagating in the electron diamagnetic drift direction separate the plasma into an edge region dominated by strong, velocity shear driven Kelvin-Helmholtz instabilities and a central core region which shows coherent Rayleigh-Taylor modes propagating in the ion diamagnetic drift direction. The simultaneous, complementary use of both probes and camera was crucial to identify the instabilities and understand the details of the very rich plasma dynamics.

Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk

PubMed Central

Lee, Eunjung; Stram, Daniel O.; Ek, Weronica E.; Onstad, Lynn E; MacGregor, Stuart; Gharahkhani, Puya; Ye, Weimin; Lagergren, Jesper; Shaheen, Nicholas J.; Murray, Liam J.; Hardie, Laura J; Gammon, Marilie D.; Chow, Wong-Ho; Risch, Harvey A.; Corley, Douglas A.; Levine, David M; Whiteman, David C.; Bernstein, Leslie; Bird, Nigel C.; Vaughan, Thomas L.; Wu, Anna H.

2015-01-01

Background Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus (BE). Methods We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (SNPs) that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 BE) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. Results After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or BE. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. Conclusions Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or BE. Impact To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE. PMID:26364162

Memory training interventions for older adults: a meta-analysis.

PubMed

Gross, Alden L; Parisi, Jeanine M; Spira, Adam P; Kueider, Alexandra M; Ko, Jean Y; Saczynski, Jane S; Samus, Quincy M; Rebok, George W

2012-01-01

A systematic review and meta-analysis of memory training research was conducted to characterize the effect of memory strategies on memory performance among cognitively intact, community-dwelling older adults, and to identify characteristics of individuals and of programs associated with improved memory. The review identified 402 publications, of which 35 studies met criteria for inclusion. The overall effect size estimate, representing the mean standardized difference in pre-post change between memory-trained and control groups, was 0.31 standard deviations (SD; 95% confidence interval (CI): 0.22, 0.39). The pre-post training effect for memory-trained interventions was 0.43 SD (95% CI: 0.29, 0.57) and the practice effect for control groups was 0.06 SD (95% CI: 0.05, 0.16). Among 10 distinct memory strategies identified in studies, meta-analytic methods revealed that training multiple strategies was associated with larger training gains (p=0.04), although this association did not reach statistical significance after adjusting for multiple comparisons. Treatment gains among memory-trained individuals were not better after training in any particular strategy, or by the average age of participants, session length, or type of control condition. These findings can inform the design of future memory training programs for older adults.

A Unified Framework for Association Analysis with Multiple Related Phenotypes

PubMed Central

Stephens, Matthew

2013-01-01

We consider the problem of assessing associations between multiple related outcome variables, and a single explanatory variable of interest. This problem arises in many settings, including genetic association studies, where the explanatory variable is genotype at a genetic variant. We outline a framework for conducting this type of analysis, based on Bayesian model comparison and model averaging for multivariate regressions. This framework unifies several common approaches to this problem, and includes both standard univariate and standard multivariate association tests as special cases. The framework also unifies the problems of testing for associations and explaining associations – that is, identifying which outcome variables are associated with genotype. This provides an alternative to the usual, but conceptually unsatisfying, approach of resorting to univariate tests when explaining and interpreting significant multivariate findings. The method is computationally tractable genome-wide for modest numbers of phenotypes (e.g. 5–10), and can be applied to summary data, without access to raw genotype and phenotype data. We illustrate the methods on both simulated examples, and to a genome-wide association study of blood lipid traits where we identify 18 potential novel genetic associations that were not identified by univariate analyses of the same data. PMID:23861737

Classroom Interaction Studies as a Source for Teacher Competencies: The Use of Case Studies with Multiple Instruments for Studying Teacher Competencies in Multicultural Classes

ERIC Educational Resources Information Center

den Brok, Perry; van Eerde, Dolly; Hajer, Maaike

2010-01-01

Dealing with ethnic and linguistic diversity is one of the major challenges in today's education. Therefore, the formulation of competencies for teachers and teacher training should take into account the specific requirements of teaching in multicultural schools. In 2002, a series of small-scale studies were conducted to identify and formulate…

A Comparative, Holistic, Multiple-Case Study of the Implementation of the Strategic Thinking Protocol© and Traditional Strategic Planning Processes at a Southeastern University

ERIC Educational Resources Information Center

Robinson, Deborah J.

2012-01-01

This study explores the strategic thinking and strategic planning efforts in a department, college and university in the Southeastern United States. The goal of the study was to identify elements of strategic planning processes that meet the unique organizational features and complexities of a higher education institution. The study employed a…

Classification of Multiple Seizure-Like States in Three Different Rodent Models of Epileptogenesis.

PubMed

Guirgis, Mirna; Serletis, Demitre; Zhang, Jane; Florez, Carlos; Dian, Joshua A; Carlen, Peter L; Bardakjian, Berj L

2014-01-01

Epilepsy is a dynamical disease and its effects are evident in over fifty million people worldwide. This study focused on objective classification of the multiple states involved in the brain's epileptiform activity. Four datasets from three different rodent hippocampal preparations were explored, wherein seizure-like-events (SLE) were induced by the perfusion of a low - Mg(2+) /high-K(+) solution or 4-Aminopyridine. Local field potentials were recorded from CA3 pyramidal neurons and interneurons and modeled as Markov processes. Specifically, hidden Markov models (HMM) were used to determine the nature of the states present. Properties of the Hilbert transform were used to construct the feature spaces for HMM training. By sequentially applying the HMM training algorithm, multiple states were identified both in episodes of SLE and nonSLE activity. Specifically, preSLE and postSLE states were differentiated and multiple inner SLE states were identified. This was accomplished using features extracted from the lower frequencies (1-4 Hz, 4-8 Hz) alongside those of both the low- (40-100 Hz) and high-gamma (100-200 Hz) of the recorded electrical activity. The learning paradigm of this HMM-based system eliminates the inherent bias associated with other learning algorithms that depend on predetermined state segmentation and renders it an appropriate candidate for SLE classification.

Identified hadron production in pp collisions measured with ALICE.

NASA Astrophysics Data System (ADS)

Corrales Morales, Yasser; ALICE Collaboration

2017-07-01

The production of identified hadrons in proton-proton collisions is frequently studied as a reference for the investigation of the strongly-interacting medium created in heavy-ion collisions. In addition, at LHC energies measurements in pp and p-Pb collisions as a function of the event multiplicity have shown some features reminiscent of those related to collective effects in Pb-Pb collisions. Thanks to its excellent PID capabilities and p Τ coverage, the ALICE detector offers a unique opportunity for the measurement of p Τ spectra, integrated yields (dN/dy) and mean transverse momenta (

) of identified light-flavour hadrons at midrapidity over a wide p Τ range. In this contribution, results on π, K, p, {{{K}}}{{S}}0, Λ, Ξ, Ω and K*0 as a function of multiplicity in pp collisions at \\sqrt{s}=7 {TeV} are presented. The results are compared with those measured in p-Pb and Pb-Pb collisions. A similar evolution of the spectral shape, the p Τ-differential particle ratios and the integrated yield ratios with the charged particle multiplicity in both small and large systems is observed. The production rates of strange hadrons in pp collisions increase more than those of non-strange particles, showing an enhancement pattern with multiplicity which is remarkably similar to the one measured in p-Pb collisions. In addition, results on the production of light flavour hadrons in pp collisions at \\sqrt{s}=13 {TeV}, the highest centre-of-mass energy reached so far in the laboratory, are also presented and the behaviour observed as a function of \\sqrt{s} are discussed.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

PubMed

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

2009-08-15

In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

Adjusting data to body size: a comparison of methods as applied to quantitative trait loci analysis of musculoskeletal phenotypes.

PubMed

Lang, Dean H; Sharkey, Neil A; Lionikas, Arimantas; Mack, Holly A; Larsson, Lars; Vogler, George P; Vandenbergh, David J; Blizard, David A; Stout, Joseph T; Stitt, Joseph P; McClearn, Gerald E

2005-05-01

The aim of this study was to compare three methods of adjusting skeletal data for body size and examine their use in QTL analyses. It was found that dividing skeletal phenotypes by body mass index induced erroneous QTL results. The preferred method of body size adjustment was multiple regression. Many skeletal studies have reported strong correlations between phenotypes for muscle, bone, and body size, and these correlations add to the difficulty in identifying genetic influence on skeletal traits that are not mediated through overall body size. Quantitative trait loci (QTL) identified for skeletal phenotypes often map to the same chromosome regions as QTLs for body size. The actions of a QTL identified as influencing BMD could therefore be mediated through the generalized actions of growth on body size or muscle mass. Three methods of adjusting skeletal phenotypes to body size were performed on morphologic, structural, and compositional measurements of the femur and tibia in 200-day-old C57BL/6J x DBA/2 (BXD) second generation (F(2)) mice (n = 400). A common method of removing the size effect has been through the use of ratios. This technique and two alternative techniques using simple and multiple regression were performed on muscle and skeletal data before QTL analyses, and the differences in QTL results were examined. The use of ratios to remove the size effect was shown to increase the size effect by inducing spurious correlations, thereby leading to inaccurate QTL results. Adjustments for body size using multiple regression eliminated these problems. Multiple regression should be used to remove the variance of co-factors related to skeletal phenotypes to allow for the study of genetic influence independent of correlated phenotypes. However, to better understand the genetic influence, adjusted and unadjusted skeletal QTL results should be compared. Additional insight can be gained by observing the difference in LOD score between the adjusted and nonadjusted phenotypes. Identifying QTLs that exert their effects on skeletal phenotypes through body size-related pathways as well as those having a more direct and independent influence on bone are equally important in deciphering the complex physiologic pathways responsible for the maintenance of bone health.

Mark-recapture with multiple, non-invasive marks.

PubMed

Bonner, Simon J; Holmberg, Jason

2013-09-01

Non-invasive marks, including pigmentation patterns, acquired scars, and genetic markers, are often used to identify individuals in mark-recapture experiments. If animals in a population can be identified from multiple, non-invasive marks then some individuals may be counted twice in the observed data. Analyzing the observed histories without accounting for these errors will provide incorrect inference about the population dynamics. Previous approaches to this problem include modeling data from only one mark and combining estimators obtained from each mark separately assuming that they are independent. Motivated by the analysis of data from the ECOCEAN online whale shark (Rhincodon typus) catalog, we describe a Bayesian method to analyze data from multiple, non-invasive marks that is based on the latent-multinomial model of Link et al. (2010, Biometrics 66, 178-185). Further to this, we describe a simplification of the Markov chain Monte Carlo algorithm of Link et al. (2010, Biometrics 66, 178-185) that leads to more efficient computation. We present results from the analysis of the ECOCEAN whale shark data and from simulation studies comparing our method with the previous approaches. © 2013, The International Biometric Society.

