WorldWideScience

Sample records for factor analyses identified

  1. Systematic review and meta-analyses of risk factors for childhood overweight identifiable during infancy

    OpenAIRE

    2012-01-01

    Objective To determine risk factors for childhood overweight that can be identified during the first year of life to facilitate early identification and targeted intervention. Design Systematic review and meta-analysis. Search strategy Electronic database search of MEDLINE, EMBASE, PubMed and CAB Abstracts. Eligibility criteria Prospective observational studies following up children from birth for at least 2 years. Results Thirty prospective studies were identified. Significant and strong ind...

  2. Analysing Java Identifier Names

    OpenAIRE

    Butler, Simon

    2016-01-01

    Identifier names are the principal means of recording and communicating ideas in source code and are a significant source of information for software developers and maintainers, and the tools that support their work. This research aims to increase understanding of identifier name content types - words, abbreviations, etc. - and phrasal structures - noun phrases, verb phrases, etc. - by improving techniques for the analysis of identifier names. The techniques and knowledge acquired can be appl...

  3. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kleijnen, J.P.C.; Helton, J.C.

    1999-04-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.

  4. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations, 2. Robustness of Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Helton, J.C.; Kleijnen, J.P.C.

    1999-03-24

    Procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses are described and illustrated. These procedures attempt to detect increasingly complex patterns in scatterplots and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. A sequence of example analyses with a large model for two-phase fluid flow illustrates how the individual procedures can differ in the variables that they identify as having effects on particular model outcomes. The example analyses indicate that the use of a sequence of procedures is a good analysis strategy and provides some assurance that an important effect is not overlooked.

  5. Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

    Science.gov (United States)

    Fortes, M R S; Nguyen, L T; Weller, M M D C A; Cánovas, A; Islas-Trejo, A; Porto-Neto, L R; Reverter, A; Lehnert, S A; Boe-Hansen, G B; Thomas, M G; Medrano, J F; Moore, S S

    2016-09-01

    Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

  6. RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord.

    Science.gov (United States)

    Brohawn, David G; O'Brien, Laura C; Bennett, James P

    2016-01-01

    ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG's). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network "hub" gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF's involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful

  7. Identifying, analysing and solving problems in practice.

    Science.gov (United States)

    Hewitt-Taylor, Jaqui

    When a problem is identified in practice, it is important to clarify exactly what it is and establish the cause before seeking a solution. This solution-seeking process should include input from those directly involved in the problematic situation, to enable individuals to contribute their perspective, appreciate why any change in practice is necessary and what will be achieved by the change. This article describes some approaches to identifying and analysing problems in practice so that effective solutions can be devised. It includes a case study and examples of how the Five Whys analysis, fishbone diagram, problem tree analysis, and Seven-S Model can be used to analyse a problem.

  8. Time delay and partial coherence analyses to identify cortical connectivities

    CERN Document Server

    Govindan, R B; Deuschl, G; Kopper, F; Raethjen, J

    2005-01-01

    Recently it has been demonstrated by Albo that partial coherence analysis is sensitive to signal to noise ratio (SNR) and that it will always identify the signal with the highest SNR among the three signals as the main (driving) influence. We propose to use time delay analysis in parallel to partial coherence analysis to identify the connectivities between the multivariate time series. Both are applied to a theoretical model (used by Albo) to analyse the connections introduced in the model. Time delay analysis identifies the connections correctly. We also apply these analyses to the electroencephalogram (EEG) and electromyogram (EMG) of essential tremor patients and EEG of normal subjects while bimanually tapping their index fingers. Biologically plausible cortico-muscular and cortico-cortical connections are identified by these methods.

  9. Anti-schistosomal Intervention Targets Identified by Lifecycle Transcriptomic Analyses

    Science.gov (United States)

    Fitzpatrick, Jennifer M.; Peak, Emily; Perally, Samirah; Chalmers, Iain W.; Barrett, John; Yoshino, Timothy P.; Ivens, Alasdair C.; Hoffmann, Karl F.

    2009-01-01

    Background Novel methods to identify anthelmintic drug and vaccine targets are urgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification of exploitable molecules essential for successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach, employing both statistical and network analyses of transcriptomic data, for identifying new immunoprophylactic and therapeutic lead targets to combat schistosomiasis. Methodology/Principal Findings Utilisation of a Schistosoma mansoni oligonucleotide DNA microarray consisting of 37,632 elements enabled gene expression profiling from 15 distinct parasite lifecycle stages, spanning three unique ecological niches. Statistical approaches of data analysis revealed differential expression of 973 gene products that minimally describe the three major characteristics of schistosome development: asexual processes within intermediate snail hosts, sexual maturation within definitive vertebrate hosts and sexual dimorphism amongst adult male and female worms. Furthermore, we identified a group of 338 constitutively expressed schistosome gene products (including 41 transcripts sharing no sequence similarity outside the Platyhelminthes), which are likely to be essential for schistosome lifecycle progression. While highly informative, statistics-led bioinformatics mining of the transcriptional dataset has limitations, including the inability to identify higher order relationships between differentially expressed transcripts and lifecycle stages. Network analysis, coupled to Gene Ontology enrichment investigations, facilitated a re-examination of the dataset and identified 387 clusters (containing 12,132 gene products) displaying novel examples of developmentally regulated classes (including 294 schistosomula and

  10. Summary of the analyses for recovery factors

    Science.gov (United States)

    Verma, Mahendra K.

    2017-07-17

    IntroductionIn order to determine the hydrocarbon potential of oil reservoirs within the U.S. sedimentary basins for which the carbon dioxide enhanced oil recovery (CO2-EOR) process has been considered suitable, the CO2 Prophet model was chosen by the U.S. Geological Survey (USGS) to be the primary source for estimating recovery-factor values for individual reservoirs. The choice was made because of the model’s reliability and the ease with which it can be used to assess a large number of reservoirs. The other two approaches—the empirical decline curve analysis (DCA) method and a review of published literature on CO2-EOR projects—were deployed to verify the results of the CO2 Prophet model. This chapter discusses the results from CO2 Prophet (chapter B, by Emil D. Attanasi, this report) and compares them with results from decline curve analysis (chapter C, by Hossein Jahediesfanjani) and those reported in the literature for selected reservoirs with adequate data for analyses (chapter D, by Ricardo A. Olea).To estimate the technically recoverable hydrocarbon potential for oil reservoirs where CO2-EOR has been applied, two of the three approaches—CO2 Prophet modeling and DCA—do not include analysis of economic factors, while the third approach—review of published literature—implicitly includes economics. For selected reservoirs, DCA has provided estimates of the technically recoverable hydrocarbon volumes, which, in combination with calculated amounts of original oil in place (OOIP), helped establish incremental CO2-EOR recovery factors for individual reservoirs.The review of published technical papers and reports has provided substantial information on recovery factors for 70 CO2-EOR projects that are either commercially profitable or classified as pilot tests. When comparing the results, it is important to bear in mind the differences and limitations of these three approaches.

  11. Identifying null meta-analyses that are ripe for updating

    Directory of Open Access Journals (Sweden)

    Fang Manchun

    2003-07-01

    Full Text Available Abstract Background As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date. Methods We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the "new participant ratio", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence. Results In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively. Conclusions Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use.

  12. [Investigation of Predisposition Biomarkers to Identify Risk Factors for Drug-induced Liver Injury in Humans: Analyses of Endogenous Metabolites in an Animal Model Mimicking Human Responders to APAP-induced Hepatotoxicity].

    Science.gov (United States)

    Kobayashi, Akio; Kondo, Kazuma; Sugai, Shoichiro

    2015-01-01

    Drug-induced liver injury is a main reason of regulatory action pertaining to drugs, including restrictions to clinical indications and withdrawal from the marketplace. Acetaminophen (APAP) is a commonly used and effective analgesic/antipyretic agent and relatively safe drug even in long-term treatment. However, it is known that APAP at therapeutic doses may cause hepatotoxicity in some individuals. Hence great efforts have been made to identify risk factors for APAP-induced chronic hepatotoxicity. We investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model. We employed daytime restricted fed (RF) rats as a modified-nutritional state model for human APAP-induced hepatotoxicity. RF and ad libitum fed (ALF) rats were given APAP at 0, 300, and 500 mg/kg for 3 months. Plasma and urinary glutathione-related metabolomes and liver function parameters were measured during the dosing period. Endogenous metabolites forming at different levels between the RF and ALF rats could be potential predisposition biomarkers for APAP-induced hepatotoxicity. In addition, RF rats were considered a useful model to estimate the contribution of nutritional state of patients to APAP-induced chronic hepatotoxicity. In this article we report our current research focusing on nutritional state as risk factor for APAP-induced chronic hepatotoxicity and our findings of hepatotoxicity biomarkers.

  13. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  14. Identifying Motivational Factors within a Multinational Company

    OpenAIRE

    Daniela Bradutanu

    2011-01-01

    The aim of the study is to identify the main motivational factors within a multinational company. The first objective is to identify work functions, formulated on Abraham Maslow’s pyramid, following the identification of the key characteristics that motivate an employee at the work place and last, but not least, the type of motivation that employees focus, intrinsic or extrinsic. The research method targeted a questionnaire based survey, including various company employees and an interv...

  15. Identifying paleotsunami deposits in Thailand using geochemical analyses

    Science.gov (United States)

    Löwhagen, Linda; Jankaew, Kruawun; Kylander, Malin; Wohlfarth, Barbara

    2014-05-01

    Paleotsunami research has received considerable attention following the devastating Indian Ocean tsunami of December 2004. Specific questions involve the magnitude, frequency and impact of past tsunamis. Phra Thong Island in the eastern Andaman Sea is an ideal location to study paleotsunami deposits in great detail (Jankaew et al., 2008). Apart from the 2004 Indian Ocean tsunami layer, three more distinct tsunami layers, separated by soil horizons have been identified and dated (Jankaew et al., 2008). In a collaborative project between Stockholm University and Chulalongkorn University, four sites on Phra Thong Island were chosen for detailed geochemical studies and additional AMS 14C dating. Paleotsunami deposits at these sites can be seen as more or less distinct sand layers embedded between the peaty soils. Here we report the initial results of XRF core scanning and loss on ignition analysis, which are supplemented by new 14C dates. The XRF data sets show a good correlation between synchronous tsunami layers along a coast-inland transect. The geochemistry moreover suggests a change in source area for the oldest tsunami layer. Further work will focus on a detailed geochemical characterization of the tsunami and soil layers, and on the influence of soil processes on the geochemical record. Reference: Jankaew, K; Atwater, B; Sawai, Y; Choowong, M; Charoentitirat, T; Martin, M; Prendergast, A, 2008. Medieval forewarning of the 2004 Indian Ocean tsunami in Thailand. Nature 455, 1228-1231.

  16. Kinship analyses identify fish dispersal events on a temperate coastline.

    Science.gov (United States)

    Schunter, C; Pascual, M; Garza, J C; Raventos, N; Macpherson, E

    2014-06-22

    Connectivity is crucial for the persistence and resilience of marine species, the establishment of networks of marine protected areas and the delineation of fishery management units. In the marine environment, understanding connectivity is still a major challenge, due to the technical difficulties of tracking larvae. Recently, parentage analysis has provided a means to address this question effectively. To be effective, this method requires limited adult movement and extensive sampling of parents, which is often not possible for marine species. An alternative approach that is less sensitive to constraints in parental movement and sampling could be the reconstruction of sibships. Here, we directly measure connectivity and larval dispersal in a temperate marine ecosystem through both analytical approaches. We use data from 178 single nucleotide polymorphism markers to perform parentage and sibship reconstruction of the black-faced blenny (Tripterygion delaisi) from an open coastline in the Mediterranean Sea. Parentage analysis revealed a decrease in dispersal success in the focal area over 1 km distance and approximately 6.5% of the juveniles were identified as self-recruits. Sibship reconstruction analysis found that, in general, full siblings did not recruit together to the same location, and that the largest distance between recruitment locations was much higher (11.5 km) than found for parent-offspring pairs (1.2 km). Direct measurements of dispersal are essential to understanding connectivity patterns in different marine habitats, and show the degree of self-replenishment and sustainability of populations of marine organisms. We demonstrate that sibship reconstruction allows direct measurements of dispersal and family structure in marine species while being more easily applied in those species for which the collection of the parental population is difficult or unfeasible.

  17. Identifying motivational factors within a multinational company

    Directory of Open Access Journals (Sweden)

    Daniela Bradutanu

    2011-08-01

    Full Text Available The aim of the study is to identify the main motivational factors within a multinational company. The first objective is to identify work functions, formulated on Abraham Maslow’s pyramid, following the identification of the key characteristics that motivate an employee at the work place and last, but not least, the type of motivation that employees focus, intrinsic or extrinsic. The research method targeted a questionnaire based survey, including various company employees and an interview with the manager. The results confirmed that in Romania, employees put great emphasis on extrinsic motivation, a certain income and job security being primary. These results have implications for managers that in order to effectively motivate staff, first, must know their needs and expectations. To identify the main needs and motivational factors we had as a starting point Maslow's pyramid.

  18. Factor analysis identifies subgroups of constipation

    Institute of Scientific and Technical Information of China (English)

    Philip G Dinning; Mike Jones; Linda Hunt; Sergio E Fuentealba; Jamshid Kalanter; Denis W King; David Z Lubowski; Nicholas J Talley; Ian J Cook

    2011-01-01

    AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging selfreport questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.

  19. Cross-culturally recurrent personality factors : Analyses of three factors

    NARCIS (Netherlands)

    De Raad, B; Peabody, D

    2005-01-01

    This study proceeds from an earlier one that examined the 'Big Five' factors (Peabody & De Raad, 2002). That study considered the substantive nature of five factors from six European psycholexical studies. The results supported Big Five Factor III (Conscientiousness), but Factors I (Extraversion) an

  20. Risk factors identified for certain lymphoma subtypes

    Science.gov (United States)

    In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

  1. Identifying Useful Auxiliary Variables for Incomplete Data Analyses: A Note on a Group Difference Examination Approach

    Science.gov (United States)

    Raykov, Tenko; Marcoulides, George A.

    2014-01-01

    This research note contributes to the discussion of methods that can be used to identify useful auxiliary variables for analyses of incomplete data sets. A latent variable approach is discussed, which is helpful in finding auxiliary variables with the property that if included in subsequent maximum likelihood analyses they may enhance considerably…

  2. Direct targets of the tomato-ripening regulator RIN identified by transcriptome and chromatin immunoprecipitation analyses.

    Science.gov (United States)

    Fujisawa, Masaki; Shima, Yoko; Higuchi, Naoki; Nakano, Toshitsugu; Koyama, Yoshiyuki; Kasumi, Takafumi; Ito, Yasuhiro

    2012-06-01

    The physiological and biochemical changes in fruit ripening produce key attributes of fruit quality including color, taste, aroma and texture. These changes are driven by the highly regulated and synchronized activation of a huge number of ripening-associated genes. In tomato (Solanum lycopersicum), a typical climacteric fruit, the MADS-box transcription factor RIN is one of the earliest-acting ripening regulators, required for both ethylene-dependent and ethylene-independent pathways. Although we previously identified several direct RIN targets, many additional targets remain unidentified, likely including key ripening-associated genes. Here, we report the identification of novel RIN targets by transcriptome and chromatin immunoprecipitation (ChIP) analyses. Transcriptome comparisons by microarray of wild-type and rin mutant tomatoes identified 342 positively regulated genes and 473 negatively regulated genes by RIN during ripening. Most of the positively regulated genes contained possible RIN-binding (CArG-box) sequences in their promoters. Subsequently, we selected six genes from the positively regulated genes and a ripening regulator gene, CNR, and assayed their promoters by quantitative ChIP-PCR to examine RIN binding. All of the seven genes, which are involved in cell wall modification, aroma and flavor development, pathogen defense and transcriptional regulation during ripening, are targets of RIN, suggesting that RIN may control multiple diverse ripening processes. In particular, RIN directly regulates the expression of the ripening-associated transcription factors, CNR, TDR4 and a GRAS family gene, providing an important clue to elucidate the complicated transcriptional cascade for fruit ripening.

  3. Identifying factors affecting optimal management of agricultural water

    Directory of Open Access Journals (Sweden)

    Masoud Samian

    2015-01-01

    In addition to quantitative methodology such as descriptive statistics and factor analysis a qualitative methodology was employed for dynamic simulation among variables through Vensim software. In this study, the factor analysis technique was used through the Kaiser-Meyer-Olkin (KMO and Bartlett tests. From the results, four key elements were identified as factors affecting the optimal management of agricultural water in Hamedan area. These factors were institutional and legal factors, technical and knowledge factors, economic factors and social factors.

  4. Genome-wide meta-analyses identify multiple loci associated with smoking behavior

    NARCIS (Netherlands)

    H. Furberg (Helena); Y. Kim (Yunjung); J. Dackor (Jennifer); E.A. Boerwinkle (Eric); N. Franceschini (Nora); D. Ardissino (Diego); L. Bernardinelli (Luisa); P.M. Mannucci (Pier); F. Mauri (Francesco); P.A. Merlini (Piera); D. Absher (Devin); T.L. Assimes (Themistocles); S.P. Fortmann (Stephen); C. Iribarren (Carlos); J.W. Knowles (Joshua); T. Quertermous (Thomas); L. Ferrucci (Luigi); T. Tanaka (Toshiko); J.C. Bis (Joshua); T. Haritunians (Talin); B. McKnight (Barbara); B.M. Psaty (Bruce); K.D. Taylor (Kent); E.L. Thacker (Evan); P. Almgren (Peter); L. Groop (Leif); C. Ladenvall (Claes); M. Boehnke (Michael); A.U. Jackson (Anne); K.L. Mohlke (Karen); H.M. Stringham (Heather); J. Tuomilehto (Jaakko); E.J. Benjamin (Emelia); S.J. Hwang; D. Levy (Daniel); S.R. Preis; R.S. Vasan (Ramachandran Srini); J. Duan (Jubao); P.V. Gejman (Pablo); D.F. Levinson (Douglas); A.R. Sanders (Alan); J. Shi (Jianxin); E.H. Lips (Esther); J.D. McKay (James); A. Agudo (Antonio); L. Barzan (Luigi); V. Bencko (Vladimir); S. Benhamou (Simone); X. Castellsagué (Xavier); C. Canova (Cristina); D.I. Conway (David); E. Fabianova (Eleonora); L. Foretova (Lenka); V. Janout (Vladimir); C.M. Healy (Claire); I. Holcátová (Ivana); K. Kjaerheim (Kristina); P. Lagiou; J. Lissowska (Jolanta); R. Lowry (Ray); T.V. MacFarlane (Tatiana); D. Mates (Dana); L. Richiardi (Lorenzo); P. Rudnai (Peter); N. Szeszenia-Dabrowska (Neonilia); D. Zaridze; A. Znaor (Ariana); M. Lathrop (Mark); P. Brennan (Paul); S. Bandinelli (Stefania); T.M. Frayling (Timothy); J.M. Guralnik (Jack); Y. Milaneschi (Yuri); J.R.B. Perry (John); D. Altshuler (David); R. Elosua (Roberto); S. Kathiresan (Sekar); G. Lucas (Gavin); O. Melander (Olle); V. Salomaa (Veikko); S.M. Schwartz (Stephen); B.F. Voight (Benjamin); B.W.J.H. Penninx (Brenda); J.H. Smit (Johannes); N. Vogelzangs (Nicole); D.I. Boomsma (Dorret); E.J.C. de Geus (Eco); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); S.J. Chanock (Stephen); F. Gu (Fangyi); S.E. Hankinson (Susan); D. Hunter (David); A. Hofman (Albert); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); S. Walter (Stefan); D.I. Chasman (Daniel); B.M. Everett (Brendan); G. Pare (Guillaume); P.M. Ridker (Paul); M.D. Li (Ming); H.H. Maes (Hermine); J. Audrain-Mcgovern (Janet); D. Posthuma (Danielle); L.M. Thornton (Laura); C. Lerman (Caryn); J. Kaprio (Jaakko); J.E. Rose (Jed); J.P.A. Ioannidis (John); P. Kraft (Peter); D.Y. Lin (Dan); P.F. Sullivan (Patrick); C.J. O'Donnell (Christopher)

    2010-01-01

    textabstractConsistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (

  5. Identifying Causal Risk Factors for Violence among Discharged Patients.

    Directory of Open Access Journals (Sweden)

    Jeremy W Coid

    Full Text Available Structured Professional Judgement (SPJ is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments.We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge, 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3 and Structural Assessment of Protective Factors (SAPROF. Information on violence was obtained via the McArthur community violence instrument and the Police National Computer.In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure on violence (outcome, risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85-12.65, P<0.001, instability (OR 5.41, 95% CI 3.44-8.50, P<0.001, and poor coping/ stress (OR 8.35, 95% CI 4.21-16.57, P<0.001. All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08-0.24, P<0.001 conveyed protective effects and explained the association of other protective factors with violence.Using two standardised SPJ instruments, predictive (lagged methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors causally associated with violence.

  6. Identifying Useful Terms to Retrieve Survival Data Meta-Analyses Publications for Bibliographic Databases Search Strategies

    Directory of Open Access Journals (Sweden)

    Daniel Corneliu LEUCUŢA

    2009-12-01

    Full Text Available Introduction: Quality research and quality evidence based medicine practice has an important pillar in a solid bibliographic documentation. Quality bibliographic documentation makes use of search strategies to retrieve articles from search engines of bibliographic databases. The AIM of this study was the identification of useful search terms to be used in search strategies that try to find meta-analyses of survival data. Materials and methods: A qualitative study based on text analysis was undertaken to identify useful terms for search strategies in abstracts of scientific papers. Survival analysis meta-analyses publication type studies, published between 1996 and 2005, were searched in Medline bibliographic database through Pubmed web interface. Each abstract was analysed and each important terms were noted down if they were considered to be useful in the creation of search strategies for analysis of survival data, or meta-analyses. Results: Pubmed search yielded 773 results. From these search results 401 (52% fulfilled inclusion criteria. The terms that were identified as useful in search strategies for meta-analyses of survival data are presented in the paper.

  7. A Systematic Review of Studies Using the Brief COPE: Religious Coping in Factor Analyses

    Directory of Open Access Journals (Sweden)

    Christian U. Krägeloh

    2011-07-01

    Full Text Available Religion is generally recognized as a major resource for dealing with stressful events, but its relationship with secular coping strategies continues to be debated. The present article provides a systematic review of the way in which analyses of the sub-scale turning to religion of the widely used Brief COPE [1] instrument are presented in peer-reviewed research articles, in order to investigate how the wealth of data published using this instrument can inform how religious coping relates to other coping strategies. Of the 212 identified articles that included turning to religion in their analyses, 80 combined sub-scale scores to form higher-order coping factors, 38 of which based on exploratory factor analyses of their own datasets. When factor analyses had used individual items as indicators, religious coping was more likely to load together with maladaptive coping strategies, and more likely with adaptive coping strategies when analyses were conducted at sub-scale level. To a large extent, the variation in the results from exploratory factor analyses appears to be due to the diverse and often inappropriate factor analytic techniques used to determine the factor structure of the Brief COPE instrument. Reports from factor analyses of the Brief COPE therefore have very little value when trying to make general conclusions about the role of religious coping in relation to secular coping methods.

  8. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    LENUS (Irish Health Repository)

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  9. Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Michael J; Yates, James W T; Evans, Neil D

    2014-05-01

    In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available.

  10. Identifying influential factors on integrated marketing planning using information technology

    Directory of Open Access Journals (Sweden)

    Karim Hamdi

    2014-07-01

    Full Text Available This paper presents an empirical investigation to identify important factors influencing integrated marketing planning using information technology. The proposed study designs a questionnaire for measuring integrated marketing planning, which consists of three categories of structural factors, behavioral factors and background factors. There are 40 questions associated with the proposed study in Likert scale. Cronbach alphas have been calculated for structural factors, behavioral factors and background factors as 0.89, 0.86 and 0.83, respectively. Using some statistical test, the study has confirmed the effects of three factors on integrated marketing. In addition, the implementation of Freedman test has revealed that structural factors were the most important factor followed by background factors and behavioral factors.

  11. Ubiquitination profiling identifies sensitivity factors for IAP antagonist treatment.

    Science.gov (United States)

    Varfolomeev, Eugene; Izrael-Tomasevic, Anita; Yu, Kebing; Bustos, Daisy; Goncharov, Tatiana; Belmont, Lisa D; Masselot, Alexandre; Bakalarski, Corey E; Kirkpatrick, Donald S; Vucic, Domagoj

    2015-02-15

    Evasion of cell death is one crucial capability acquired by tumour cells to ward-off anti-tumour therapies and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote cancer cell survival by mediating proliferative signalling and blocking cell death in response to diverse stimuli. Using immunoaffinity enrichment and MS, ubiquitination sites on thousands of proteins were profiled upon initiation of cell death by IAP antagonists in IAP antagonist-sensitive and -resistant breast cancer cell lines. Our analyses identified hundreds of proteins with elevated levels of ubiquitin-remnant [K-GG (Lys-Gly-Gly)] peptides upon activation of cell death by the IAP antagonist BV6. The majority of these were observed in BV6-sensitive, but not-resistant, cells. Among these were known pro-apoptotic regulators, including CYC (cytochrome c), RIP1 (receptor-interacting protein 1) and a selection of proteins known to reside in the mitochondria or regulate NF-κB (nuclear factor κB) signalling. Analysis of early time-points revealed that IAP antagonist treatment stimulated rapid ubiquitination of NF-κB signalling proteins, including TRAF2 [TNF (tumour necrosis factor) receptor-associated factor 2], HOIL-1 (haem-oxidized iron-regulatory protein 2 ubiquitin ligase-1), NEMO (NF-κB essential modifier), as well as c-IAP1 (cellular IAP1) auto-ubiquitination. Knockdown of several NF-κB pathway members reduced BV6-induced cell death and TNF production in sensitive cell lines. Importantly, RIP1 was found to be constitutively ubiquitinated in sensitive breast-cancer cell lines at higher basal level than in resistant cell lines. Together, these data show the diverse and temporally defined roles of protein ubiquitination following IAP-antagonist treatment and provide critical insights into predictive diagnostics that may enhance clinical efficacy.

  12. Classification of L2 Vocabulary Learning Strategies: Evidence from Exploratory and Confirmatory Factor Analyses

    Science.gov (United States)

    Zhang, Bo; Li, Changyu

    2011-01-01

    This research presents a classification theory for the L2 vocabulary learning strategies. Based on the exploratory and confirmatory factor analyses of strategies that adult Chinese English learners used, this theory identifies six categories, four of which are related to the cognitive process in lexical acquisition and the other two are…

  13. Design factors analyses of second-loop PRHRS

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    ZHANG Hongyan

    2017-05-01

    Full Text Available In order to study the operating characteristics of a second-loop Passive Residual Heat Removal System (PRHRS, the transient thermal analysis code RELAP5 is used to build simulation models of the main coolant system and second-loop PRHRS. Transient calculations and comparative analyses under station blackout accident and one-side feed water line break accident conditions are conducted for three critical design factors of the second-loop PRHRS:design capacity, emergency makeup tank and isolation valve opening speed. The impacts of the discussed design factors on the operating characteristics of the second-loop PRHRS are summarized based on calculations and analyses. The analysis results indicate that the system safety and cooling rate should be taken into consideration in designing PRHRS's capacity,and water injection from emergency makeup tank to steam generator can provide advantage to system cooling in the event of accident,and system startup performance can be improved by reducing the opening speed of isolation valve. The results can provide references for the design of the second-loop PRHRS in nuclear power plants.

  14. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease

    Science.gov (United States)

    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R

    2015-01-01

    Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891

  15. Using Factor Analysis to Identify Topic Preferences Within MBA Courses

    Directory of Open Access Journals (Sweden)

    Earl Chrysler

    2003-02-01

    Full Text Available This study demonstrates the role of a principal components factor analysis in conducting a gap analysis as to the desired characteristics of business alumni. Typically, gap analyses merely compare the emphases that should be given to areas of inquiry with perceptions of actual emphases. As a result, the focus is upon depth of coverage. A neglected area in need of investigation is the breadth of topic dimensions and their differences between the normative (should offer and the descriptive (actually offer. The implications of factor structures, as well as traditional gap analyses, are developed and discussed in the context of outcomes assessment.

  16. Using mixed methods to identify factors influencing patient flow.

    Science.gov (United States)

    Van Vaerenbergh, Cindy

    2009-11-01

    An effective method of identifying operational factors that influence patient flow can potentially lead to improvements and thus have huge benefits on the efficiency of hospital departments. This paper presents a new inductive mixed-method approach to identify operational factors that influence patient flow through an accident and emergency (A&E) department. Preliminary explorative observations were conducted, followed by semi-structured interviews with key stakeholders. A questionnaire survey of all medical, nursing, porter and clerical staff was then conducted. The observations provided factors for further exploration: skill-mix, long working hours, equipment availability, lack of orientation programmes, inefficient IT use and issues regarding communication structures. Interviewees highlighted several factors, including availability of medical supervision and senior nursing staff, nursing documentation issues, lack of morale due to overcrowding, personality differences and factors relating to the department layout. The questionnaire respondents strongly supported the importance of the previously identified factors. This paper demonstrates an effective mixed-method approach that can be replicated by other health-care managers to identify factors influencing patient flow. Further benefits include increased volume and quality of data, increased staff awareness for the influence of internal factors on patient flow and enhancing the evidence base for future decision making when prioritizing A&E projects.

  17. Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth.

    Directory of Open Access Journals (Sweden)

    Richard A White

    Full Text Available It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing, which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.

  18. Can novel genetic analyses help to identify low-dispersal marine invasive species?

    Science.gov (United States)

    Teske, Peter R; Sandoval-Castillo, Jonathan; Waters, Jonathan M; Beheregaray, Luciano B

    2014-07-01

    Genetic methods can be a powerful tool to resolve the native versus introduced status of populations whose taxonomy and biogeography are poorly understood. The genetic study of introduced species is presently dominated by analyses that identify signatures of recent colonization by means of summary statistics. Unfortunately, such approaches cannot be used in low-dispersal species, in which recently established populations originating from elsewhere in the species' native range also experience periods of low population size because they are founded by few individuals. We tested whether coalescent-based molecular analyses that provide detailed information about demographic history supported the hypothesis that a sea squirt whose distribution is centered on Tasmania was recently introduced to mainland Australia and New Zealand through human activities. Methods comparing trends in population size (Bayesian Skyline Plots and Approximate Bayesian Computation) were no more informative than summary statistics, likely because of recent intra-Tasmanian dispersal. However, IMa2 estimates of divergence between putatively native and introduced populations provided information at a temporal scale suitable to differentiate between recent (potentially anthropogenic) introductions and ancient divergence, and indicated that all three non-Tasmanian populations were founded during the period of European settlement. While this approach can be affected by inaccurate molecular dating, it has considerable (albeit largely unexplored) potential to corroborate nongenetic information in species with limited dispersal capabilities.

  19. Use of a latency-based demand assessment to identify potential demands for functional analyses.

    Science.gov (United States)

    Call, Nathan A; Miller, Sarah J; Mintz, Joslyn Cynkus; Mevers, Joanna Lomas; Scheithauer, Mindy C; Eshelman, Julie E; Beavers, Gracie A

    2016-12-01

    Unlike potential tangible positive reinforcers, which are typically identified for inclusion in functional analyses empirically using preference assessments, demands are most often selected arbitrarily or based on caregiver report. The present study evaluated the use of a demand assessment with 12 participants who exhibited escape-maintained problem behavior. Participants were exposed to 10 demands, with aversiveness measured by average latency to the first instance of problem behavior. In subsequent functional analyses, results of a demand condition that included the demand with the shortest latency to problem behavior resulted in identification of an escape function for 11 of the participants. In contrast, a demand condition that included the demand with the longest latency resulted in identification of an escape function for only 5 participants. The implication of these findings is that for the remaining 7 participants, selection of the demand for the functional analysis without using the results of the demand assessment could have produced a false-negative finding. © 2016 Society for the Experimental Analysis of Behavior.