Study of the production of charged pions, kaons, and protons in pPb collisions at $$\\sqrt{s_{NN}} =\\; $$ s N N = 5.02 $$\\,\\text {TeV}$$ TeV

DOE PAGES

Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; ...

2014-06-01

Spectra of identified charged hadrons are measured in pPb collisions with the CMS detector at the LHC at sqrt(sNN) = 5.02 TeV. Charged pions, kaons, and protons in the transverse-momentum range pt approximately 0.1-1.7 GeV and laboratory rapidity abs(y) < 1 are identified via their energy loss in the silicon tracker. The average pt increases with particle mass and the charged multiplicity of the event. The increase of the average pt with charged multiplicity is greater for heavier hadrons. Comparisons to Monte Carlo event generators reveal that EPOS LHC, which incorporates additional hydrodynamic evolution of the created system, is ablemore » to reproduce most of the data features, unlike HIJING and AMPT. The pt spectra and integrated yields are also compared to those measured in pp and PbPb collisions at various energies. The average transverse momentum and particle ratio measurements indicate that particle production at LHC energies is strongly correlated with event particle multiplicity.« less

Study of the production of charged pions, kaons, and protons in pPb collisions at [Formula: see text]5.02[Formula: see text].

PubMed

Chatrchyan, S; Khachatryan, V; Sirunyan, A M; Tumasyan, A; Adam, W; Bergauer, T; Dragicevic, M; Erö, J; Fabjan, C; Friedl, M; Frühwirth, R; Ghete, V M; Hörmann, N; Hrubec, J; Jeitler, M; Kiesenhofer, W; Knünz, V; Krammer, M; Krätschmer, I; Liko, D; Mikulec, I; Rabady, D; Rahbaran, B; Rohringer, C; Rohringer, H; Schöfbeck, R; Strauss, J; Taurok, A; Treberer-Treberspurg, W; Waltenberger, W; Wulz, C-E; Mossolov, V; Shumeiko, N; Suarez Gonzalez, J; Alderweireldt, S; Bansal, M; Bansal, S; Cornelis, T; De Wolf, E A; Janssen, X; Knutsson, A; Luyckx, S; Mucibello, L; Ochesanu, S; Roland, B; Rougny, R; Staykova, Z; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Blekman, F; Blyweert, S; D'Hondt, J; Kalogeropoulos, A; Keaveney, J; Maes, M; Olbrechts, A; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Onsem, G P; Villella, I; Caillol, C; Clerbaux, B; De Lentdecker, G; Favart, L; Gay, A P R; Hreus, T; Léonard, A; Marage, P E; Mohammadi, A; Perniè, L; Reis, T; Seva, T; Thomas, L; Van der Velde, C; Vanlaer, P; Wang, J; Adler, V; Beernaert, K; Benucci, L; Cimmino, A; Costantini, S; Dildick, S; Garcia, G; Klein, B; Lellouch, J; Marinov, A; Mccartin, J; Rios, A A Ocampo; Ryckbosch, D; Sigamani, M; Strobbe, N; Thyssen, F; Tytgat, M; Walsh, S; Yazgan, E; Zaganidis, N; Basegmez, S; Beluffi, C; Bruno, G; Castello, R; Caudron, A; Ceard, L; Delaere, C; du Pree, T; Favart, D; Forthomme, L; Giammanco, A; Hollar, J; Jez, P; Lemaitre, V; Liao, J; Militaru, O; Nuttens, C; Pagano, D; Pin, A; Piotrzkowski, K; Popov, A; Selvaggi, M; Garcia, J M Vizan; Beliy, N; Caebergs, T; Daubie, E; Hammad, G H; Alves, G A; Martins Junior, M Correa; Martins, T; Pol, M E; Souza, M H G; Aldá Júnior, W L; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; De Jesus Damiao, D; De Oliveira Martins, C; De Souza, S Fonseca; Malbouisson, H; Malek, M; Figueiredo, D Matos; Mundim, L; Nogima, H; Da Silva, W L Prado; Santoro, A; Sznajder, A; Manganote, E J Tonelli; Pereira, A Vilela; Dias, F A; Tomei, T R Fernandez Perez; Lagana, C; Novaes, S F; Padula, Sandra S; Bernardes, C A; Gregores, E M; Mercadante, P G; Genchev, V; Iaydjiev, P; Piperov, S; Rodozov, M; Sultanov, G; Vutova, M; Dimitrov, A; Hadjiiska, R; Kozhuharov, V; Litov, L; Pavlov, B; Petkov, P; Bian, J G; Chen, G M; Chen, H S; Jiang, C H; Liang, D; Liang, S; Meng, X; Tao, J; Wang, X; Wang, Z; Xiao, H; Xu, M; Asawatangtrakuldee, C; Ban, Y; Guo, Y; Li, W; Liu, S; Mao, Y; Qian, S J; Teng, H; Wang, D; Zhang, L; Zou, W; Avila, C; Montoya, C A Carrillo; Sierra, L F Chaparro; Gomez, J P; Moreno, B Gomez; Sanabria, J C; Godinovic, N; Lelas, D; Plestina, R; Polic, D; Puljak, I; Antunovic, Z; Kovac, M; Brigljevic, V; Duric, S; Kadija, K; Luetic, J; Mekterovic, D; Morovic, S; Tikvica, L; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Finger, M; Finger, M; Abdelalim, A A; Assran, Y; Elgammal, S; Ellithi Kamel, A; Mahmoud, M A; Radi, A; Kadastik, M; Müntel, M; Murumaa, M; Raidal, M; Rebane, L; Tiko, A; Eerola, P; Fedi, G; Voutilainen, M; Härkönen, J; Karimäki, V; Kinnunen, R; Kortelainen, M J; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Mäenpää, T; Peltola, T; Tuominen, E; Tuominiemi, J; Tuovinen, E; Wendland, L; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Fabbro, B; Faure, J L; Ferri, F; Ganjour, S; Givernaud, A; Gras, P; de Monchenault, G Hamel; Jarry, P; Locci, E; Malcles, J; Millischer, L; Nayak, A; Rander, J; Rosowsky, A; Titov, M; Baffioni, S; Beaudette, F; Benhabib, L; Bluj, M; Busson, P; Charlot, C; Daci, N; Dahms, T; Dalchenko, M; Dobrzynski, L; Florent, A; de Cassagnac, R Granier; Haguenauer, M; Miné, P; Mironov, C; Naranjo, I N; Nguyen, M; Ochando, C; Paganini, P; Sabes, D; Salerno, R; Sirois, Y; Veelken, C; Zabi, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Chabert, E C; Collard, C; Conte, E; Drouhin, F; Fontaine, J-C; Gelé, D; Goerlach, U; Goetzmann, C; Juillot, P; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Beaupere, N; Boudoul, G; Brochet, S; Chasserat, J; Chierici, R; Contardo, D; Depasse, P; El Mamouni, H; Fay, J; Gascon, S; Gouzevitch, M; Ille, B; Kurca, T; Lethuillier, M; Mirabito, L; Perries, S; Sgandurra, L; Sordini, V; Vander Donckt, M; Verdier, P; Viret, S; Tsamalaidze, Z; Autermann, C; Beranek, S; Calpas, B; Edelhoff, M; Feld, L; Heracleous, N; Hindrichs, O; Klein, K; Ostapchuk, A; Perieanu, A; Raupach, F; Sammet, J; Schael, S; Sprenger, D; Weber, H; Wittmer, B; Zhukov, V; Ata, M; Caudron, J; Dietz-Laursonn, E; Duchardt, D; Erdmann, M; Fischer, R; Güth, A; Hebbeker, T; Heidemann, C; Hoepfner, K; Klingebiel, D; Kreuzer, P; Merschmeyer, M; Meyer, A; Olschewski, M; Padeken, K; Papacz, P; Pieta, H; Reithler, H; Schmitz, S A; Sonnenschein, L; Steggemann, J; Teyssier, D; Thüer, S; Weber, M; Cherepanov, V; Erdogan, Y; Flügge, G; Geenen, H; Geisler, M; Haj Ahmad, W; Hoehle, F; Kargoll, B; Kress, T; Kuessel, Y; Lingemann, J; Nowack, A; Nugent, I M; Perchalla, L; Pooth, O; Stahl, A; Aldaya Martin, M; Asin, I; Bartosik, N; Behr, J; Behrenhoff, W; Behrens, U; Bergholz, M; Bethani, A; Borras, K; Burgmeier, A; Cakir, A; Calligaris, L; Campbell, A; Choudhury, S; Costanza, F; Diez Pardos, C; Dooling, S; Dorland, T; Eckerlin, G; Eckstein, D; Flucke, G; Geiser, A; Glushkov, I; Gunnellini, P; Habib, S; Hauk, J; Hellwig, G; Horton, D; Jung, H; Kasemann, M; Katsas, P; Kleinwort, C; Kluge, H; Krämer, M; Krücker, D; Kuznetsova, E; Lange, W; Leonard, J; Lipka, K; Lohmann, W; Lutz, B; Mankel, R; Marfin, I; Melzer-Pellmann, I-A; Meyer, A B; Mnich, J; Mussgiller, A; Naumann-Emme, S; Novgorodova, O; Nowak, F; Olzem, J; Perrey, H; Petrukhin, A; Pitzl, D; Placakyte, R; Raspereza, A; Cipriano, P M Ribeiro; Riedl, C; Ron, E; Sahin, M Ö; Salfeld-Nebgen, J; Schmidt, R; Schoerner-Sadenius, T; Sen, N; Stein, M; Walsh, R; Wissing, C; Blobel, V; Enderle, H; Erfle, J; Garutti, E; Gebbert, U; Görner, M; Gosselink, M; Haller, J; Heine, K; Höing, R S; Kaussen, G; Kirschenmann, H; Klanner, R; Kogler, R; Lange, J; Marchesini, I; Peiffer, T; Pietsch, N; Rathjens, D; Sander, C; Schettler, H; Schleper, P; Schlieckau, E; Schmidt, A; Schröder, M; Schum, T; Seidel, M; Sibille, J; Sola, V; Stadie, H; Steinbrück, G; Thomsen, J; Troendle, D; Usai, E; Vanelderen, L; Barth, C; Baus, C; Berger, J; Böser, C; Butz, E; Chwalek, T; De Boer, W; Descroix, A; Dierlamm, A; Feindt, M; Guthoff, M; Hartmann, F; Hauth, T; Held, H; Hoffmann, K H; Husemann, U; Katkov, I; Komaragiri, J R; Kornmayer, A; Lobelle Pardo, P; Martschei, D; Müller, Th; Niegel, M; Nürnberg, A; Oberst, O; Ott, J; Quast, G; Rabbertz, K; Ratnikov, F; Röcker, S; Schilling, F-P; Schott, G; Simonis, H J; Stober, F M; Ulrich, R; Wagner-Kuhr, J; Wayand, S; Weiler, T; Zeise, M; Anagnostou, G; Daskalakis, G; Geralis, T; Kesisoglou, S; Kyriakis, A; Loukas, D; Markou, A; Markou, C; Ntomari, E; Gouskos, L; Panagiotou, A; Saoulidou, N; Stiliaris, E; Aslanoglou, X; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Paradas, E; Bencze, G; Hajdu, C; Hidas, P; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Molnar, J; Palinkas, J; Szillasi, Z; Karancsi, J; Raics, P; Trocsanyi, Z L; Ujvari, B; Swain, S K; Beri, S B; Bhatnagar, V; Dhingra, N; Gupta, R; Kaur, M; Mehta, M Z; Mittal, M; Nishu, N; Saini, L K; Sharma, A; Singh, J B; Kumar, Ashok; Kumar, Arun; Ahuja, S; Bhardwaj, A; Choudhary, B C; Malhotra, S; Naimuddin, M; Ranjan, K; Saxena, P; Sharma, V; Shivpuri, R K; Banerjee, S; Bhattacharya, S; Chatterjee, K; Dutta, S; Gomber, B; Jain, Sa; Jain, Sh; Khurana, R; Modak, A; Mukherjee, S; Roy, D; Sarkar, S; Sharan, M; Abdulsalam, A; Dutta, D; Kailas, S; Kumar, V; Mohanty, A K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Chatterjee, R M; Ganguly, S; Ghosh, S; Guchait, M; Gurtu, A; Kole, G; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Mohanty, G B; Parida, B; Sudhakar, K; Wickramage, N; Dugad, S; Arfaei, H; Bakhshiansohi, H; Etesami, S M; Fahim, A; Jafari, A; Khakzad, M; Najafabadi, M Mohammadi; Mehdiabadi, S Paktinat; Safarzadeh, B; Zeinali, M; Grunewald, M; Abbrescia, M; Barbone, L; Calabria, C; Chhibra, S S; Colaleo, A; Creanza, D; De Filippis, N; De Palma, M; Fiore, L; Iaselli, G; Maggi, G; Maggi, M; Marangelli, B; My, S; Nuzzo, S; Pacifico, N; Pompili, A; Pugliese, G; Selvaggi, G; Silvestris, L; Singh, G; Venditti, R; Verwilligen, P; Zito, G; Abbiendi, G; Benvenuti, A C; Bonacorsi, D; Braibant-Giacomelli, S; Brigliadori, L; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Codispoti, G; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Grandi, C; Guiducci, L; Marcellini, S; Masetti, G; Meneghelli, M; Montanari, A; Navarria, F L; Odorici, F; Perrotta, A; Primavera, F; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Travaglini, R; Albergo, S; Chiorboli, M; Costa, S; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Frosali, S; Gallo, E; Gonzi, S; Gori, V; Lenzi, P; Meschini, M; Paoletti, S; Sguazzoni, G; Tropiano, A; Benussi, L; Bianco, S; Piccolo, D; Fabbricatore, P; 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Bose, S; Claes, D R; Dominguez, A; Eads, M; Suarez, R Gonzalez; Keller, J; Kravchenko, I; Lazo-Flores, J; Malik, S; Meier, F; Snow, G R; Dolen, J; Godshalk, A; Iashvili, I; Jain, S; Kharchilava, A; Kumar, A; Rappoccio, S; Wan, Z; Alverson, G; Barberis, E; Baumgartel, D; Chasco, M; Haley, J; Massironi, A; Nash, D; Orimoto, T; Trocino, D; Wood, D; Zhang, J; Anastassov, A; Hahn, K A; Kubik, A; Lusito, L; Mucia, N; Odell, N; Pollack, B; Pozdnyakov, A; Schmitt, M; Stoynev, S; Sung, K; Velasco, M; Won, S; Berry, D; Brinkerhoff, A; Chan, K M; Hildreth, M; Jessop, C; Karmgard, D J; Kolb, J; Lannon, K; Luo, W; Lynch, S; Marinelli, N; Morse, D M; Pearson, T; Planer, M; Ruchti, R; Slaunwhite, J; Valls, N; Wayne, M; Wolf, M; Antonelli, L; Bylsma, B; Durkin, L S; Hill, C; Hughes, R; Kotov, K; Ling, T Y; Puigh, D; Rodenburg, M; Smith, G; Vuosalo, C; Winer, B L; Wolfe, H; Berry, E; Elmer, P; Halyo, V; Hebda, P; Hegeman, J; Hunt, A; Jindal, P; Koay, S A; Lujan, P; Marlow, D; Medvedeva, T; Mooney, M; Olsen, J; Piroué, P; Quan, X; Raval, A; Saka, H; Stickland, D; Tully, C; Werner, J S; Zenz, S C; Zuranski, A; Brownson, E; Lopez, A; Mendez, H; Ramirez Vargas, J E; Alagoz, E; Benedetti, D; Bolla, G; Bortoletto, D; De Mattia, M; Everett, A; Hu, Z; Jones, M; Jung, K; Koybasi, O; Kress, M; Leonardo, N; Lopes Pegna, D; Maroussov, V; Merkel, P; Miller, D H; Neumeister, N; Shipsey, I; Silvers, D; Svyatkovskiy, A; Vidal Marono, M; Wang, F; Xie, W; Xu, L; Yoo, H D; Zablocki, J; Zheng, Y; Guragain, S; Parashar, N; Adair, A; Akgun, B; Ecklund, K M; Geurts, F J M; Padley, B P; Redjimi, R; Roberts, J; Zabel, J; Betchart, B; Bodek, A; Covarelli, R; de Barbaro, P; Demina, R; Eshaq, Y; Ferbel, T; Garcia-Bellido, A; Goldenzweig, P; Han, J; Harel, A; Miner, D C; Petrillo, G; Vishnevskiy, D; Zielinski, M; Bhatti, A; Ciesielski, R; Demortier, L; Goulianos, K; Lungu, G; Malik, S; Mesropian, C; Arora, S; Barker, A; Chou, J P; Contreras-Campana, C; Contreras-Campana, E; Duggan, D; Ferencek, D; Gershtein, Y; Gray, R; Halkiadakis, E; Hidas, D; Lath, A; Panwalkar, S; Park, M; Patel, R; Rekovic, V; Robles, J; Salur, S; Schnetzer, S; Seitz, C; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Cerizza, G; Hollingsworth, M; Rose, K; Spanier, S; Yang, Z C; York, A; Bouhali, O; Eusebi, R; Flanagan, W; Gilmore, J; Kamon, T; Khotilovich, V; Montalvo, R; Osipenkov, I; Pakhotin, Y; Perloff, A; Roe, J; Safonov, A; Sakuma, T; Suarez, I; Tatarinov, A; Toback, D; Akchurin, N; Cowden, C; Damgov, J; Dragoiu, C; Dudero, P R; Jeong, C; Kovitanggoon, K; Lee, S W; Libeiro, T; Volobouev, I; Appelt, E; Delannoy, A G; Greene, S; Gurrola, A; Johns, W; Maguire, C; Melo, A; Sharma, M; Sheldon, P; Snook, B; Tuo, S; Velkovska, J; Arenton, M W; Boutle, S; Cox, B; Francis, B; Goodell, J; Hirosky, R; Ledovskoy, A; Lin, C; Neu, C; Wood, J; Gollapinni, S; Harr, R; Karchin, P E; Don, C Kottachchi Kankanamge; Lamichhane, P; Sakharov, A; Belknap, D A; Borrello, L; Carlsmith, D; Cepeda, M; Dasu, S; Friis, E; Grothe, M; Hall-Wilton, R; Herndon, M; Hervé, A; Klabbers, P; Klukas, J; Lanaro, A; Loveless, R; Mohapatra, A; Mozer, M U; Ojalvo, I; Pierro, G A; Polese, G; Ross, I; Savin, A; Smith, W H; Swanson, J

Spectra of identified charged hadrons are measured in pPb collisions with the CMS detector at the LHC at [Formula: see text]. Charged pions, kaons, and protons in the transverse-momentum range [Formula: see text]-1.7[Formula: see text] and laboratory rapidity [Formula: see text] are identified via their energy loss in the silicon tracker. The average [Formula: see text] increases with particle mass and the charged multiplicity of the event. The increase of the average [Formula: see text] with charged multiplicity is greater for heavier hadrons. Comparisons to Monte Carlo event generators reveal that Epos Lhc, which incorporates additional hydrodynamic evolution of the created system, is able to reproduce most of the data features, unlike Hijing and Ampt. The [Formula: see text] spectra and integrated yields are also compared to those measured in pp and PbPb collisions at various energies. The average transverse momentum and particle ratio measurements indicate that particle production at LHC energies is strongly correlated with event particle multiplicity.

Mining Missing Membrane Proteins by High-pH Reverse-Phase StageTip Fractionation and Multiple Reaction Monitoring Mass Spectrometry.

PubMed

Kitata, Reta Birhanu; Dimayacyac-Esleta, Baby Rorielyn T; Choong, Wai-Kok; Tsai, Chia-Feng; Lin, Tai-Du; Tsou, Chih-Chiang; Weng, Shao-Hsing; Chen, Yi-Ju; Yang, Pan-Chyr; Arco, Susan D; Nesvizhskii, Alexey I; Sung, Ting-Yi; Chen, Yu-Ju

2015-09-04

Despite significant efforts in the past decade toward complete mapping of the human proteome, 3564 proteins (neXtProt, 09-2014) are still "missing proteins". Over one-third of these missing proteins are annotated as membrane proteins, owing to their relatively challenging accessibility with standard shotgun proteomics. Using nonsmall cell lung cancer (NSCLC) as a model study, we aim to mine missing proteins from disease-associated membrane proteome, which may be still largely under-represented. To increase identification coverage, we employed Hp-RP StageTip prefractionation of membrane-enriched samples from 11 NSCLC cell lines. Analysis of membrane samples from 20 pairs of tumor and adjacent normal lung tissue was incorporated to include physiologically expressed membrane proteins. Using multiple search engines (X!Tandem, Comet, and Mascot) and stringent evaluation of FDR (MAYU and PeptideShaker), we identified 7702 proteins (66% membrane proteins) and 178 missing proteins (74 membrane proteins) with PSM-, peptide-, and protein-level FDR of 1%. Through multiple reaction monitoring using synthetic peptides, we provided additional evidence of eight missing proteins including seven with transmembrane helix domains. This study demonstrates that mining missing proteins focused on cancer membrane subproteome can greatly contribute to map the whole human proteome. All data were deposited into ProteomeXchange with the identifier PXD002224.

Multiple sclerosis and employment: Associations of psychological factors and work instability.

PubMed

Wicks, Charlotte Rose; Ward, Karl; Stroud, Amanda; Tennant, Alan; Ford, Helen L

2016-10-12

People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. To investigate the associations between psychological factors and work instability in people with multiple sclerosis. A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (χ2 p < 0.001). Those with probable depression at baseline had 7.1 times increased odds of medium/high work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term.