  20. An Illumination Modeling System for Human Factors Analyses

    Science.gov (United States)

    Huynh, Thong; Maida, James C.; Bond, Robert L. (Technical Monitor)

    2002-01-01

    Seeing is critical to human performance. Lighting is critical for seeing. Therefore, lighting is critical to human performance. This is common sense, and here on earth, it is easily taken for granted. However, on orbit, because the sun will rise or set every 45 minutes on average, humans working in space must cope with extremely dynamic lighting conditions. Contrast conditions of harsh shadowing and glare is also severe. The prediction of lighting conditions for critical operations is essential. Crew training can factor lighting into the lesson plans when necessary. Mission planners can determine whether low-light video cameras are required or whether additional luminaires need to be flown. The optimization of the quantity and quality of light is needed because of the effects on crew safety, on electrical power and on equipment maintainability. To address all of these issues, an illumination modeling system has been developed by the Graphics Research and Analyses Facility (GRAF) and Lighting Environment Test Facility (LETF) in the Space Human Factors Laboratory at NASA Johnson Space Center. The system uses physically based ray tracing software (Radiance) developed at Lawrence Berkeley Laboratories, a human factors oriented geometric modeling system (PLAID) and an extensive database of humans and environments. Material reflectivity properties of major surfaces and critical surfaces are measured using a gonio-reflectometer. Luminaires (lights) are measured for beam spread distribution, color and intensity. Video camera performances are measured for color and light sensitivity. 3D geometric models of humans and the environment are combined with the material and light models to form a system capable of predicting lighting conditions and visibility conditions in space.

  1. Identifying and analysing protostellar disc fragments in smoothed particle hydrodynamics simulations

    Science.gov (United States)

    Hall, Cassandra; Forgan, Duncan; Rice, Ken

    2017-09-01

    We present a new method of identifying protostellar disc fragments in a simulation based on density derivatives, and analyse our data using this and the existing CLUMPFIND method, which is based on an ordered search over all particles in gravitational potential energy. Using smoothed particle hydrodynamics, we carry out nine simulations of a 0.25 M⊙ disc around a 1 M⊙ star, all of which fragment to form at least two bound objects. We find that when using all particles ordered in gravitational potential space, only fragments that survive the duration of the simulation are detected. When we use the density derivative method, all fragments are detected, so the two methods are complementary, as using the two methods together allows us to identify all fragments, and to then determine those that are likely to be destroyed. We find a tentative empirical relationship between the dominant azimuthal wavenumber in the disc m and the maximum semimajor axis a fragment may achieve in a simulation, such that amax∝1/m. We find the fragment destruction rate to be around half that predicted from population synthesis models. This is due to fragment-fragment interactions in the early gas phase of the disc, which can cause scattering and eccentricity pumping on short time-scales, and affects the fragment's internal structure. We therefore caution that measurements of eccentricity as a function of semimajor axis may not necessarily constrain the formation mechanism of giant planets and brown dwarfs.

  2. [Analyses prognostic factors relevant to sudden sensorineural hearing loss].

    Science.gov (United States)

    Wang, Jun; Xiao, Shuifang; Zeng, Zhengang; Zhen, Zhen; Zhang, Xuexi; Lin, Feng; Dong, Mingmin; Lu, Wei; Qin, Zhaobing; Zuo, Bin; Bai, Xianfeng

    2015-06-01

    To investigate the prognostic factors relevant to sudden sensorineural hearing loss. The internationally accepted standardized clinical research methods, unified design, and unified program were adopted to conduct the prospective clinical multi-center study. The sudden deafness patients between 18 to 65 years old, with the course of this disorder less than two weeks, and without any medical treatments were collected, and then, divided into four types according to the hearing curve: type A, acute sensorineural hearing loss in low tone frequencies; type B, acute sensorineural hearing loss in high tone frequencies; type C, acute sensorineural hearing loss in all frequencies; and type D, total deafness. The factors, in terms of age, gender, type of initial audiogram, time delay before the first visit, and severity of hearing loss, were included in the analyses. A total of 1 024 cases with single side sudden deafness were collected in the study from 33 hospitals in China from August 2007 to October 2011, inclusive of for 492 males (48.05%) and 532 females (51.95%). The average age was (41.2 ± 12.8) years old. There were 553 cases (54.00%) in left ear, and 471 cases (46.00%) in right ear. The curative effects of different types were shown as follows: the type in low tone frequencies had the highest rate of 90.73%, the type in all frequencies was 82.59%; the type of total deafness was 70.29%; and the type in high tone frequencies had the lowest rate of 65.96%. It had significant difference of the effective rate between different types (χ(2) = 231.58, P = 0.000). Age, time delay before first visit, and severity of initial hearing loss were significantly correlated with hearing improvement. Initial audiogram of SSNHL might predict hearing recovery. The young in age and a short time delay before starting treatment are positive prognostic factors for hearing recovery in SSNHL. The initial severity of hearing loss is negative prognostic factor of hearing recovery.

  3. Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia.

    Science.gov (United States)

    Sugranyes, Gisela; Kyriakopoulos, Marinos; Dima, Danai; O'Muircheartaigh, Jonathan; Corrigall, Richard; Pendelbury, Gabrielle; Hayes, Daniel; Calhoun, Vince D; Frangou, Sophia

    2012-07-01

    Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity. We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted "features" [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources. Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum. This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Trends Analyses for Several Factors Affected by Tropical Cyclones

    Directory of Open Access Journals (Sweden)

    Md. T. Islam

    2011-01-01

    Full Text Available Problem statement: This study presents an analytical investigation for the trends of several factors such as number of death of peoples, damages of wealth, flood surge heights, wind speed and radius of the severe storm due to tropical cyclones in Bangladesh. Approach: The study is performed by conducting the field visits to cyclone site, collected data and information on damages and deaths of peoples during field visits, necessary data related to tropical cyclones obtained from available publications and news-study. The data since the period of the independence of Bangladesh (nearly 40 years are analyzed. Results: The analyses showed that the 17 major cyclones have been occurred since 1970. Among these 17 major cyclones, the 5 cyclones were tragically severe that killed over 400 thousand peoples. It is observed that the coast of the Bay of Bengal is particularly vulnerable to tropical cyclones. It is revealed that Bangladesh is more vulnerable to devastating cyclones in the recent years because the frequency of the severe cyclones has increased remarkably. Conclusion/Recommendation: The return period of the major cyclones was decreased drastically in recent years and the country, especially, the Bengal Bay is predominantly helpless during the cyclone seasons.

  5. Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B

    2012-10-01

    Full Text Available Abstract Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA compared to polyarticular juvenile idiopathic arthritis (POLY. We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR and number of affected joints (joint count, JC. Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF of SJIA compared to samples from the later arthritis-predominant phase (AF. Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with

  6. INNOVATIVE STRATEGIES TO IDENTIFY M. TUBERCULOSIS ANTIGENS AND EPITOPES USING GENOME-WIDE ANALYSES

    Directory of Open Access Journals (Sweden)

    Annemieke eGeluk

    2014-06-01

    Full Text Available In view of the fact that only a small part of the Mtb expressome has been explored for identification of antigens capable of activating human T-cell responses, which is critically required for the design of better TB vaccination strategies, more emphasis should be placed on innovative ways to discover new Mtb antigens and explore their function at the several stages of infection. Better protective antigens for TB vaccines are urgently needed, also in view of the disappointing results of the MVA85 vaccine which failed to induce additional protection in BCG vaccinated infants [54]. Moreover, immune responses to relevant antigens may be useful to identify TB-specific biomarker signatures. Here we describe the potency of novel tools and strategies to reveal such Mtb antigens. Using proteins specific for different Mtb infection phases, many new antigens of the latency-associated Mtb DosR regulon as well as Rpf proteins, associated with resuscitating TB, were discovered that were recognized by CD4+ and CD8+ T-cells. Furthermore, by employing MHC binding algorithms and bioinformatics combined with high throughput human T-cell screens and tetramers, HLA-class Ia restricted poly-functional CD8+ T-cells were identified in TB patients. Comparable methods, led to the identification of HLA-E-restricted Mtb epitopes recognized by CD8+ T-cells. A genome-wide unbiased antigen discovery approach was applied to analyse the in vivo Mtb gene expression profiles in the lungs of mice, resulting in the identification of IVE-TB antigens, which are expressed during infection in the lung, the main target organ of Mtb. IVE-TB antigens induce strong T cell responses in long-term latently Mtb infected individuals, and represent an interesting new group of TB antigens for vaccination. In summary, new tools have helped expand our view on the Mtb antigenome involved in human cellular immunity and provided new candidates for TB vaccination.

  7. Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche.

    Directory of Open Access Journals (Sweden)

    Yao-Zhong Liu

    2009-03-01

    Full Text Available For females, menarche is a most significant physiological event. Age at menarche (AAM is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects--all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan, which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR q<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09 x 10(-3 and 4.37 x 10(-3, respectively, in the Chinese cohort and combined p values (obtained by Fisher's method of 5.19 x 10(-5 and 1.02 x 10(-4, respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2, a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM.

  8. Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments.

    Science.gov (United States)

    Noto, Jennifer M; Chopra, Abha; Loh, John T; Romero-Gallo, Judith; Piazuelo, M Blanca; Watson, Mark; Leary, Shay; Beckett, Amber C; Wilson, Keith T; Cover, Timothy L; Mallal, Simon; Israel, Dawn A; Peek, Richard M

    2017-09-18

    Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease. Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed. A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034). These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Identifying public health policymakers' sources of information: comparing survey and network analyses.

    Science.gov (United States)

    Oliver, Kathryn A; de Vocht, Frank; Money, Annemarie; Everett, Martin

    2017-05-01

    Research suggests that policymakers often use personal contacts to find information and advice. However, the main sources of information for public health policymakers are not known. This study aims to describe policymakers' sources of information. A questionnaire survey of public health policymakers across Greater Manchester (GM) was carried out (response rate 48%). All policy actors above Director level involved in public health policy (finding, analyzing or producing information, producing or implementing policy) in GM were included in the sampling frame. Respondents were provided with a list of sources of information and asked which they used (categorical data) and to name specific individuals who acted as sources of information (network data). Data were analyzed using frequencies and network analysis. The most frequently chosen sources of information from the categorical data were NICE, government websites and Directors of Public Health. However, the network data showed that the main sources of information in the network were actually mid-level managers in the NHS, who had no direct expertise in public health. Academics and researchers did not feature in the network. Both survey and network analyses provide useful insights into how policymakers access information. Network analysis offers practical and theoretical contributions to the evidence-based policy debate. Identifying individuals who act as key users and producers of evidence allows academics to target actors likely to use and disseminate their work.

  10. Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

    Science.gov (United States)

    Zhang, Lei; Choi, Hyung Jin; Estrada, Karol; Leo, Paul J; Li, Jian; Pei, Yu-Fang; Zhang, Yinping; Lin, Yong; Shen, Hui; Liu, Yao-Zhong; Liu, Yongjun; Zhao, Yingchun; Zhang, Ji-Gang; Tian, Qing; Wang, Yu-ping; Han, Yingying; Ran, Shu; Hai, Rong; Zhu, Xue-Zhen; Wu, Shuyan; Yan, Han; Liu, Xiaogang; Yang, Tie-Lin; Guo, Yan; Zhang, Feng; Guo, Yan-fang; Chen, Yuan; Chen, Xiangding; Tan, Lijun; Zhang, Lishu; Deng, Fei-Yan; Deng, Hongyi; Rivadeneira, Fernando; Duncan, Emma L; Lee, Jong Young; Han, Bok Ghee; Cho, Nam H; Nicholson, Geoffrey C; McCloskey, Eugene; Eastell, Richard; Prince, Richard L; Eisman, John A; Jones, Graeme; Reid, Ian R; Sambrook, Philip N; Dennison, Elaine M; Danoy, Patrick; Yerges-Armstrong, Laura M; Streeten, Elizabeth A; Hu, Tian; Xiang, Shuanglin; Papasian, Christopher J; Brown, Matthew A; Shin, Chan Soo; Uitterlinden, André G; Deng, Hong-Wen

    2014-04-01

    Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

  11. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  12. Identifying influential factors of business process performance using dependency analysis

    Science.gov (United States)

    Wetzstein, Branimir; Leitner, Philipp; Rosenberg, Florian; Dustdar, Schahram; Leymann, Frank

    2011-02-01

    We present a comprehensive framework for identifying influential factors of business process performance. In particular, our approach combines monitoring of process events and Quality of Service (QoS) measurements with dependency analysis to effectively identify influential factors. The framework uses data mining techniques to construct tree structures to represent dependencies of a key performance indicator (KPI) on process and QoS metrics. These dependency trees allow business analysts to determine how process KPIs depend on lower-level process metrics and QoS characteristics of the IT infrastructure. The structure of the dependencies enables a drill-down analysis of single factors of influence to gain a deeper knowledge why certain KPI targets are not met.

  13. A comparison of computational methods for identifying virulence factors.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zheng

    Full Text Available Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.

  14. Large-scale association analyses identifies 13 new susceptibility loci for coronary artery disease

    Science.gov (United States)

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, Cardiogenics, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Do, Ron; Doering, Angela; Eifert, Sandra; El Mokhtari, Nour Eddine; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; Faire, Ulf de; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J.Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J.P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Linsel-Nitschke, Patrick; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O’Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 cases and 64,762 controls of European descent, followed by genotyping of top association signals in 60,738 additional individuals. This genomic analysis identified 13 novel loci harboring one or more SNPs that were associated with CAD at P<5×10−8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 novel loci displayed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6 to 17 percent increase in the risk of CAD per allele. Notably, only three of the novel loci displayed significant association with traditional CAD risk factors, while the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the novel CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. PMID:21378990

  15. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    risks (RRs), eg, mucinous differentiation (RR, 9.0), tumor-infiltrating lymphocytes (RR, 7.5), absence of necrosis (RR, 7.5), and expanding growth pattern (RR, 5.0) into a 7-factor index, the presence of at least 4 features identified the MMR-defective tumors with 92.3% sensitivity and 75.3% specificity...... were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative...

  16. Exploratory and confirmatory factor analyses of the pervasive developmental disorders rating scale for young children with autistic disorder.

    Science.gov (United States)

    Eaves, Ronald C; Williams, Thomas O

    2006-03-01

    In this study, the authors examined the construct validity of the Pervasive Developmental Disorder Rating Scale (PDDRS; R. C. Eaves, 1993), which is a screening instrument used to identify individuals with autistic disorder and other pervasive developmental disorders. The PDDRS is purported to measure 3 factors--arousal, affect, and cognition-that collectively make up the construct of autism. Using scores from 199 children (aged 1-6 years) diagnosed with autistic disorder, the authors submitted data to exploratory and confirmatory factor analyses. In the 1st series of analyses, the authors analyzed a user-specified 3-factor solution using principal axis factor analysis with a promax rotation to evaluate the assertion of a correlated 3-factor structure. Next, the authors analyzed 1-factor and 2-factor solutions to determine if they provided a better factor structure for the data. In the 2nd series, the authors conducted confirmatory factor analyses, which compared the theorized hierarchical 2nd-order factor model with 5 plausible competing models. The results of the exploratory analyses supported the 3-factor solution. With the confirmatory analyses, the 2nd-order factor model provided the best fit for the data. The exploratory and confirmatory analyses supported the theoretical assumptions undergirding the development of the PDDRS. The authors discuss theoretical implications, practical implications, and areas for further research.

  17. Identifying critical factors for implementing good agricultural practice

    Directory of Open Access Journals (Sweden)

    Nelson Gutiérrez Guzmán

    2010-05-01

    Full Text Available This paper deals with identifying the critical factors (CFs involved in implementing a good agricultural practice (GAP programme for coffee and fruit farmers in the Huila department of Colombia. An exploratory factor analysis using principal component analy- sis (PCA factorisation was used. Data matrixes were constructed from the results of applying two defined-structure assessment tools to the populations being studied: Starbucks’ coffee and farmer equity (CAFE practices for small-scale coffee growers and coffee-producers and the EUREPGAP V2.1 Oct.2004 / checklist for fruit and vegetables, as applied to fruit-producers. This inves- tigation led to identifying 6 CFs which must be considered when implementing a GAP programme: infrastructure, established production activities, preparing and maintaining records, environmental awareness, workers’ welfare and safety and quality con- trol.

  18. Skin barrier and contact allergy: Genetic risk factor analyses

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine

    2013-01-01

    by extracting epidermal proteins from human surgical waste samples and stratum corneum scrapings followed by binding studies using immobilized metal affinity chromatography. Results As suggested by Kaplan-Meier event history analyses, FLG null mutations lowered the age of onset of nickel dermatitis, when ear...

  19. Calibrating partial factors for Danish railway embankments using probabilistic analyses

    Institute of Scientific and Technical Information of China (English)

    Michael R. Lodahl; Kristian T.Brødbæk; Carsten S.Sørensen

    2014-01-01

    High costs are connected with upgrading railway embankments throughout Denmark using the partial factors for geotechnical design calibrated for general application. One way to reduce the costs is reliability-based calibration of the partial factors to a reasonable safety level taking into account the specific design situations and uncertainties relevant to railway embankments. A reliability-based design has been investigated, resulting in an optimal partial factor for the considered subsoil. With a stochastic soil model to simulate the undrained shear strength of soft soil deposits, the partial factor is calibrated using asymptotic sampling for the reliability assessment. The calibration shows that the partial factor can be reduced significantly compared to the value specified in the Danish National Annex to DS/EN 1997-1 (2007), Eurocode 7.

  20. Calibrating partial factors for Danish railway embankments using probabilistic analyses

    Directory of Open Access Journals (Sweden)

    Michael R. Lodahl

    2014-04-01

    Full Text Available High costs are connected with upgrading railway embankments throughout Denmark using the partial factors for geotechnical design calibrated for general application. One way to reduce the costs is reliability-based calibration of the partial factors to a reasonable safety level taking into account the specific design situations and uncertainties relevant to railway embankments. A reliability-based design has been investigated, resulting in an optimal partial factor for the considered subsoil. With a stochastic soil model to simulate the undrained shear strength of soft soil deposits, the partial factor is calibrated using asymptotic sampling for the reliability assessment. The calibration shows that the partial factor can be reduced significantly compared to the value specified in the Danish National Annex to DS/EN 1997-1 (2007, Eurocode 7.

  1. Identifying important motivational factors for professionals in Greek hospitals

    Science.gov (United States)

    Kontodimopoulos, Nick; Paleologou, Victoria; Niakas, Dimitris

    2009-01-01

    Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements) was used. Three categories of health care professionals, doctors (N = 354), nurses (N = 581) and office workers (N = 418), working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P incentive only for professionals in managerial positions. Health professionals in private hospitals were motivated by all factors significantly more than their public-hospital counterparts. Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation. PMID:19754968

  2. Identifying key hospital service quality factors in online health communities.

    Science.gov (United States)

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

    2015-04-07

    The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

  3. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  4. What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing.

    Directory of Open Access Journals (Sweden)

    Minsam Ko

    Full Text Available Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers' online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans' interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users.

  5. IDENTIFYING MOTIVATION FACTOR INVOLVEMENT OF SARAWAK MALAY WOMEN ENTREPRENEUR

    Directory of Open Access Journals (Sweden)

    Masyantie Mohamad

    2016-03-01

    Full Text Available Sarawak multilayered cake among Sarawak product signature famous among the local as well as international tourist visiting Sarawak. In fact, Sarawak Malay women entrepreneurs have become very necessary players in the entrepreneurial field specifically in this cottage industries from the early introduction of this business, they have facing various problem in this businesses. Thus, this research aims to build an understanding of motivational factor that encourage Sarawak Malay women entrepreneurial experiences especially in multilayered cake businesses. Using qualitative methods, this research aims to identify the entrepreneurial motivations factors; with regards to start-up motivation by Sarawak Malay women. The finding shows that the motivations that influence Malay women within Kuching, Sarawak areas to start and grow their business are involve self-driven and context driven that motivate them involve in multilayered cakes businesses.

  6. Identifying important motivational factors for professionals in Greek hospitals

    Directory of Open Access Journals (Sweden)

    Niakas Dimitris

    2009-09-01

    Full Text Available Abstract Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements was used. Three categories of health care professionals, doctors (N = 354, nurses (N = 581 and office workers (N = 418, working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P P Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation.

  7. Identifying perinatal risk factors for infant maltreatment: an ecological approach

    Directory of Open Access Journals (Sweden)

    Hallisey Elaine J

    2006-12-01

    Full Text Available Abstract Background Child maltreatment and its consequences are a persistent problem throughout the world. Public health workers, human services officials, and others are interested in new and efficient ways to determine which geographic areas to target for intervention programs and resources. To improve assessment efforts, selected perinatal factors were examined, both individually and in various combinations, to determine if they are associated with increased risk of infant maltreatment. State of Georgia birth records and abuse and neglect data were analyzed using an area-based, ecological approach with the census tract as a surrogate for the community. Cartographic visualization suggested some correlation exists between risk factors and child maltreatment, so bivariate and multivariate regression were performed. The presence of spatial autocorrelation precluded the use of traditional ordinary least squares regression, therefore a spatial regression model coupled with maximum likelihood estimation was employed. Results Results indicate that all individual factors or their combinations are significantly associated with increased risk of infant maltreatment. The set of perinatal risk factors that best predicts infant maltreatment rates are: mother smoked during pregnancy, families with three or more siblings, maternal age less than 20 years, births to unmarried mothers, Medicaid beneficiaries, and inadequate prenatal care. Conclusion This model enables public health to take a proactive stance, to reasonably predict areas where poor outcomes are likely to occur, and to therefore more efficiently allocate resources. U.S. states that routinely collect the variables the National Center for Health Statistics (NCHS defines for birth certificates can easily identify areas that are at high risk for infant maltreatment. The authors recommend that agencies charged with reducing child maltreatment target communities that demonstrate the perinatal risks

  8. Identifying neural correlates of visual consciousness with ALE meta-analyses.

    Science.gov (United States)

    Bisenius, Sandrine; Trapp, Sabrina; Neumann, Jane; Schroeter, Matthias L

    2015-11-15

    Neural correlates of consciousness (NCC) have been a topic of study for nearly two decades. In functional imaging studies, several regions have been proposed to constitute possible candidates for NCC, but as of yet, no quantitative summary of the literature on NCC has been done. The question whether single (striate or extrastriate) regions or a network consisting of extrastriate areas that project directly to fronto-parietal regions are necessary and sufficient neural correlates for visual consciousness is still highly debated [e.g., Rees et al., 2002, Nat Rev. Neurosci 3, 261-270; Tong, 2003, Nat Rev. Neurosci 4, 219-229]. The aim of this work was to elucidate this issue and give a synopsis of the present state of the art by conducting systematic and quantitative meta-analyses across functional magnetic resonance imaging (fMRI) studies using several standard paradigms for conscious visual perception. In these paradigms, consciousness is operationalized via perceptual changes, while the visual stimulus remains invariant. An activation likelihood estimation (ALE) meta-analysis was performed, representing the best approach for voxel-wise meta-analyses to date. In addition to computing a meta-analysis across all paradigms, separate meta-analyses on bistable perception and masking paradigms were conducted to assess whether these paradigms show common or different NCC. For the overall meta-analysis, we found significant clusters of activation in inferior and middle occipital gyrus; fusiform gyrus; inferior temporal gyrus; caudate nucleus; insula; inferior, middle, and superior frontal gyri; precuneus; as well as in inferior and superior parietal lobules. These results suggest a subcortical-extrastriate-fronto-parietal network rather than a single region that constitutes the necessary NCC. The results of our exploratory paradigm-specific meta-analyses suggest that this subcortical-extrastriate-fronto-parietal network might be differentially activated as a function of the

  9. Treks'n Rapids: Identifying Motivational Factors for Adventure Sports

    Directory of Open Access Journals (Sweden)

    Kshitij Saxena

    2010-01-01

    Full Text Available Problem statement: Treks’n Rapids, a leading adventure sports and human resource enrichment company in India, wanted to identify main motivational factors of attraction towards adventure sports among youths of National Capital Region. Objective was to improve the effectiveness of integrated marketing communications strategy. Adventure sports are categorized into four classes: (1 mountain sports; (2 extreme sports like bungee jumping and free fall; (3 rafting and kayaking; (4 paragliding, sky diving and skiing. A total of fifteen motivational factors have been identified with the help of literature review and an exploratory study. These are: Thrill, Requires zeal/energy, Spells status, Builds confidence, Helps in personality development, Instills self-belief, Creates unique identity, Is a stress buster, Helps in goal-setting, Is challenging, Requires toughness, Builds sense of achievement, Is a unique experience, It is fun/adventure and Improved technology has reduced risk. Approach: A questionnaire was created and sent to over 500 people online. Through word of mouth people were encouraged to visit the website and respond to the questionnaire. Fifty-seven responses were obtained. These were analyzed using SPSS. Results: Only two factors were extracted. First all the 57 responses were analyzed as a whole to find out the main motivational factors. Next each of the four individual categories of adventure sports was separately analyzed and results were found to be highly consistent. Two composite variables that emerged are labeled as: (1 characteristics of the adventure sports encompassing: thrill, challenge, fun, toughness and zeal required; (2 characteristics of the self like: building confidence, personality development, sense of achievement, status, self-belief and help in goal setting. Resultant factors were used to discriminate respondents based on gender and spend. In both the cases more than 73% of original grouped cases were found to be

  10. Identifying Human Factors Issues in Aircraft Maintenance Operations

    Science.gov (United States)

    Veinott, Elizabeth S.; Kanki, Barbara G.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    Maintenance operations incidents submitted to the Aviation Safety Reporting System (ASRS) between 1986-1992 were systematically analyzed in order to identify issues relevant to human factors and crew coordination. This exploratory analysis involved 95 ASRS reports which represented a wide range of maintenance incidents. The reports were coded and analyzed according to the type of error (e.g, wrong part, procedural error, non-procedural error), contributing factors (e.g., individual, within-team, cross-team, procedure, tools), result of the error (e.g., aircraft damage or not) as well as the operational impact (e.g., aircraft flown to destination, air return, delay at gate). The main findings indicate that procedural errors were most common (48.4%) and that individual and team actions contributed to the errors in more than 50% of the cases. As for operational results, most errors were either corrected after landing at the destination (51.6%) or required the flight crew to stop enroute (29.5%). Interactions among these variables are also discussed. This analysis is a first step toward developing a taxonomy of crew coordination problems in maintenance. By understanding what variables are important and how they are interrelated, we may develop intervention strategies that are better tailored to the human factor issues involved.

  11. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with se

  12. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  13. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

    DEFF Research Database (Denmark)

    Sinner, Moritz F; Tucker, Nathan R; Lunetta, Kathryn L

    2014-01-01

    BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-re...

  14. Asthma trajectories in early childhood: identifying modifiable factors.

    Directory of Open Access Journals (Sweden)

    Lidia Panico

    Full Text Available BACKGROUND: There are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories. DATA AND METHODS: The Millennium Cohort Study is a large, representative birth cohort of British children born in 2000-2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity. RESULTS: Our model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample; a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%; a trajectory with high prevalence of both wheeze and other atopic symptoms (9%; and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%. These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation. CONCLUSION: Using data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles

  15. Analyses of the xylem sap proteomes identified candidate Fusarium virguliforme proteinacious toxins.

    Directory of Open Access Journals (Sweden)

    Nilwala S Abeysekara

    Full Text Available BACKGROUND: Sudden death syndrome (SDS caused by the ascomycete fungus, Fusarium virguliforme, exhibits root necrosis and leaf scorch or foliar SDS. The pathogen has never been identified from the above ground diseased foliar tissues. Foliar SDS is believed to be caused by host selective toxins, including FvTox1, secreted by the fungus. This study investigated if the xylem sap of F. virguliforme-infected soybean plants contains secreted F. virguliforme-proteins, some of which could cause foliar SDS development. RESULTS: Xylem sap samples were collected from five biological replications of F. virguliforme-infected and uninfected soybean plants under controlled conditions. We identified five F. virguliforme proteins from the xylem sap of the F. virguliforme-infected soybean plants by conducting LC-ESI-MS/MS analysis. These five proteins were also present in the excreted proteome of the pathogen in culture filtrates. One of these proteins showed high sequence identity to cerato-platanin, a phytotoxin produced by Ceratocystis fimbriata f. sp. platani to cause canker stain disease in the plane tree. Of over 500 soybean proteins identified in this study, 112 were present in at least 80% of the sap samples collected from F. virguliforme-infected and -uninfected control plants. We have identified four soybean defense proteins from the xylem sap of F. virguliforme-infected soybean plants. The data have been deposited to the ProteomeXchange with identifier PXD000873. CONCLUSION: This study confirms that a few F. virguliforme proteins travel through the xylem, some of which could be involved in foliar SDS development. We have identified five candidate proteinaceous toxins, one of which showed high similarity to a previously characterized phytotoxin. We have also shown the presence of four soybean defense proteins in the xylem sap of F. virguliforme-infected soybean plants. This study laid the foundation for studying the molecular basis of foliar SDS

  16. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer.

    Science.gov (United States)

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh'd; Singh, Ajay P

    2016-06-29

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA-damage and -repair responses, p53 and HIF1α. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer.

  17. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses.

    Directory of Open Access Journals (Sweden)

    Jessica L Gilbert

    Full Text Available Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (P<0.001 were found with sweetness (R2 = 0.70, texture (R2 = 0.68, and flavor (R2 = 0.63. Sourness had a significantly negative relationship with overall liking (R2 = 0.55. The relationship between flavor and texture liking was also linear (R2 = 0.73, P<0.0001 demonstrating interaction between olfaction and somatosensation. Partial least squares analysis was used to identify sugars, acids, and volatile compounds contributing to liking and sensory intensities, and revealed strong effects of fructose, pH, and several volatile compounds upon all sensory parameters measured. To assess the feasibility of breeding for flavor components, a three year study was conducted to compare genetic and environmental influences on flavor biochemistry. Panelists could discern genotypic variation in blueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, β-caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their

  18. Comparative analyses identify molecular signature of MRI-classified SVZ-associated glioblastoma.

    Science.gov (United States)

    Lin, Chin-Hsing Annie; Rhodes, Christopher T; Lin, ChenWei; Phillips, Joanna J; Berger, Mitchel S

    2017-04-18

    Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM. In the absence of IDH mutation, several genes associated with metabolism are differentially expressed in these subtypes of primary GBM, implicating metabolic reprogramming occurs in tumor microenvironment. Furthermore, histone lysine methyltransferase EZH2 was upregulated while histone lysine demethylases KDM2 and KDM4 were downregulated in both group I and II primary GBM. Lastly, we identified 9 common genes across large data sets of gene expression profiles among MRI-classified group I/II GBM, a large cohort of GBM subtypes from TCGA, and glioma stem cells by unsupervised clustering comparison. These commonly upregulated genes have known functions in cell cycle, centromere assembly, chromosome segregation, and mitotic progression. Our findings highlight altered expression of genes important in chromosome integrity across all GBM, suggesting a common mechanism of disrupted fidelity of chromosome structure in GBM.

  19. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

    Science.gov (United States)

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Xu, Chun; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana; Lee, Annette T; Mason, Andrew L; Myers, Robert P; Peltekian, Kevork M; Ghent, Cameron N; Bernuzzi, Francesca; Zuin, Massimo; Rosina, Floriano; Borghesio, Elisabetta; Floreani, Annarosa; Lazzari, Roberta; Niro, Grazia; Andriulli, Angelo; Muratori, Luigi; Muratori, Paolo; Almasio, Piero L; Andreone, Pietro; Margotti, Marzia; Brunetto, Maurizia; Coco, Barbara; Alvaro, Domenico; Bragazzi, Maria C; Marra, Fabio; Pisano, Alessandro; Rigamonti, Cristina; Colombo, Massimo; Marzioni, Marco; Benedetti, Antonio; Fabris, Luca; Strazzabosco, Mario; Portincasa, Piero; Palmieri, Vincenzo O; Tiribelli, Claudio; Croce, Lory; Bruno, Savino; Rossi, Sonia; Vinci, Maria; Prisco, Cleofe; Mattalia, Alberto; Toniutto, Pierluigi; Picciotto, Antonio; Galli, Andrea; Ferrari, Carlo; Colombo, Silvia; Casella, Giovanni; Morini, Lorenzo; Caporaso, Nicola; Colli, Agostino; Spinzi, Giancarlo; Montanari, Renzo; Gregersen, Peter K; Heathcote, E Jenny; Hirschfield, Gideon M; Siminovitch, Katherine A; Amos, Christopher I; Gershwin, M Eric; Seldin, Michael F

    2011-01-01

    A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38). PMID:20639880

  20. Identifying Key Workplace Stressors Affecting Twentieth Air Force: Analyses Conducted from December 2012 Through February 2013

    Science.gov (United States)

    2014-01-01

    approaches from which to choose, the NEO Personality Inventory–Revised and the IPIP Big Five Factor Markers scale are excellent starting points for 20 AF...large- scale survey was not a viable option. Instead, we con- ducted a series of in-depth group interviews (i.e., focus groups) and piloted some...answer is yes. We included two measures of stress—a single item eval- uating how stressful they perceived their jobs to be and a scale measur- ing job

  1. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses.