Quantification of Circulating Clonal Plasma Cells via Multiparametric Flow Cytometry Identifies Patients with Smoldering Multiple Myeloma at High Risk of Progression

PubMed Central

Gonsalves, Wilson I.; Rajkumar, S. Vincent; Dispenzieri, Angela; Dingli, David; Timm, Michael M.; Morice, William G.; Lacy, Martha Q.; Buadi, Francis K.; Go, Ronald S.; Leung, Nelson; Kapoor, Prashant; Hayman, Suzanne R.; Lust, John A.; Russell, Stephen J.; Zeldenrust, Steven R.; Hwa, Lisa; Kourelis, Taxiarchis V.; Kyle, Robert A.; Gertz, Morie A.; Kumar, Shaji K.

2017-01-01

The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to multiple myeloma (MM). The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ≥ 150 cPCs (N = 9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ≥ 150 cPCs was 9 months compared to not reached for patients with < 150 cPCs (P < 0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage. PMID:27457702

Genome-wide association studies for multiple diseases of the German Shepherd Dog

PubMed Central

Tsai, Kate L.; Noorai, Rooksana E.; Starr-Moss, Alison N.; Quignon, Pascale; Rinz, Caitlin J.; Ostrander, Elaine A.; Steiner, Jörg M.; Murphy, Keith E.

2012-01-01

The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder. PMID:22105877

Physical activity and exercise training in multiple sclerosis: a review and content analysis of qualitative research identifying perceived determinants and consequences.

PubMed

Learmonth, Yvonne C; Motl, Robert W

2016-01-01

This systematic review was conducted to provide rich and deep evidence of the perceived determinants and consequences of physical activity and exercise based on qualitative research in multiple sclerosis (MS). Electronic databases and article reference lists were searched to identify qualitative studies of physical activity and exercise in MS. Studies were included if they were written in English and examined consequences/determinants of physical activity in persons with MS. Content analysis of perceived determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities framework and Social Cognitive Theory, respectively. Nineteen articles were reviewed. The most commonly identified perceived barriers of physical activity and exercise were related to the environmental (i.e. minimal or no disabled facilities, and minimal or conflicting advice from healthcare professionals) and related to personal barriers (i.e. fatigue, and fear and apprehension). The most commonly identified perceived facilitators of physical activity were related to the environment (i.e. the type of exercise modality and peer support) and related to personal facilitators (i.e. appropriate exercise and feelings of accomplishment). The most commonly identified perceived beneficial consequences of physical activity and exercise were maintaining physical functions, increased social participation and feelings of self-management and control. The most commonly identified perceived adverse consequences were increased fatigue and feelings of frustration and lost control. Results will inform future research on the perceived determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing professional education and interventions for physical activity and exercise in MS. Physical activity and exercise behaviour in people with multiple sclerosis (MS) is subject to a number of modifiable determinants. Healthcare professionals working to promote physical activity and exercise in those with MS should choose to endorse the positive benefits of participation. Future physical activity interventions for those with MS may be improved by incorporating behavioural management strategies.

Application of the key characteristics of carcinogens in cancer hazard identification

PubMed Central

Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

2018-01-01

Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322

Application of the key characteristics of carcinogens in cancer hazard identification.

PubMed

Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

2018-04-05

Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as 'is genotoxic,' 'is immunosuppressive' or 'modulates receptor-mediated effects,' and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.

Older Persons’ Transitions in Care (OPTIC): a study protocol

PubMed Central

2012-01-01

Background Changes in health status, triggered by events such as infections, falls, and geriatric syndromes, are common among nursing home (NH) residents and necessitate transitions between NHs and Emergency Departments (EDs). During transitions, residents frequently experience care that is delayed, unnecessary, not evidence-based, potentially unsafe, and fragmented. Furthermore, a high proportion of residents and their family caregivers report substantial unmet needs during transitions. This study is part of a program of research whose overall aim is to improve quality of care for frail older adults who reside in NHs. The purpose of this study is to identify successful transitions from multiple perspectives and to identify organizational and individual factors related to transition success, in order to inform improvements in care for frail elderly NH residents during transitions to and from acute care. Specific objectives are to: 1. define successful and unsuccessful elements of transitions from multiple perspectives; 2. develop and test a practical tool to assess transition success; 3. assess transition processes in a discrete set of transfers in two study sites over a one year period; 4. assess the influence of organizational factors in key practice locations, e.g., NHs, emergency medical services (EMS), and EDs, on transition success; and 5. identify opportunities for evidence-informed management and quality improvement decisions related to the management of NH – ED transitions. Methods/Design This is a mixed-methods observational study incorporating an integrated knowledge translation (IKT) approach. It uses data from multiple levels (facility, care unit, individual) and sources (healthcare providers, residents, health records, and administrative databases). Discussion Key to study success is operationalizing the IKT approach by using a partnership model in which the OPTIC governance structure provides for team decision-makers and researchers to participate equally in developing study goals, design, data collection, analysis and implications of findings. As preliminary and ongoing study findings are developed, their implications for practice and policy in study settings will be discussed by the research team and shared with study site administrators and staff. The study is designed to investigate the complexities of transitions and to enhance the potential for successful and sustained improvement of these transitions. PMID:23241360

Common Student Misconceptions in Exercise Physiology and Biochemistry

ERIC Educational Resources Information Center

Morton, James P.; Doran, Dominic A.; MacLaren, Don P. M.

2008-01-01

The present study represents a preliminary investigation designed to identify common misconceptions in students' understanding of physiological and biochemical topics within the academic domain of sport and exercise sciences. A specifically designed misconception inventory (consisting of 10 multiple-choice questions) was administered to a cohort…

Healthcare Information Technology Backsourcing, Problematic Outsourcing Manipulations, and Multisupplier Backsourcing Methodologies

ERIC Educational Resources Information Center

Garske, Steven Ray

2010-01-01

Backsourcing is the act of an organization changing an outsourcing relationship through insourcing, vendor change, or elimination of the outsourced service. This study discovered numerous problematic outsourcing manipulations conducted by suppliers, and identified backsourcing methodologies to correct these manipulations across multiple supplier…

Broad-scale patterns of invertebrate richness and community composition in temporary rivers: effects of flow intermittence

EPA Science Inventory

A central goal in ecology is to identify general relationships between environmental drivers and community patterns. In this study, we investigated the relationships between aquatic invertebrate communities and river flow intermittence across multiple continents. Particularly, we...

Measurement and Modeling of Near Road & Near-Port Air Quality

EPA Science Inventory

Air pollution from mobile sources has been identified by numerous organizations as a potential public health concern. Based upon multiple near-road and near-source monitoring studies, both busy roadways and large emission sources at ports can significantly impact local air qualit...

Self-Directed Teacher Learning in Collaborative Contexts

ERIC Educational Resources Information Center

Slavit, David; Roth McDuffie, Amy

2013-01-01

Two related case studies of secondary mathematics teachers examine the roles and conditions helpful in initiating, directing, and/or supporting teachers' own professional development. Using multiple data sources from school-based and professional settings, we applied analytic induction to identify patterns of similarities and differences in…

A Review of Empirical Analyses of Disinvestment Initiatives.

PubMed

Chambers, James D; Salem, Mark N; D'Cruz, Brittany N; Subedi, Prasun; Kamal-Bahl, Sachin J; Neumann, Peter J

Disinvesting in low-value health care services provides opportunities for investment in higher value care and thus an increase in health care efficiency. To identify international experience with disinvestment initiatives and to review empirical analyses of disinvestment initiatives. We performed a literature search using the PubMed database to identify international experience with disinvestment initiatives. We also reviewed empirical analyses of disinvestment initiatives. We identified 26 unique disinvestment initiatives implemented across 11 countries. Nineteen addressed multiple intervention types, six addressed only drugs, and one addressed only devices. We reviewed 18 empirical analyses of disinvestment initiatives: 7 reported that the initiative was successful, 8 reported that the initiative was unsuccessful, and 3 reported that findings were mixed; that is, the study considered multiple services and reported a decrease in the use of some but not others. Thirty-seven low-value services were evaluated across the 18 empirical analyses, for 14 (38%) of which the disinvestment initiative led to a decline in use. Six of the seven studies that reported the disinvestment initiative to be successful included an attempt to promote the disinvestment initiative among participating clinicians. The success of disinvestment initiatives has been mixed, with fewer than half the identified empirical studies reporting that use of the low-value service was reduced. Our findings suggest that promotion of the disinvestment initiative among clinicians is a key component to the success of the disinvestment initiative. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

PubMed

Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

2017-10-17

Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

Utilization of the Seniors Falls Investigation Methodology to identify system-wide causes of falls in community-dwelling seniors.

PubMed

Zecevic, Aleksandra A; Salmoni, Alan W; Lewko, John H; Vandervoort, Anthoney A; Speechley, Mark

2009-10-01

As a highly heterogeneous group, seniors live in complex environments influenced by multiple physical and social structures that affect their safety. Until now, the major approach to falls research has been person centered. However, in industrial settings, the individuals involved in an accident are seen as the inheritors of system defects. The objective of the present study was to investigate safety deficiencies that contributed to falls in community-dwelling seniors using a systems approach. The investigations were conducted using the Seniors Falls Investigation Methodology (SFIM), an adapted version of a method used to examine transportation accidents, such as airplane crashes. Fifteen seniors, who experienced a fall or near fall, participated in multiple case studies. A cross-case synthesis was used to summarize findings and identify common patterns of causes and safety deficiencies. Falls and near falls are a result of latent unsafe conditions, and unsafe acts and decisions combined in a diverse set of circumstances. If not identified and removed, these unsafe conditions can cause falls for other seniors. This study provided compelling evidence that causes of falling are systemic and develop over time. It demonstrated that the systems approach is needed to expand the focus from the individual to multilayered organizational and supervisory causes. The SFIM demonstrated capability to identify causes of falls that will allow better prevention and management programs, hence advancing seniors' safety. SFIM shows great potential for implementation in organized settings, such as hospitals and long-term care homes.

Efficacy of aquatic therapy for multiple sclerosis: a systematic review.

PubMed

Corvillo, Iluminada; Varela, Enrique; Armijo, Francisco; Alvarez-Badillo, Antonio; Armijo, Onica; Maraver, Francisco

2017-12-01

Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. The aim of this study was to systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option. The databases PubMed, Scopus, WoS and PEDro were searched to identify relevant reports published from January 1, 2011 to April 30, 2016. Of 306 articles identified, only 10 fulfilled the inclusion criteria: 5 randomized controlled, 2 simple randomized quasi-experimental, 1 semi-experimental, 1 blind controlled pilot and 1 pilot. Evidence that aquatic treatment improves quality of life in affected patients was very good in two studies, good in four, fair in two and weak in two.

Resting-state fMRI correlations: From link-wise unreliability to whole brain stability.