    Science.gov (United States)

    Gilbert, Jessica L; Guthart, Matthew J; Gezan, Salvador A; Pisaroglo de Carvalho, Melissa; Schwieterman, Michael L; Colquhoun, Thomas A; Bartoshuk, Linda M; Sims, Charles A; Clark, David G; Olmstead, James W

    2015-01-01

    Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids) genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (Pflavor (R2 = 0.63). Sourness had a significantly negative relationship with overall liking (R2 = 0.55). The relationship between flavor and texture liking was also linear (R2 = 0.73, Pflavor components, a three year study was conducted to compare genetic and environmental influences on flavor biochemistry. Panelists could discern genotypic variation in blueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, β-caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their breeding is worthwhile.

  2. Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.

    Science.gov (United States)

    Mendizabal, Isabel; Shi, Lei; Keller, Thomas E; Konopka, Genevieve; Preuss, Todd M; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V

    2016-11-01

    How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.

    Science.gov (United States)

    Hancock, Dana B; Eijgelsheim, Mark; Wilk, Jemma B; Gharib, Sina A; Loehr, Laura R; Marciante, Kristin D; Franceschini, Nora; van Durme, Yannick M T A; Chen, Ting-Hsu; Barr, R Graham; Schabath, Matthew B; Couper, David J; Brusselle, Guy G; Psaty, Bruce M; van Duijn, Cornelia M; Rotter, Jerome I; Uitterlinden, André G; Hofman, Albert; Punjabi, Naresh M; Rivadeneira, Fernando; Morrison, Alanna C; Enright, Paul L; North, Kari E; Heckbert, Susan R; Lumley, Thomas; Stricker, Bruno H C; O'Connor, George T; London, Stephanie J

    2010-01-01

    Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV(1)) and its ratio to forced vital capacity (FEV(1)/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV(1)/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV(1) (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.

  4. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

    Science.gov (United States)

    Lesseur, Corina; Diergaarde, Brenda; Olshan, Andrew F; Wünsch-Filho, Victor; Ness, Andrew R; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, José; Franceschi, Silvia; Lagiou, Pagona; Macfarlane, Gary J; Richiardi, Lorenzo; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Kristina; Zaridze, David; Johansson, Mattias; Menezes, Ana M; Curado, Maria Paula; Robinson, Max; Ahrens, Wolfgang; Canova, Cristina; Znaor, Ariana; Castellsagué, Xavier; Conway, David I; Holcátová, Ivana; Mates, Dana; Vilensky, Marta; Healy, Claire M; Szeszenia-Dąbrowska, Neonila; Fabiánová, Eleonóra; Lissowska, Jolanta; Grandis, Jennifer R; Weissler, Mark C; Tajara, Eloiza H; Nunes, Fabio D; de Carvalho, Marcos B; Thomas, Steve; Hung, Rayjean J; Peters, Wilbert H M; Herrero, Rolando; Cadoni, Gabriella; Bueno-de-Mesquita, H Bas; Steffen, Annika; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valérie; Chabrier, Amélie; Anantharaman, Devasena; Boffetta, Paolo; Amos, Christopher I; McKay, James D; Brennan, Paul

    2016-12-01

    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

  5. Genetic and functional analyses identify DISC1 as a novel callosal agenesis candidate gene.

    Science.gov (United States)

    Osbun, Nathan; Li, Jiang; O'Driscoll, Mary C; Strominger, Zoe; Wakahiro, Mari; Rider, Eric; Bukshpun, Polina; Boland, Elena; Spurrell, Cailyn H; Schackwitz, Wendy; Pennacchio, Len A; Dobyns, William B; Black, Graeme C M; Sherr, Elliott H

    2011-08-01

    Agenesis of the corpus callosum (AgCC) is a congenital brain malformation that occurs in approximately 1:1,000-1:6,000 births. Several syndromes associated with AgCC have been traced to single gene mutations; however, the majority of AgCC causes remain unidentified. We investigated a mother and two children who all shared complete AgCC and a chromosomal deletion at 1q42. We fine mapped this deletion and show that it includes Disrupted-in-Schizophrenia 1 (DISC1), a gene implicated in schizophrenia and other psychiatric disorders. Furthermore, we report a de novo chromosomal deletion at 1q42.13 to q44, which includes DISC1, in another individual with AgCC. We resequenced DISC1 in a cohort of 144 well-characterized AgCC individuals and identified 20 sequence changes, of which 4 are rare potentially pathogenic variants. Two of these variants were undetected in 768 control chromosomes. One of these is a splice site mutation at the 5' boundary of exon 11 that dramatically reduces full-length mRNA expression of DISC1, but not of shorter forms. We investigated the developmental expression of mouse DISC1 and find that it is highly expressed in the embryonic corpus callosum at a critical time for callosal formation. Taken together our results suggest a significant role for DISC1 in corpus callosum development.

  6. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

    Science.gov (United States)

    Hoffmann, Thomas J; Ehret, Georg B; Nandakumar, Priyanka; Ranatunga, Dilrini; Schaefer, Catherine; Kwok, Pui-Yan; Iribarren, Carlos; Chakravarti, Aravinda; Risch, Neil

    2017-01-01

    Longitudinal electronic health records on 99,785 Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort individuals provided 1,342,814 systolic and diastolic blood pressure measurements for a genome-wide association study on long-term average systolic, diastolic, and pulse pressure. We identified 39 new loci among 75 genome-wide significant loci (P ≤ 5 × 10(-8)), with most replicating in the combined International Consortium for Blood Pressure (ICBP; n = 69,396) and UK Biobank (UKB; n = 152,081) studies. Combining GERA with ICBP yielded 36 additional new loci, with most replicating in UKB. Combining all three studies (n = 321,262) yielded 241 additional genome-wide significant loci, although no replication sample was available for these. All associated loci explained 2.9%, 2.5%, and 3.1% of variation in systolic, diastolic, and pulse pressure, respectively, in GERA non-Hispanic whites. Using multiple blood pressure measurements in GERA doubled the variance explained. A normalized risk score was associated with time to onset of hypertension (hazards ratio = 1.18, P = 8.2 × 10(-45)). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery.

  7. Coupled biophysical global ocean model and molecular genetic analyses identify multiple introductions of cryptogenic species.

    Science.gov (United States)

    Dawson, Michael N; Sen Gupta, Alex; England, Matthew H

    2005-08-23

    The anthropogenic introduction of exotic species is one of the greatest modern threats to marine biodiversity. Yet exotic species introductions remain difficult to predict and are easily misunderstood because knowledge of natural dispersal patterns, species diversity, and biogeography is often insufficient to distinguish between a broadly dispersed natural population and an exotic one. Here we compare a global molecular phylogeny of a representative marine meroplanktonic taxon, the moon-jellyfish Aurelia, with natural dispersion patterns predicted by a global biophysical ocean model. Despite assumed high dispersal ability, the phylogeny reveals many cryptic species and predominantly regional structure with one notable exception: the globally distributed Aurelia sp.1, which, molecular data suggest, may occasionally traverse the Pacific unaided. This possibility is refuted by the ocean model, which shows much more limited dispersion and patterns of distribution broadly consistent with modern biogeographic zones, thus identifying multiple introductions worldwide of this cryptogenic species. This approach also supports existing evidence that (i) the occurrence in Hawaii of Aurelia sp. 4 and other native Indo-West Pacific species with similar life histories is most likely due to anthropogenic translocation, and (ii) there may be a route for rare natural colonization of northeast North America by the European marine snail Littorina littorea, whose status as endemic or exotic is unclear.

  8. Identifying differential transcription factor binding in ChIP-seq

    Directory of Open Access Journals (Sweden)

    Dai-Ying eWu

    2015-04-01

    Full Text Available ChIP seq is a widely used assay to measure genome-wide protein binding. The decrease in costs associated with sequencing has led to a rise in the number of studies that investigate protein binding across treatment conditions or cell lines. In addition to the identification of binding sites, new studies evaluate the variation in protein binding between conditions. A number of approaches to study differential transcription factor binding have recently been developed. Several of these methods build upon established methods from RNA-seq to quantify differences in read counts. We compare how these new approaches perform on different data sets from the ENCODE project to illustrate the impact of data processing pipelines under different study designs. The performance of normalization methods for differential ChIP-seq depends strongly on the variation in total amount of protein bound between conditions, with total read count outperforming effective library size, or variants thereof, when a large variation in binding was studied. Use of input subtraction to correct for non-specific binding showed a relatively modest impact on the number of differential peaks found and the fold change accuracy to biological validation, however a larger impact might be expected for samples with more extreme copy number variations between them. Still, it did identify a small subset of novel differential regions while excluding some differential peaks in regions with high background signal.These results highlight proper scaling for between-sample data normalization as critical for differential transcription factor binding analysis and suggest bioinformaticians need to know about the variation in level of total protein binding between conditions to select the best analysis method. At the same time, validation using fold-change estimates from qRT-PCR suggests there is still room for further method improvement.

  9. Identifying differential transcription factor binding in ChIP-seq.

    Science.gov (United States)

    Wu, Dai-Ying; Bittencourt, Danielle; Stallcup, Michael R; Siegmund, Kimberly D

    2015-01-01

    ChIP seq is a widely used assay to measure genome-wide protein binding. The decrease in costs associated with sequencing has led to a rise in the number of studies that investigate protein binding across treatment conditions or cell lines. In addition to the identification of binding sites, new studies evaluate the variation in protein binding between conditions. A number of approaches to study differential transcription factor binding have recently been developed. Several of these methods build upon established methods from RNA-seq to quantify differences in read counts. We compare how these new approaches perform on different data sets from the ENCODE project to illustrate the impact of data processing pipelines under different study designs. The performance of normalization methods for differential ChIP-seq depends strongly on the variation in total amount of protein bound between conditions, with total read count outperforming effective library size, or variants thereof, when a large variation in binding was studied. Use of input subtraction to correct for non-specific binding showed a relatively modest impact on the number of differential peaks found and the fold change accuracy to biological validation, however a larger impact might be expected for samples with more extreme copy number variations between them. Still, it did identify a small subset of novel differential regions while excluding some differential peaks in regions with high background signal. These results highlight proper scaling for between-sample data normalization as critical for differential transcription factor binding analysis and suggest bioinformaticians need to know about the variation in level of total protein binding between conditions to select the best analysis method. At the same time, validation using fold-change estimates from qRT-PCR suggests there is still room for further method improvement.

  10. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  11. Using Logistic Regression to Identify Risk Factors Causing Rollover Collisions

    Directory of Open Access Journals (Sweden)

    Essam Dabbour

    2012-12-01

    Full Text Available Rollover collisions are among the most serious collisions that usually result in severe injuries or fatalities. In 2009, there were 8,732 fatal rollover collisions in the United States of America that resulted in the death of 9,833 persons. Those numbers represent approximately 28% and 29% of the total numbers of fatal collisions and fatalities, respectively. The main objective of this paper is to examine the impact of different risk factors that may contribute to this type of serious collisions to help develop countermeasures that limit them. To avoid the bias that may be caused by interactions among different drivers, this analysis focuses on rollover related to single-vehicle collisions so that the behavior of the driver of the collided vehicle can be analyzed more effectively. Logistic regression technique is utilized to analyze single-vehicle rollover collisions that occurred on state and interstate highways in the states of Ohio and Washington in 2009. The results obtained from this analysis have the potential to help decision makers identify different strategies to limit the severity of this type of collisions.

  12. How to Identify and Prioritize Psychosocial Factors Impacting Stress Level.

    Directory of Open Access Journals (Sweden)

    Mounia N Hocine

    Full Text Available We develop a methodological approach to identify and prioritize psychosocial factors (stressors requiring priority action to reduce stress levels. Data analysis was carried out on a random sample of 10 000 French employees who completed, during a routine interview with the occupational physician, a 25-item questionnaire about stress levels, as well as a questionnaire about 58 stressors grouped into 5 latent variables: job control, job context, relationships at work, tasks performed and recognition. Our method combines Importance-Performance Analysis, a valuable approach for prioritizing improvements in the quality of services, with Partial Least Squares-Path modeling, a Structural Equation Modeling approach widely applied in psychosocial research. Findings on our data suggest two areas worthy of attention: one with five stressors on which decision makers should concentrate, and another with five stressors that managers should leave alone when acting to reduce stress levels. We show that IPA is robust when answers to questions are dichotomized, as opposed to the initial 6-point Likert scale. We believe that our approach will be a useful tool for experts and decision-makers in the field of stress management and prevention.

  13. Development and Validation of a Method to Identify Children With Social Complexity Risk Factors.

    Science.gov (United States)

    Schrager, Sheree M; Arthur, Kimberly C; Nelson, Justine; Edwards, Anne R; Murphy, J Michael; Mangione-Smith, Rita; Chen, Alex Y

    2016-09-01

    We sought to develop and validate a method to identify social complexity risk factors (eg, limited English proficiency) using Minnesota state administrative data. A secondary objective was to examine the relationship between social complexity and caregiver-reported need for care coordination. A total of 460 caregivers of children with noncomplex chronic conditions enrolled in a Minnesota public health care program were surveyed and administrative data on these caregivers and children were obtained. We validated the administrative measures by examining their concordance with caregiver-reported indicators of social complexity risk factors using tetrachoric correlations. Logistic regression analyses subsequently assessed the association between social complexity risk factors identified using Minnesota's state administrative data and caregiver-reported need for care coordination, adjusting for child demographics. Concordance between administrative and caregiver-reported data was moderate to high (correlation range 0.31-0.94, all P values risk factor was significantly associated with need for care coordination before (unadjusted odds ratio = 1.65; 95% confidence interval, 1.07-2.53) but not after adjusting for child demographic factors (adjusted odds ratio = 1.53; 95% confidence interval, 0.98-2.37). Social complexity risk factors may be accurately obtained from state administrative data. The presence of these risk factors may heighten a family's need for care coordination and/or other services for children with chronic illness, even those not considered medically complex. Copyright © 2016 by the American Academy of Pediatrics.

  14. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

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    Samuel E Jones

    2016-08-01

    Full Text Available Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8, including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12 and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10. The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8. For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16 and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9. Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05; undersleeping and BMI (rG = 0.147, P = 1x10-5 and oversleeping and BMI (rG = 0.097, P = 0.04, Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and

  15. Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

    OpenAIRE

    2014-01-01

    Aim Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. Methods We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal ti...

  16. Identifying Sociological Factors for the Success of Space Exploration

    Science.gov (United States)

    Lundquist, C. A.; Tarter, D.; Coleman, A.

    Astrosociology factors relevant to success of future space exploration may best be identified through studies of sociological circumstances of past successful explorations, such as the Apollo-Lunar Missions. These studies benefit from access to primary records of the past programs. The Archives and Special Collections Division of the Salmon Library at the University of Alabama Huntsville (UAH) houses large collections of material from the early periods of the space age. The Huntsville campus of the University of Alabama System had its birth in the mid-1950s at the time when the von Braun rocket team was relocated from Texas to Huntsville. The University, the City of Huntsville and the US Government rocket organizations developed in parallel over subsequent years. As a result, the University has a significant space heritage and focus. This is true not only for the engineering and science disciplines, but also for the social sciences. The life of the University spans the period when Huntsville government and industrial organizations were responsible for producing the rocket vehicles to first take mankind to the Moon. That endeavor was surely as significant sociologically as technologically. In the 1980s, Donald E. Tarter, conducted a series of video interviews with some leading members of the original von Braun team. Although the interviews ranged over many engineering subjects, they also recorded personal features of people involved in the Apollo lunar exploration program and the interactions between these people. Such knowledge was of course an objective. These interviews are now in the collections of the UAH Library Archives, along with extensive documentation from the same period. Under sponsorship of the Archives and the NASA-Marshall Retiree Association, the interview series was restarted in 2006 to obtain comparable oral-history interviews with more than fifty US born members of the rocket team from the 1960s. Again these video interviews are rich with

  17. Meta-analyses identify 13 novel loci associated with age at menopause and highlights DNA repair and immune pathways

    Science.gov (United States)

    Stolk, Lisette; Perry, John RB; Chasman, Daniel I; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M; Ernst, Florian; Esko, Tõnu; Franceschini, Nora; Gudbjartsson, Daniel F; Hottenga, Jouke-Jan; Kraft, Peter; McArdle, Patick F; Porcu, Eleonora; Shin, So-Youn; Smith, Albert V; van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V; Albrecht, Eva; Alizadeh, Behrooz Z; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J; Burri, Andrea; Campbell, Harry; Chanock, Stephen J; Chen, Constance; Cornelis, Marilyn C; Corre, Tanguy; Coviello, Andrea D; d’Adamo, Pio; Davies, Gail; de Faire, Ulf; de Geus, Eco JC; Deary, Ian J; Dedoussis, George VZ; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G; Fauser, Bart CJM; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R; Garcia, Melissa E; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E; Hall, Per; Haller, Toomas; Hankinson, Susan E; Hass, Merli; Hayward, Caroline; Heath, Andrew C; Hofman, Albert; Ingelsson, Erik; Janssens, A Cecile JW; Johnson, Andrew D; Karasik, David; Kardia, Sharon LR; Keyzer, Jules; Kiel, Douglas P; Kolcic, Ivana; Kutalik, Zoltán; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop SE; Lawlor, Debbie A; Liu, Jianjun; Lopez, Lorna M; Louwers, Yvonne V; Magnusson, Patrik KE; Marongiu, Mara; Martin, Nicholas G; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B; Nyholt, Dale R; Onland-Moret, N. Charlotte; Palotie, Aarno; Paré, Guillaume; Parker, Alex N; Pedersen, Nancy L; Peeters, Petra HM; Pistis, Giorgio; Plump, Andrew S; Polasek, Ozren; Pop, Victor JM; Psaty, Bruce M; Räikkönen, Katri; Rehnberg, Emil; Rotter, Jerome I; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N; Starr, John M; Stathopoulou, Maria G; Stirrups, Kathleen; Stolk, Ronald P; Styrkarsdottir, Unnur; Sun, Yan V; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; van Dam, Rob M; van der Schouw, Yvonne T; van Gils, Carla H; van Nierop, Peter; Vink, Jacqueline M; Visscher, Peter M; Voorhuis, Marlies; Waeber, Gérard; Wallaschofski, Henri; Wichmann, H Erich; Widen, Elisabeth; Gent, Colette JM Wijnands-van; Willemsen, Gonneke; Wilson, James F; Wolffenbuttel, Bruce HR; Wright, Alan F; Yerges-Armstrong, Laura M; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M. Carola; Zygmunt, Marek; Arnold, Alice M; Boomsma, Dorret I; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W; Gudnason, Vilmundur; Harris, Tamara B; Hu, Frank B; Hunter, David J; Launer, Lenore J; Metspalu, Andres; Montgomery, Grant W; Oostra, Ben A; Ridker, Paul M; Sanna, Serena; Schlessinger, David; Spector, Tim D; Stefansson, Kari; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, André G; van Duijn, Cornelia M; Völzke, Henry; Murray, Anna; Murabito, Joanne M; Visser, Jenny A; Lunetta, Kathryn L

    2011-01-01

    To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci (P < 5 × 10−8). The new loci included genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1) and immune function (IL11, NLRP11, BAT2). Gene-set enrichment pathway analyses using the full GWAS dataset identified exodeoxyribonuclease, NFκB signalling and mitochondrial dysfunction as biological processes related to timing of menopause. PMID:22267201

  18. Dimensionality of the Chinese Dyadic Adjustment Scale Based on Confirmatory Factor Analyses

    Science.gov (United States)

    Shek, Daniel T. L.; Cheung, C. K.

    2008-01-01

    Based on the responses of 1,501 Chinese married adults to the Chinese version of the Dyadic Adjustment Scale (C-DAS), confirmatory factor analyses showed that four factors were abstracted from the C-DAS (Dyadic Consensus, Dyadic Cohesion, Dyadic Satisfaction and Affectional Expression) and these four primary factors were subsumed under a…

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

    Directory of Open Access Journals (Sweden)

    Jingjing Liang

    2017-05-01

    Full Text Available 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.

  20. Development of a Body Image Concern Scale using both exploratory and confirmatory factor analyses in Chinese university students

    Directory of Open Access Journals (Sweden)

    He W

    2017-05-01

    Full Text Available Wenxin He, Qiming Zheng, Yutian Ji, Chanchan Shen, Qisha Zhu, Wei Wang Department of Clinical Psychology and Psychiatry, School of Public Health, Zhejiang University College of Medicine, Hangzhou, People’s Republic of China Background: The body dysmorphic disorder is prevalent in general population and in psychiatric, dermatological, and plastic-surgery patients, but there lacks a structure-validated, comprehensive self-report measure of body image concerns, which is established through both exploratory and confirmatory factor analyses. Methods: We have composed a 34-item matrix targeting the body image concerns and trialed it in 328 male and 365 female Chinese university students. Answers to the matrix dealt with treatments including exploratory factor analyses, reserve of qualified items, and confirmatory factor analyses of latent structures. Results: Six latent factors, namely the Social Avoidance, Appearance Dissatisfaction, Preoccupation with Reassurance, Perceived Distress/Discrimination, Defect Hiding, and Embarrassment in Public, were identified. The factors and their respective items have composed a 24-item questionnaire named as the Body Image Concern Scale. Each factor earned a satisfactory internal reliability, and the intercorrelations between these factors were in a median level. Women scored significantly higher than men did on the Appearance Dissatisfaction, Preoccupation with Reassurance, and Defect Hiding. Conclusion: The Body Image Concern Scale has displayed its structure validation and gender preponderance in Chinese university students. Keywords: body dysmorphic disorder, body image, factor analysis, questionnaire development

  1. Identifying and ranking the factors affecting the adoption of biofuels

    Directory of Open Access Journals (Sweden)

    Saeed Azizi

    2016-09-01

    Full Text Available This paper presents an empirical investigation to determine the important factors influencing on adoption of biofuels from consumer’s perspective. The study designs a questionnaire in Likert scale and distributes it among 211 randomly selected people who use green products in city of Tehran, Iran. Cronbach alpha is calculated as 0.812, which is well above the acceptable level. Using principle component with Varimax rotation, the study has determined five important factors including social commitment, product usefulness, infrastructure, management approach and customer oriented, which influence the most on adaptation of biofuels.

  2. X-factor for innovation: identifying future excellent professionals

    NARCIS (Netherlands)

    Banis-den Hertog, Jaantje Hazina

    2016-01-01

    In this study we wanted to identify which type of individual is capable of achieving professional excellence. Our main question therefore read: which individual antecedents predict professional excellence? We chose to focus on personality traits and specifically on proactive personality - the entrep

  3. Identifying factors that influence workplace learning in postgraduate medical education.

    NARCIS (Netherlands)

    Stok-Koch, E.G.H.J.; Bolhuis, S.M.; Koopmans, R.T.C.M.

    2007-01-01

    CONTEXT: In their postgraduate educational programs, residents are immersed in a complex workplace. To improve the quality of the training program, it is necessary to gain insight into the factors that influence the process of learning in the workplace. METHODS: An exploratory study was carried out

  4. Identifying factors that influence workplace learning in postgraduate medical educaton

    NARCIS (Netherlands)

    L. Stok-Koch; R. Koopmans; Dr. S. Bolhuis

    2007-01-01

    In their postgraduate educational programs, residents are immersed in a complex workplace. To improve the quality of the training program, it is necessary to gain insight into the factors that influence the process of learning in the workplace. An exploratory study was carried out among 56 nursing

  5. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina;

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  6. Identifying factors that influence workplace learning in postgraduate medical education.

    NARCIS (Netherlands)

    Stok-Koch, E.G.H.J.; Bolhuis, S.M.; Koopmans, R.T.C.M.

    2007-01-01

    CONTEXT: In their postgraduate educational programs, residents are immersed in a complex workplace. To improve the quality of the training program, it is necessary to gain insight into the factors that influence the process of learning in the workplace. METHODS: An exploratory study was carried out

  7. Identifying factors that influence workplace learning in postgraduate medical educaton

    NARCIS (Netherlands)

    Stok-Koch, L.; Bolhuis, S.; Koopmans, R.

    2007-01-01

    In their postgraduate educational programs, residents are immersed in a complex workplace. To improve the quality of the training program, it is necessary to gain insight into the factors that influence the process of learning in the workplace. An exploratory study was carried out among 56 nursing h

  8. Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

    Science.gov (United States)

    Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

  9. Identifying factors that influence workplace learning in postgraduate medical educaton

    OpenAIRE

    Stok-Koch, L.; Bolhuis, S.; Koopmans, R.

    2007-01-01

    In their postgraduate educational programs, residents are immersed in a complex workplace. To improve the quality of the training program, it is necessary to gain insight into the factors that influence the process of learning in the workplace. An exploratory study was carried out among 56 nursing home physicians in training (NHPT) and 62 supervisors. They participated in semi-structured group interviews, in which they discussed four questions regarding workplace learning. Qualitative analysi...

  10. Novel Application of Statistical Methods to Identify New Urinary Incontinence Risk Factors

    Directory of Open Access Journals (Sweden)

    Theophilus O. Ogunyemi

    2012-01-01

    Full Text Available Longitudinal data for studying urinary incontinence (UI risk factors are rare. Data from one study, the hallmark Medical, Epidemiological, and Social Aspects of Aging (MESA, have been analyzed in the past; however, repeated measures analyses that are crucial for analyzing longitudinal data have not been applied. We tested a novel application of statistical methods to identify UI risk factors in older women. MESA data were collected at baseline and yearly from a sample of 1955 men and women in the community. Only women responding to the 762 baseline and 559 follow-up questions at one year in each respective survey were examined. To test their utility in mining large data sets, and as a preliminary step to creating a predictive index for developing UI, logistic regression, generalized estimating equations (GEEs, and proportional hazard regression (PHREG methods were used on the existing MESA data. The GEE and PHREG combination identified 15 significant risk factors associated with developing UI out of which six of them, namely, urinary frequency, urgency, any urine loss, urine loss after emptying, subject’s anticipation, and doctor’s proactivity, are found most highly significant by both methods. These six factors are potential candidates for constructing a future UI predictive index.

  11. Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer.

    Directory of Open Access Journals (Sweden)

    Xiao-Min Wang

    Full Text Available OBJECTIVE: To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes. METHODS: To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes' biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n = 135 and matched adjacent normal tissues by immunohistochemical (IHC staining. RESULTS: Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis. CONCLUSIONS: We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.

  12. Study identifies socio-cultural factors affecting demographic behaviour.

    Science.gov (United States)

    1994-01-01

    The United Nations Educational, Scientific, and Cultural Organization (UNESCO) is undertaking a project that will produce a state-of-the-art paper on sociocultural factors affecting demographic behavior. Particular emphasis will be placed on reproductive behavior in Africa, Asia, Latin America, and the Arab states region. The extent to which this information is incorporated in current population policies and programs will also be examined, and recommendations will be made. The factors to be studied include family and kinship structure; gender status and role; patterns of sexual relations and procreation in general and adolescent sexual behavior and fertility; religion, beliefs, customs, and traditions concerned with sexual relations and procreation; child rearing, socialization, and education; status and role of women; and sociocultural change, change agents, and influentials. The literature search will provide an inventory of methodologies. Guidelines on the use of the methodologies will be drafted for use by project personnel. These will later be tested in pilot studies in rural and urban communities in selected developing countries. The goal is to design programs that will accelerate contraceptive acceptance and sustain contraceptive practice by being sensitive to the sociocultural influences on the reproductive behavior of different subpopulations.

  13. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    Science.gov (United States)

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  14. Identifying the Relevant Factors in Newspaper Advertising Effectiveness

    Directory of Open Access Journals (Sweden)

    Cristóbal Benavides

    2014-01-01

    Full Text Available Este estudio explora varios factores con el fin de establecer cuáles son losmás importantes en motivar a los lectores de periódicos locales a comprar,visitar tiendas y buscar información adicional acerca de los productos oservicios promovidos en los anuncios. El comportamiento durante el pro-ceso de compra es consecuencia de una compleja interacción de dimen-siones culturales, sociales, personales y psicológicas. Este proceso –el cualse produce antes de la acción– tiene implicaciones relevantes y los depar-tamentos de mercadeo deben prestar atención a ello. Una serie de hipóte-sis basadas en la forma como la publicidad atrae a los consumidores y encómo afecta la toma de decisiones al momento de la compra fueron puestasa prueba usando una encuesta que fue administrada a una muestra de 1.333personas encuestadas en Chile. También se realizó un análisis discriminan-te para averiguar por qué algunos lectores de periódicos se ven motivadosa comprar bienes o servicios, visitar una tienda o buscar más información.Los resultados muestran que el atractivo de la oferta anunciada es el factormás importante para explicar el comportamiento posterior del consumidor.

  15. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    DEFF Research Database (Denmark)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted...... genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated...... with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us...

  16. Identifying Unique Neighborhood Characteristics to Guide Health Planning for Stroke and Heart Attack: Fuzzy Cluster and Discriminant Analyses Approaches

    Science.gov (United States)

    Pedigo, Ashley; Seaver, William; Odoi, Agricola

    2011-01-01

    Background Socioeconomic, demographic, and geographic factors are known determinants of stroke and myocardial infarction (MI) risk. Clustering of these factors in neighborhoods needs to be taken into consideration during planning, prioritization and implementation of health programs intended to reduce disparities. Given the complex and multidimensional nature of these factors, multivariate methods are needed to identify neighborhood clusters of these determinants so as to better understand the unique neighborhood profiles. This information is critical for evidence-based health planning and service provision. Therefore, this study used a robust multivariate approach to classify neighborhoods and identify their socio-demographic characteristics so as to provide information for evidence-based neighborhood health planning for stroke and MI. Methods and Findings The study was performed in East Tennessee Appalachia, an area with one of the highest stroke and MI risks in USA. Robust principal component analysis was performed on neighborhood (census tract) socioeconomic and demographic characteristics, obtained from the US Census, to reduce the dimensionality and influence of outliers in the data. Fuzzy cluster analysis was used to classify neighborhoods into Peer Neighborhoods (PNs) based on their socioeconomic and demographic characteristics. Nearest neighbor discriminant analysis and decision trees were used to validate PNs and determine the characteristics important for discrimination. Stroke and MI mortality risks were compared across PNs. Four distinct PNs were identified and their unique characteristics and potential health needs described. The highest risk of stroke and MI mortality tended to occur in less affluent PNs located in urban areas, while the suburban most affluent PNs had the lowest risk. Conclusions Implementation of this multivariate strategy provides health planners useful information to better understand and effectively plan for the unique

  17. Using intervention time series analyses to assess the effects of imperfectly identifiable natural events: a general method and example

    Directory of Open Access Journals (Sweden)

    Day Carolyn

    2006-04-01

    Full Text Available Abstract Background Intervention time series analysis (ITSA is an important method for analysing the effect of sudden events on time series data. ITSA methods are quasi-experimental in nature and the validity of modelling with these methods depends upon assumptions about the timing of the intervention and the response of the process to it. Method This paper describes how to apply ITSA to analyse the impact of unplanned events on time series when the timing of the event is not accurately known, and so the problems of ITSA methods are magnified by uncertainty in the point of onset of the unplanned intervention. Results The methods are illustrated using the example of the Australian Heroin Shortage of 2001, which provided an opportunity to study the health and social consequences of an abrupt change in heroin availability in an environment of widespread harm reduction measures. Conclusion Application of these methods enables valuable insights about the consequences of unplanned and poorly identified interventions while minimising the risk of spurious results.

  18. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

    Science.gov (United States)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P; Manning, Alisa K; Grarup, Niels; Sim, Xueling; Barnes, Daniel R; Witkowska, Kate; Staley, James R; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T; Nielsen, Sune Fallgaard; Rasheed, Asif; Samuel, Maria; Zhao, Wei; Bonnycastle, Lori L; Jackson, Anne U; Narisu, Narisu; Swift, Amy J; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R; Stančáková, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E; Bork-Jensen, Jette; Gjesing, Anette P; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S; Zhang, He; Donnelly, Louise A; Groves, Christopher J; Rayner, N William; Neville, Matt J; Robertson, Neil R; Yiorkas, Andrianos M; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P; Poveda, Alaitz; Varga, Tibor V; Caslake, Muriel; de Craen, Anton J M; Trompet, Stella; Luan, Jian'an; Scott, Robert A; Harris, Sarah E; Liewald, David C M; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Göran; Renström, Frida; Huffman, Jennifer E; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S; Felix, Janine F; Uria-Nickelsen, Maria; Malarstig, Anders; Reilly, Dermot F; Hoek, Maarten; Vogt, Thomas F; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S; Highland, Heather M; Justice, Anne E; Marouli, Eirini; Lindström, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W; Dedoussis, George; Spector, Timothy D; Jousilahti, Pekka; Männistö, Satu; Deary, Ian J; Starr, John M; Langenberg, Claudia; Wareham, Nick J; Brown, Morris J; Dominiczak, Anna F; Connell, John M; Jukema, J Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J; Esko, Tõnu; Mägi, Reedik; Metspalu, Andres; de Boer, Rudolf A; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I W; Numans, Mattijs E; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R B; Korpi-Hyövälti, Eeva; Oksa, Heikki; Chambers, John C; Kooner, Jaspal S; Blakemore, Alexandra I F; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S F; Morris, Andrew D; Palmer, Colin N A; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J; Tuomi, Tiinamaija; Groop, Leif; Käräjämäki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S; Majumder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I; Poulter, Neil; Stanton, Alice V; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrières, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J; Hayward, Caroline; Scotland, Generation; Collins, Francis S; Mohlke, Karen L; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D; Nordestgaard, Børge Grønne; Caulfield, Mark J; Mahajan, Anubha; Morris, Andrew P; Tomaszewski, Maciej; Samani, Nilesh J; Saleheen, Danish; Asselbergs, Folkert W; Lindgren, Cecilia M; Danesh, John; Wain, Louise V; Butterworth, Adam S; Howson, Joanna M M; Munroe, Patricia B

    2016-10-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

  19. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    Science.gov (United States)

    Barnes, Daniel R; Witkowska, Kate; Staley, James R; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T; Fallgaard Nielsen, Sune; Rasheed, Asif; Samuel, Maria; Zhao, Wei; Bonnycastle, Lori L; Jackson, Anne U; Narisu, Narisu; Swift, Amy J; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R; Stančáková, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E; Bork-Jensen, Jette; Gjesing, Anette P; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S; Zhang, He; Donnelly, Louise A; Groves, Christopher J; Rayner, N William; Neville, Matt J; Robertson, Neil R; Yiorkas, Andrianos M; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P; Poveda, Alaitz; Varga, Tibor V; Caslake, Muriel; de Craen, Anton JM; Trompet, Stella; Luan, Jian’an; Scott, Robert A; Harris, Sarah E; Liewald, David CM; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Göran; Renström, Frida; Huffman, Jennifer E; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S; Felix, Janine F; Uria-Nickelsen, Maria; Malarstig, Anders; Reily, Dermot F; Hoek, Maarten; Vogt, Thomas; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh F; Highland, Heather M; Justice, Anne E; Marouli, Eirini; Lindström, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W; Dedoussis, George; Spector, Timothy D; Jousilahti, Pekka; Männistö, Satu; Deary, Ian J; Starr, John M; Langenberg, Claudia; Wareham, Nick J; Brown, Morris J; Dominiczak, Anna F; Connell, John M; Jukema, J Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J; Esko, Tõnu; Mägi, Reedik; Metspalu, Andres; de Boer, Rudolf A; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul IW; Numans, Mattijs E; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva RB; Korpi-Hyövälti, Eeva; Oksa, Heikki; Chambers, John C; Kooner, Jaspal S; Blakemore, Alexandra IF; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex SF; Morris, Andrew D; Palmer, Colin NA; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J; Tuomi, Tiinamaija; Groop, Leif; Käräjämäki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S; Shafi Majumder, Abdulla al; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I; Poulter, Neil; Stanton, Alice V; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrières, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David; Hayward, Caroline; Scotland, Generation; Collins, Francis S; Mohlke, Karen L; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D; Nordestgaard, Børge Grønne; Caulfield, Mark J; Mahajan, Anubha; Morris, Andrew P; Tomaszewski, Maciej; Samani, Nilesh J

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. PMID:27618447

  20. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    DEFF Research Database (Denmark)

    Surendran, Praveen; Drenos, Fotios; Young, Robin

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up...... to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common...... variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology...

  1. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  2. A new technique for analysing interacting factors affecting biodiversity patterns: crossed-DPCoA.

    Science.gov (United States)

    Pavoine, Sandrine; Blondel, Jacques; Dufour, Anne B; Gasc, Amandine; Bonsall, Michael B

    2013-01-01

    We developed an approach for analysing the effects of two crossed factors A and B on the functional, taxonomic or phylogenetic composition of communities. The methodology, known as crossed-DPCoA, defines a space where species, communities and the levels of the two factors are organised as a set of points. In this space, the Euclidean distance between two species-specific points is a measure of the (functional, taxonomic or phylogenetic) dissimilarity. The communities are positioned at the centroid of their constitutive species; and the levels of two factors at the centroid of the communities associated with them. We develop two versions for crossed-DPCoA, the first one moves the levels of factor B to the centre of the space and analyses the axes of highest variance in the coordinates of the levels of factor A. It is related to previous ordination approaches such as partial canonical correspondence analysis and partial non-symmetrical correspondence analysis. The second version projects all points on the orthogonal complement of the space generated by the principal axes of factor B. This second version should be preferred when there is an a priori suspicion that factor A and B are associated. We apply the two versions of crossed-DPCoA to analyse the phylogenetic composition of Central European and Mediterranean bird communities. Applying crossed-DPCoA on bird communities supports the hypothesis that allopatric speciation processes during the Quaternary occurred in open and patchily distributed landscapes, while the lack of geographic barriers to dispersal among forest habitats may explain the homogeneity of forest bird communities over the whole western Palaearctic. Generalizing several ordination analyses commonly used in ecology, crossed-DPCoA provides an approach for analysing the effects of crossed factors on functional, taxonomic and phylogenetic diversity, environmental and geographic structure of species niches, and more broadly the role of genetics on

  3. A new technique for analysing interacting factors affecting biodiversity patterns: crossed-DPCoA.

    Directory of Open Access Journals (Sweden)

    Sandrine Pavoine

    Full Text Available We developed an approach for analysing the effects of two crossed factors A and B on the functional, taxonomic or phylogenetic composition of communities. The methodology, known as crossed-DPCoA, defines a space where species, communities and the levels of the two factors are organised as a set of points. In this space, the Euclidean distance between two species-specific points is a measure of the (functional, taxonomic or phylogenetic dissimilarity. The communities are positioned at the centroid of their constitutive species; and the levels of two factors at the centroid of the communities associated with them. We develop two versions for crossed-DPCoA, the first one moves the levels of factor B to the centre of the space and analyses the axes of highest variance in the coordinates of the levels of factor A. It is related to previous ordination approaches such as partial canonical correspondence analysis and partial non-symmetrical correspondence analysis. The second version projects all points on the orthogonal complement of the space generated by the principal axes of factor B. This second version should be preferred when there is an a priori suspicion that factor A and B are associated. We apply the two versions of crossed-DPCoA to analyse the phylogenetic composition of Central European and Mediterranean bird communities. Applying crossed-DPCoA on bird communities supports the hypothesis that allopatric speciation processes during the Quaternary occurred in open and patchily distributed landscapes, while the lack of geographic barriers to dispersal among forest habitats may explain the homogeneity of forest bird communities over the whole western Palaearctic. Generalizing several ordination analyses commonly used in ecology, crossed-DPCoA provides an approach for analysing the effects of crossed factors on functional, taxonomic and phylogenetic diversity, environmental and geographic structure of species niches, and more broadly the role of

  4. Prognostic model for brain metastases from lung adenocarcinoma identified with epidermal growth factor receptor mutation status.

    Science.gov (United States)

    Li, Hongwei; Wang, Weili; Jia, Haixia; Lian, Jianhong; Cao, Jianzhong; Zhang, Xiaqin; Song, Xing; Jia, Sufang; Li, Zhengran; Cao, Xing; Zhou, Wei; Han, Songye; Yang, Weihua; Xi, Yanfen; Lian, Shenming

    2017-09-01

    Several indices have been developed to predict survival of brain metastases (BM) based on prognostic factors. However, such models were designed for general brain metastases from different kinds of cancers, and prognostic factors vary between cancers and histological subtypes. Recently, studies have indicated that epidermal growth factor receptor (EGFR) mutation status may be a potential prognostic biological factor in BM from lung adenocarcinoma. Thus, we sought to define the role of EGFR mutation in prognoses and introduce a prognostic model specific for BM from lung adenocarcinoma. Data of 256 patients with BM from lung adenocarcinoma identified with EGFR mutations were collected. Independent prognostic factors were confirmed using a Cox regression model. The new prognostic model was developed based on the results of multivariable analyses. The score of each factor was calculated by six-month survival. Prognostic groups were divided into low, medium, and high risk based on the total scores. The prediction ability of the new model was compared to the three existing models. EGFR mutation and Karnofsky performance status were independent prognostic factors and were thus integrated into the new prognostic model. The new model was superior to the three other scoring systems regarding the prediction of three, six, and 12-month survival by pairwise comparison of the area under the curve. Our proposed prognostic model specific for BM from lung adenocarcinoma incorporating EGFR mutation status was valid in predicting patient survival. Further verification is warranted, with prospective testing using large sample sizes. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  5. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

    Science.gov (United States)

    Li, Xu; Wang, Wenqi; Wang, Jiadong; Malovannaya, Anna; Xi, Yuanxin; Li, Wei; Guerra, Rudy; Hawke, David H; Qin, Jun; Chen, Junjie

    2015-01-21

    The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein-protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein-protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein-protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs.

  6. Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer.

    Directory of Open Access Journals (Sweden)

    Ram Bhupal Reddy

    Full Text Available The head and neck squamous cell carcinoma (HNSCC transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20 profiled using Agilent (4X44K G4112F and Affymetrix (HGU133A, U133A_2, U133Plus 2 platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA. Principal Component Analysis (PCA and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4. Validation in the HNSCC-specific database (N = 528 in The Cancer Genome Atlas (TCGA identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2 that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12 and post treatment (Group II; N = 12 patients identified 8 genes significantly associated with the disease (Area under curve>0.6. Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6 to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00 in Group I while UBE2V2 and CRYM were highly sensitive (>0.8 in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05. The meta-analysis approach adopted in this study has

  7. The Analysing Children's Creative Thinking Framework: Development of an Observation-Led Approach to Identifying and Analysing Young Children's Creative Thinking

    Science.gov (United States)

    Robson, Sue

    2014-01-01

    Increased international recognition of the value of supporting creative thinking suggests the value of development of approaches to its identification in children. Development of an observation-led framework, the Analysing Children's Creative Thinking (ACCT) framework, is described, and a case made for the validity of inferring creative thinking…

  8. Comparative analyses of developmental transcription factor repertoires in sponges reveal unexpected complexity of the earliest animals.

    Science.gov (United States)

    Fortunato, Sofia A V; Adamski, Marcin; Adamska, Maja

    2015-12-01

    Developmental transcription factors (DTFs) control development of animals by affecting expression of target genes, some of which are transcription factors themselves. In bilaterians and cnidarians, conserved DTFs are involved in homologous processes such as gastrulation or specification of neurons. The genome of Amphimedon queenslandica, the first sponge to be sequenced, revealed that only a fraction of these conserved DTF families are present in demosponges. This finding was in line with the view that morphological complexity in the animal lineage correlates with developmental toolkit complexity. However, as the phylum Porifera is very diverse, Amphimedon's genome may not be representative of all sponges. The recently sequenced genomes of calcareous sponges Sycon ciliatum and Leucosolenia complicata allowed investigations of DTFs in a sponge lineage evolutionarily distant from demosponges. Surprisingly, the phylogenetic analyses of identified DTFs revealed striking differences between the calcareous sponges and Amphimedon. As these differences appear to be a result of independent gene loss events in the two sponge lineages, the last common ancestor of sponges had to possess a much more diverse repertoire of DTFs than extant sponges. Developmental expression of sponge homologs of genes involved in specification of the Bilaterian endomesoderm and the neurosensory cells suggests that roles of many DTFs date back to the last common ancestor of all animals. Strikingly, even DTFs displaying apparent pan-metazoan conservation of sequence and function are not immune to being lost from individual species genomes. The quest for a comprehensive picture of the developmental toolkit in the last common metazoan ancestor is thus greatly benefitting from the increasing accessibility of sequencing, allowing comparisons of multiple genomes within each phylum.

  9. Identifying Active Faults in Northeast North America Using Hypocenters and Multiscale Edge Wavelet Analyses of Potential Fields

    Science.gov (United States)

    Carpenter, K.; Horowitz, F.; Ebinger, C. J.; Navarrete, L. C.; Diaz-Etchevehere, D.

    2015-12-01

    Multiscale edge Poisson wavelet analyses of potential field data ("worms") have a physical interpretation as the locations of lateral boundaries in a source distribution that exactly generates the observed field. The worm technique is therefore well-suited to analyses of crustal-scale stuctures that could be reactivated by tectonic stress or by fluid injection processes, providing new tools to analyze existing continental-scale data sets. Northeastern North America (US, Canada) hosts potentially damaging intraplate earthquakes, yet many of the Proterozoic structures are covered by thick sedimentary sequences or dense vegetation, and crustal structure is relatively poorly known.For the purpose of extending basement structure beneath the Appalachian basin and establishing a consistent regional basis for comparison, we use worms to identify steeply dipping structures in compiled gravity and magnetic anomaly data sets. We compare results to intraplate earthquake locations to assess seismic hazards. Clearly, not all locations of lateral boundaries are faults, and we do not expect all faults to have shown activity in the ~50 years of seismic records available. However, proximity statistics between hypocenters and worms are of interest since they assist in the identification and location of a subset of potentially active faults. We compare structures of lateral mass-density or magnetization contrast with locations of earthquake hypocenters cataloged from the ISC, the NEIC, and the ANF from the EarthScope Transportable Array. We develop a GIS based method for calculating hypocenter/worm proximity, and we will show statistics and maps from this method for the region at the meeting.

  10. Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what is the role of glucocorticoid therapy?

    Science.gov (United States)

    van der Goes, M C; Hoes, J N; Cramer, M J; van der Veen, M J; van der Werf, J H; Bijlsma, J W J; Jacobs, J W G

    2014-01-01

    To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.

  11. Identifying and prioritizing the factors effective in customer satisfaction using the TOPSIS method

    Directory of Open Access Journals (Sweden)

    H Forougozar

    2014-01-01

    Full Text Available Introduction: Customer satisfaction has been suggested as one of the interesting and challenging issues of management in the new millennium. In addition, oral and dental health and the quality of the services the health centers delivered to the patients directly affect the customer satisfaction. Therefore, the present study aimed to identify, investigate, and rank the factors affecting the customer satisfaction in the department of dentistry of Shiraz Farhangiyan health center. Method: The present descriptive study was conducted on the specialists and patients of the department of dentistry of Shiraz Farhangiyan health center. The validity of the questionnaire utilized in the study was confirmed by expert professors and its reliability was approved using the Cronbach’s alpha formula. Finally, the study data were analyzed in SPSS statistical software (v. 16, using inferential statistics. Results: All the hypotheses were confirmed by the results of the statistical analyses and quality, services, and expenditures revealed to affect the customer satisfaction in the department of dentistry of Shiraz Farhangiyan health center. Moreover, these factors were ranked using the TOPSIS method and the results showed quality and expenditures as the most and the least effective factors in customer satisfaction, respectively. Conclusion: Since restoring and arranging the organization based on the customer needs is among the main priorities of designing an organization, managers are suggested to take measures for organizational reformation based on the customers’ priorities. Of course, conducting such programs is of utmost importance in health and treatment environments, leading to provision of better services and facilitation of learning, education, and research. Thus, identifying the effective factors in customer satisfaction and ranking them are highly important.

  12. A structured elicitation method to identify key direct risk factors for the management of natural resources.

    Science.gov (United States)

    Smith, Michael; Wallace, Ken; Lewis, Loretta; Wagner, Christian

    2015-11-01

    The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators), fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1) the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2) the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

  13. The Chinese Family Assessment Instrument (C-FAI): Hierarchical Confirmatory Factor Analyses and Factorial Invariance

    Science.gov (United States)

    Shek, Daniel T. L.; Ma, Cecilia M. S.

    2010-01-01

    Objective: This paper examines the dimensionality and factorial invariance of the Chinese Family Assessment Instrument (C-FAI) using multigroup confirmatory factor analyses (MCFAs). Method: A total of 3,649 students responded to the C-FAI in a community survey. Results: Results showed that there are five dimensions of the C-FAI (communication,…

  14. Dimensionality of the Chinese Positive Youth Development Scale: Confirmatory Factor Analyses

    Science.gov (United States)

    Shek, Daniel T. L.; Ma, Cecilia M. S.

    2010-01-01

    This paper examines the dimensionality and factorial invariance of the Chinese Positive Youth Development Scale (CPYDS) using multigroup confirmatory factor analyses (MCFA). Secondary 1 students (N = 5,649) responded to the CPYDS in the context of a positive youth development program. Results showed that there are 15 basic dimensions of the CPYDS…

  15. Community-level physiological profiling analyses show potential to identify the copiotrophic bacteria present in soil environments

    Science.gov (United States)

    Lladó, Salvador; Baldrian, Petr

    2017-01-01

    Community-level physiological profiling (CLPP) analyses from very diverse environments are frequently used with the aim of characterizing the metabolic versatility of whole environmental bacterial communities. While the limitations of the methodology for the characterization of whole communities are well known, we propose that CLPP combined with high-throughput sequencing and qPCR can be utilized to identify the copiotrophic, fast-growing fraction of the bacterial community of soil environments, where oligotrophic taxa are usually dominant. In the present work we have used this approach to analyze samples of litter and soil from a coniferous forest in the Czech Republic using BIOLOG GN2 plates. Monosaccharides and amino acids were utilized significantly faster than other C substrates, such as organic acids, in both litter and soil samples. Bacterial biodiversity in CLPP wells was significantly lower than in the original community, independently of the carbon source. Bacterial communities became highly enriched in taxa that typically showed low abundance in the original soil, belonging mostly to the Gammaproteobacteria and the genus Pseudomonas, indicating that the copiotrophic strains, favoured by the high nutrient content, are rare in forest litter and soil. In contrast, taxa abundant in the original samples were rarely found to grow at sufficient rates under the CLPP conditions. Our results show that CLPP is useful to detect copiotrophic bacteria from the soil environments and that bacterial growth is substrate specific. PMID:28170446

  16. Application of diffusion maps to identify human factors of self-reported anomalies in aviation.

    Science.gov (United States)

    Andrzejczak, Chris; Karwowski, Waldemar; Mikusinski, Piotr

    2012-01-01

    A study investigating what factors are present leading to pilots submitting voluntary anomaly reports regarding their flight performance was conducted. Diffusion Maps (DM) were selected as the method of choice for performing dimensionality reduction on text records for this study. Diffusion Maps have seen successful use in other domains such as image classification and pattern recognition. High-dimensionality data in the form of narrative text reports from the NASA Aviation Safety Reporting System (ASRS) were clustered and categorized by way of dimensionality reduction. Supervised analyses were performed to create a baseline document clustering system. Dimensionality reduction techniques identified concepts or keywords within records, and allowed the creation of a framework for an unsupervised document classification system. Results from the unsupervised clustering algorithm performed similarly to the supervised methods outlined in the study. The dimensionality reduction was performed on 100 of the most commonly occurring words within 126,000 text records describing commercial aviation incidents. This study demonstrates that unsupervised machine clustering and organization of incident reports is possible based on unbiased inputs. Findings from this study reinforced traditional views on what factors contribute to civil aviation anomalies, however, new associations between previously unrelated factors and conditions were also found.

  17. Identifying the critical factors that influence intraocular pressure using an automated regression tree

    Directory of Open Access Journals (Sweden)

    Nishanee Rampersad

    2017-01-01

    Full Text Available Background: Assessment of intraocular pressure (IOP is an important test in glaucoma. In addition, anterior segment variables may be useful in screening for glaucoma risk. Studies have investigated the associations between IOP and anterior segment variables using traditional statistical methods. The classification and regression tree (CART method provides another dimension to detect important variables in a relationship automatically.Aim: To identify the critical factors that influence IOP using a regression tree.Methods: A quantitative cross-sectional research design was used. Anterior segment variables were measured in 700 participants using the iVue100 optical coherence tomographer, Oculus Keratograph and Nidek US-500 ultrasonographer. A Goldmann applanation tonometer was used to measure IOP. Data from only the right eyes were analysed because of high levels of interocular symmetry. A regression tree model was generated with the CART method and Pearson’s correlation coefficients were used to assess the relationships between the ocular variables.Results: The mean IOP for the entire sample was 14.63 mmHg ± 2.40 mmHg. The CART method selected three anterior segment variables in the regression tree model. Central corneal thickness was the most important variable with a cut-off value of 527 µm. The other important variables included average paracentral corneal thickness and axial anterior chamber depth. Corneal thickness measurements increased towards the periphery and were significantly correlated with IOP (r ≥ 0.50, p ≤ 0.001.Conclusion: The CART method identified the anterior segment variables that influenced IOP. Understanding the relationship between IOP and anterior segment variables may help to clinically identify patients with ocular risk factors associated with elevated IOPs.

  18. Genome-wide gene expression profile analyses identify CTTN as a potential prognostic marker in esophageal cancer.

    Directory of Open Access Journals (Sweden)

    Pei Lu

    Full Text Available AIM: Esophageal squamous cell carcinoma (ESCC is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. METHODS: We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR, tissue microarrays (TMAs and immunohistochemistry (IHC staining. RESULTS: Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤-1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26 and two underexpressed (HMGCS2 and SORBS2 were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN was observed in 126/198 (63.6% of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000, pathologic stage (P = 0.000 and poor survival (P<0.001 of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05. CONCLUSION: Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets.

  19. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  20. Stochastic analyses to identify wellfield withdrawal effects on surface-water and groundwater in Miami-Dade County, Florida.

    Science.gov (United States)

    Swain, Eric

    2012-12-30

    Several stochastic analyses were conducted in Miami-Dade County, Florida, to evaluate the effects of wellfield withdrawal on aquifer water levels, canal stage, and canal flow. Multiyear data for withdrawals at four water-supply wellfields, water levels at the S-121 canal control structure and groundwater head at a nearby monitoring well were used to determine the interrelation between wellfield withdrawals and water levels in the canal and aquifer. A spectral analysis was performed first on the wellfield withdrawals, showing similar patterns of fluctuations, but no well-defined seasonality. In order to compare water-level response with withdrawals at each wellfield, the intercorrelation effects between wellfields was removed through a 'causal chain' approach where the inter-wellfield correlation is used to isolate the wellfield/water-level correlation. Most computed correlations have magnitudes less than 5 percent, but with statistical significance above 90 percent. Results indicate that withdrawals from the wellfields most distant from the canal had no significant correlation to the canal levels. However the highest correlation was not at the wellfield closest to the canal, but at the two wellfields at the intermediate distance that have higher withdrawal rates. The hydraulic interconnectivity of the canal with the rest of the canal network, covering the study area, allows the canal equalizes with all connected canals. This explains why proximity to a particular canal location does not appear to be as important a factor as the withdrawal rate. Groundwater levels are more highly correlated to a wellfield on the same side of the canal, and to pumping wells in the same wellfield on the same side of the canal. This indicates that canals are an effective barrier and source/sink for the groundwater. Further nonlinear correlation analysis indicates that high withdrawal rates disproportionally affect water levels and are the predominant effect on the canal.

  1. Quantitative Proteomic Analyses Identify ABA-Related Proteins and Signal Pathways in Maize Leaves under Drought Conditions.

    Science.gov (United States)

    Zhao, Yulong; Wang, Yankai; Yang, Hao; Wang, Wei; Wu, Jianyu; Hu, Xiuli

    2016-01-01

    Drought stress is one of major factors resulting in maize yield loss. The roles of abscisic acid (ABA) have been widely studied in crops in response to drought stress. However, more attention is needed to identify key ABA-related proteins and also gain deeper molecular insights about drought stress in maize. Based on this need, the physiology and proteomics of the ABA-deficient maize mutant vp5 and its wild-type Vp5 under drought stress were examined and analyzed. Malondialdehyde content increased and quantum efficiency of photosystem II decreased under drought stress in both genotypes. However, the magnitude of the increase or decrease was significantly higher in vp5 than in Vp5. A total of 7051 proteins with overlapping expression patterns among three replicates in the two genotypes were identified by Multiplex run iTRAQ-based quantitative proteomic and liquid chromatography-tandem mass spectrometry methods, of which the expression of only 150 proteins (130 in Vp5, 27 in vp5) showed changes of at least 1.5-fold under drought stress. Among the 150 proteins, 67 and 60 proteins were up-regulated and down-regulated by drought stress in an ABA-dependent way, respectively. ABA was found to play active roles in regulating signaling pathways related to photosynthesis, oxidative phosphorylation (mainly related to ATP synthesis), and glutathione metabolism (involved in antioxidative reaction) in the maize response to drought stress. Our results provide an extensive dataset of ABA-dependent, drought-regulated proteins in maize plants, which may help to elucidate the underlying mechanisms of ABA-enhanced tolerance to drought stress in maize.

  2. Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

    Science.gov (United States)

    Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

    2002-12-30

    Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before.

  3. Germline DNA copy number aberrations identified as potential prognostic factors for breast cancer recurrence.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available Breast cancer recurrence (BCR is a common treatment outcome despite curative-intent primary treatment of non-metastatic breast cancer. Currently used prognostic and predictive factors utilize tumor-based markers, and are not optimal determinants of risk of BCR. Germline-based copy number aberrations (CNAs have not been evaluated as determinants of predisposition to experience BCR. In this study, we accessed germline DNA from 369 female breast cancer subjects who received curative-intent primary treatment following diagnosis. Of these, 155 experienced BCR and 214 did not, after a median duration of follow up after breast cancer diagnosis of 6.35 years (range = 0.60-21.78 and 8.60 years (range = 3.08-13.57, respectively. Whole genome CNA genotyping was performed on the Affymetrix SNP array 6.0 platform. CNAs were identified using the SNP-Fast Adaptive States Segmentation Technique 2 algorithm implemented in Nexus Copy Number 6.0. Six samples were removed due to poor quality scores, leaving 363 samples for further analysis. We identified 18,561 CNAs with ≥1 kb as a predefined cut-off for observed aberrations. Univariate survival analyses (log-rank tests identified seven CNAs (two copy number gains and five copy neutral-loss of heterozygosities, CN-LOHs showing significant differences (P<2.01×10(-5 in recurrence-free survival (RFS probabilities with and without CNAs.We also observed three additional but distinct CN-LOHs showing significant differences in RFS probabilities (P<2.86×10(-5 when analyses were restricted to stratified cases (luminal A, n = 208 only. After adjusting for tumor stage and grade in multivariate analyses (Cox proportional hazards models, all the CNAs remained strongly associated with the phenotype of BCR. Of these, we confirmed three CNAs at 17q11.2, 11q13.1 and 6q24.1 in representative samples using independent genotyping platforms. Our results suggest further investigations on the potential use of germline DNA

  4. Round Robin Analyses on Stress Intensity Factors of Inner Surface Cracks in Welded Stainless Steel Pipes

    Directory of Open Access Journals (Sweden)

    Chang-Gi Han

    2016-12-01

    Full Text Available Austenitic stainless steels (ASSs are widely used for nuclear pipes as they exhibit a good combination of mechanical properties and corrosion resistance. However, high tensile residual stresses may occur in ASS welds because postweld heat treatment is not generally conducted in order to avoid sensitization, which causes a stress corrosion crack. In this study, round robin analyses on stress intensity factors (SIFs were carried out to examine the appropriateness of structural integrity assessment methods for ASS pipe welds with two types of circumferential cracks. Typical stress profiles were generated from finite element analyses by considering residual stresses and normal operating conditions. Then, SIFs of cracked ASS pipes were determined by analytical equations represented in fitness-for-service assessment codes as well as reference finite element analyses. The discrepancies of estimated SIFs among round robin participants were confirmed due to different assessment procedures and relevant considerations, as well as the mistakes of participants. The effects of uncertainty factors on SIFs were deducted from sensitivity analyses and, based on the similarity and conservatism compared with detailed finite element analysis results, the R6 code, taking into account the applied internal pressure and combination of stress components, was recommended as the optimum procedure for SIF estimation.

  5. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study

    Directory of Open Access Journals (Sweden)

    Aschemann-Witzel Jessica

    2012-02-01

    Full Text Available Abstract Background Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Results Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. Conclusions The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly

  6. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study.

    Science.gov (United States)

    Aschemann-Witzel, Jessica; Perez-Cueto, Federico J A; Niedzwiedzka, Barbara; Verbeke, Wim; Bech-Larsen, Tino

    2012-02-21

    Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly transferable to the public health sector. Whether or not a particular

  7. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study

    Science.gov (United States)

    2012-01-01

    Background Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Results Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. Conclusions The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly transferable to the public health

  8. Analyses of the contributing factors associated with foodborne outbreaks in school settings (2000-2010).

    Science.gov (United States)

    Venuto, Margaret; Garcia, Kristin

    2015-03-01

    State-reported school foodborne outbreaks account for about 3.8% (n = 464) of all outbreaks and 8.2% (n = 20,667) of all illnesses reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System. Of 464 school foodborne outbreaks, 122 (26%) outbreaks, 7,603 illnesses, and 301 reported food safety errors met the criteria for inclusion in the analyses. The purpose of the authors' study was to examine the role of contributing factors in school foodborne outbreaks. Contamination factors accounted for the greatest proportion (49.2%) of outbreaks involving some level of food handling interaction by a school food service worker, followed by proliferation (34.9%) and survival factors (15.9%). Over 56% of all illnesses were associated with norovirus and food service worker practices. The results of these analyses highlight the importance of effective food safety education programs that focus on the role of contributing factors and prevention of foodborne disease from food safety errors.

  9. Identifying work ability promoting factors for home care aides and assistant nurses

    Directory of Open Access Journals (Sweden)

    Larsson Agneta

    2012-01-01

    Full Text Available Abstract Background In workplace health promotion, all potential resources needs to be taken into consideration, not only factors relating to the absence of injury and the physical health of the workers, but also psychological aspects. A dynamic balance between the resources of the individual employees and the demands of work is an important prerequisite. In the home care services, there is a noticeable trend towards increased psychosocial strain on employees at work. There are a high frequency of work-related musculoskeletal disorders and injuries, and a low prevalence of sustainable work ability. The aim of this research was to identify factors promoting work ability and self-efficacy in care aides and assistant nurses within home care services. Methods This study is based on cross-sectional data collected in a municipality in northern Sweden. Care aides (n = 58 and assistant nurses (n = 79 replied to a self-administered questionnaire (response rate 46%. Hierarchical multiple regression analyses were performed to assess the influence of several independent variables on self-efficacy (model 1 and work ability (model 2 for care aides and assistant nurses separately. Results Perceptions of personal safety, self-efficacy and musculoskeletal wellbeing contributed to work ability for assistant nurses (R2adj of 0.36, p 2adj of 0.29, p = 0.001. Self-efficacy was associated with the safety climate and the physical demands of the job in both professions (R2adj of 0.24, p = 0.003 for care aides, and also by sex and age for the assistant nurses (R2adj of 0.31, p Conclusions The intermediate factors contributed differently to work ability in the two professions. Self-efficacy, personal safety and musculoskeletal wellbeing were important for the assistant nurses, while the work ability of the care aides was associated with the safety climate, but also with the non-changeable factors age and seniority. All these factors are important to acknowledge in

  10. Prospective Analyses of Childhood Factors and Antisocial Behavior for Students with High-Incidence Disabilities

    Science.gov (United States)

    Chen, Chin-Chih; Symons, Frank J.; Reynolds, Arthur J.