PubMed

Pannunzi, Mario; Hindriks, Rikkert; Bettinardi, Ruggero G; Wenger, Elisabeth; Lisofsky, Nina; Martensson, Johan; Butler, Oisin; Filevich, Elisa; Becker, Maxi; Lochstet, Martyna; Kühn, Simone; Deco, Gustavo

2017-08-15

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze within- and between-subject variability and test-retest reliability of resting-state functional connectivity (FC) in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. We adopt a statistical framework that enables us to identify different sources of variability in FC. We show that the low reliability of single links can be significantly improved by using multiple scans per subject. Moreover, in contrast to earlier studies, we show that spatial heterogeneity in FC reliability is not significant. Finally, we demonstrate that despite the low reliability of individual links, the information carried by the whole-brain FC matrix is robust and can be used as a functional fingerprint to identify individual subjects from the population. Copyright © 2017 Elsevier Inc. All rights reserved.

An international comparison study of pharmacy students' achievement goals and their relationship to assessment type and scores.

PubMed

Alrakaf, Saleh; Anderson, Claire; Coulman, Sion A; John, Dai N; Tordoff, June; Sainsbury, Erica; Rose, Grenville; Smith, Lorraine

2015-04-25

To identify pharmacy students' preferred achievement goals in a multi-national undergraduate population, to investigate achievement goal preferences across comparable degree programs, and to identify relationships between achievement goals, academic performance, and assessment type. The Achievement Goal Questionnaire was administered to second year students in 4 universities in Australia, New Zealand, England, and Wales. Academic performance was measured using total scores, multiple-choice questions, and written answers (short essay). Four hundred eighty-six second year students participated. Students showed an overall preference for the mastery-approach goal orientation across all sites. The predicted relationships between goal orientation and multiple-choice questions, and written answers scores, were significant. This study is the first of its kind to examine pharmacy students' achievement goals at a multi-national level and to differentiate between assessment type and measures of achievement motivation. Students adopting a mastery-approach goal are more likely to gain high scores in assessments that measure understanding and depth of knowledge.

An International Comparison Study of Pharmacy Students’ Achievement Goals and their Relationship to Assessment Type and Scores

PubMed Central

Anderson, Claire; Coulman, Sion A.; John, Dai N.; Tordoff, June; Sainsbury, Erica; Rose, Grenville; Smith, Lorraine

2015-01-01

Objective: To identify pharmacy students’ preferred achievement goals in a multi-national undergraduate population, to investigate achievement goal preferences across comparable degree programs, and to identify relationships between achievement goals, academic performance, and assessment type. Methods: The Achievement Goal Questionnaire was administered to second year students in 4 universities in Australia, New Zealand, England, and Wales. Academic performance was measured using total scores, multiple-choice questions, and written answers (short essay). Results: Four hundred eighty-six second year students participated. Students showed an overall preference for the mastery-approach goal orientation across all sites. The predicted relationships between goal orientation and multiple-choice questions, and written answers scores, were significant. Conclusion: This study is the first of its kind to examine pharmacy students’ achievement goals at a multi-national level and to differentiate between assessment type and measures of achievement motivation. Students adopting a mastery-approach goal are more likely to gain high scores in assessments that measure understanding and depth of knowledge. PMID:25995510

Multiple Discipline science assessment. [considering astronomy, astrophysics, cosmology, gravitation and geophysics when planning planetary missions

NASA Technical Reports Server (NTRS)

Wells, W. C.

1978-01-01

Various science disciplines were examined to determine where and when it is appropriate to include their objectives in the planning of planetary missions. The disciplines considered are solar astronomy, stellar and galactic astronomy, solar physics, cosmology and gravitational physics, the geosciences and the applied sciences. For each discipline, science objectives are identified which could provide a multiple discipline opportunity utilizing either a single spacecraft or two spacecraft delivered by a single launch vehicle. Opportunities using a common engineering system are also considered. The most promising opportunities identified include observations of solar images and relativistic effects using the Mercury orbiter; collection of samples exposed to solar radiation using the Mars surface sample return; studies of interstellar neutral H and He, magnetic fields, cosmic rays, and solar physics during Pluto or Neptune flybys; using the Mars orbiter to obtain solar images from 0.2 AU synchronous or from 90 deg orbit; and the study of the structure and composition of the atmosphere using atmospheric probes and remotely piloted vehicles.

Intimate partner violence and anxiety disorders in pregnancy: the importance of vocational training of the nursing staff in facing them1

PubMed Central

Fonseca-Machado, Mariana de Oliveira; Monteiro, Juliana Cristina dos Santos; Haas, Vanderlei José; Abrão, Ana Cristina Freitas de Vilhena; Gomes-Sponholz, Flávia

2015-01-01

Objective: to identify the relationship between posttraumatic stress disorder, trait and state anxiety, and intimate partner violence during pregnancy. Method: observational, cross-sectional study developed with 358 pregnant women. The Posttraumatic Stress Disorder Checklist - Civilian Version was used, as well as the State-Trait Anxiety Inventory and an adapted version of the instrument used in the World Health Organization Multi-country Study on Women's Health and Domestic Violence. Results: after adjusting to the multiple logistic regression model, intimate partner violence, occurred during pregnancy, was associated with the indication of posttraumatic stress disorder. The adjusted multiple linear regression models showed that the victims of violence, in the current pregnancy, had higher symptom scores of trait and state anxiety than non-victims. Conclusion: recognizing the intimate partner violence as a clinically relevant and identifiable risk factor for the occurrence of anxiety disorders during pregnancy can be a first step in the prevention thereof. PMID:26487135

Prevalence of carpal fracture in Singapore.

PubMed

Hey, Hwee Weng Dennis; Dennis, Hey Hwee Weng; Chong, Alphonsus Khin Sze; Sze, Alphonsus Chong Khin; Murphy, Diarmuid

2011-02-01

To determine the prevalence of carpal fracture in Singapore, to compare demographic differences between isolated scaphoid and other carpal fractures, and to identify parameters associated with multiple carpal fractures. A total of 149 patients with 162 carpal fractures seen at the National University Hospital in 2009 were enrolled into the study. We retrospectively reviewed their case records and radiographic studies. Pertinent demographic data including patient age, gender, occupation, injured wrist, dominant hand, mechanism of injury, and type of carpal fracture were then recorded and statistically analyzed. We also performed a separate analysis of isolated scaphoid versus other carpal fractures and single versus multiple carpal fractures. Patients with carpal fracture were predominantly male (132), below 40 years of age (116), and usually right hand dominant (136). The more common occupations were students (30), full-time military national servicemen (24), and construction workers (14). Most presented after a fall on an outstretched hand from standing height (81). The scaphoid was the most common single carpal fracture (99). This was followed by triquetrum (27), hamate (5), pisiform (4), lunate (2), capitate (1), and trapezium (1). No fracture of the trapezoid was encountered. Ten patients had multiple carpal fractures, of which 4 were perilunate fracture dislocations. The mean age and male/female ratio for isolated scaphoid and other carpal fractures was 26 years versus 41 years (p<.001) and 13:1 versus 4:1 (p=.036), respectively. A high-energy mechanism of injury was the only parameter associated with multiple carpal fractures (p=.009). The prevalence of carpal fracture in our population was consistent with studies performed in other countries. Military conscription was identified as an at-risk activity predisposing to carpal fracture. Isolated scaphoid and other carpal fractures exhibit different demographics in terms of age and gender, which may be related to differences in the mechanism of injury. A high-energy mechanism of injury was associated with multiple carpal fractures. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Zoonotic and Vector-Borne Infections Among Urban Homeless and Marginalized People in the United States and Europe, 1990-2014.

PubMed

Leibler, Jessica H; Zakhour, Christine M; Gadhoke, Preety; Gaeta, Jessie M

2016-07-01

In high-income countries, homeless individuals in urban areas often live in crowded conditions with limited sanitation and personal hygiene. The environment of homelessness in high-income countries may result in intensified exposure to ectoparasites and urban wildlife, which can transmit infections. To date, there have been no systematic evaluations of the published literature to assess vector-borne and zoonotic disease risk to these populations. The primary objectives of this study were to identify diversity, prevalence, and risk factors for vector-borne and zoonotic infections among people experiencing homelessness and extreme poverty in urban areas of high-income countries. We conducted a systematic review and narrative synthesis of published epidemiologic studies of zoonotic and vector-borne infections among urban homeless and very poor people in the United States and Europe from 1990 to 2014. Thirty-one observational studies and 14 case studies were identified (n = 45). Seroprevalence to the human louse-borne pathogen Bartonella quintana (seroprevalence range: 0-37.5%) was identified most frequently, with clinical disease specifically observed among HIV-positive individuals. Seropositivity to Bartonella henselae (range: 0-10.3%) and Rickettsia akari (range: 0-16.2%) was noted in multiple studies. Serological evidence of exposure to Rickettsia typhi, Rickettsia prowazekii, Bartonella elizabethae, West Nile virus, Borellia recurrentis, lymphocytic choriomeningitis virus, Wohlfartiimonas chitiniclastica, Seoul hantavirus (SEOV), and Leptospira species was also identified in published studies, with SEOV associated with chronic renal disease later in life. HIV infection, injection drug use, and heavy drinking were noted across multiple studies as risk factors for infection with vector-borne and zoonotic pathogens. B. quintana was the most frequently reported vector-borne infection identified in our article. Delousing efforts and active surveillance among HIV-positive individuals, who are at elevated risk of complication from B. quintana infection, are advised to reduce morbidity. Given documented exposure to rodent-borne zoonoses among urban homeless and marginalized people, reducing human contact with rodents remains an important public health priority.

Statistical testing and power analysis for brain-wide association study.

PubMed

Gong, Weikang; Wan, Lin; Lu, Wenlian; Ma, Liang; Cheng, Fan; Cheng, Wei; Grünewald, Stefan; Feng, Jianfeng

2018-04-05

The identification of connexel-wise associations, which involves examining functional connectivities between pairwise voxels across the whole brain, is both statistically and computationally challenging. Although such a connexel-wise methodology has recently been adopted by brain-wide association studies (BWAS) to identify connectivity changes in several mental disorders, such as schizophrenia, autism and depression, the multiple correction and power analysis methods designed specifically for connexel-wise analysis are still lacking. Therefore, we herein report the development of a rigorous statistical framework for connexel-wise significance testing based on the Gaussian random field theory. It includes controlling the family-wise error rate (FWER) of multiple hypothesis testings using topological inference methods, and calculating power and sample size for a connexel-wise study. Our theoretical framework can control the false-positive rate accurately, as validated empirically using two resting-state fMRI datasets. Compared with Bonferroni correction and false discovery rate (FDR), it can reduce false-positive rate and increase statistical power by appropriately utilizing the spatial information of fMRI data. Importantly, our method bypasses the need of non-parametric permutation to correct for multiple comparison, thus, it can efficiently tackle large datasets with high resolution fMRI images. The utility of our method is shown in a case-control study. Our approach can identify altered functional connectivities in a major depression disorder dataset, whereas existing methods fail. A software package is available at https://github.com/weikanggong/BWAS. Copyright © 2018 Elsevier B.V. All rights reserved.