    2011-01-01

    This prospective longitudinal study investigated the association between childhood factors (individual, family, and school characteristics) and later antisocial behavior (official juvenile delinquency and adult crime) for students identified with high-incidence disabilities (i.e., learning disabilities, emotional disturbance). The sample consisted…

  11. Human factors evaluation of remote afterloading brachytherapy. Supporting analyses of human-system interfaces, procedures and practices, training and organizational practices and policies. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    Callan, J.R.; Kelly, R.T.; Quinn, M.L. [Pacific Science & Engineering Group, San Diego, CA (United States)] [and others

    1995-07-01

    A human factors project on the use of nuclear by-product material to treat cancer using remotely operated afterloaders was undertaken by the Nuclear Regulatory Commission. The purpose of the project was to identify factors that contribute to human error in the system for remote afterloading brachytherapy (RAB). This report documents the findings from the second, third, fourth, and fifth phases of the project, which involved detailed analyses of four major aspects of the RAB system linked to human error: human-system interfaces; procedures and practices; training practices and policies; and organizational practices and policies, respectively. Findings based on these analyses provided factual and conceptual support for the final phase of this project, which identified factors leading to human error in RAB. The impact of those factors on RAB performance was then evaluated and prioritized in terms of safety significance, and alternative approaches for resolving safety significant problems were identified and evaluated.

  12. Identifying and assessing the factors affecting skill gap in digital marketing in communication industry companies

    Directory of Open Access Journals (Sweden)

    Fereshteh Ghotbifar

    2017-03-01

    Full Text Available As far as new communication channels are concerned, there have been extensive developments in communications and marketing in digital era. Today, therefore, companies try to take advantage of digital marketing channels to provide suitable services to customers to improve their satisfaction level. However, this study aimed to identify and assess factors affecting skill gap in digital marketing. This was descriptive correlation study. The population consisted of experts in communications industry to identify most important skill gaps in digital marketing and factors affecting them; also, managers and specialists of these companies were investigated to determine the role of identified factors in reducing skills gaps. Using localized questionnaire and interviewing with ten experts who were selected by Delphi snowball method, the skill gaps in marketing and factors affecting them were identified. Also, a researcher made questionnaire with 32 questions was distributed among 226 employees to investigate the identified factors role in reducing skills gap in digital marketing. The results showed that from four identified factors, the components including operational strategic factors and environmental factors had direct and positive impact on creating skill gap in digital marketing of studied companies. The environmental factors such as social and cultural conditions, religion, technology, and economy had more proactive impact on skills gap in digital marketing. Also, the results showed that among skills gaps in digital marketing of studied companies, the skills (Principles of Communication and (Predicting Future had the highest and lowest gaps, respectively.

  13. Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses.

    Science.gov (United States)

    Shaffer, John R; Feingold, Eleanor; Wang, Xiaojing; Tcuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Polk, Deborah E; Wendell, Steve; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

    2012-03-09

    Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h(2) = 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.

  14. Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

    Directory of Open Access Journals (Sweden)

    Shaffer John R

    2012-03-01

    Full Text Available Abstract Background Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. Methods The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA and factor analysis (FA, two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. Results The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97, pit and fissure surface caries (r = 0.95, and smooth surface caries (r = 0.89. However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81, but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h2 = 30-65%, p = 0.043-0.006, whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. Conclusions This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding

  15. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    DEFF Research Database (Denmark)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes...

  16. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Maegi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loic; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; St Pourcain, Beate; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tonu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Mueller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Goeran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindstrom, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Koerner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josee; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Ines

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes ri

  17. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Maegi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loic; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; St Pourcain, Beate; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tonu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Mueller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Goeran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindstrom, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Koerner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josee; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Ines

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes ri

  18. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); R. Wojciechowski (Robert); Q. Fan (Qiao); J. Guggenheim (Jean); R. Höhn (René); S. MacGregor (Stuart); A.W. Hewit (Alex); A. Nag (Abhishek); C-Y. Cheng (Ching-Yu); E. Yonova-Doing (Ekaterina); X. Zhou (Xin); M.K. Ikram (Kamran); G.H.S. Buitendijk (Gabrielle); G. Mcmahon (George); J.P. Kemp (John); B.S. Pourcain (Beate); C.L. Simpson (Claire); M.J. Mäkelä; T. Lehtimäki (Terho); M. Kähönen (Mika); A.D. Paterson (Andrew); M. Hosseini (Mehran); H.S. Wong (Hoi Suen); L. Xu (Liang); J.B. Jonas; O. Pärssinen (Olavi); J. Wedenoja (Juho); S.P. Yip (Shea Ping); D.W.H. Ho (Daniel); C.P. Pang (Chi); L.J. Chen (Li); K.P. Burdon (Kathryn); J.E. Craig (Jamie); B.E.K. Klein (Barbara); B.E.K. Klein (Barbara); T. Haller (Toomas); A. Metspalu (Andres); C.C. Khor; E.S. Tai (Shyong); T. Aung (Tin); E.N. Vithana (Eranga); W.-T. Tay (Wan-Ting); V.A. Barathi (Veluchamy); P. Chen (Ping); R. Li (Rui); J. Liao (Jie); Y. Zheng (Yuhui); R.T.H. Ong (Rick Twee-Hee); A. Döring (Angela); D.M. Evans (David); N. Timpson (Nicholas); A. Verkerk; T. Meitinger (Thomas); O. Raitakari (Olli); F. Hawthorne (Felicia); T.D. Spector (Timothy); L.C. Karssen (Lennart); M. Pirastu (Mario); D. Murgia (Daniela); W.Q. Ang (Wei); A. Mishra (Aniket); G.W. Montgomery (Grant); C.E. Pennell (Craig); P. Cumberland (Phillippa); I. Cotlarciuc (Ioana); P. Mitchell (Paul); J.J. Wang (Jie Jin); M. Schache (Maria); S. Janmahasathian (Sarayut); R.P. Igo Jr. (Robert); J.H. Lass Jr. (Jonathan); E.Y. Chew (Emily); S.K. Iyengar (Sudha); T.G.M.F. Gorgels (Theo); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); Z. Vatavuk (Zoran); J.F. Wilson (James); B. Fleck (Brian); T. Zeller (Tanja); A. Mirshahi (Alireza); C. Müller (Christian); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); A. Hofman (Albert); B.A. Oostra (Ben); N. Amin (Najaf); A.A.B. Bergen (Arthur); Y.Y. Teo (Yik Ying); J.S. Rahi (Jugnoo); V. Vitart (Veronique); C. Williams (Cathy); P.N. Baird (Paul); T.Y. Wong (Tien); K. Oexle (Konrad); A.F.H. Pfeiffer (Andreas); D.A. Mackey (David); T.L. Young (Terri); C.M. van Duijn (Cock); S-M. Saw (Seang-Mei); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); C.C.W. Klaver (Caroline); C.J. Hammond (Christopher)

    2013-01-01

    textabstractRefractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European anc

  19. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); R. Wojciechowski (Robert); Q. Fan (Qiao); J. Guggenheim (Jean); R. Höhn (René); S. MacGregor (Stuart); A.W. Hewit (Alex); A. Nag (Abhishek); C-Y. Cheng (Ching-Yu); E. Yonova-Doing (Ekaterina); X. Zhou (Xin); M.K. Ikram (Kamran); G.H.S. Buitendijk (Gabrielle); G. Mcmahon (George); J.P. Kemp (John); B.S. Pourcain (Beate); C.L. Simpson (Claire); M.J. Mäkelä; T. Lehtimäki (Terho); M. Kähönen (Mika); A.D. Paterson (Andrew); M. Hosseini (Mehran); H.S. Wong (Hoi Suen); L. Xu (Liang); J.B. Jonas; O. Pärssinen (Olavi); J. Wedenoja (Juho); S.P. Yip (Shea Ping); D.W.H. Ho (Daniel); C.P. Pang (Chi); L.J. Chen (Li); K.P. Burdon (Kathryn); J.E. Craig (Jamie); B.E.K. Klein (Barbara); B.E.K. Klein (Barbara); T. Haller (Toomas); A. Metspalu (Andres); C.C. Khor; E.S. Tai (Shyong); T. Aung (Tin); E.N. Vithana (Eranga); W.-T. Tay (Wan-Ting); V.A. Barathi (Veluchamy); P. Chen (Ping); R. Li (Rui); J. Liao (Jie); Y. Zheng (Yuhui); R.T.H. Ong (Rick Twee-Hee); A. Döring (Angela); D.M. Evans (David); N.J. Timpson (Nicholas); A. Verkerk; T. Meitinger (Thomas); O. Raitakari (Olli); F. Hawthorne (Felicia); T.D. Spector (Timothy); L.C. Karssen (Lennart); M. Pirastu (Mario); D. Murgia (Daniela); W.Q. Ang (Wei); A. Mishra (Aniket); G.W. Montgomery (Grant); C.E. Pennell (Craig); P. Cumberland (Phillippa); I. Cotlarciuc (Ioana); P. Mitchell (Paul); J.J. Wang (Jie Jin); M. Schache (Maria); S. Janmahasathian (Sarayut); R.P. Igo Jr. (Robert); J.H. Lass Jr. (Jonathan); E.Y. Chew (Emily); S.K. Iyengar (Sudha); T.G.M.F. Gorgels (Theo); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); Z. Vatavuk (Zoran); J.F. Wilson (James); B. Fleck (Brian); T. Zeller (Tanja); A. Mirshahi (Alireza); C. Müller (Christian); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); A. Hofman (Albert); B.A. Oostra (Ben); N. Amin (Najaf); A.A.B. Bergen (Arthur); Y.Y. Teo (Yik Ying); J.S. Rahi (Jugnoo); V. Vitart (Veronique); C. Williams (Cathy); P.N. Baird (Paul); T.Y. Wong (Tien); K. Oexle (Konrad); A.F.H. Pfeiffer (Andreas); D.A. Mackey (David); T.L. Young (Terri); C.M. van Duijn (Cock); S-M. Saw (Seang-Mei); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); C.C.W. Klaver (Caroline); C.J. Hammond (Christopher)

    2013-01-01

    textabstractRefractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European

  20. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Maegi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loic; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; St Pourcain, Beate; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tonu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Mueller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Goeran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindstrom, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Koerner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josee; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Ines

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes

  1. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

    NARCIS (Netherlands)

    Stolk, Lisette; Perry, John R. B.; Chasman, Daniel I.; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M.; Ernst, Florian; Esko, Tonu; Franceschini, Nora; Gudbjartsson, Daniel F.; Hottenga, Jouke-Jan; Kraft, Peter; McArdle, Patrick F.; Porcu, Eleonora; Shin, So-Youn; Smith, Albert V.; van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V.; Albrecht, Eva; Alizadeh, Behrooz Z.; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S.; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J.; Burri, Andrea; Campbell, Harry; Chanock, Stephen J.; Chen, Constance; Cornelis, Marilyn C.; Corre, Tanguy; Coviello, Andrea D.; d'Adamo, Pio; Davies, Gail; de Faire, Ulf; de Geus, Eco J. C.; Deary, Ian J.; Dedoussis, George V. Z.; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G.; Fauser, Bart C. J. M.; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R.; Garcia, Melissa E.; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E.; Hall, Per; Haller, Toomas; Hankinson, Susan E.; Hass, Merli; Hayward, Caroline; Heath, Andrew C.; Hofman, Albert; Ingelsson, Erik; Janssens, A. Cecile J. W.; Johnson, Andrew D.; Karasik, David; Kardia, Sharon L. R.; Keyzer, Jules; Kiel, Douglas P.; Kolcic, Ivana; Kutalik, Zoltan; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop S. E.; Lawlor, Debbie A.; Liu, Jianjun; Lopez, Lorna M.; Louwers, Yvonne V.; Magnusson, Patrik K. E.; Marongiu, Mara; Martin, Nicholas G.; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E.; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B.; Nyholt, Dale R.; Onland-Moret, N. Charlotte; Palotie, Aarno; Pare, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peeters, Petra H. M.; Pistis, Giorgio; Plump, Andrew S.; Polasek, Ozren; Pop, Victor J. M.; Psaty, Bruce M.; Raikkonen, Katri; Rehnberg, Emil; Rotter, Jerome I.; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A.; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N.; Starr, John M.; Stathopoulou, Maria G.; Stirrups, Kathleen; Stolk, Ronald P.; Styrkarsdottir, Unnur; Sun, Yan V.; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; van Dam, Rob M.; van der Schouw, Yvonne T.; van Gils, Carla H.; van Nierop, Peter; Vink, Jacqueline M.; Visscher, Peter M.; Voorhuis, Marlies; Waeber, Gerard; Wallaschofski, Henri; Wichmann, H. Erich; Widen, Elisabeth; Wijnands-van Gent, Colette J. M.; Willemsen, Gonneke; Wilson, James F.; Wolffenbuttel, Bruce H. R.; Wright, Alan F.; Yerges-Armstrong, Laura M.; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M. Carola; Zygmunt, Marek; Arnold, Alice M.; Boomsma, Dorret I.; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W.; Gudnason, Vilmundur; Harris, Tamara B.; Hu, Frank B.; Hunter, David J.; Launer, Lenore J.; Metspalu, Andres; Montgomery, Grant W.; Oostra, Ben A.; Ridker, Paul M.; Sanna, Serena; Schlessinger, David; Spector, Tim D.; Stefansson, Kari; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Voelzke, Henry; Murray, Anna; Murabito, Joanne M.; Visser, Jenny A.; Lunetta, Kathryn L.

    To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural

  2. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

    NARCIS (Netherlands)

    Stolk, Lisette; Perry, John R B; Chasman, Daniel I; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M; Ernst, Florian; Esko, Tõnu; Franceschini, Nora; Gudbjartsson, Daniel F; Hottenga, Jouke-Jan; Kraft, Peter; McArdle, Patrick F; Porcu, Eleonora; Shin, So-Youn; Smith, Albert V; van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V; Albrecht, Eva; Alizadeh, Behrooz Z; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J; Burri, Andrea; Campbell, Harry; Chanock, Stephen J; Chen, Constance; Cornelis, Marilyn C; Corre, Tanguy; Coviello, Andrea D; d'Adamo, Pio; Davies, Gail; de Faire, Ulf; de Geus, Eco J C; Deary, Ian J; Dedoussis, George V Z; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G; Fauser, Bart C J M; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R; Garcia, Melissa E; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E; Hall, Per; Haller, Toomas; Hankinson, Susan E; Hass, Merli; Hayward, Caroline; Heath, Andrew C; Hofman, Albert; Ingelsson, Erik; Janssens, A Cecile J W; Johnson, Andrew D; Karasik, David; Kardia, Sharon L R; Keyzer, Jules; Kiel, Douglas P; Kolcic, Ivana; Kutalik, Zoltán; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop S E; Lawlor, Debbie A; Liu, Jianjun; Lopez, Lorna M; Louwers, Yvonne V; Magnusson, Patrik K E; Marongiu, Mara; Martin, Nicholas G; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B; Nyholt, Dale R; Onland-Moret, N Charlotte; Palotie, Aarno; Paré, Guillaume; Parker, Alex N; Pedersen, Nancy L; Peeters, Petra H M; Pistis, Giorgio; Plump, Andrew S; Polasek, Ozren; Pop, Victor J M; Psaty, Bruce M; Räikkönen, Katri; Rehnberg, Emil; Rotter, Jerome I; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N; Starr, John M; Stathopoulou, Maria G; Stirrups, Kathleen; Stolk, Ronald P; Styrkarsdottir, Unnur; Sun, Yan V; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; van Dam, Rob M; van der Schouw, Yvonne T; van Gils, Carla H; van Nierop, Peter; Vink, Jacqueline M; Visscher, Peter M; Voorhuis, Marlies; Waeber, Gérard; Wallaschofski, Henri; Wichmann, H Erich; Widen, Elisabeth; Wijnands-van Gent, Colette J M; Willemsen, Gonneke; Wilson, James F; Wolffenbuttel, Bruce H R; Wright, Alan F; Yerges-Armstrong, Laura M; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M Carola; Zygmunt, Marek; Arnold, Alice M; Boomsma, Dorret I; Buring, Julie E; Crisponi, Laura; Demerath, Ellen W; Gudnason, Vilmundur; Harris, Tamara B; Hu, Frank B; Hunter, David J; Launer, Lenore J; Metspalu, Andres; Montgomery, Grant W; Oostra, Ben A; Ridker, Paul M; Sanna, Serena; Schlessinger, David; Spector, Tim D; Stefansson, Kari; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, André G; van Duijn, Cornelia M; Völzke, Henry; Murray, Anna; Murabito, Joanne M; Visser, Jenny A; Lunetta, Kathryn L

    2012-01-01

    To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural men

  3. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

    NARCIS (Netherlands)

    L. Stolk (Lisette); J.R.B. Perry (John); D.I. Chasman (Daniel); C. He (Chunyan); M. Mangino (Massimo); P. Sulem (Patrick); M. Barbalic (maja); L. Broer (Linda); E.M. Byrne (Enda); F.D.J. Ernst (Florian); T. Esko (Tõnu); N. Franceschini (Nora); D.F. Gudbjartsson (Daniel); J.J. Hottenga (Jouke Jan); P. Kraft (Peter); P.F. McArdle (Patrick); E. Porcu (Eleonora); S.-Y. Shin; G.D. Smith; S. van Wingerden (Sophie); G. Zhai (Guangju); W.V. Zhuang; E. Albrecht (Eva); B.Z. Alizadeh (Behrooz); T. Aspelund (Thor); S. Bandinelli (Stefania); G. Lauc (Gordan); J.S. Beckmann (Jacques); M. Boban (Mladen); E.A. Boerwinkle (Eric); F.J.M. Broekmans (Frank); A. Burri (Andrea); H. Campbell (Harry); S.J. Chanock (Stephen); C. Chen (Constance); M. Cornelis (Marilyn); T. Corre (Tanguy); A.D. Coviello (Andrea); P. d' Adamo (Pio); G. Davies (Gail); U. de Faire (Ulf); E.J.C. de Geus (Eco); I.J. Deary (Ian); G.V. Dedoussis (George); P. Deloukas (Panagiotis); S. Ebrahim (Shanil); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); B.C.J.M. Fauser (Bart); L. Ferreli (Liana); L. Ferrucci (Luigi); K. Fischer (Krista); A.R. Folsom (Aaron); M. Garcia (Melissa); P. Gasparini (Paolo); C. Gieger (Christian); N.L. Glazer (Nicole); D.E. Grobbee (Diederick); P. Hall (Per); T. Haller (Toomas); S.E. Hankinson (Susan); M. Hass (Merli); C. Hayward (Caroline); A.C. Heath (Andrew); A. Hofman (Albert); E. Ingelsson (Erik); A.C.J.W. Janssens (Cécile); A.D. Johnson (Andrew); D. Karasik (David); S.L.R. Kardia (Sharon); J.J. de Keyzer (Jules); D.P. Kiel (Douglas); I. Kolcic (Ivana); Z. Kutalik (Zoltán); J. Lahti (Jari); S. Lai (Sandra); T. Laisk (Triin); J.S.E. Laven (Joop); D.A. Lawlor (Debbie); J. Liu (Jianjun); L.M. Lopez (Lorna); Y.V. Louwers (Yvonne); P.K. Magnusson (Patrik); M. Marongiu (Mara); N.G. Martin (Nicholas); I.M. Klaric (Irena Martinovic); C. Masciullo (Corrado); B. McKnight (Barbara); S.E. Medland (Sarah Elizabeth); D. Melzer (David); V. Mooser (Vincent); P. Navarro (Pau); A.B. Newman (Anne); D.R. Nyholt (Dale); N.C. Onland-Moret (Charlotte); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); P.H.M. Peeters (Petra); G. Pistis (Giorgio); A.S. Plump (Andrew); O. Polasek (Ozren); V. Pop (Victor); B.M. Psaty (Bruce); K. R Currency Signikkönen (Katri); E. Rehnberg (Emil); J.I. Rotter (Jerome); I. Rudan (Igor); C. Sala (Cinzia); A. Salumets (Andres); A. Scuteri (Angelo); A. Singleton (Andrew); J.A. Smith (Jennifer A); H. Snieder (Harold); N. Soranzo (Nicole); S.N. Stacey (Simon); J.M. Starr (John); M.G. Stathopoulou (Maria G); K. Stirrups (Kathy); R.P. Stolk (Ronald); U. Styrkarsdottir (Unnur); Y.V. Sun (Yan); A. Tenesa (Albert); B. Thorand (Barbara); D. Toniolo (Daniela); L. Tryggvadottir (Laufey); K. Tsui (Kim); S. Ulivi (Shelia); R.M. van Dam (Rob); Y.T. van der Schouw (Yvonne); C.H. van Gils (Carla); P.W.M. van Nierop (Peter); J.M. Vink (Jacqueline); P.M. Visscher (Peter); M. Voorhuis (Marlies); G. Waeber (Gérard); H. Wallaschofski (Henri); H.E. Wichmann (Heinz Erich); E. Widen (Elisabeth); C.J.M. Wijnands-Van Gent (Colette J M); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); B.H.R. Wolffenbuttel (Bruce); A.F. Wright (Alan); L.M. Yerges-Armstrong (Laura); T. Zemunik (Tatijana); L. Zgaga (Lina); M.C. Zillikens (Carola); M. Zygmunt (Marek); A.M. Arnold (Alice); D.I. Boomsma (Dorret); J.E. Buring (Julie); L. Crisponi (Laura); E.W. Demerath (Ellen); V. Gudnason (Vilmundur); T.B. Harris (Tamara); F.B. Hu (Frank); D. Hunter (David); L.J. Launer (Lenore); A. Metspalu (Andres); G.W. Montgomery (Grant); B.A. Oostra (Ben); P.M. Ridker (Paul); S. Sanna (Serena); D. Schlessinger (David); T.D. Spector (Timothy); J-A. Zwart (John-Anker); E.A. Streeten (Elizabeth); U. Thorsteinsdottir (Unnur); M. Uda (Manuela); A.G. Uitterlinden (André); C.M. van Duijn (Cock); H. Völzke (Henry); A. Murray (Anna); J. Murabito (Joanne); J.A. Visser (Jenny); K.L. Lunetta (Kathryn)

    2012-01-01

    textabstractTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at

  4. Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Deng, Min; Wei, Ling; Zuo, Xianbo; Tian, Yanghua; Xie, Fei; Hu, Panpan; Zhu, Chunyan; Yu, Fengqiong; Meng, Yu; Wang, Honghao; Zhang, Fangfang; Ma, Huijuan; Ye, Rong; Cheng, Huaidong; Du, Jing; Dong, Wenwen; Zhou, Shanshan; Wang, Changqing; Wang, Yu; Wang, Jingye; Chen, Xianwen; Sun, Zhongwu; Zhou, Nong; Jiang, Yubao; Liu, Xiuxiu; Li, Xiaogang; Zhang, Nan; Liu, Na; Guan, Yingjun; Han, Yongsheng; Han, Yongzhu; Lv, Xinyi; Fu, Yu; Yu, Hui; Xi, Chunhua; Xie, Dandan; Zhao, Qiyuan; Xie, Peng; Wang, Xin; Zhang, Zhijun; Shen, Lu; Cui, Yong; Yin, Xianyong; Cheng, Hui; Liang, Bo; Zheng, Xiaodong; Lee, Tatia M. C.; Chen, Gang; Zhou, Fusheng; Veldink, Hendrik; Robberecht, Wim; Landers, John E.; Andersen, Peter M.; Al-Chalabi, Ammar; Shaw, Chris; Liu, Chunfeng; Tang, Beisha; Xiao, Shangxi; Robertson, Janice; Zhang, Fengyu; van den Berg, Leonard H.; Sun, Liangdan; Liu, Jianjun; Yang, Sen; Ju, Xiaodong; Wang, Kai; Zhang, Xuejun

    2013-01-01

    To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were ana

  5. Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains

    OpenAIRE

    Jason, Leonard A.; Sunnquist, Madison; Brown, Abigail; Furst, Jacob; Cid, Marjoe; Farietta, Jillianna; Kot, Bobby; Bloomer, Craig; Nicholson, Laura; Williams, Yolonda; Jantke, Rachel; Newton, Julia L.; Strand, Elin Bolle

    2015-01-01

    The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisti...

  6. Analyses of in vivo interactions between transcription factors and the archaeal RNA polymerase.

    Science.gov (United States)

    Walker, Julie E; Santangelo, Thomas J

    2015-09-15

    Transcription factors regulate the activities of RNA polymerase (RNAP) at each stage of the transcription cycle. Many basal transcription factors with common ancestry are employed in eukaryotic and archaeal systems that directly bind to RNAP and influence intramolecular movements of RNAP and modulate DNA or RNA interactions. We describe and employ a flexible methodology to directly probe and quantify the binding of transcription factors to RNAP in vivo. We demonstrate that binding of the conserved and essential archaeal transcription factor TFE to the archaeal RNAP is directed, in part, by interactions with the RpoE subunit of RNAP. As the surfaces involved are conserved in many eukaryotic and archaeal systems, the identified TFE-RNAP interactions are likely conserved in archaeal-eukaryal systems and represent an important point of contact that can influence the efficiency of transcription initiation.

  7. Systematic Selection of Key Logistic Regression Variables for Risk Prediction Analyses: A Five-Factor Maximum Model.

    Science.gov (United States)

    Hewett, Timothy E; Webster, Kate E; Hurd, Wendy J

    2017-08-16

    The evolution of clinical practice and medical technology has yielded an increasing number of clinical measures and tests to assess a patient's progression and return to sport readiness after injury. The plethora of available tests may be burdensome to clinicians in the absence of evidence that demonstrates the utility of a given measurement. Thus, there is a critical need to identify a discrete number of metrics to capture during clinical assessment to effectively and concisely guide patient care. The data sources included Pubmed and PMC Pubmed Central articles on the topic. Therefore, we present a systematic approach to injury risk analyses and how this concept may be used in algorithms for risk analyses for primary anterior cruciate ligament (ACL) injury in healthy athletes and patients after ACL reconstruction. In this article, we present the five-factor maximum model, which states that in any predictive model, a maximum of 5 variables will contribute in a meaningful manner to any risk factor analysis. We demonstrate how this model already exists for prevention of primary ACL injury, how this model may guide development of the second ACL injury risk analysis, and how the five-factor maximum model may be applied across the injury spectrum for development of the injury risk analysis.

  8. Identify and Classify Critical Success Factor of Agile Software Development Methodology Using Mind Map

    Directory of Open Access Journals (Sweden)

    Tasneem Abd El Hameed

    2016-05-01

    Full Text Available Selecting the right method, right personnel and right practices, and applying them adequately, determine the success of software development. In this paper, a qualitative study is carried out among the critical factors of success from previous studies. The factors of success match with their relative principles to illustrate the most valuable factor for agile approach success, this paper also prove that the twelve principles poorly identified for few factors resulting from qualitative and quantitative past studies. Dimensions and Factors are presented using Critical success Dimensions and Factors Mind Map Model.

  9. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI).

    Science.gov (United States)

    Escoffery, Cam; Bamps, Yvan; LaFrance, W Curt; Stoll, Shelley; Shegog, Ross; Buelow, Janice; Shafer, Patricia; Thompson, Nancy J; McGee, Robin E; Hatfield, Katherine

    2015-09-01

    The purpose of this study was to test the psychometric properties of an enhanced Adult Epilepsy Self-Management Measurement Instrument (AESMMI). An instrument of 113 items, covering 10 a priori self-management domains, was generated through a multiphase process, based on a review of the literature, validated epilepsy and other chronic condition self-management scales and expert input. Reliability and exploratory factor analyses were conducted on data collected from 422 adults with epilepsy. The instrument was reduced to 65 items, converging on 11 factors: Health-care Communication, Coping, Treatment Management, Seizure Tracking, Social Support, Seizure Response, Wellness, Medication Adherence, Safety, Stress Management, and Proactivity. Exploratory factors supported the construct validity for 6 a priori domains, albeit with significant changes in the retained items or in their scope and 3 new factors. One a priori domain was split in 2 subscales pertaining to treatment. The configuration of the 11 factors provides additional insight into epilepsy self-management behaviors. Internal consistency reliability of the 65-item instrument was high (α=.935). Correlations with independent measures of health status, quality of life, depression, seizure severity, and life impact of epilepsy further validated the instrument. This instrument shows potential for use in research and clinical settings and for assessing intervention outcomes and self-management behaviors in adults with epilepsy.

  10. Demographic, socioeconomic, and behavioral factors affecting patterns of tooth decay in the permanent dentition: principal components and factor analyses.

    Science.gov (United States)

    Shaffer, John R; Polk, Deborah E; Feingold, Eleanor; Wang, Xiaojing; Cuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

    2013-08-01

    Dental caries of the permanent dentition is a multifactorial disease resulting from the complex interplay of endogenous and environmental risk factors. The disease is not easily quantitated due to the innumerable possible combinations of carious lesions across individual tooth surfaces of the permanent dentition. Global measures of decay, such as the DMFS index (which was developed for surveillance applications), may not be optimal for studying the epidemiology of dental caries because they ignore the distinct patterns of decay across the dentition. We hypothesize that specific risk factors may manifest their effects on specific tooth surfaces leading to patterns of decay that can be identified and studied. In this study, we utilized two statistical methods of extracting patterns of decay from surface-level caries data to create novel phenotypes with which to study the risk factors affecting dental caries. Intra-oral dental examinations were performed on 1068 participants aged 18-75 years to assess dental caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not and used as input for principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori knowledge of the patterns. Demographic (age, sex, birth year, race/ethnicity, and educational attainment), anthropometric (height, body mass index, waist circumference), endogenous (saliva flow), and environmental (tooth brushing frequency, home water source, and home water fluoride) risk factors were tested for association with the caries patterns identified by PCA and FA, as well as DMFS, for comparison. The ten strongest patterns (i.e. those that explain the most variation in the data set) extracted by PCA and FA were considered. The three strongest patterns identified by PCA reflected (i) global extent of decay (i.e. comparable to DMFS index), (ii) pit and fissure surface caries and (iii) smooth surface caries, respectively. The

  11. Naturalistic cycling study: identifying risk factors for on-road commuter cyclists.

    Science.gov (United States)

    Johnson, Marilyn; Charlton, Judith; Oxley, Jennifer; Newstead, Stuart

    2010-01-01

    The study aim was to identify risk factors for collisions/near-collisions involving on-road commuter cyclists and drivers. A naturalistic cycling study was conducted in Melbourne, Australia, with cyclists wearing helmet-mounted video cameras. Video recordings captured cyclists' perspective of the road and traffic behaviours including head checks, reactions and manoeuvres. The 100-car naturalistic driving study analysis technique was adapted for data analysis and events were classified by severity: collision, near-collision and incident. Participants were adult cyclists and each filmed 12 hours of commuter cycling trips over a 4-week period. In total, 127 hours and 38 minutes were analysed for 13 participants, 54 events were identified: 2 collisions, 6 near-collisions and 46 incidents. Prior to events, 88.9% of cyclists travelled in a safe/legal manner. Sideswipe was the most frequent event type (40.7%). Most events occurred at an intersection/intersection-related location (70.3%). The vehicle driver was judged at fault in the majority of events (87.0%) and no post-event driver reaction was observed (83.3%). Cross tabulations revealed significant associations between event severity and: cyclist reaction, cyclist post-event manoeuvre, pre-event driver behaviour, other vehicle involved, driver reaction, visual obstruction, cyclist head check (left), event type and vehicle location (proad cyclists and to indicate early before turning/changing lanes when sharing the roadway with cyclists are discussed. Findings will contribute to the development of effective countermeasures to reduce cyclist trauma.

  12. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

    National Research Council Canada - National Science Library

    Kandeel, Amr M; Talaat, Maha; Afifi, Salma A; El-Sayed, Nasr M; Abdel Fadeel, Moustafa A; Hajjeh, Rana A; Mahoney, Frank J

    2012-01-01

    .... We conducted a case-control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two...

  13. Combinatory microarray and SuperSAGE analyses identify pairing-dependently transcribed genes in Schistosoma mansoni males, including follistatin.

    Directory of Open Access Journals (Sweden)

    Silke Leutner

    2013-11-01

    Full Text Available BACKGROUND: Schistosomiasis is a disease of world-wide importance and is caused by parasitic flatworms of the genus Schistosoma. These parasites exhibit a unique reproduction biology as the female's sexual maturation depends on a constant pairing-contact to the male. Pairing leads to gonad differentiation in the female, and even gene expression of some gonad-associated genes is controlled by pairing. In contrast, no morphological changes have been observed in males, although first data indicated an effect of pairing also on gene transcription in males. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the influence of pairing on males, we performed a combinatory approach applying SuperSAGE and microarray hybridization, generating the most comprehensive data-set on differential transcription available to date. Of 6,326 sense transcripts detected by both analyses, 29 were significantly differentially transcribed. Besides mutual confirmation, the two methods complemented each other as shown by data comparison and real-time PCR, which revealed a number of genes with consistent regulation across all methods. One of the candidate genes, follistatin of S. mansoni (SmFst was characterized in more detail by in situ hybridization and yeast two-hybrid (Y2H interaction analyses with potential binding partners. CONCLUSIONS/SIGNIFICANCE: Beyond confirming previously hypothesized differences in metabolic processes between pairing-experienced (EM and pairing-unexperienced males (UM, our data indicate that neuronal processes are involved in male-female interaction but also TGFβ-signaling. One candidate revealing significant down-regulation in EM was the TGFβ-pathway controlling molecule follistatin (SmFst. First functional analyses demonstrated SmFst interaction with the S. mansoni TGFβ-receptor agonists inhibin/activin (SmInAct and bone morphogenic protein (SmBMP, and all molecules colocalized in the testes. This indicates a yet unknown role of the TGF

  14. Gonad RNA-specific qRT-PCR analyses identify genes with potential functions in schistosome reproduction such as SmFz1 and SmFGFRs

    Directory of Open Access Journals (Sweden)

    Steffen eHahnel

    2014-06-01

    Full Text Available In the search for new strategies to fight schistosomiasis, the unique reproductive biology of Schistosoma mansoni has come into the focus of research. The development of the gonads and the ability of egg production are fundamental not only for continuing the life cycle but also for pathogenicity.Previous studies of schistosome biology demonstrated an influence of pairing on gonad development of the female and on gene expression profiles in both genders. Due to the limited access to specific tissues, however, most of these studies were done at the level of whole worms neglecting individual tissues that may be targets of pairing-dependent processes.Recently, we established a protocol allowing the isolation of testes and ovaries from adult S. mansoni. Here, we describe tissue-specific qRT-PCR analyses comparing transcript levels of selected genes on the basis of RNA from gonads and whole worms. Gene expression in ovary and testes was in some cases found to be significantly influenced by pairing, which was not traceable in whole worms. Among the candidate genes identified as regulated by pairing in gonads were the frizzled homolog SmFz1 and the two fibroblast growth factor receptor homologs SmFGFR-A and SmFGFR-B. First functional characterizations were done, including comparative qRT-PCR analyses, in situ-localization experiments, heterologous expression in Xenopus oocytes (SmFGFR-A/B, and inhibitor studies using the Fz/Dvl-pathway inhibitor 3289-8625, or BIBF1120 blocking FGFR-signaling. Besides confirming gonad localization and receptor functions, inhibitor-induced phenotypes were observed in vitro such as decreased egg production as well as drastic effects on gonad differentiation, morphology, embryogenesis, and survival of adult worms.In summary, these results emphasise the usefulness of tissue specific qRT-PCRs for selection of candidate genes with important roles in reproduction, allowing subsequent studies to determine their suitability as

  15. ObStruct: a method to objectively analyse factors driving population structure using Bayesian ancestry profiles.

    Directory of Open Access Journals (Sweden)

    Velimir Gayevskiy

    Full Text Available Bayesian inference methods are extensively used to detect the presence of population structure given genetic data. The primary output of software implementing these methods are ancestry profiles of sampled individuals. While these profiles robustly partition the data into subgroups, currently there is no objective method to determine whether the fixed factor of interest (e.g. geographic origin correlates with inferred subgroups or not, and if so, which populations are driving this correlation. We present ObStruct, a novel tool to objectively analyse the nature of structure revealed in Bayesian ancestry profiles using established statistical methods. ObStruct evaluates the extent of structural similarity between sampled and inferred populations, tests the significance of population differentiation, provides information on the contribution of sampled and inferred populations to the observed structure and crucially determines whether the predetermined factor of interest correlates with inferred population structure. Analyses of simulated and experimental data highlight ObStruct's ability to objectively assess the nature of structure in populations. We show the method is capable of capturing an increase in the level of structure with increasing time since divergence between simulated populations. Further, we applied the method to a highly structured dataset of 1,484 humans from seven continents and a less structured dataset of 179 Saccharomyces cerevisiae from three regions in New Zealand. Our results show that ObStruct provides an objective metric to classify the degree, drivers and significance of inferred structure, as well as providing novel insights into the relationships between sampled populations, and adds a final step to the pipeline for population structure analyses.

  16. Identifying consumer segments in health services markets: an application of conjoint and cluster analyses to the ambulatory care pharmacy market.

    Science.gov (United States)

    Carrol, N V; Gagon, J P

    1983-01-01

    Because of increasing competition, it is becoming more important that health care providers pursue consumer-based market segmentation strategies. This paper presents a methodology for identifying and describing consumer segments in health service markets, and demonstrates the use of the methodology by presenting a study of consumer segments in the ambulatory care pharmacy market.

  17. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P.; Manning, Alisa K.; Grarup, Niels; Sim, Xueling; Barnes, Daniel R.; Witkowska, Kate; Staley, James R.; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F.; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T.; Nielsen, Sune Fallgaard; Rasheed, Asif; Samue, Maria; Zhao, Wei; Bonnycastle, Lori L.; Jackson, Anne U.; Narisu, Narisu; Swift, Amy J.; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R.; Stancakova, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E.; Bork-Jensen, Jette; Gjesing, Anette P.; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S.; Zhang, He; Donnelly, Louise A.; Groves, Christopher J.; Rayner, N. William; Neville, Matt J.; Robertson, Neil R.; Yiorkas, Andrianos M.; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M.; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P.; Poveda, Alaitz; Varga, Tibor V.; Caslake, Muriel; de Craen, Anton J. M.; Trompet, Stella; Luan, Jian'an; Scott, Robert A.; Harris, Sarah E.; Liewald, David C. M.; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Goran; Renstrom, Frida; Huffman, Jennifer E.; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S.; Felix, Janine F.; Uria-Nickelsen, Maria; Malarstign, Anders; Reilly, Dermot F.; Hoek, Maarten; Vogt, Thomas F.; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S.; Highland, Heather M.; Justice, Anne E.; Marouli, Eirini; Lindstrom, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A.; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W.; Dedoussis, George; Spector, Timothy D.; Jousilahti, Pekka; Mannisto, Satu; Deary, Ian J.; Starr, John M.; Langenberg, Claudia; Wareham, Nick J.; Brown, Morris J.; Dominiczak, Anna F.; Connell, John M.; Jukema, J. Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J.; Esko, Tonu; Magi, Reedik; Metspalu, Andres; de Boer, Rudolf A.; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I. W.; Numans, Mattijs E.; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R. B.; Korpi-Hyovalti, Eeva; Oksa, Heikki; Chambers, John C.; Kooner, Jaspal S.; Blakemore, Alexandra I. F.; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L.; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J.; Tuomi, Tiinamaija; Groop, Leif; Karajamaki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S.; Majmnder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I.; Poulter, Neil; Stanton, Alice V.; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrieres, Jean; Kee, Frank; Kuulasmaa, Kari; Muller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J.; Hayward, Caroline; Scotland, Generation; Collins, Francis S.; Mohlke, Karen L.; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M.; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D.; Nordestgaard, Borge Gronne; Caulfield, Mark J.; Mahajan, Anubha; Morris, Andrew P.; Tomaszewski, Maciej; Samani, Nilesh J.; Saleheen, Danish; Asselbergs, Folkert W.; Lindgren, Cecilia M.; Danesh, John; Wain, Louise V.; Butterworth, Adam S.; Howson, Joanna M. M.; Munroe, Patricia B.

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192

  18. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P; Manning, Alisa K; Grarup, Niels; Sim, Xueling; Barnes, Daniel R; Witkowska, Kate; Staley, James R; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T; Nielsen, Sune Fallgaard; Rasheed, Asif; Samuel, Maria; Zhao, Wei; Bonnycastle, Lori L; Jackson, Anne U; Narisu, Narisu; Swift, Amy J; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R; Stančáková, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E; Bork-Jensen, Jette; Gjesing, Anette P; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S; Zhang, He; Donnelly, Louise A; Groves, Christopher J; Rayner, N William; Neville, Matt J; Robertson, Neil R; Yiorkas, Andrianos M; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P; Poveda, Alaitz; Varga, Tibor V; Caslake, Muriel; de Craen, Anton J M; Trompet, Stella; Luan, Jian'an; Scott, Robert A; Harris, Sarah E; Liewald, David C M; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Göran; Renström, Frida; Huffman, Jennifer E; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S; Felix, Janine F; Uria-Nickelsen, Maria; Malarstig, Anders; Reilly, Dermot F; Hoek, Maarten; Vogt, Thomas F; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S; Highland, Heather M; Justice, Anne E; Marouli, Eirini; Lindström, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W; Dedoussis, George; Spector, Timothy D; Jousilahti, Pekka; Männistö, Satu; Deary, Ian J; Starr, John M; Langenberg, Claudia; Wareham, Nick J; Brown, Morris J; Dominiczak, Anna F; Connell, John M; Jukema, J Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J; Esko, Tõnu; Mägi, Reedik; Metspalu, Andres; de Boer, Rudolf A; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I W; Numans, Mattijs E; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R B; Korpi-Hyövälti, Eeva; Oksa, Heikki; Chambers, John C; Kooner, Jaspal S; Blakemore, Alexandra I F; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S F; Morris, Andrew D; Palmer, Colin N A; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J; Tuomi, Tiinamaija; Groop, Leif; Käräjämäki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S; Majumder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I; Poulter, Neil; Stanton, Alice V; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrières, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J; Hayward, Caroline; Scotland, Generation; Collins, Francis S; Mohlke, Karen L; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D; Nordestgaard, Børge Grønne; Caulfield, Mark J; Mahajan, Anubha; Morris, Andrew P; Tomaszewski, Maciej; Samani, Nilesh J; Saleheen, Danish; Asselbergs, Folkert W; Lindgren, Cecilia M; Danesh, John; Wain, Louise V; Butterworth, Adam S; Howson, Joanna M M; Munroe, Patricia B

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192

  19. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, P. (Praveen); F. Drenos (Fotios); R. Young (Robin); H. Warren (Helen); Cook, J.P. (James P.); A.K. Manning (Alisa); N. Grarup (Niels); X. Sim (Xueling); D. Barnes (Daniel); H.E. Witkowska (Ewa); J.R. Staley (James R.); V. Tragante (Vinicius); T. Tukiainen (Taru); H. Yaghootkar (Hanieh); Masca, N. (Nicholas); C.M. Freitag (Christine); T. Ferreira (Teresa); O. Giannakopoulou (Olga); Tinker, A. (Andrew); M. Harakalova (Magdalena); E. Mihailov (Evelin); Liu, C. (Chunyu); A. Kraja (Aldi); S.F. Nielsen (Sune); A. Rasheed (Asif); M. Samuel (Maria); W. Zhao (Wei); L.L. Bonnycastle (Lori); A.U. Jackson (Anne); N. Narisu (Narisu); A.J. Swift (Amy); L. Southam (Lorraine); J. Marten (Jonathan); J.R. Huyghe (Jeroen R.); A. Stancáková (Alena); C. Fava (Cristiano); Ohlsson, T. (Therese); A. Matchan (Angela); K. Stirrups (Kathy); J. Bork-Jensen (Jette); A.P. Gjesing (Anette); Kontto, J. (Jukka); M. Perola (Markus); S. Shaw-Hawkins (Sue); A.S. Havulinna (Aki); Zhang, H. (He); L.A. Donnelly (Louise); C.J. Groves (Christopher); N.W. Rayner (Nigel William); M.J. Neville (Matthew); N.R. Robertson (Neil); Yiorkas, A.M. (Andrianos M.); K.H. Herzig; E. Kajantie (Eero); W. Zhang (Weihua); S.M. Willems (Sara); L. Lannfelt (Lars); G. Malerba (Giovanni); N. Soranzo (Nicole); E. Trabetti (Elisabetta); N. Verweij (Niek); E. Evangelou (Evangelos); A. Moayyeri (Alireza); Vergnaud, A.-C. (Anne-Claire); C.P. Nelson (Christopher P.); Poveda, A. (Alaitz); T.V. Varga (Tibor V.); M. Caslake (Muriel); A.J.M. De Craen (Anton J. M.); S. Trompet (Stella); J. Luan (Jian'An); R.A. Scott (Robert); S.E. Harris (Sarah); D.C. Liewald (David C.); R.E. Marioni (Riccardo); C. Menni (Cristina); A.-E. Farmaki (Aliki-Eleni); G. Hallmans (Göran); F. Renström (Frida); J.E. Huffman (Jennifer); Hassinen, M. (Maija); S. Burgess (Stephen); Vasan, R.S. (Ramachandran S.); J.F. Felix (Janine); Uria-Nickelsen, M. (Maria); A. Mälarstig (Anders); Reilly, D.F. (Dermot F.); Hoek, M. (Maarten); Vogt, T.F. (Thomas F.); H. Lin (Honghuang); W. Lieb (Wolfgang); M. Traylor (Matthew); H.S. Markus (Hugh); H. Highland (Heather); A.E. Justice (Anne); E. Marouli (Eirini); J. Lindström (Jaana); M. Uusitupa (Matti); P. Komulainen (Pirjo); T.A. Lakka (Timo); R. Rauramaa (Rainer); O. Polasek (Ozren); I. Rudan (Igor); Rolandsson, O. (Olov); P.W. Franks (Paul); G.V. Dedoussis (George); T.D. Spector (Timothy); P. Jousilahti (Pekka); S. Männistö (Satu); I.J. Deary (Ian J.); J.M. Starr (John); C. Langenberg (Claudia); N.J. Wareham (Nick); M.J. Brown (Morris); A. Dominiczak (Anna); Connell, J.M. (John M.); J.W. Jukema (Jan Wouter); N. Sattar (Naveed); I. Ford (Ian); Packard, C.J. (Chris J.); T. Esko (Tõnu); R. Mägi (Reedik); A. Metspalu (Andres); R.A. de Boer (Rudolf); Van Der Meer, P. (Peter); P. van der Harst (Pim); G. Gambaro (Giovanni); Ingelsson, E. (Erik); W.H.L. Kao (Wen); P.I.W. de Bakker (Paul); M.E. Numans (Mattijs); I. Brandslund (Ivan); Christensen, C. (Cramer); Petersen, E.R.B. (Eva R. B.); E. Korpi-Hyövälti (Eeva); H. Oksa (Heikki); J.C. Chambers (John); J.S. Kooner (Jaspal S.); A.I.F. Blakemore (Alexandra); S. Franks (Steve); M.-R. Jarvelin (Marjo-Riitta); L.L.N. Husemoen (Lise Lotte); Linneberg, A. (Allan); T. Skaaby (Tea); Thuesen, B. (Betina); F. Karpe (Fredrik); J. Tuomilehto (Jaakko); A.S.F. Doney (Alex); A.D. Morris (Andrew); C.N.A. Palmer (Colin); O.L. Holmen (Oddgeir); K. Hveem (Kristian); C.J. Willer (Cristen); T. Tuomi (Tiinamaija); L. Groop (Leif); Käräjämäki, A. (Annemari); A. Palotie (Aarno); S. Ripatti (Samuli); V. Salomaa (Veikko); D.S. Alam (Dewan S.); Majumder, A.A.S. (Abdulla Al Shafi); E. di Angelantonio (Emanuele); R. Chowdhury (Rajiv); M.I. McCarthy (Mark); N.R. Poulter (Neil); A. Stanton (Alice); P. Sever (Peter); P. Amouyel (Philippe); D. Arveiler (Dominique); Blankenberg, S. (Stefan); J. Ferrieres (Jean); F. Kee (Frank); K. Kuulasmaa (Kari); M. Müller-Nurasyid (Martina); G. Veronesi (Giovanni); J. Virtamo (Jarmo); P. Deloukas (Panagiotis); P. Elliott (Paul); E. Zeggini (Eleftheria); S. Kathiresan (Sekar); O. Melander (Olle); J. Kuusisto (Johanna); M. Laakso (Markku); S. Padmanabhan (Sandosh); D. Porteous (David); C. Hayward (Caroline); G. Scotland (Generation); F.S. Collins (Francis); K.L. Mohlke (Karen); T. Hansen (T.); O. Pedersen (Oluf); M. Boehnke (Michael); H.M. Stringham (Heather); R. Frossard; C. Newton-Cheh (Christopher); M.D. Tobin (Martin); B.G. Nordestgaard (Børge); M. Caulfield (Mark); A. Mahajan (Anubha); A.P. Morris (Andrew); Tomaszewski, M. (Maciej); N.J. Samani (Nilesh); Saleheen, D. (Danish); F.W. Asselbergs (Folkert); C.M. Lindgren (Cecilia M.); J. Danesh (John); Wain, L.V. (Louise V.); A.S. Butterworth (Adam); Howson, J.M.M. (Joanna M. M.); P. Munroe (Patricia)

    2016-01-01

    textabstractHigh blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants

  20. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P.; Manning, Alisa K.; Grarup, Niels; Sim, Xueling; Barnes, Daniel R.; Witkowska, Kate; Staley, James R.; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F.; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T.; Nielsen, Sune Fallgaard; Rasheed, Asif; Samue, Maria; Zhao, Wei; Bonnycastle, Lori L.; Jackson, Anne U.; Narisu, Narisu; Swift, Amy J.; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R.; Stancakova, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E.; Bork-Jensen, Jette; Gjesing, Anette P.; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S.; Zhang, He; Donnelly, Louise A.; Groves, Christopher J.; Rayner, N. William; Neville, Matt J.; Robertson, Neil R.; Yiorkas, Andrianos M.; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M.; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P.; Poveda, Alaitz; Varga, Tibor V.; Caslake, Muriel; de Craen, Anton J. M.; Trompet, Stella; Luan, Jian'an; Scott, Robert A.; Harris, Sarah E.; Liewald, David C. M.; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Goran; Renstrom, Frida; Huffman, Jennifer E.; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S.; Felix, Janine F.; Uria-Nickelsen, Maria; Malarstign, Anders; Reilly, Dermot F.; Hoek, Maarten; Vogt, Thomas F.; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S.; Highland, Heather M.; Justice, Anne E.; Marouli, Eirini; Lindstrom, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A.; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W.; Dedoussis, George; Spector, Timothy D.; Jousilahti, Pekka; Mannisto, Satu; Deary, Ian J.; Starr, John M.; Langenberg, Claudia; Wareham, Nick J.; Brown, Morris J.; Dominiczak, Anna F.; Connell, John M.; Jukema, J. Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J.; Esko, Tonu; Magi, Reedik; Metspalu, Andres; de Boer, Rudolf A.; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I. W.; Numans, Mattijs E.; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R. B.; Korpi-Hyovalti, Eeva; Oksa, Heikki; Chambers, John C.; Kooner, Jaspal S.; Blakemore, Alexandra I. F.; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L.; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J.; Tuomi, Tiinamaija; Groop, Leif; Karajamaki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S.; Majmnder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I.; Poulter, Neil; Stanton, Alice V.; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrieres, Jean; Kee, Frank; Kuulasmaa, Kari; Muller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J.; Hayward, Caroline; Scotland, Generation; Collins, Francis S.; Mohlke, Karen L.; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M.; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D.; Nordestgaard, Borge Gronne; Caulfield, Mark J.; Mahajan, Anubha; Morris, Andrew P.; Tomaszewski, Maciej; Samani, Nilesh J.; Saleheen, Danish; Asselbergs, Folkert W.; Lindgren, Cecilia M.; Danesh, John; Wain, Louise V.; Butterworth, Adam S.; Howson, Joanna M. M.; Munroe, Patricia B.

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to

  1. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, P. (Praveen); F. Drenos (Fotios); R. Young (Robin); H. Warren (Helen); Cook, J.P. (James P.); A.K. Manning (Alisa); N. Grarup (Niels); X. Sim (Xueling); D. Barnes (Daniel); H.E. Witkowska (Ewa); J.R. Staley (James R.); V. Tragante (Vinicius); T. Tukiainen (Taru); H. Yaghootkar (Hanieh); Masca, N. (Nicholas); C.M. Freitag (Christine); T. Ferreira (Teresa); O. Giannakopoulou (Olga); Tinker, A. (Andrew); M. Harakalova (Magdalena); E. Mihailov (Evelin); Liu, C. (Chunyu); A. Kraja (Aldi); S.F. Nielsen (Sune); A. Rasheed (Asif); M. Samuel (Maria); W. Zhao (Wei); L.L. Bonnycastle (Lori); A.U. Jackson (Anne); N. Narisu (Narisu); A.J. Swift (Amy); L. Southam (Lorraine); J. Marten (Jonathan); J.R. Huyghe (Jeroen R.); A. Stancáková (Alena); C. Fava (Cristiano); Ohlsson, T. (Therese); A. Matchan (Angela); K. Stirrups (Kathy); J. Bork-Jensen (Jette); A.P. Gjesing (Anette); Kontto, J. (Jukka); M. Perola (Markus); S. Shaw-Hawkins (Sue); A.S. Havulinna (Aki); Zhang, H. (He); L.A. Donnelly (Louise); C.J. Groves (Christopher); N.W. Rayner (Nigel William); M.J. Neville (Matthew); N.R. Robertson (Neil); Yiorkas, A.M. (Andrianos M.); K.H. Herzig; E. Kajantie (Eero); W. Zhang (Weihua); S.M. Willems (Sara); L. Lannfelt (Lars); G. Malerba (Giovanni); N. Soranzo (Nicole); E. Trabetti (Elisabetta); N. Verweij (Niek); E. Evangelou (Evangelos); A. Moayyeri (Alireza); Vergnaud, A.-C. (Anne-Claire); C.P. Nelson (Christopher P.); Poveda, A. (Alaitz); T.V. Varga (Tibor V.); M. Caslake (Muriel); A.J.M. De Craen (Anton J. M.); S. Trompet (Stella); J. Luan (Jian'An); R.A. Scott (Robert); S.E. Harris (Sarah); D.C. Liewald (David C.); R.E. Marioni (Riccardo); C. Menni (Cristina); A.-E. Farmaki (Aliki-Eleni); G. Hallmans (Göran); F. Renström (Frida); J.E. Huffman (Jennifer); Hassinen, M. (Maija); S. Burgess (Stephen); Vasan, R.S. (Ramachandran S.); J.F. Felix (Janine); Uria-Nickelsen, M. (Maria); A. Mälarstig (Anders); Reilly, D.F. (Dermot F.); Hoek, M. (Maarten); Vogt, T.F. (Thomas F.); H. Lin (Honghuang); W. Lieb (Wolfgang); M. Traylor (Matthew); H.S. Markus (Hugh); H. Highland (Heather); A.E. Justice (Anne); E. Marouli (Eirini); J. Lindström (Jaana); M. Uusitupa (Matti); P. Komulainen (Pirjo); T.A. Lakka (Timo); R. Rauramaa (Rainer); O. Polasek (Ozren); I. Rudan (Igor); Rolandsson, O. (Olov); P.W. Franks (Paul); G.V. Dedoussis (George); T.D. Spector (Timothy); P. Jousilahti (Pekka); S. Männistö (Satu); I.J. Deary (Ian J.); J.M. Starr (John); C. Langenberg (Claudia); N.J. Wareham (Nick); M.J. Brown (Morris); A. Dominiczak (Anna); Connell, J.M. (John M.); J.W. Jukema (Jan Wouter); N. Sattar (Naveed); I. Ford (Ian); Packard, C.J. (Chris J.); T. Esko (Tõnu); R. Mägi (Reedik); A. Metspalu (Andres); R.A. de Boer (Rudolf); Van Der Meer, P. (Peter); P. van der Harst (Pim); G. Gambaro (Giovanni); Ingelsson, E. (Erik); W.H.L. Kao (Wen); P.I.W. de Bakker (Paul); M.E. Numans (Mattijs); I. Brandslund (Ivan); Christensen, C. (Cramer); Petersen, E.R.B. (Eva R. B.); E. Korpi-Hyövälti (Eeva); H. Oksa (Heikki); J.C. Chambers (John); J.S. Kooner (Jaspal S.); A.I.F. Blakemore (Alexandra); S. Franks (Steve); M.-R. Jarvelin (Marjo-Riitta); L.L.N. Husemoen (Lise Lotte); Linneberg, A. (Allan); T. Skaaby (Tea); Thuesen, B. (Betina); F. Karpe (Fredrik); J. Tuomilehto (Jaakko); A.S.F. Doney (Alex); A.D. Morris (Andrew); C.N.A. Palmer (Colin); O.L. Holmen (Oddgeir); K. Hveem (Kristian); C.J. Willer (Cristen); T. Tuomi (Tiinamaija); L. Groop (Leif); Käräjämäki, A. (Annemari); A. Palotie (Aarno); S. Ripatti (Samuli); V. Salomaa (Veikko); D.S. Alam (Dewan S.); Majumder, A.A.S. (Abdulla Al Shafi); E. di Angelantonio (Emanuele); R. Chowdhury (Rajiv); M.I. McCarthy (Mark); N.R. Poulter (Neil); A. Stanton (Alice); P. Sever (Peter); P. Amouyel (Philippe); D. Arveiler (Dominique); Blankenberg, S. (Stefan); J. Ferrieres (Jean); F. Kee (Frank); K. Kuulasmaa (Kari); M. Müller-Nurasyid (Martina); G. Veronesi (Giovanni); J. Virtamo (Jarmo); P. Deloukas (Panagiotis); P. Elliott (Paul); E. Zeggini (Eleftheria); S. Kathiresan (Sekar); O. Melander (Olle); J. Kuusisto (Johanna); M. Laakso (Markku); S. Padmanabhan (Sandosh); D. Porteous (David); C. Hayward (Caroline); G. Scotland (Generation); F.S. Collins (Francis); K.L. Mohlke (Karen); T. Hansen (T.); O. Pedersen (Oluf); M. Boehnke (Michael); H.M. Stringham (Heather); R. Frossard; C. Newton-Cheh (Christopher); M.D. Tobin (Martin); B.G. Nordestgaard (Børge); M. Caulfield (Mark); A. Mahajan (Anubha); A.P. Morris (Andrew); Tomaszewski, M. (Maciej); N.J. Samani (Nilesh); Saleheen, D. (Danish); F.W. Asselbergs (Folkert); C.M. Lindgren (Cecilia M.); J. Danesh (John); Wain, L.V. (Louise V.); A.S. Butterworth (Adam); Howson, J.M.M. (Joanna M. M.); P. Munroe (Patricia)

    2016-01-01

    textabstractHigh blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants

  2. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P; Manning, Alisa K; Grarup, Niels; Sim, Xueling; Barnes, Daniel R; Witkowska, Kate; Staley, James R; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T; Nielsen, Sune Fallgaard; Rasheed, Asif; Samuel, Maria; Zhao, Wei; Bonnycastle, Lori L; Jackson, Anne U; Narisu, Narisu; Swift, Amy J; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R; Stančáková, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E; Bork-Jensen, Jette; Gjesing, Anette P; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S; Zhang, He; Donnelly, Louise A; Groves, Christopher J; Rayner, N William; Neville, Matt J; Robertson, Neil R; Yiorkas, Andrianos M; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P; Poveda, Alaitz; Varga, Tibor V; Caslake, Muriel; de Craen, Anton J M; Trompet, Stella; Luan, Jian'an; Scott, Robert A; Harris, Sarah E; Liewald, David C M; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Göran; Renström, Frida; Huffman, Jennifer E; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S; Felix, Janine F; Uria-Nickelsen, Maria; Malarstig, Anders; Reilly, Dermot F; Hoek, Maarten; Vogt, Thomas F; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S; Highland, Heather M; Justice, Anne E; Marouli, Eirini; Lindström, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W; Dedoussis, George; Spector, Timothy D; Jousilahti, Pekka; Männistö, Satu; Deary, Ian J; Starr, John M; Langenberg, Claudia; Wareham, Nick J; Brown, Morris J; Dominiczak, Anna F; Connell, John M; Jukema, J Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J; Esko, Tõnu; Mägi, Reedik; Metspalu, Andres; de Boer, Rudolf A; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I W; Numans, Mattijs E; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R B; Korpi-Hyövälti, Eeva; Oksa, Heikki; Chambers, John C; Kooner, Jaspal S; Blakemore, Alexandra I F; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S F; Morris, Andrew D; Palmer, Colin N A; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J; Tuomi, Tiinamaija; Groop, Leif; Käräjämäki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S; Majumder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I; Poulter, Neil; Stanton, Alice V; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrières, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J; Hayward, Caroline; Scotland, Generation; Collins, Francis S; Mohlke, Karen L; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D; Nordestgaard, Børge Grønne; Caulfield, Mark J; Mahajan, Anubha; Morris, Andrew P; Tomaszewski, Maciej; Samani, Nilesh J; Saleheen, Danish; Asselbergs, Folkert W; Lindgren, Cecilia M; Danesh, John; Wain, Louise V; Butterworth, Adam S; Howson, Joanna M M; Munroe, Patricia B

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to

  3. Identifying Some Factors That Might Predispose Drug Abuse among Learners in a South African Township School

    Science.gov (United States)

    Grobler, R.; Khatite, M.

    2012-01-01

    This study inquires into some of the factors that might predispose the use and abuse of drugs among secondary school learners in a township school. The objective of this research is to identify these factors and to offer a few suggestions on how the abuse may be prevented. A quantitative research strategy is used and a document analysis technique…

  4. Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Rossing, Mary Anne; Lee, Alice W

    2013-01-01

    There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied....

  5. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    Science.gov (United States)

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  6. High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

    Science.gov (United States)

    Tsuruda, Jennifer M; Harris, Jeffrey W; Bourgeois, Lanie; Danka, Robert G; Hunt, Greg J

    2012-01-01

    Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

  7. Environmental Association Analyses Identify Candidates for Abiotic Stress Tolerance in Glycine soja, the Wild Progenitor of Cultivated Soybeans.

    Science.gov (United States)

    Anderson, Justin E; Kono, Thomas J Y; Stupar, Robert M; Kantar, Michael B; Morrell, Peter L

    2016-04-07

    Natural populations across a species range demonstrate population structure owing to neutral processes such as localized origins of mutations and migration limitations. Selection also acts on a subset of loci, contributing to local adaptation. An understanding of the genetic basis of adaptation to local environmental conditions is a fundamental goal in basic biological research. When applied to crop wild relatives, this same research provides the opportunity to identify adaptive genetic variation that may be used to breed for crops better adapted to novel or changing environments. The present study explores an ex situ conservation collection, the USDA germplasm collection, genotyped at 32,416 SNPs to identify population structure and test for associations with bioclimatic and biophysical variables in Glycine soja, the wild progenitor of Glycine max (soybean). Candidate loci were detected that putatively contribute to adaptation to abiotic stresses. The identification of potentially adaptive variants in this ex situ collection may permit a more targeted use of germplasm collections.

  8. CREB3 subfamily transcription factors are not created equal: Recent insights from global analyses and animal models

    Directory of Open Access Journals (Sweden)

    Chan Chi-Ping

    2011-02-01

    Full Text Available Abstract The CREB3 subfamily of membrane-bound bZIP transcription factors has five members in mammals known as CREB3 and CREB3L1-L4. One current model suggests that CREB3 subfamily transcription factors are similar to ATF6 in regulated intramembrane proteolysis and transcriptional activation. Particularly, they were all thought to be proteolytically activated in response to endoplasmic reticulum (ER stress to stimulate genes that are involved in unfolded protein response (UPR. Although the physiological inducers of their proteolytic activation remain to be identified, recent findings from microarray analyses, RNAi screens and gene knockouts not only demonstrated their critical roles in regulating development, metabolism, secretion, survival and tumorigenesis, but also revealed cell type-specific patterns in the activation of their target genes. Members of the CREB3 subfamily show differential activity despite their structural similarity. The spectrum of their biological function expands beyond ER stress and UPR. Further analyses are required to elucidate the mechanism of their proteolytic activation and the molecular basis of their target recognition.