Candidate gene analysis for Alzheimer's disease in adults with Down syndrome.

PubMed

Lee, Joseph H; Lee, Annie J; Dang, Lam-Ha; Pang, Deborah; Kisselev, Sergey; Krinsky-McHale, Sharon J; Zigman, Warren B; Luchsinger, José A; Silverman, Wayne; Tycko, Benjamin; Clark, Lorraine N; Schupf, Nicole

2017-08-01

Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer's disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g., age at onset of AD, amyloid β levels) among adults with DS, suggesting the importance of factors that modify risk within this particularly vulnerable population, including genotypic variability. Previous genetic studies in the general population have identified multiple genes that are associated with AD. This study examined the contribution of polymorphisms in these genes to the risk of AD in adults with DS ranging from 30 to 78 years of age at study entry (N = 320). We used multiple logistic regressions to estimate the likelihood of AD using single-nucleotide polymorphisms (SNPs) in candidate genes, adjusting for age, sex, race/ethnicity, level of intellectual disability and APOE genotype. This study identified multiple SNPs in APP and CST3 that were associated with AD at a gene-wise level empirical p-value of 0.05, with odds ratios in the range of 1.5-2. SNPs in MARK4 were marginally associated with AD. CST3 and MARK4 may contribute to our understanding of potential mechanisms where CST3 may contribute to the amyloid pathway by inhibiting plaque formation, and MARK4 may contribute to the regulation of the transition between stable and dynamic microtubules. Copyright © 2017 Elsevier Inc. All rights reserved.

Hazards and Health Risks Encountered by Manual Sand Dredgers from Udupi, India: A Cross-sectional Study

PubMed Central

Shaikh, Alfiya; Nayak, Priyanka; Navada, Rajesh

2017-01-01

Introduction Globalization and urbanization have resulted in an increased demand on sand dredging. Legal and environmental restrictions on automated dredging have led to a rise in manual technique. The working techniques and environment involved in manual sand dredging may expose the workers to multiple work related disorders. Aim To determine the health risks and occupational hazards involved in manual sand dredging. Materials and Methods An assessment schedule was developed and content was validated by five experts for the study. A cross-sectional study was then conducted using this assessment schedule. Thirty manual sand dredgers were recruited from three randomly selected docks on Swarna riverbed in Udupi district, Karnataka, India. A detailed work and worksite assessments were conducted using systematic observation and close-ended questions. Work-related health risk evaluation included onsite-evaluation and self-reported health complains. Results The prevalence of musculoskeletal pain and discomfort was 93.34% with lower back (70%), shoulder (56.7%) and neck (46.7%) involvements being most common regions. Prevalence of sensory deficits at multiple site and ear pain was 66.6% and 76.6% respectively. All the workers recruited, complained of dermatological and ophthalmic involvements. Also, lack of health and safety measures like personal protective devices and security schemes were identified. Conclusion This study shows a high prevalence of multiple work-related disorders and hazards involved in manual sand dredging, a highly demanding job in coastal Karnataka. Lack of health and safety measures were also identified. PMID:28892936

Return to work outcomes for workers with mental health conditions: A retrospective cohort study.

PubMed

Prang, Khic-Houy; Bohensky, Megan; Smith, Peter; Collie, Alex

2016-01-01

The aims of this study were to describe predictors of sustained return to work (RTW) among a cohort of workers with compensated work-related mental health conditions (MHCs); and to examine predictors of subsequent absences due to the same condition. This study was a retrospective analysis of compensation claims data in Victoria, Australia. We selected workers with an accepted wage replacement claim due to a work-related MHC from 1 January 2002 to 31 December 2009, with two years of follow-up data. We identified 8358 workers meeting our inclusion criteria. The median age of workers was 44 years (Interquartile range (IQR): 36-51) and 56% were female. In a multivariable Cox regression analysis, older age, being from a small organisation, working in some specific industry segments, consulting a psychiatrist or psychologist, using medications, and having a previous claim were all associated with a delayed RTW. Workers experiencing work pressure, assault/workplace violence or other mental stress factors, working in the public administration and safety industry and having a medical incapacity certification between 3-4 days and 5-7 days had a higher rate of multiple RTW attempts. This study identified a number of risk factors associated with a delayed RTW and multiple attempts at RTW. Predictors may help identify high-risk groups and facilitate the RTW process of workers with MHCs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissection of genetic architecture of rice plant height and heading date by multiple-strategy-based association studies

PubMed Central

Zhou, Liyuan; Liu, Shouye; Wu, Weixun; Chen, Daibo; Zhan, Xiaodeng; Zhu, Aike; Zhang, Yingxin; Cheng, Shihua; Cao, Liyong; Lou, Xiangyang; Xu, Haiming

2016-01-01

Xieyou9308 is a certified super hybrid rice cultivar with a high grain yield. To investigate its underlying genetic basis of high yield potential, a recombinant inbred line (RIL) population derived from the cross between the maintainer line XieqingzaoB (XQZB) and the restorer line Zhonghui9308 (ZH9308) was constructed for identification of quantitative trait SNPs (QTSs) associated with two important agronomic traits, plant height (PH) and heading date (HD). By re-sequencing of 138 recombinant inbred lines (RILs), a total of ~0.7 million SNPs were identified for the association studies on the PH and HD. Three association mapping strategies (including hypothesis-free genome-wide association and its two complementary hypothesis-engaged ones, QTL-based association and gene-based association) were adopted for data analysis. Using a saturated mixed linear model including epistasis and environmental interaction, we identified a total of 31 QTSs associated with either the PH or the HD. The total estimated heritability across three analyses ranged from 37.22% to 45.63% and from 37.53% to 55.96% for the PH and HD, respectively. In this study we examined the feasibility of association studies in an experimental population (RIL) and identified several common loci through multiple strategies which could be preferred candidates for further research. PMID:27406081

The Counseling Opportunity Structure: Examining Correlates of Four-Year College-Going Rates

ERIC Educational Resources Information Center

Engberg, Mark E.; Gilbert, Aliza J.

2014-01-01

This study examines the relationships between the normative and resource dimensions of a high school counseling department and four-year college-going rates. Utilizing data from the High School Longitudinal Study of 2009 (HSLS: 09), we employ multiple regression and latent class analysis to identify salient factors related to the college-going…

Violence on the US-Mexico Border and the Capital Students Use in Response

ERIC Educational Resources Information Center

Araujo, Blanca; de la Piedra, Maria Teresa

2013-01-01

Recent studies have identified multiple forms of capital that Latino students acquire in their homes and communities. Influenced by these studies, this article examines how transnational students of Mexican origin use various forms of their community's cultural wealth as tools to survive situations of violence in Mexico. In this article, we…

Impingement heat transfer from turbulent air jets to flat plates: A literature survey

NASA Technical Reports Server (NTRS)

Livingood, J. N. B.; Hrycak, P.

1973-01-01

Heat transfer characteristics of single and multiple turbulent air jets impinging on flat surfaces have been studied by many investigators. Results of many of these studies are summarized. Suggested correlations for use in the design of cooled turbine blades are noted, and areas where further research would be advisable are identified.

Making the Connection--Factors Influencing Implementation of Evidence Supported and Non-Evaluated Lifestyle Interventions in Healthcare: A Multiple Case Study

ERIC Educational Resources Information Center

van de Glind, Irene; Heinen, Maud; Geense, Wytske; Mesters, Ilse; Wensing, Michel; van Achterberg, Theo

2015-01-01

Many implementation barriers relate to lifestyle interventions (LIs) being developed by scientists. Exploring whether implementation of non-evaluated LIs is less complicated, might offer insight how to improve the use of effective interventions. This study aimed to identify influencing factors for implementation and compare factors between…

Legacies of Lead in Charm City's Soil: Lessons from the Baltimore Ecosystem Study

Treesearch

Kirsten Schwarz; Richard Pouyat; Ian Yesilonis

2016-01-01

Understanding the spatial distribution of soil lead has been a focus of the Baltimore Ecosystem Study since its inception in 1997. Through multiple research projects that span spatial scales and use different methodologies, three overarching patterns have been identified: (1) soil lead concentrations often exceed state and federal regulatory limits; (2) the variability...

Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L.) Moench) and related model species

PubMed Central

Modise, David M.; Gemeildien, Junaid; Ndimba, Bongani K.; Christoffels, Alan

2018-01-01

Background Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations. Methods In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO), Trait Ontology (TO), Plant Ontology (PO), Growth Ontology (GRO) and Environment Ontology (EO) were used to semantically integrate drought related information. Results Target genes linked to Quantitative Trait Loci (QTLs) controlling yield and stress tolerance in sorghum (Sorghum bicolor (L.) Moench) and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%), salt (32%), cold (20%), heat (8%) and oxidative stress (25%) were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs associated with different traits that are responsive to multiple stresses. Ontology mapping was used to validate the identified genes, while reconstruction of the phylogenetic tree was instrumental to infer the evolutionary relationship of the sorghum orthologs. The results also show specific genes responsible for various interrelated components of drought response mechanism such as drought tolerance, drought avoidance and drought escape. Conclusions We submit that this approach is novel and to our knowledge, has not been used previously in any other research; it enables us to perform cross-species queries for genes that are likely to be associated with multiple stress tolerance, as a means to identify novel targets for engineering stress resistance in sorghum and possibly, in other crop species. PMID:29590108

The Concept Mastery in the Perspective of Gender of Junior High School Students on Eclipse Theme in Multiple Intelligences-based of Integrated Earth and Space Science Learning

NASA Astrophysics Data System (ADS)

Liliawati, W.; Utama, J. A.; Mursydah, L. S.

2017-03-01

The purpose of this study is to identify gender-based concept mastery differences of junior high school students after the implementation of multiple intelligences-based integrated earth and space science learning. Pretest-posttest group design was employed to two different classes at one of junior high school on eclipse theme in Tasikmalaya West Java: one class for boys (14 students) and one class of girls (18 students). The two-class received same treatment. The instrument of concepts mastery used in this study was open-ended eight essay questions. Reliability test result of this instrument was 0.9 (category: high) while for validity test results were high and very high category. We used instruments of multiple intelligences identification and learning activity observation sheet for our analysis. The results showed that normalized N-gain of concept mastery for boys and girls were improved, respectively 0.39 and 0.65. Concept mastery for both classes differs significantly. The dominant multiple intelligences for boys were in kinesthetic while girls dominated in the rest of multiple intelligences. Therefor we concluded that the concept mastery was influenced by gender and student’s multiple intelligences. Based on this finding we suggested to considering the factor of gender and students’ multiple intelligences given in the learning activity.

Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years.