  9. Niche Divergence versus Neutral Processes: Combined Environmental and Genetic Analyses Identify Contrasting Patterns of Differentiation in Recently Diverged Pine Species

    OpenAIRE

    Alejandra Moreno-Letelier; Alejandra Ortíz-Medrano; Daniel Piñero

    2013-01-01

    BACKGROUND AND AIMS: Solving relationships of recently diverged taxa, poses a challenge due to shared polymorphism and weak reproductive barriers. Multiple lines of evidence are needed to identify independently evolving lineages. This is especially true of long-lived species with large effective population sizes, and slow rates of lineage sorting. North American pines are an interesting group to test this multiple approach. Our aim is to combine cytoplasmic genetic markers with environmental ...

  10. Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle.

    OpenAIRE

    Rome, Sophie; Lecomte, Virginie; Meugnier, Emmanuelle; Rieusset, Jennifer; Debard, Cyrille; Euthine, Vanessa; Vidal, Hubert; Lefai, Etienne

    2008-01-01

    International audience; In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modifi...

  11. Signature of Nonstationarity in Precipitation Extremes over Urbanizing Regions in India Identified through a Multivariate Frequency Analyses

    Science.gov (United States)

    Singh, Jitendra; Hari, Vittal; Sharma, Tarul; Karmakar, Subhankar; Ghosh, Subimal

    2016-04-01

    The statistical assumption of stationarity in hydrologic extreme time/event series has been relied heavily in frequency analysis. However, due to the analytically perceivable impacts of climate change, urbanization and concomitant land use pattern, assumption of stationarity in hydrologic time series will draw erroneous results, which in turn may affect the policy and decision-making. Past studies provided sufficient evidences on changes in the characteristics of Indian monsoon precipitation extremes and further it has been attributed to climate change and urbanization, which shows need of nonstationary analysis on the Indian monsoon extremes. Therefore, a comprehensive multivariate nonstationary frequency analysis has been conducted for the entire India to identify the precipitation characteristics (intensity, duration and depth) responsible for significant nonstationarity in the Indian monsoon. We use 1o resolution of precipitation data for a period of 1901-2004, in a Generalized Additive Model for Location, Scale and Shape (GAMLSS) framework. A cluster of GAMLSS models has been developed by considering nonstationarity in different combinations of distribution parameters through different regression techniques, and the best-fit model is further applied for bivariate analysis. A population density data has been utilized to identify the urban, urbanizing and rural regions. The results showed significant differences in the stationary and nonstationary bivariate return periods for the urbanizing grids, when compared to urbanized and rural grids. A comprehensive multivariate analysis has also been conducted to identify the precipitation characteristics particularly responsible for imprinting signature of nonstationarity.

  12. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.

    Science.gov (United States)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    2016-09-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.

  13. Patient and carer identified factors which contribute to safety incidents in primary care: a qualitative study.

    Science.gov (United States)

    Hernan, Andrea L; Giles, Sally J; Fuller, Jeffrey; Johnson, Julie K; Walker, Christine; Dunbar, James A

    2015-09-01

    Patients can have an important role in reducing harm in primary-care settings. Learning from patient experience and feedback could improve patient safety. Evidence that captures patients' views of the various contributory factors to creating safe primary care is largely absent. The aim of this study was to address this evidence gap. Four focus groups and eight semistructured interviews were conducted with 34 patients and carers from south-east Australia. Participants were asked to describe their experiences of primary care. Audio recordings were transcribed verbatim and specific factors that contribute to safety incidents were identified in the analysis using the Yorkshire Contributory Factors Framework (YCFF). Other factors emerging from the data were also ascertained and added to the analytical framework. Thirteen factors that contribute to safety incidents in primary care were ascertained. Five unique factors for the primary-care setting were discovered in conjunction with eight factors present in the YCFF from hospital settings. The five unique primary care contributing factors to safety incidents represented a range of levels within the primary-care system from local working conditions to the upstream organisational level and the external policy context. The 13 factors included communication, access, patient factors, external policy context, dignity and respect, primary-secondary interface, continuity of care, task performance, task characteristics, time in the consultation, safety culture, team factors and the physical environment. Patient and carer feedback of this type could help primary-care professionals better understand and identify potential safety concerns and make appropriate service improvements. The comprehensive range of factors identified provides the groundwork for developing tools that systematically capture the multiple contributory factors to patient safety. Published by the BMJ Publishing Group Limited. For permission to use (where not

  14. RNA-Seq and RNA Immunoprecipitation Analyses of the Transcriptome of Streptomyces coelicolor Identify Substrates for RNase III

    Science.gov (United States)

    Gatewood, Marcha L.; Bralley, Patricia; Weil, M. Ryan

    2012-01-01

    RNase III is a key enzyme in the pathways of RNA degradation and processing in bacteria and has been suggested as a global regulator of antibiotic production in Streptomyces coelicolor. Using RNA-Seq, we have examined the transcriptomes of S. coelicolor M145 and an RNase III (rnc)-null mutant of that strain. RNA preparations with reduced levels of structural RNAs were prepared by subtractive hybridization prior to RNA-Seq analysis. We initially identified 7,800 transcripts of known and putative protein-coding genes in M145 and the null mutant, JSE1880, along with transcripts of 21 rRNA genes and 65 tRNA genes. Approximately 3,100 of the protein-coding transcripts were categorized as low-abundance transcripts. For further analysis, we selected those transcripts of known and putative protein-coding genes whose levels changed by ≥2-fold between the two S. coelicolor strains and organized those transcripts into 16 functional categories. We refined our analysis by performing RNA immunoprecipitation of the mRNA preparation from JSE1880 using a mutant RNase III protein that binds to transcripts but does not cleave them. This analysis identified ca. 800 transcripts that were enriched in the RNA immunoprecipitates, including 28 transcripts whose levels also changed by ≥2-fold in the RNA-Seq analysis. We compare our results with those obtained by microarray analysis of the S. coelicolor transcriptome and with studies describing the characterization of small noncoding RNAs. We have also used the RNA immunoprecipitation results to identify new substrates for RNase III cleavage. PMID:22389483

  15. Identifying Contextual Factors of Employee Satisfaction of Performance Management at a Thai State Enterprise

    Directory of Open Access Journals (Sweden)

    Molraudee Saratun

    2013-10-01

    Full Text Available Although there has been an increase in Performance Management (PM literature over the years arguing that PM perceptions are likely to be a function of PM process components and contextual factors, the actual relationship between the contextual factors and employee satisfaction of PM remains little explored. Extending previous research, this study examines relationships between contextual factors and employees’ PM satisfaction. Derived from the literature, these contextual factors are motivation and empowerment of employees, role conflict, role ambiguity, perceived or- ganisational support, procedural justice and distributive justice. Seven directional hypotheses are tested accordingly through a series of regression analyses. This article finds that these contextual factors, with the exception of role conflict, are directly predictive of enhanced employees’ PM satis- faction at the Thai state enterprise.

  16. Identifying Virulence-Associated Genes Using Transcriptomic and Proteomic Association Analyses of the Plant Parasitic Nematode Bursaphelenchus mucronatus

    Science.gov (United States)

    Zhou, Lifeng; Chen, Fengmao; Pan, Hongyang; Ye, Jianren; Dong, Xuejiao; Li, Chunyan; Lin, Fengling

    2016-01-01

    Bursaphelenchus mucronatus (B. mucronatus) isolates that originate from different regions may vary in their virulence, but their virulence-associated genes and proteins are poorly understood. Thus, we conducted an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) to analyse transcriptomic and proteomic data of highly and weakly virulent B. mucronatus isolates during the pathogenic processes. Approximately 40,000 annotated unigenes and 5000 proteins were gained from the isolates. When we matched all of the proteins with their detected transcripts, a low correlation coefficient of r = 0.138 was found, indicating probable post-transcriptional gene regulation involved in the pathogenic processes. A functional analysis showed that five differentially expressed proteins which were all highly expressed in the highly virulent isolate were involved in the pathogenic processes of nematodes. Peroxiredoxin, fatty acid- and retinol-binding protein, and glutathione peroxidase relate to resistance against plant defence responses, while β-1,4-endoglucanase and expansin are associated with the breakdown of plant cell walls. Thus, the pathogenesis of B. mucronatus depends on its successful survival in host plants. Our work adds to the understanding of B. mucronatus’ pathogenesis, and will aid in controlling B. mucronatus and other pinewood nematode species complexes in the future. PMID:27618012

  17. Identifying Virulence-Associated Genes Using Transcriptomic and Proteomic Association Analyses of the Plant Parasitic Nematode Bursaphelenchus mucronatus

    Directory of Open Access Journals (Sweden)

    Lifeng Zhou

    2016-09-01

    Full Text Available Bursaphelenchus mucronatus (B. mucronatus isolates that originate from different regions may vary in their virulence, but their virulence-associated genes and proteins are poorly understood. Thus, we conducted an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ to analyse transcriptomic and proteomic data of highly and weakly virulent B. mucronatus isolates during the pathogenic processes. Approximately 40,000 annotated unigenes and 5000 proteins were gained from the isolates. When we matched all of the proteins with their detected transcripts, a low correlation coefficient of r = 0.138 was found, indicating probable post-transcriptional gene regulation involved in the pathogenic processes. A functional analysis showed that five differentially expressed proteins which were all highly expressed in the highly virulent isolate were involved in the pathogenic processes of nematodes. Peroxiredoxin, fatty acid- and retinol-binding protein, and glutathione peroxidase relate to resistance against plant defence responses, while β-1,4-endoglucanase and expansin are associated with the breakdown of plant cell walls. Thus, the pathogenesis of B. mucronatus depends on its successful survival in host plants. Our work adds to the understanding of B. mucronatus’ pathogenesis, and will aid in controlling B. mucronatus and other pinewood nematode species complexes in the future.

  18. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer.

    Science.gov (United States)

    Yang, Da; Sun, Yan; Hu, Limei; Zheng, Hong; Ji, Ping; Pecot, Chad V; Zhao, Yanrui; Reynolds, Sheila; Cheng, Hanyin; Rupaimoole, Rajesha; Cogdell, David; Nykter, Matti; Broaddus, Russell; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Liu, Jinsong; Shmulevich, Ilya; Sood, Anil K; Chen, Kexin; Zhang, Wei

    2013-02-11

    Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.

  19. Interactional power: observing and identifying power in interaction analyses of adult education situations depending on power notions and data types

    Directory of Open Access Journals (Sweden)

    Sigrid Nolda

    2014-04-01

    Full Text Available Since the 1970s, various aspects of power have been at the focus of theoretical and empirical adult education research. Despite the actual interest in political and discursive aspects of power, this article emphasizes the importance of interactional studies when observing and identifying power based on various types of data. As for German interaction studies, three phases can be distinguished, characterized by a observations of failed participation based on records of classroom behaviour, b the identification of mutual power negotiation in classroom and counselling situations based on transcriptions, and c the identification of the power of physical settings in adult education classrooms and in counselling sessions based on visual data. It is presumed that observing/identifying power in adult education classrooms and counselling sessions generally depends not only on the notions of power underlying the studies but also on the data types produced and the methods applied for their interpretation. In addition, the question is raised whether the identification of power can be considered a power practice used by adult education researchers.

  20. Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

    Directory of Open Access Journals (Sweden)

    Fry Rebecca C

    2011-04-01

    Full Text Available Abstract Background Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored. Results In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis. Conclusions This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.

  1. Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity

    Science.gov (United States)

    Yu, Yanqin; Zuo, Xianbo; He, Miao; Gao, Jinping; Fu, Yuchuan; Qin, Chuanqi; Meng, Liuyan; Wang, Wenjun; Song, Yaling; Cheng, Yong; Zhou, Fusheng; Chen, Gang; Zheng, Xiaodong; Wang, Xinhuan; Liang, Bo; Zhu, Zhengwei; Fu, Xiazhou; Sheng, Yujun; Hao, Jiebing; Liu, Zhongyin; Yan, Hansong; Mangold, Elisabeth; Ruczinski, Ingo; Liu, Jianjun; Marazita, Mary L.; Ludwig, Kerstin U.; Beaty, Terri H.; Zhang, Xuejun; Sun, Liangdan; Bian, Zhuan

    2017-01-01

    Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation. PMID:28232668

  2. Assessing an organizational culture instrument based on the Competing Values Framework: Exploratory and confirmatory factor analyses

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    Mohr David C

    2007-04-01

    Full Text Available Abstract Background The Competing Values Framework (CVF has been widely used in health services research to assess organizational culture as a predictor of quality improvement implementation, employee and patient satisfaction, and team functioning, among other outcomes. CVF instruments generally are presented as well-validated with reliable aggregated subscales. However, only one study in the health sector has been conducted for the express purpose of validation, and that study population was limited to hospital managers from a single geographic locale. Methods We used exploratory and confirmatory factor analyses to examine the underlying structure of data from a CVF instrument. We analyzed cross-sectional data from a work environment survey conducted in the Veterans Health Administration (VHA. The study population comprised all staff in non-supervisory positions. The survey included 14 items adapted from a popular CVF instrument, which measures organizational culture according to four subscales: hierarchical, entrepreneurial, team, and rational. Results Data from 71,776 non-supervisory employees (approximate response rate 51% from 168 VHA facilities were used in this analysis. Internal consistency of the subscales was moderate to strong (α = 0.68 to 0.85. However, the entrepreneurial, team, and rational subscales had higher correlations across subscales than within, indicating poor divergent properties. Exploratory factor analysis revealed two factors, comprising the ten items from the entrepreneurial, team, and rational subscales loading on the first factor, and two items from the hierarchical subscale loading on the second factor, along with one item from the rational subscale that cross-loaded on both factors. Results from confirmatory factor analysis suggested that the two-subscale solution provides a more parsimonious fit to the data as compared to the original four-subscale model. Conclusion This study suggests that there may be problems

  3. A model for analysing factors which may influence quality management procedures in higher education

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    Cătălin MAICAN

    2015-12-01

    Full Text Available In all universities, the Office for Quality Assurance defines the procedure for assessing the performance of the teaching staff, with a view to establishing students’ perception as regards the teachers’ activity from the point of view of the quality of the teaching process, of the relationship with the students and of the assistance provided for learning. The present paper aims at creating a combined model for evaluation, based on Data Mining statistical methods: starting from the findings revealed by the evaluations teachers performed to students, using the cluster analysis and the discriminant analysis, we identified the subjects which produced significant differences between students’ grades, subjects which were subsequently subjected to an evaluation by students. The results of these analyses allowed the formulation of certain measures for enhancing the quality of the evaluation process.

  4. Shelter dogs and their destiny. A retrospective analysis to identify predictive factors - a pilot study

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    Simona Cannas

    2014-10-01

    Full Text Available Consequences of a long stay in dog shelter have particular signifi cance, because, since 1991, the Italian law (14/08/1991, n.281 prohibits euthanasia of dogs unless “they are seriously ill, incurable or proven dangerous”. Caught dogs are recovered for a quarantine period in the sanitary kennel, if they are not returned to the owner, they are moved to shelters until adoption or death. The aim of this work was to identify the relationship between dogs characteristics and their destiny in order to define useful predictors to better manage the stay of dogs in shelter. We analysed the records of all dogs recovered in a sanitary kennel from 2005 to 2010 and subsequently moved to shelters (n=771. Descriptive and inferential statistics were performed in order to investigate possible factors that might affect adoptability of sheltered dogs. The characteristics of dogs that spent more time in PVCS, before being transfer to the CR, were: large size, male gender and age between 11 months and 2 years (p ≤ 0,05. Male dogs spent more days in CR, as opposed to female (p ≤ 0,05. In our sample 76% dogs were adopted, 18% were still in the shelter, 4% died and 2% were euthanized. Female dogs were adopted more than males; young dogs more than elderly (over seven years; sizes medium and small more than large. It would be interesting use the data from this research and complete them with information regarding dogs behaviour, to better manage dogs during the stay in shelter and to improve their relocation.

  5. Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains.

    Science.gov (United States)

    Jason, Leonard A; Sunnquist, Madison; Brown, Abigail; Furst, Jacob; Cid, Marjoe; Farietta, Jillianna; Kot, Bobby; Bloomer, Craig; Nicholson, Laura; Williams, Yolonda; Jantke, Rachel; Newton, Julia L; Strand, Elin Bolle

    2015-09-01

    The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.

  6. Multivariate Analyses and Classification of Inertial Sensor Data to Identify Aging Effects on the Timed-Up-and-Go Test.

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    Danique Vervoort

    Full Text Available Many tests can crudely quantify age-related mobility decrease but instrumented versions of mobility tests could increase their specificity and sensitivity. The Timed-up-and-Go (TUG test includes several elements that people use in daily life. The test has different transition phases: rise from a chair, walk, 180° turn, walk back, turn, and sit-down on a chair. For this reason the TUG is an often used test to evaluate in a standardized way possible decline in balance and walking ability due to age and or pathology. Using inertial sensors, qualitative information about the performance of the sub-phases can provide more specific information about a decline in balance and walking ability. The first aim of our study was to identify variables extracted from the instrumented timed-up-and-go (iTUG that most effectively distinguished performance differences across age (age 18-75. Second, we determined the discriminative ability of those identified variables to classify a younger (age 18-45 and older age group (age 46-75. From healthy adults (n = 59, trunk accelerations and angular velocities were recorded during iTUG performance. iTUG phases were detected with wavelet-analysis. Using a Partial Least Square (PLS model, from the 72-iTUG variables calculated across phases, those that explained most of the covariance between variables and age were extracted. Subsequently, a PLS-discriminant analysis (DA assessed classification power of the identified iTUG variables to discriminate the age groups. 27 variables, related to turning, walking and the stand-to-sit movement explained 71% of the variation in age. The PLS-DA with these 27 variables showed a sensitivity and specificity of 90% and 85%. Based on this model, the iTUG can accurately distinguish young and older adults. Such data can serve as a reference for pathological aging with respect to a widely used mobility test. Mobility tests like the TUG supplemented with smart technology could be used in

  7. Multivariate Analyses and Classification of Inertial Sensor Data to Identify Aging Effects on the Timed-Up-and-Go Test.

    Science.gov (United States)

    Vervoort, Danique; Vuillerme, Nicolas; Kosse, Nienke; Hortobágyi, Tibor; Lamoth, Claudine J C

    2016-01-01

    Many tests can crudely quantify age-related mobility decrease but instrumented versions of mobility tests could increase their specificity and sensitivity. The Timed-up-and-Go (TUG) test includes several elements that people use in daily life. The test has different transition phases: rise from a chair, walk, 180° turn, walk back, turn, and sit-down on a chair. For this reason the TUG is an often used test to evaluate in a standardized way possible decline in balance and walking ability due to age and or pathology. Using inertial sensors, qualitative information about the performance of the sub-phases can provide more specific information about a decline in balance and walking ability. The first aim of our study was to identify variables extracted from the instrumented timed-up-and-go (iTUG) that most effectively distinguished performance differences across age (age 18-75). Second, we determined the discriminative ability of those identified variables to classify a younger (age 18-45) and older age group (age 46-75). From healthy adults (n = 59), trunk accelerations and angular velocities were recorded during iTUG performance. iTUG phases were detected with wavelet-analysis. Using a Partial Least Square (PLS) model, from the 72-iTUG variables calculated across phases, those that explained most of the covariance between variables and age were extracted. Subsequently, a PLS-discriminant analysis (DA) assessed classification power of the identified iTUG variables to discriminate the age groups. 27 variables, related to turning, walking and the stand-to-sit movement explained 71% of the variation in age. The PLS-DA with these 27 variables showed a sensitivity and specificity of 90% and 85%. Based on this model, the iTUG can accurately distinguish young and older adults. Such data can serve as a reference for pathological aging with respect to a widely used mobility test. Mobility tests like the TUG supplemented with smart technology could be used in clinical practice.

  8. Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

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    Cai-Jun Wu

    2015-01-01

    Full Text Available Background: Animal models of asphyxiation cardiac arrest (ACA are frequently used in basic research to mirror the clinical course of cardiac arrest (CA. The rates of the return of spontaneous circulation (ROSC in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic (ROC curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983, and the optimum cut-off value was 15.62 (specificity 95.7% and sensitivity 80.0%. Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

  9. Pan-genome analyses identify lineage- and niche-specific markers of evolution and adaptation in Epsilonproteobacteria

    Directory of Open Access Journals (Sweden)

    Ying eZhang

    2014-03-01

    Full Text Available The rapidly increasing availability of complete bacterial genomes has created new opportunities for reconstructing bacterial evolution, but it has also highlighted the difficulty to fully understand the genomic and functional variations occurring among different lineages. Using the class Epsilonproteobacteria as a case study, we investigated the composition, flexibility, and function of its pan-genomes. Models were constructed to extrapolate the expansion of pan-genomes at three different taxonomic levels. The results show that, for Epsilonproteobacteria the seemingly large genome variations among strains of the same species are less noticeable when compared with groups at higher taxonomic ranks, indicating that genome stability is imposed by the potential existence of taxonomic boundaries. The analyses of pan-genomes has also defined a set of universally conserved core genes, based on which a phylogenetic tree was constructed to confirm that thermophilic species from deep-sea hydrothermal vents represent the most ancient lineages of Epsilonproteobacteria. Moreover, by comparing the flexible genome of a chemoautotrophic deep-sea vent species to 1 genomes of species belonging to the same genus, but inhabiting different environments, and 2 genomes of other vent species, but belonging to different genera, we were able to delineate the relative importance of lineage-specific versus niche-specific genes. This result not only emphasizes the overall importance of phylogenetic proximity in shaping the variable part of the genome, but also highlights the adaptive functions of niche-specific genes. Overall, by modeling the expansion of pan-genomes and analyzing core and flexible genes, this study provides snapshots on how the complex processes of gene acquisition, conservation, and removal affect the evolution of different species, and contribute to the metabolic diversity and versatility of Epsilonproteobacteria.

  10. Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

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    Wang Tzi-Yuan

    2011-08-01

    Full Text Available Abstract Background Neocallimastix patriciarum is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (GHs produced by this anaerobic fungus. Results We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to N. patriciarum to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx and secretome (ESI-Trap LC-MS/MS, we identified 219 putative GH contigs and classified them into 25 GH families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the GH1, GH3, GH5, GH6, GH9, GH18, GH43 and GH48 gene families, which were highly expressed in N. patriciarum cultures grown on different feedstocks. Conclusions These GH genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143 and one exocellulase (W5-CAT26 showed strong activities and could potentially be developed into commercial enzymes.

  11. Using an interdisciplinary approach to identify factors that affect clinicians' compliance with evidence-based guidelines.

    Science.gov (United States)

    Gurses, Ayse P; Marsteller, Jill A; Ozok, A Ant; Xiao, Yan; Owens, Sharon; Pronovost, Peter J

    2010-08-01

    Our objective was to identify factors that affect clinicians' compliance with the evidence-based guidelines using an interdisciplinary approach and develop a conceptual framework that can provide a comprehensive and practical guide for designing effective interventions. A literature review and a brainstorming session with 11 researchers from a variety of scientific disciplines were used to identify theoretical and conceptual models describing clinicians' guideline compliance. MEDLINE, EMBASE, CINAHL, and the bibliographies of the papers identified were used as data sources for identifying the relevant theoretical and conceptual models. Thirteen different models that originated from various disciplines including medicine, rural sociology, psychology, human factors and systems engineering, organizational management, marketing, and health education were identified. Four main categories of factors that affect compliance emerged from our analysis: clinician characteristics, guideline characteristics, system characteristics, and implementation characteristics. Based on these findings, we developed an interdisciplinary conceptual framework that specifies the expected interrelationships among these four categories of factors and their impact on clinicians' compliance. An interdisciplinary approach is needed to improve clinicians' compliance with evidence-based guidelines. The conceptual framework from this research can provide a comprehensive and systematic guide to identify barriers to guideline compliance and design effective interventions to improve patient safety.

  12. Identifying risk factors for Plasmodium infection and anaemia in Kinshasa, Democratic Republic of Congo.

    Science.gov (United States)

    Ferrari, Giovanfrancesco; Ntuku, Henry M T; Ross, Amanda; Schmidlin, Sandro; Kalemwa, Didier M; Tshefu, Antoinette K; Lengeler, Christian

    2016-07-15

    There is little data on the risk factors for malaria infection in large cities in central Africa and in all age groups. There may be different associations with the risk factors for areas with different malaria transmission intensities such as the effect of fever or age. This study aimed at identifying risk factors associated with Plasmodium infection and anaemia among children 6-59 months and individuals aged older than 5 years in Kinshasa, a large city with heterogeneity in malaria prevalence. This study analysed data from 3342 children aged 6-59 months from 25 non-rural health zones (HZs) and for 816 individuals aged older than 5 years from two HZs in Kinshasa (non-rural), collected during a cross sectional malaria survey in 2011. Logistic regression with random effects was used to investigate predictors for malaria and anaemia. Differences in risk factors in areas with a prevalence of less than 10 and 10 % or greater were investigated. There was evidence of a different age-pattern in the two transmission settings. For children under 5 years, the highest prevalence of malaria was observed in the 48-59 months group in both transmission settings, but it increased more gently for the lower transmission HZs (p = 0.009). In a separate analysis in children over 5 years in two selected HZs, the peak prevalence was in 5-9 years old in the higher transmission setting and in 15-19 years old in the lower transmission setting. Reported fever was associated with malaria in both transmission strata, with no evidence of a difference in these associations (p = 0.71); however in children older than 5 years there was a significant interaction with a stronger association in the low transmission HZ. Insecticide-treated net (ITN) use was associated with a lower risk of malaria infection in children 6-59 months in the high transmission HZs. Similar estimates were found in children over 5 years and the lower transmission HZ but the associations there were not

  13. Niche divergence versus neutral processes: combined environmental and genetic analyses identify contrasting patterns of differentiation in recently diverged pine species.

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    Alejandra Moreno-Letelier

    Full Text Available BACKGROUND AND AIMS: Solving relationships of recently diverged taxa, poses a challenge due to shared polymorphism and weak reproductive barriers. Multiple lines of evidence are needed to identify independently evolving lineages. This is especially true of long-lived species with large effective population sizes, and slow rates of lineage sorting. North American pines are an interesting group to test this multiple approach. Our aim is to combine cytoplasmic genetic markers with environmental information to clarify species boundaries and relationships of the species complex of Pinus flexilis, Pinus ayacahuite, and Pinus strobiformis. METHODS: Mitochondrial and chloroplast sequences were combined with previously obtained microsatellite data and contrasted with environmental information to reconstruct phylogenetic relationships of the species complex. Ecological niche models were compared to test if ecological divergence is significant among species. KEY RESULTS AND CONCLUSION: Separately, both genetic and ecological evidence support a clear differentiation of all three species but with different topology, but also reveal an ancestral contact zone between P. strobiformis and P. ayacahuite. The marked ecological differentiation of P. flexilis suggests that ecological speciation has occurred in this lineage, but this is not reflected in neutral markers. The inclusion of environmental traits in phylogenetic reconstruction improved the resolution of internal branches. We suggest that combining environmental and genetic information would be useful for species delimitation and phylogenetic studies in other recently diverged species complexes.

  14. Transcriptomic and metabolomic analyses identify a role for chlorophyll catabolism and phytoalexin during Medicago nonhost resistance against Asian soybean rust.

    Science.gov (United States)

    Ishiga, Yasuhiro; Uppalapati, Srinivasa Rao; Gill, Upinder S; Huhman, David; Tang, Yuhong; Mysore, Kirankumar S

    2015-08-12

    Asian soybean rust (ASR) caused by Phakopsora pachyrhizi is a devastating foliar disease affecting soybean production worldwide. Understanding nonhost resistance against ASR may provide an avenue to engineer soybean to confer durable resistance against ASR. We characterized a Medicago truncatula-ASR pathosystem to study molecular mechanisms of nonhost resistance. Although urediniospores formed appressoria and penetrated into epidermal cells of M. truncatula, P. pachyrhizi failed to sporulate. Transcriptomic analysis revealed the induction of phenylpropanoid, flavonoid and isoflavonoid metabolic pathway genes involved in the production of phytoalexin medicarpin in M. truncatula upon infection with P. pachyrhizi. Furthermore, genes involved in chlorophyll catabolism were induced during nonhost resistance. We further characterized one of the chlorophyll catabolism genes, Stay-green (SGR), and demonstrated that the M. truncatula sgr mutant and alfalfa SGR-RNAi lines showed hypersensitive-response-like enhanced cell death upon inoculation with P. pachyrhizi. Consistent with transcriptomic analysis, metabolomic analysis also revealed the accumulation of medicarpin and its intermediate metabolites. In vitro assay showed that medicarpin inhibited urediniospore germination and differentiation. In addition, several triterpenoid saponin glycosides accumulated in M. truncatula upon inoculation with P. pachyrhizi. In summary, using multi-omic approaches, we identified a correlation between phytoalexin production and M. truncatula defense responses against ASR.

  15. Meta-analyses of genome-wide association studies identify multiple novel loci associated with pulmonary function

    Science.gov (United States)

    Hancock, Dana B.; Eijgelsheim, Mark; Wilk, Jemma B.; Gharib, Sina A.; Loehr, Laura R.; Marciante, Kristin D.; Franceschini, Nora; van Durme, Yannick M.T.A.; Chen, Ting-hsu; Barr, R. Graham; Schabath, Matthew B.; Couper, David J.; Brusselle, Guy G.; Psaty, Bruce M.; van Duijn, Cornelia M.; Rotter, Jerome I.; Uitterlinden, André G.; Hofman, Albert; Punjabi, Naresh M.; Rivadeneira, Fernando; Morrison, Alanna C.; Enright, Paul L.; North, Kari E.; Heckbert, Susan R.; Lumley, Thomas; Stricker, Bruno H.Ch.; O’Connor, George T.; London, Stephanie J.

    2010-01-01

    Measurements of lung function by spirometry are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important measures, forced expiratory volume in the first second (FEV1) and its ratio to forced vital capacity (FEV1/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE consortium studies: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Rotterdam Study (RS). We identified eight loci associated with FEV1/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1, and HTR4) and one locus associated with FEV1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (PPID1) replicated with the SpiroMeta consortium. Our findings of novel loci influencing pulmonary function may offer insights into chronic lung disease pathogenesis. PMID:20010835

  16. Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2

    Institute of Scientific and Technical Information of China (English)

    Mohamed Abu-Farha; Sylvain Lanouette; Fred Elisma; Véronique Tremblay; Jeffery Butson; Daniel Figeys; Jean-Francois Couture

    2011-01-01

    The SMYD (SET and MYND domain) family of lysine methyltransferases (KMTs) plays pivotal roles in various cellular processes,including gene expression regulation and DNA damage response.Initially identified as genuine histone methyltransferases,specific members of this family have recently been shown to methylate non-histone proteins such as p53,VEGFR,and the retinoblastoma tumor suppressor (pRb).To gain further functional insights into this family of KMTs,we generated the protein interaction network for three different human SMYD proteins (SMYD2,SMYD3,and SMYDS).Characterization of each SMYD protein network revealed that they associate with both shared and unique sets of proteins.Among those,we found that HsP90 and several of its co-chaperones interact specifically with the tetratrico peptide repeat (TPR)-containing SMYD2 and SMYD3.Moreover,using proteomic and biochemical techniques,we provide evidence that SMYD2 methylates K209 and K615 on HSP90 nucleotide-binding and dimerization domains,respectively.In addition,we found that each methylation site displays unique reactivity in regard to the presence of HsP90 co-chaperones,pH,and demethylation by the lysine amine oxidase LSD1,suggesting that alternative mechanisms control HsP90 methylation by SMYD2.Altogether,this study highlights the ability of SMYD proteins to form unique protein complexes that may underlie their various biological functions and the SMYD2-mediated methylation of the key molecular chaperone HSP90.%The SMYD (SET and MYND domain) family of lysine methyltransferases (KMTs) plays pivotal roles in various cellular processes, including gene expression regulation and DNA damage response. Initially identified as genuine histone methyltransferases, specific members of this family have recently been shown to methylate non-histone proteins such as p53, VEGFR, and the retinoblastoma tumor suppressor (pRb). To gain further functional insights into this family of KMTs, we generated the protein interaction

  17. Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets.