PubMed

Fragoso, Yara Dadalti; Alves-Leon, Soniza Vieira; Barreira, Amilton Antunes; Callegaro, Dagoberto; Brito Ferreira, Maria Lucia; Finkelsztejn, Alessandro; Gomes, Sidney; Magno Goncalves, Marcus Vinicius; Moraes Machado, Maria Iris; Marques, Vanessa Daccach; Cunha Matta, Andre Palma; Papais-Alvarenga, Regina Maria; Apostolos Pereira, Samira Luisa; Tauil, Carlos Bernardo

2015-08-01

There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control. Copyright © 2015 Elsevier Inc. All rights reserved.

Stochastic control system parameter identifiability

NASA Technical Reports Server (NTRS)

Lee, C. H.; Herget, C. J.

1975-01-01

The parameter identification problem of general discrete time, nonlinear, multiple input/multiple output dynamic systems with Gaussian white distributed measurement errors is considered. The knowledge of the system parameterization was assumed to be known. Concepts of local parameter identifiability and local constrained maximum likelihood parameter identifiability were established. A set of sufficient conditions for the existence of a region of parameter identifiability was derived. A computation procedure employing interval arithmetic was provided for finding the regions of parameter identifiability. If the vector of the true parameters is locally constrained maximum likelihood (CML) identifiable, then with probability one, the vector of true parameters is a unique maximal point of the maximum likelihood function in the region of parameter identifiability and the constrained maximum likelihood estimation sequence will converge to the vector of true parameters.

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

PubMed

Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

2017-06-01

We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

Fusing Data Mining, Machine Learning and Traditional Statistics to Detect Biomarkers Associated with Depression

PubMed Central

Dipnall, Joanna F.

2016-01-01

Background Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. Methods The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009–2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. Results After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). Conclusion The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin. PMID:26848571

Fusing Data Mining, Machine Learning and Traditional Statistics to Detect Biomarkers Associated with Depression.

PubMed

Dipnall, Joanna F; Pasco, Julie A; Berk, Michael; Williams, Lana J; Dodd, Seetal; Jacka, Felice N; Meyer, Denny

2016-01-01

Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.

A systematic review of school-based eHealth interventions targeting alcohol use, smoking, physical inactivity, diet, sedentary behaviour and sleep among adolescents: a review protocol.

PubMed

Champion, Katrina E; Newton, Nicola C; Spring, Bonnie; Wafford, Q Eileen; Parmenter, Belinda J; Teesson, Maree

2017-12-06

Six key behavioural risk factors (risky alcohol use, smoking, poor diet, physical inactivity, sedentary behaviour and unhealthy sleep patterns) have been identified as strong determinants of chronic disease, such as cardiovascular disease, diabetes and cancers. School-based interventions targeting these multiple health risk behaviours among adolescents have the potential to halt the trajectory towards later disease, whilst online and mobile technology interventions offer advantages in terms of student engagement, reach and scalability. Despite this, the efficacy of eHealth school-based interventions targeting these six health risk behaviours among adolescents has not been evaluated. The proposed systematic review aims to address this by determining the nature and efficacy of existing eHealth school-based interventions targeting multiple health risk behaviours among adolescents. A systematic search of the MEDLINE, Embase, PsycINFO and Cochrane Library databases will be conducted to identify eligible published papers. Eligible studies will be randomised controlled trials, including cluster randomised controlled trials, of interventions targeting two or more of the following lifestyle risk behaviours: alcohol use, smoking, poor diet, physical inactivity, sedentary behaviour and sleep. Eligible studies will be those evaluating interventions delivered in a secondary school setting among participants 11-18 years of age, via an eHealth platform (Internet, computers of mobile technology). Two reviewers will independently screen studies for eligibility, extract data and assess the risk of bias. Study outcomes will be summarised in a narrative synthesis, and meta-analyses will be conducted where it is appropriate to combine studies. It is anticipated that the results from this review will serve to inform the development of future eHealth multiple health behaviour interventions for adolescents by identifying common characteristics of effective programs and highlighting knowledge gaps in the evidence base. PROSPERO CRD42017072163.

Joint source based analysis of multiple brain structures in studying major depressive disorder

NASA Astrophysics Data System (ADS)

Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

2014-03-01

We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

Breast Cancer and Modifiable Lifestyle Factors in Argentinean Women: Addressing Missing Data in a Case-Control Study

PubMed Central

Coquet, Julia Becaria; Tumas, Natalia; Osella, Alberto Ruben; Tanzi, Matteo; Franco, Isabella; Diaz, Maria Del Pilar

2016-01-01

A number of studies have evidenced the effect of modifiable lifestyle factors such as diet, breastfeeding and nutritional status on breast cancer risk. However, none have addressed the missing data problem in nutritional epidemiologic research in South America. Missing data is a frequent problem in breast cancer studies and epidemiological settings in general. Estimates of effect obtained from these studies may be biased, if no appropriate method for handling missing data is applied. We performed Multiple Imputation for missing values on covariates in a breast cancer case-control study of Córdoba (Argentina) to optimize risk estimates. Data was obtained from a breast cancer case control study from 2008 to 2015 (318 cases, 526 controls). Complete case analysis and multiple imputation using chained equations were the methods applied to estimate the effects of a Traditional dietary pattern and other recognized factors associated with breast cancer. Physical activity and socioeconomic status were imputed. Logistic regression models were performed. When complete case analysis was performed only 31% of women were considered. Although a positive association of Traditional dietary pattern and breast cancer was observed from both approaches (complete case analysis OR=1.3, 95%CI=1.0-1.7; multiple imputation OR=1.4, 95%CI=1.2-1.7), effects of other covariates, like BMI and breastfeeding, were only identified when multiple imputation was considered. A Traditional dietary pattern, BMI and breastfeeding are associated with the occurrence of breast cancer in this Argentinean population when multiple imputation is appropriately performed. Multiple Imputation is suggested in Latin America’s epidemiologic studies to optimize effect estimates in the future. PMID:27892664

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams

USGS Publications Warehouse

Black, R.W.; Moran, P.W.; Frankforter, J.D.

2011-01-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria. ?? 2010 The Author(s).

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams.

PubMed

Black, Robert W; Moran, Patrick W; Frankforter, Jill D

2011-04-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria.

GeneNetFinder2: Improved Inference of Dynamic Gene Regulatory Relations with Multiple Regulators.

PubMed

Han, Kyungsook; Lee, Jeonghoon

2016-01-01

A gene involved in complex regulatory interactions may have multiple regulators since gene expression in such interactions is often controlled by more than one gene. Another thing that makes gene regulatory interactions complicated is that regulatory interactions are not static, but change over time during the cell cycle. Most research so far has focused on identifying gene regulatory relations between individual genes in a particular stage of the cell cycle. In this study we developed a method for identifying dynamic gene regulations of several types from the time-series gene expression data. The method can find gene regulations with multiple regulators that work in combination or individually as well as those with single regulators. The method has been implemented as the second version of GeneNetFinder (hereafter called GeneNetFinder2) and tested on several gene expression datasets. Experimental results with gene expression data revealed the existence of genes that are not regulated by individual genes but rather by a combination of several genes. Such gene regulatory relations cannot be found by conventional methods. Our method finds such regulatory relations as well as those with multiple, independent regulators or single regulators, and represents gene regulatory relations as a dynamic network in which different gene regulatory relations are shown in different stages of the cell cycle. GeneNetFinder2 is available at http://bclab.inha.ac.kr/GeneNetFinder and will be useful for modeling dynamic gene regulations with multiple regulators.

Patterns of adverse childhood experiences and substance use among young adults: A latent class analysis.

PubMed

Shin, Sunny H; McDonald, Shelby Elaine; Conley, David

2018-03-01

Adverse childhood experiences (ACEs) have been strongly linked with subsequent substance use. The aim of this study was to investigate how different patterns of ACEs influence substance use in young adulthood. Using a community sample of young individuals (N=336; ages 18-25), we performed latent class analyses (LCA) to identify homogenous groups of young people with similar patterns of ACEs. Exposure to ACEs incorporates 13 childhood adversities including childhood maltreatment, household dysfunction, and community violence. Multiple linear and logistic regression models were used in an effort to examine the associations between ACEs classes and four young adult outcomes such as alcohol-related problems, current tobacco use, drug dependence symptoms, and psychological distress. LCA identified four heterogeneous classes of young people distinguished by different patterns of ACEs exposure: Low ACEs (56%), Household Dysfunction/Community Violence (14%), Emotional ACEs (14%), and High/Multiple ACEs (16%). Multiple regression analyses found that compared to those in the Low ACEs class, young adults in the High/Multiple ACEs class reported more alcohol-related problems, current tobacco use, and psychological symptoms, controlling for sociodemographic characteristics and common risk factors for substance use such as peer substance use. Our findings confirm that for many young people, ACEs occur as multiple rather than single experiences. The results of this research suggest that exposure to poly-victimization during childhood is particularly related to substance use during young adulthood. Copyright © 2017 Elsevier Ltd. All rights reserved.

The challenges, advantages and future of phenome-wide association studies.

PubMed

Hebbring, Scott J

2014-02-01

Over the last decade, significant technological breakthroughs have revolutionized human genomic research in the form of genome-wide association studies (GWASs). GWASs have identified thousands of statistically significant genetic variants associated with hundreds of human conditions including many with immunological aetiologies (e.g. multiple sclerosis, ankylosing spondylitis and rheumatoid arthritis). Unfortunately, most GWASs fail to identify clinically significant associations. Identifying biologically significant variants by GWAS also presents a challenge. The GWAS is a phenotype-to-genotype approach. As a complementary/alternative approach to the GWAS, investigators have begun to exploit extensive electronic medical record systems to conduct a genotype-to-phenotype approach when studying human disease - specifically, the phenome-wide association study (PheWAS). Although the PheWAS approach is in its infancy, this method has already demonstrated its capacity to rediscover important genetic associations related to immunological diseases/conditions. Furthermore, PheWAS has the advantage of identifying genetic variants with pleiotropic properties. This is particularly relevant for HLA variants. For example, PheWAS results have demonstrated that the HLA-DRB1 variant associated with multiple sclerosis may also be associated with erythematous conditions including rosacea. Likewise, PheWAS has demonstrated that the HLA-B genotype is not only associated with spondylopathies, uveitis, and variability in platelet count, but may also play an important role in other conditions, such as mastoiditis. This review will discuss and compare general PheWAS methodologies, describe both the challenges and advantages of the PheWAS, and provide insight into the potential directions in which PheWAS may lead. © 2013 The Authors. Immunology Published by John Wiley & Sons Ltd.

Multiple pregnancies achieved with IVF/ICSI and risk of specific congenital malformations: a meta-analysis of cohort studies.

PubMed

Zheng, Zan; Chen, Letao; Yang, Tubao; Yu, Hong; Wang, Hua; Qin, Jiabi

2018-04-01

Studies comparing risk of specific congenital malformations (CM) between multiple pregnancies resulting from IVF/intracytoplasmic sperm injection (ICSI) and those conceived naturally report conflicting results; furthermore, there is a lack of a complete overview. This meta-analysis aimed to address which types of CM are increased in IVF/ICSI multiple pregnancies compared with those conceived naturally. All studies testing the association between IVF/ICSI multiple pregnancies and specific CM identified in various databases were considered. The literature search yielded 856 records, of which 21 cohort studies were included for analysis. Overall, multiple pregnancies achieved with IVF/ICSI experienced a significantly higher risk of chromosomal defects (relative risk [RR] = 1.36; 95% confidence interval [CI]: 1.04-1.77), urogenital (RR = 1.18; 95% CI: 1.03-1.36) and circulatory (RR = 1.22; 95% CI: 1.01-1.47) system malformations. However, the remaining specific CM, such as cleft lip and/or palate, eye, ear, face and neck, respiratory, musculoskeletal, nervous and digestive system malformations, were similar in the two groups. No substantial heterogeneity was observed for most outcomes except for digestive (P = 0.094; I 2 = 38.3%) and circulatory (P = 0.070; I 2 = 35.2%) system malformations. These findings provide additional information on risks of IVF/ICSI for use when counselling patients. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Multiple Object Based RFID System Using Security Level

NASA Astrophysics Data System (ADS)

Kim, Jiyeon; Jung, Jongjin; Ryu, Ukjae; Ko, Hoon; Joe, Susan; Lee, Yongjun; Kim, Boyeon; Chang, Yunseok; Lee, Kyoonha

2007-12-01

RFID systems are increasingly applied for operational convenience in wide range of industries and individual life. However, it is uneasy for a person to control many tags because common RFID systems have the restriction that a tag used to identify just a single object. In addition, RFID systems can make some serious problems in violation of privacy and security because of their radio frequency communication. In this paper, we propose a multiple object RFID tag which can keep multiple object identifiers for different applications in a same tag. The proposed tag allows simultaneous access for their pair applications. We also propose an authentication protocol for multiple object tag to prevent serious problems of security and privacy in RFID applications. Especially, we focus on efficiency of the authentication protocol by considering security levels of applications. In the proposed protocol, the applications go through different authentication procedures according to security level of the object identifier stored in the tag. We implemented the proposed RFID scheme and made experimental results about efficiency and stability for the scheme.

Turning challenges into design principles: Telemonitoring systems for patients with multiple chronic conditions.

PubMed

Sultan, Mehwish; Kuluski, Kerry; McIsaac, Warren J; Cafazzo, Joseph A; Seto, Emily

2018-01-01

People with multiple chronic conditions often struggle with managing their health. The purpose of this research was to identify specific challenges of patients with multiple chronic conditions and to use the findings to form design principles for a telemonitoring system tailored for these patients. Semi-structured interviews with 15 patients with multiple chronic conditions and 10 clinicians were conducted to gain an understanding of their needs and preferences for a smartphone-based telemonitoring system. The interviews were analyzed using a conventional content analysis technique, resulting in six themes. Design principles developed from the themes included that the system must be modular to accommodate various combinations of conditions, reinforce a routine, consolidate record keeping, as well as provide actionable feedback to the patients. Designing an application for multiple chronic conditions is complex due to variability in patient conditions, and therefore, design principles developed in this study can help with future innovations aimed to help manage this population.

Instantaneous and Time Averaged Flow Fields of Multiple Vortices in the Tip Region of a Ducted Propulsor

NASA Astrophysics Data System (ADS)

Oweis, Ghanem; Steven, Ceccio

2003-11-01

PIV data of the flow field in the immediate vicinity of the trailing edge of a ducted propeller at the tip revealed the existence of multiple vorticity concentrations. The multiple vortices in each instantaneous PIV field were identified and individually characterized. The measurements of the multiple vortices were combined with a Gaussian vortex model to reconstruct the vorticity and velocity fields. The major features of the original experimental field were recovered, and the correlation between the two fields was good. The time averaged field and velocity fluctuations were also measured. We will discuss why the "typical" instantaneous tip vortex and the tip vortex from the time averaged field are substantially different. We attempt to explain the cause of these differences. Knowledge of the instantaneous flow field variability is used to understand the causes of the measured velocity fluctuations. The results from this study have an impact on the understanding of the roll-up of tip vortices, and the dynamics of multiple vortices.

Revisiting the Phylogeny of the Animal Formins: Two New Subtypes, Relationships with Multiple Wing Hairs Proteins, and a Lost Human Formin.

PubMed

Pruyne, David

2016-01-01

Formins are a widespread family of eukaryotic cytoskeleton-organizing proteins. Many species encode multiple formin isoforms, and for animals, much of this reflects the presence of multiple conserved subtypes. Earlier phylogenetic analyses identified seven major formin subtypes in animals (DAAM, DIAPH, FHOD, FMN, FMNL, INF, and GRID2IP/delphilin), but left a handful of formins, particularly from nematodes, unassigned. In this new analysis drawing from genomic data from a wider range of taxa, nine formin subtypes are identified that encompass all the animal formins analyzed here. Included in this analysis are Multiple Wing Hairs proteins (MWH), which bear homology to formin N-terminal domains. Originally identified in Drosophila melanogaster and other arthropods, MWH-related proteins are also identified here in some nematodes (including Caenorhabditis elegans), and are shown to be related to a novel MWH-related formin (MWHF) subtype. One surprising result of this work is the discovery that a family of pleckstrin homology domain-containing formins (PHCFs) is represented in many vertebrates, but is strikingly absent from placental mammals. Consistent with a relatively recent loss of this formin, the human genome retains fragments of a defunct homologous formin gene.

Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family.

PubMed

Stone, Jacquelyn A; Nicola, Anthony V; Baum, Linda G; Aguilar, Hector C

2016-02-01

O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. These are all important functions of viral glycoproteins. These phenotypes were broadly conserved for equivalent NiV mutants. Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses.

Anthropometric characteristics and risk of multiple myeloma.

PubMed

Blair, Cindy K; Cerhan, James R; Folsom, Aaron R; Ross, Julie A

2005-09-01

Few studies have examined obesity and risk for multiple myeloma, and the results are inconsistent. Laboratory evidence suggests mechanisms through which obesity could influence carcinogenesis of this hematopoietic malignancy. We examined the association between anthropometric characteristics and incident multiple myeloma in a prospective, population-based sample of 37,083 postmenopausal women. In 1986, the women completed a mailed questionnaire that included self-report of height and weight, and friend measurement of waist and hip circumferences. During 16 years of follow up, 95 cases of multiple myeloma were identified through linkage to the Iowa Cancer Registry. In an age-adjusted model, women in the highest category of several anthropometric measurements compared with the lowest category were at increased risk of developing multiple myeloma. For body mass index (kg/m), the rate ratio (95% confidence interval) was 1.5 (0.92-2.6); for weight, 1.9 (1.1-3.4); for waist circumference, 2.0 (1.1-3.5); and for hip circumference, 1.8 (1.0-3.0). Greater adiposity may increase the risk of multiple myeloma.

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

PubMed

Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael

2018-02-13

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Multiple role adaptation among women who have children and re-enter nursing school in Taiwan.

PubMed

Lin, Li-Ling

2005-03-01

This study assessed multiple role adaptation within maternal and student roles among female RNs who had children and returned to school for baccalaureate degrees in Taiwan. Using Roy's Adaptation Model as the theoretical framework, relationships were explored among demographic (number of children, age of youngest child, employment status), physical (sleep quality, health perception, activity), and psychosocial factors (self-identity, role expectation, role involvement, social support) and multiple role adaptation (role accumulation). The sample included 118 mother-students who had at least one child younger than age 18 and who were studying in nursing programs in Taiwan. The highest correlation was found between activity and role accumulation followed by significant correlations between sleep quality, health perception, maternal role expectation, and age of youngest child and role accumulation. In regression analyses, the complete model explained 46% of the variance in role accumulation. Implications for education and future research are identified.

A systematic review of effective interventions for reducing multiple health risk behaviors in adolescence.

PubMed

Hale, Daniel R; Fitzgerald-Yau, Natasha; Viner, Russell Mark

2014-05-01

We systematically searched 9 biomedical and social science databases (1980-2012) for primary and secondary interventions that prevented or reduced 2 or more adolescent health risk behaviors (tobacco use, alcohol use, illicit drug use, risky sexual behavior, aggressive acts). We identified 44 randomized controlled trials of universal or selective interventions and were effective for multiple health risk behaviors. Most were school based, conducted in the United States, and effective for multiple forms of substance use. Effects were small, in line with findings for other universal prevention programs. In some studies, effects for more than 1 health risk behavior only emerged at long-term follow-up. Integrated prevention programs are feasible and effective and may be more efficient than discrete prevention strategies.

Single Versus Multiple Solid Organ Injuries Following Blunt Abdominal Trauma.

PubMed

El-Menyar, Ayman; Abdelrahman, Husham; Al-Hassani, Ammar; Peralta, Ruben; AbdelAziz, Hiba; Latifi, Rifat; Al-Thani, Hassan

2017-11-01

We aimed to describe the pattern of solid organ injuries (SOIs) and analyze the characteristics, management and outcomes based on the multiplicity of SOIs. A retrospective study in a Level 1 trauma center was conducted and included patients admitted with blunt abdominal trauma between 2011 and 2014. Data were analyzed and compared for patients with single versus multiple SOIs. A total of 504 patients with SOIs were identified with a mean age of 28 ± 13 years. The most frequently injured organ was liver (45%) followed by spleen (30%) and kidney (18%). One-fifth of patients had multiple SOIs, of that 87% had two injured organs. Patients with multiple SOIs had higher frequency of head injury and injury severity scores (p < 0.05). The majority of SOIs were treated nonoperatively, whereas operative management was required in a quarter of patients, mostly in patients with multiple SOIs (p = 0.01). Blood transfusion, sepsis and hospital stay were greater in multiple than single SOIs (p < 0.05). The overall mortality was 11% which was comparable between the two groups. In patients with single SOIs, the mortality was significantly higher in those who had pancreatic (28.6%) or hepatic injuries (13%) than the other SOIs. SOIs represent one-tenth of trauma admissions in Qatar. Although liver was the most frequently injured organ, the rate of mortality was higher in pancreatic injury. Patients with multiple SOIs had higher morbidity which required frequent operative management. Further prospective studies are needed to develop management algorithm based on the multiplicity of SOIs.

Gulf War Illness Inflammation Reduction Trial

DTIC Science & Technology

2015-10-01

study comparing blood samples from Gulf War veterans with and without multiple symptoms of pain, fatigue, and cognitive dysfunction. The goal of the...pilot study was to identify a potential therapeutic target for the treatment of GWI. Examination to the peripheral blood revealed the biomarker...understood. Therefore, we performed a pilot study comparing blood samples from Gulf War veterans who very GWI- with blood 6 from veterans who were