    Science.gov (United States)

    Fazlollahi, Mina; Muroff, Ivor; Lee, Eunjee; Causton, Helen C; Bussemaker, Harmen J

    2016-03-29

    Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

  18. An automatic system to identify heart disease risk factors in clinical texts over time.

    Science.gov (United States)

    Chen, Qingcai; Li, Haodi; Tang, Buzhou; Wang, Xiaolong; Liu, Xin; Liu, Zengjian; Liu, Shu; Wang, Weida; Deng, Qiwen; Zhu, Suisong; Chen, Yangxin; Wang, Jingfeng

    2015-12-01

    Despite recent progress in prediction and prevention, heart disease remains a leading cause of death. One preliminary step in heart disease prediction and prevention is risk factor identification. Many studies have been proposed to identify risk factors associated with heart disease; however, none have attempted to identify all risk factors. In 2014, the National Center of Informatics for Integrating Biology and Beside (i2b2) issued a clinical natural language processing (NLP) challenge that involved a track (track 2) for identifying heart disease risk factors in clinical texts over time. This track aimed to identify medically relevant information related to heart disease risk and track the progression over sets of longitudinal patient medical records. Identification of tags and attributes associated with disease presence and progression, risk factors, and medications in patient medical history were required. Our participation led to development of a hybrid pipeline system based on both machine learning-based and rule-based approaches. Evaluation using the challenge corpus revealed that our system achieved an F1-score of 92.68%, making it the top-ranked system (without additional annotations) of the 2014 i2b2 clinical NLP challenge. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Identifying Risk Factors for PTSD in Women Seeking Medical Help after Rape

    OpenAIRE

    Anna Tiihonen Möller; Torbjörn Bäckström; Hans Peter Söndergaard; Lotti Helström

    2014-01-01

    Objectives: Rape has been found to be the trauma most commonly associated with Posttraumatic Stress Disorder (PTSD) among women. It is therefore important to be able to identify those women at greatest risk of developing PTSD. The aims of the present study were to analyze the PTSD prevalence six months after sexual assaults and identify the major risk factors for developing PTSD. Methods: Participants were 317 female victims of rape who sought help at the Emergency Clinic for Raped Women at S...

  20. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors

    OpenAIRE

    Aleem Aamer

    2010-01-01

    Renal involvement in patients with sickle cell disease (SCD) is associated with signi-ficant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with pro-teinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure cr...

  1. A Fuzzy DEMATEL Method to Identify Critical Success Factors of Knowledge Management Adoption in Supply Chain

    OpenAIRE

    Sachin K. Patil; Kant, R.

    2013-01-01

    In globalisation of business, Knowledge Management (KM) plays an important role in Supply Chain (SC) to create, build and maintain competitive advantage through utilisation of knowledge and through collaborative practices. Literature review have suggested the performance of KM adoption in SC may be affected by various influencing factors but it is always difficult for the practitioners to improve all aspects at the same time. The aim of this study is to identify Critical Success Factors (CSFs...

  2. metagene Profiles Analyses Reveal Regulatory Element's Factor-Specific Recruitment Patterns.

    Science.gov (United States)

    Joly Beauparlant, Charles; Lamaze, Fabien C; Deschênes, Astrid; Samb, Rawane; Lemaçon, Audrey; Belleau, Pascal; Bilodeau, Steve; Droit, Arnaud

    2016-08-01

    ChIP-Sequencing (ChIP-Seq) provides a vast amount of information regarding the localization of proteins across the genome. The aggregation of ChIP-Seq enrichment signal in a metagene plot is an approach commonly used to summarize data complexity and to obtain a high level visual representation of the general occupancy pattern of a protein. Here we present the R package metagene, the graphical interface Imetagene and the companion package similaRpeak. Together, they provide a framework to integrate, summarize and compare the ChIP-Seq enrichment signal from complex experimental designs. Those packages identify and quantify similarities or dissimilarities in patterns between large numbers of ChIP-Seq profiles. We used metagene to investigate the differential occupancy of regulatory factors at noncoding regulatory regions (promoters and enhancers) in relation to transcriptional activity in GM12878 B-lymphocytes. The relationships between occupancy patterns and transcriptional activity suggest two different mechanisms of action for transcriptional control: i) a "gradient effect" where the regulatory factor occupancy levels follow transcription and ii) a "threshold effect" where the regulatory factor occupancy levels max out prior to reaching maximal transcription. metagene, Imetagene and similaRpeak are implemented in R under the Artistic license 2.0 and are available on Bioconductor.

  3. metagene Profiles Analyses Reveal Regulatory Element’s Factor-Specific Recruitment Patterns

    Science.gov (United States)

    Samb, Rawane; Lemaçon, Audrey; Bilodeau, Steve; Droit, Arnaud

    2016-01-01

    ChIP-Sequencing (ChIP-Seq) provides a vast amount of information regarding the localization of proteins across the genome. The aggregation of ChIP-Seq enrichment signal in a metagene plot is an approach commonly used to summarize data complexity and to obtain a high level visual representation of the general occupancy pattern of a protein. Here we present the R package metagene, the graphical interface Imetagene and the companion package similaRpeak. Together, they provide a framework to integrate, summarize and compare the ChIP-Seq enrichment signal from complex experimental designs. Those packages identify and quantify similarities or dissimilarities in patterns between large numbers of ChIP-Seq profiles. We used metagene to investigate the differential occupancy of regulatory factors at noncoding regulatory regions (promoters and enhancers) in relation to transcriptional activity in GM12878 B-lymphocytes. The relationships between occupancy patterns and transcriptional activity suggest two different mechanisms of action for transcriptional control: i) a “gradient effect” where the regulatory factor occupancy levels follow transcription and ii) a “threshold effect” where the regulatory factor occupancy levels max out prior to reaching maximal transcription. metagene, Imetagene and similaRpeak are implemented in R under the Artistic license 2.0 and are available on Bioconductor. PMID:27538250

  4. Identifying Protective Factors to Promote Health in American Indian and Alaska Native Adolescents: A Literature Review.

    Science.gov (United States)

    Henson, Michele; Sabo, Samantha; Trujillo, Aurora; Teufel-Shone, Nicolette

    2017-04-01

    Exposure to protective factors, conditions that protect against the occurrence of an undesirable outcome or promote the occurrence of a desirable outcome within an adolescent's environment, can foster healthy adolescent behaviors and reduce adult morbidity and mortality. Yet, little is known about the nature and effect of protective factors on the positive social and health outcomes among American Indian and Alaska Native (AIAN) adolescents. We conducted a review of the literature to identify the protective factors associated with positive health outcomes among AIAN adolescents. We consulted Elsevier Science Direct, ERIC EBSCOhost, PubMed, and the Web of Science databases. A total of 3421 articles were encountered. Excluded publications were those that did not focus on AIAN adolescents (n = 3341), did not identify protective factors (n = 56), were not original research studies (n = 8), or were not written in the English language. We identified nine categories of protective factors positively associated with health and social outcomes, including: current and/or future aspirations, personal wellness, positive self-image, self-efficacy, non-familial connectedness, family connectedness, positive opportunities, positive social norms, and cultural connectedness. Such factors positively influenced adolescent alcohol, tobacco, and substance use; delinquent and violent behavior; emotional health including depression, suicide attempt; resilience; and academic success. Protective factors spanned multiple domains of the socio-ecological model. Strengths-based health promotion efforts that leverage local, innate protective factors and work with AIANs to create environments rich in protective factors are key to improving the health and wellbeing of AIAN adolescents.

  5. Air Force Officer Qualifying Test Form T: Initial Item-, Test-, Factor-,and Composite-Level Analyses

    Science.gov (United States)

    2016-12-01

    AFRL-RH-WP-TR-2016-0093 AIR FORCE OFFICER QUALIFYING TEST FORM T: INITIAL ITEM-, TEST -, FACTOR-, AND COMPOSITE-LEVEL ANALYSES...July 2016 – 28 Nov 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER FA8650-11-C-6158 Air Force Officer Qualifying Test Form T...Initial Item-, Test -, Factor-, and Composite-Level Analyses 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) 5d. PROJECT

  6. An assessment of recently published gene expression data analyses: reporting experimental design and statistical factors

    Directory of Open Access Journals (Sweden)

    Azuaje Francisco

    2006-06-01

    Full Text Available Abstract Background The analysis of large-scale gene expression data is a fundamental approach to functional genomics and the identification of potential drug targets. Results derived from such studies cannot be trusted unless they are adequately designed and reported. The purpose of this study is to assess current practices on the reporting of experimental design and statistical analyses in gene expression-based studies. Methods We reviewed hundreds of MEDLINE-indexed papers involving gene expression data analysis, which were published between 2003 and 2005. These papers were examined on the basis of their reporting of several factors, such as sample size, statistical power and software availability. Results Among the examined papers, we concentrated on 293 papers consisting of applications and new methodologies. These papers did not report approaches to sample size and statistical power estimation. Explicit statements on data transformation and descriptions of the normalisation techniques applied prior to data analyses (e.g. classification were not reported in 57 (37.5% and 104 (68.4% of the methodology papers respectively. With regard to papers presenting biomedical-relevant applications, 41(29.1 % of these papers did not report on data normalisation and 83 (58.9% did not describe the normalisation technique applied. Clustering-based analysis, the t-test and ANOVA represent the most widely applied techniques in microarray data analysis. But remarkably, only 5 (3.5% of the application papers included statements or references to assumption about variance homogeneity for the application of the t-test and ANOVA. There is still a need to promote the reporting of software packages applied or their availability. Conclusion Recently-published gene expression data analysis studies may lack key information required for properly assessing their design quality and potential impact. There is a need for more rigorous reporting of important experimental

  7. An exploratory study to identify critical factors of innovation culture in organizations

    Directory of Open Access Journals (Sweden)

    Hamed Asgari

    2013-07-01

    Full Text Available During the past two decades, there has been a growing trend on knowledge-based organizations. Innovation, on the other hand, plays essential role on building competitive business units. In this paper, we present an exploratory study to identify critical factors of innovation culture in organizations. We detect important factors influencing innovation culture in construction industry based on the implementation of factor analysis. The proposed study designs a questionnaire and distributes it among 400 experts who are involved in construction industry. Cronbach alpha has been calculated as 0.779, which validates the overall questionnaire. The results of factor analysis have indicated that six factors of building cultural infrastructures, education, organizational vision, established culture, strategic culture and flexible culture are the most important items influencing innovation culture.

  8. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Cinegaglia, Naiara C; Andrade, Sonia Cristina S; Tokar, Tomas;

    2016-01-01

    of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma....

  9. Lessons for public health campaigns from analysing commercial food marketing success factors

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; JA Perez-Cueto, Federico; Niedzwiedzka, Barbara

    2012-01-01

    Background: Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public...... sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods: In this case-study analysis, 27 recent and successful commercial food...... and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects...

  10. Analysing physical fitness and biomechanical factors that determine tennis serve performance

    Directory of Open Access Journals (Sweden)

    Ertuğrul Gelen

    2009-11-01

    Full Text Available Normal 0 21 false false false TR X-NONE X-NONE MicrosoftInternetExplorer4 The purpose of the study is to analyse the fitness and the biomechanical factors which determine the velocity of the ball during serve in tennis (VBTS. The subjects of the study were fifteen male tournament level tennis player between the ages of sixteen and twenty five (18,8 ± 2,70 age/year. The physical fitness measurement of the study were; length, body weight, skinfold, diameter, circumference and length of the body, body composition, isometric handgrip strength, vertical jump, upper extremity range of motion (ROM and isokinetic strength. The angular velocity of racket head, racket handhold, middle finger, wrist, elbow, shoulder and hip joints on three axis during serve shoot were used for the biomechanical measurement.  The relationship between VBTS with physical fitness and biomechanical factors were measured with Pearson Correlation. The analysis showed that there was significant positive relation between VBTS and length, negative relation with mesomorphy; positive relation between ROM of shoulder dominant internal and external rotation, trunk hyper-extension, left lateral flexion and right rotation, negative relation in dominant wrist flexion, positive relation between isokinetic strength characteristics such as shoulder and elbow extension, shoulder internal and external rotation, wrist flexion, handgrip isometric strength, also in biomechanical measures, positive relation between in Y axis elbow, wrist, finger and head of the racket. As a result, fitness and biomechanical parameters that are intensively used in tennis determine VBTS. We think trainers may speed up VBTS by improved parameters and accelerated training programmes.

  11. Osteoporosis among Fallers without Concomitant Fracture Identified in an Emergency Department: Frequencies and Risk Factors

    DEFF Research Database (Denmark)

    Glintborg, Bente; Hesse, Ulrik; Houe, Thomas

    2011-01-01

    aged 50-80 years sustaining a low-energy fall without fracture were identified from an ED (n = 199). Patients answered a questionnaire on risk factors and underwent osteodensitometry. Data was compared to a group of patients routinely referred to osteodensitometry from general practice (n = 201......We aimed to determine whether the Emergency Department (ED) is a suitable entrance point for osteoporosis screening among fallers without concomitant fracture compared to referral from general practice. Furthermore, to identify factors associated with osteoporosis among fallers. Methods. Patients......). Results. Among the 199 included fallers, 41 (21%) had osteoporosis. Among these, 35 (85%) reported either previous fracture or reduced body height (>3¿cm). These two risk factors were more frequent among fallers with osteoporosis compared to fallers with normal bone mineral density or osteopenia (previous...

  12. An international survey to identify the intrinsic and extrinsic factors of research studies most likely to change orthopaedic practice.

    Science.gov (United States)

    Thornley, P; de Sa, D; Evaniew, N; Farrokhyar, F; Bhandari, M; Ghert, M

    2016-04-01

    Evidence -based medicine (EBM) is designed to inform clinical decision-making within all medical specialties, including orthopaedic surgery. We recently published a pilot survey of the Canadian Orthopaedic Association (COA) membership and demonstrated that the adoption of EBM principles is variable among Canadian orthopaedic surgeons. The objective of this study was to conduct a broader international survey of orthopaedic surgeons to identify characteristics of research studies perceived as being most influential in informing clinical decision-making. A 29-question electronic survey was distributed to the readership of an established orthopaedic journal with international readership. The survey aimed to analyse the influence of both extrinsic (journal quality, investigator profiles, etc.) and intrinsic characteristics (study design, sample size, etc.) of research studies in relation to their influence on practice patterns. A total of 353 surgeons completed the survey. Surgeons achieved consensus on the 'importance' of three key designs on their practices: randomised controlled trials (94%), meta-analyses (75%) and systematic reviews (66%). The vast majority of respondents support the use of current evidence over historical clinical training; however subjective factors such as journal reputation (72%) and investigator profile (68%) continue to influence clinical decision-making strongly. Although intrinsic factors such as study design and sample size have some influence on clinical decision-making, surgeon respondents are equally influenced by extrinsic factors such as investigator reputation and perceived journal quality.Cite this article: Dr M. Ghert. An international survey to identify the intrinsic and extrinsic factors of research studies most likely to change orthopaedic practice. Bone Joint Res 2016;5:130-136. DOI: 10.1302/2046-3758.54.2000578. © 2016 Ghert et al.

  13. Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

    Science.gov (United States)

    Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

    2017-03-01

    To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely

  14. Concept of ground facilities and the analyses of the factors for cost estimation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. Y.; Choi, H. J.; Choi, J. W.; Kim, S. K.; Cho, D. K

    2007-09-15

    The geologic disposal of spent fuels generated from the nuclear power plants is the only way to protect the human beings and the surrounding environments present and future. The direct disposal of the spent fuels from the nuclear power plants is considered, and a Korean Reference HLW disposal System(KRS) suitable for our representative geological conditions have been developed. In this study, the concept of the spent fuel encapsulation process as a key of the above ground facilities for deep geological disposal was established. To do this, the design requirements, such as the functions and the spent fuel accumulations, were reviewed. Also, the design principles and the bases were established. Based on the requirements and the bases, the encapsulation process of the spent fuel from receiving spent fuel of nuclear power plants to transferring canister into the underground repository was established. Simulation for the above-ground facility in graphic circumstances through KRS design concept and disposal scenarios for spent nuclear fuel showed that an appropriate process was performed based on facility design concept and required for more improvement on construction facility by actual demonstration test. And, based on the concept of the above ground facilities for the Korean Reference HLW disposal System, the analyses of the factors for the cost estimation was carried out.

  15. Can hospital audit teams identify case management problems, analyse their causes, identify and implement improvements? A cross-sectional process evaluation of obstetric near-miss case reviews in Benin

    Directory of Open Access Journals (Sweden)

    Borchert Matthias

    2012-10-01

    Full Text Available Abstract Background Obstetric near-miss case reviews are being promoted as a quality assurance intervention suitable for hospitals in low income countries. We introduced such reviews in five district, regional and national hospitals in Benin, West Africa. In a cross-sectional study we analysed the extent to which the hospital audit teams were able to identify case management problems (CMPs, analyse their causes, agree on solutions and put these solutions into practice. Methods We analysed case summaries, women’s interview transcripts and audit minutes produced by the audit teams for 67 meetings concerning one woman with near-miss complications each. We compared the proportion of CMPs identified by an external assessment team to the number found by the audit teams. For the latter, we described the CMP causes identified, solutions proposed and implemented by the audit teams. Results Audit meetings were conducted regularly and were well attended. Audit teams identified half of the 714 CMPs; they were more likely to find managerial ones (71% than the ones relating to treatment (30%. Most identified CMPs were valid. Almost all causes of CMPs were plausible, but often too superficial to be of great value for directing remedial action. Audit teams suggested solutions, most of them promising ones, for 38% of the CMPs they had identified, but recorded their implementation only for a minority (8.5%. Conclusions The importance of following-up and documenting the implementation of solutions should be stressed in future audit interventions. Tools facilitating the follow-up should be made available. Near-miss case reviews hold promise, but their effectiveness to improve the quality of care sustainably and on a large scale still needs to be established.

  16. Identifying the Prognosis Factors in Death after Liver Transplantation via Adaptive LASSO in Iran

    Directory of Open Access Journals (Sweden)

    Hadi Raeisi Shahraki

    2016-01-01

    Full Text Available Despite the widespread use of liver transplantation as a routine therapy in liver diseases, the effective factors on its outcomes are still controversial. This study attempted to identify the most effective factors on death after liver transplantation. For this purpose, modified least absolute shrinkage and selection operator (LASSO, called Adaptive LASSO, was utilized. One of the best advantages of this method is considering high number of factors. Therefore, in a historical cohort study from 2008 to 2013, the clinical findings of 680 patients undergoing liver transplant surgery were considered. Ridge and Adaptive LASSO regression methods were then implemented to identify the most effective factors on death. To compare the performance of these two models, receiver operating characteristic (ROC curve was used. According to the results, 12 factors in Ridge regression and 9 ones in Adaptive LASSO regression were significant. The area under the ROC curve (AUC of Adaptive LASSO was equal to 89% (95% CI: 86%–91%, which was significantly greater than Ridge regression (64%, 95% CI: 61%–68% (p<0.001. As a conclusion, the significant factors and the performance criteria revealed the superiority of Adaptive LASSO method as a penalized model versus traditional regression model in the present study.

  17. Identifying Items to Assess Methodological Quality in Physical Therapy Trials: A Factor Analysis

    Science.gov (United States)

    Cummings, Greta G.; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

    2014-01-01

    Background Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. Objective The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). Design A methodological research design was used, and an EFA was performed. Methods Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Results Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Limitation Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. Conclusions To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor

  18. Identifying items to assess methodological quality in physical therapy trials: a factor analysis.

    Science.gov (United States)

    Armijo-Olivo, Susan; Cummings, Greta G; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

    2014-09-01

    Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). A methodological research design was used, and an EFA was performed. Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items.

  19. Analyses on the tectonic thermal evolution and influence factors in the deep-water Qiongdongnan Basin

    Institute of Scientific and Technical Information of China (English)

    WANG Zhenfeng; SHI Xiaobin; YANG Jun; HUANG Baojia; SUN Zhen; WANG Yahui; JIANG Haiyan; YU Chuanhai; YANG Xiaoqiu

    2014-01-01

    To reveal the tectonic thermal evolution and influence factors on the present heat flow distribution, based on 154 heat flow data, the present heat flow distribution features of the main tectonic units are first analyzed in detail, then the tectonic thermal evolution histories of 20 profiles are reestablished crossing the main deep-water sags with a structural, thermal and sedimentary coupled numerical model. On the basis of the present geothermal features, the Qiongdongnan Basin could be divided into three regions: the northern shelf and upper slope region with a heat flow of 50–70 mW/m2, most of the central depression zone of 70–85 mW/m2, and a NE trending high heat flow zone of 85–105 mW/m2 lying in the eastern basin. Numerical modeling shows that during the syn-rift phase, the heat flow increases generally with time, and is higher in basement high area than in its adjacent sags. At the end of the syn-rift phase, the heat flow in the deep-water sags was in a range of 60–85 mW/m2, while in the basement high area, it was in a range of 75–100 mW/m2. During the post-rift phase, the heat flow decreased gradually, and tended to be more uniform in the basement highs and sags. However, an extensive magmatism, which equivalently happened at around 5 Ma, has greatly increased the heat flow values, and the relict heat still contributes about 10–25 mW/m2to the present surface heat flow in the central depression zone and the southern uplift zone. Further analyses suggested that the present high heat flow in the deep-water Qiongdongnan Basin is a combined result of the thermal anomaly in the upper mantle, highly thinning of the lithosphere, and the recent extensive magma-tism. Other secondary factors might have affected the heat flow distribution features in some local regions. These factors include basement and seafloor topography, sediment heat generation, thermal blanketing, local magmatic injecting and hydrothermal activities related to faulting and

  20. Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A Decision Tree Approach

    Science.gov (United States)

    Ortega-Campos, Elena; García-García, Juan; Gil-Fenoy, Maria José; Zaldívar-Basurto, Flor

    2016-01-01

    Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members. PMID:27611313

  1. Identifying and ranking the factors affecting entrepreneurial marketing to facilitate exports

    Directory of Open Access Journals (Sweden)

    Mehdi Habibzadeh

    2016-04-01

    Full Text Available Small and medium enterprises (SMEs are believed the most important components of today’s businesses and they can boost the growth of economy. This paper presents an empirical investigation to identify and rank important factors influencing on entrepreneurial marketing to facilitate exports of SMEs. The study designs a questionnaire in Likert scale and distributes it among 387 randomly selected entrepreneurs who act as managers of some SMEs in city of Tehran, Iran. Cronbach alpha is calculated as 0.873, which is well above the acceptable level. Using principle component analysis, the study has determined four factors including competitive intelligence, competitive advantage, external factors and internal factors to facilitate the export of SMEs.

  2. Clusters of Factors Identify A High Prevalence of Pregnancy Involvement Among US Adolescent Males.

    Science.gov (United States)

    Lau, May; Lin, Hua; Flores, Glenn

    2015-08-01

    The study purpose was to use recursive partitioning analysis (RPA) to identify factors that, when clustered, are associated with a high prevalence of pregnancy involvement among US adolescent males. The National Survey of Family Growth is a nationally representative survey of individuals 15-44 years old. RPA was done for the 2002 and 2006-2010 cycles to identify factors which, when combined, identify adolescent males with the highest prevalence of pregnancy involvement. Pregnancy-involvement prevalence among adolescent males was 6 %. Two clusters of adolescent males have the highest pregnancy-involvement prevalence, at 84-87 %. In RPA, the highest pregnancy-involvement prevalence (87 %) was seen in adolescent males who ever HIV tested, had >4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment of 4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment ≥11th grade, were >17 years old, and had their first contraceptive education ≥10th grade, had a pregnancy-involvement prevalence of 84 %. Pregnancy-prevention efforts among adolescent males who have been involved in a pregnancy may need to target risk factors identified in clusters with the highest pregnancy prevalence to prevent subsequent pregnancies in these adolescent males and improve their future outcomes.

  3. Sensitized mutagenesis screen in Factor V Leiden mice identifies thrombosis suppressor loci.

    Science.gov (United States)

    Westrick, Randal J; Tomberg, Kärt; Siebert, Amy E; Zhu, Guojing; Winn, Mary E; Dobies, Sarah L; Manning, Sara L; Brake, Marisa A; Cleuren, Audrey C; Hobbs, Linzi M; Mishack, Lena M; Johnston, Alexander J; Kotnik, Emilee; Siemieniak, David R; Xu, Jishu; Li, Jun Z; Saunders, Thomas L; Ginsburg, David

    2017-09-05

    Factor V Leiden (F5(L) ) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for F5(L) (F5(L/L) ) and haploinsufficient for tissue factor pathway inhibitor (Tfpi(+/-) ). F8 deficiency enhanced the survival of F5(L/L)Tfpi(+/-) mice, demonstrating that F5(L/L)Tfpi(+/-) lethality is genetically suppressible. ENU-mutagenized F5(L/L) males and F5(L/+)Tfpi(+/-) females were crossed to generate 6,729 progeny, with 98 F5(L/L)Tfpi(+/-) offspring surviving until weaning. Sixteen lines, referred to as "modifier of Factor 5 Leiden (MF5L1-16)," exhibited transmission of a putative thrombosuppressor to subsequent generations. Linkage analysis in MF5L6 identified a chromosome 3 locus containing the tissue factor gene (F3). Although no ENU-induced F3 mutation was identified, haploinsufficiency for F3 (F3(+/-) ) suppressed F5(L/L)Tfpi(+/-) lethality. Whole-exome sequencing in MF5L12 identified an Actr2 gene point mutation (p.R258G) as the sole candidate. Inheritance of this variant is associated with suppression of F5(L/L)Tfpi(+/-) lethality (P = 1.7 × 10(-6)), suggesting that Actr2(p.R258G) is thrombosuppressive. CRISPR/Cas9 experiments to generate an independent Actr2 knockin/knockout demonstrated that Actr2 haploinsufficiency is lethal, supporting a hypomorphic or gain-of-function mechanism of action for Actr2(p.R258G) Our findings identify F8 and the Tfpi/F3 axis as key regulators in determining thrombosis balance in the setting of F5(L) and also suggest a role for Actr2 in this process.

  4. Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion.

    Science.gov (United States)

    Sundaramoorthy, Sriramkumar; Vázquez-Novelle, María Dolores; Lekomtsev, Sergey; Howell, Michael; Petronczki, Mark

    2014-11-18

    Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation during cell division. Using functional genomic screening, we identify a set of 26 pre-mRNA splicing factors that are required for sister chromatid cohesion in human cells. Loss of spliceosome subunits increases the dissociation rate of cohesin from chromatin and abrogates cohesion after DNA replication, ultimately causing mitotic catastrophe. Depletion of splicing factors causes defective processing of the pre-mRNA encoding sororin, a factor required for the stable association of cohesin with chromatin, and an associated reduction of sororin protein level. Expression of an intronless version of sororin and depletion of the cohesin release protein WAPL suppress the cohesion defect in cells lacking splicing factors. We propose that spliceosome components contribute to sister chromatid cohesion and mitotic chromosome segregation through splicing of sororin pre-mRNA. Our results highlight the loss of cohesion as an early cellular consequence of compromised splicing. This may have clinical implications because SF3B1, a splicing factor that we identify to be essential for cohesion, is recurrently mutated in chronic lymphocytic leukaemia.

  5. Identifying the Prognosis Factors in Death after Liver Transplantation via Adaptive LASSO in Iran.

    Science.gov (United States)

    Raeisi Shahraki, Hadi; Pourahmad, Saeedeh; Ayatollahi, Seyyed Mohammad Taghi

    2016-01-01

    Despite the widespread use of liver transplantation as a routine therapy in liver diseases, the effective factors on its outcomes are still controversial. This study attempted to identify the most effective factors on death after liver transplantation. For this purpose, modified least absolute shrinkage and selection operator (LASSO), called Adaptive LASSO, was utilized. One of the best advantages of this method is considering high number of factors. Therefore, in a historical cohort study from 2008 to 2013, the clinical findings of 680 patients undergoing liver transplant surgery were considered. Ridge and Adaptive LASSO regression methods were then implemented to identify the most effective factors on death. To compare the performance of these two models, receiver operating characteristic (ROC) curve was used. According to the results, 12 factors in Ridge regression and 9 ones in Adaptive LASSO regression were significant. The area under the ROC curve (AUC) of Adaptive LASSO was equal to 89% (95% CI: 86%-91%), which was significantly greater than Ridge regression (64%, 95% CI: 61%-68%) (p LASSO method as a penalized model versus traditional regression model in the present study.

  6. Factors associated with stroke survivor behaviors as identified by family caregivers.

    Science.gov (United States)

    Gonzalez, Carmanny; Bakas, Tamilyn

    2013-01-01

    Stroke survivor behaviors that caregivers identify as bothersome can lead to family caregiver stress, which can result in premature institutionalization of the survivor. The purpose of this study was to explore demographic and theory-based factors associated with survivor bothersome behaviors as identified by family caregivers. A secondary analysis of a combined sample of 96 family caregivers of stroke survivors was conducted using baseline data from two existing studies. Bothersome behaviors were measured using the Revised Memory and Behavior Problems Checklist (RMBPC). Theory-based factors were measured using well-validated scales. Male stroke survivors exhibited more bothersome behaviors (t = 3.53, p caregiver depressive symptoms, task difficulty, life changes, and threat appraisal (F[5, 88] = 10.82, p caregivers. © 2013 Association of Rehabilitation Nurses.

  7. Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies.

    Science.gov (United States)

    Poppe, Bruce; Vandesompele, Jo; Schoch, Claudia; Lindvall, Charlotta; Mrozek, Krzysztof; Bloomfield, Clara D; Beverloo, H Berna; Michaux, Lucienne; Dastugue, Nicole; Herens, Christian; Yigit, Nurten; De Paepe, Anne; Hagemeijer, Anne; Speleman, Frank

    2004-01-01

    MLL amplification was recently recognized as a recurrent aberration in acute myeloid leukemia (AML) and myelodys-plastic syndrome (MDS), associated with adverse prognosis and karyotype complexity. Here we present detailed results of fluorescence in situ hybridization (FISH) and expression analyses of MLL and 5 selected 11q candidate oncogenes (CBL, DDX6, ETS1, FLI1, and PLZF) in 31 patient samples and one cell line with 11q23 gain. FISH analyses revealed that the 11q23 amplicon invariably encompassed MLL, DDX6, ETS1, and FLI1, whereas expression analyses identified MLL and DDX6 as the most differentially expressed genes among samples with and without 11q23 copy gain or amplification. In MLL-amplified samples, a significant transcriptional up-regulation of MEIS1, PROML1, ADAM10, NKG2D, and ITPA was noted. Further analyses, designed to elucidate a possible role of the 11q overexpressed genes (MLL, DDX6, FLI1, and ETS1) in unselected MDS and AML samples, revealed a significant upregulation of MLL in MDS. Our findings confirm the MLL gene as a prominent target of 11q23 amplification and provide further evidence for an etiologic role for MLL gain of function in myeloid malignancies. In addition, our results indicate that the transcriptional program associated with MLL rearrangements and MLL overexpression displays significant similarities.

  8. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Crichlow, G.; Lubetsky, J; Leng, L; Bucala, R; Lolis, E

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.

  9. Expression and Protein Interaction Analyses Reveal Combinatorial Interactions of LBD Transcription Factors During Arabidopsis Pollen Development.

    Science.gov (United States)

    Kim, Mirim; Kim, Min-Jung; Pandey, Shashank; Kim, Jungmook

    2016-11-01

    LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor gene family members play key roles in diverse aspects of plant development. LBD10 and LBD27 have been shown to be essential for pollen development in Arabidopsis thaliana. From the previous RNA sequencing (RNA-Seq) data set of Arabidopsis pollen, we identified the mRNAs of LBD22, LBD25 and LBD36 in addition to LBD10 and LBD27 in Arabidopsis pollen. Here we conducted expression and cellular analysis using GFP:GUS (green fluorescent protein:β-glucuronidase) reporter gene and subcellular localization assays using LBD:GFP fusion proteins expressed under the control of their own promoters in Arabidopsis. We found that these LBD proteins display spatially and temporally distinct and overlapping expression patterns during pollen development. Bimolecular fluorescence complementation and GST (glutathione S-transferase) pull-down assays demonstrated that protein-protein interactions occur among the LBDs exhibiting overlapping expression during pollen development. We further showed that LBD10, LBD22, LBD25, LBD27 and LBD36 interact with each other to form heterodimers, which are localized to the nucleus in Arabidopsis protoplasts. Taken together, these results suggest that combinatorial interactions among LBD proteins may be important for their function in pollen development in Arabidopsis.

  10. Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

    Directory of Open Access Journals (Sweden)

    Zhi-Juan eFeng

    2015-12-01

    Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

  11. Foxtail Millet NF-Y Families: Genome-Wide Survey and Evolution Analyses Identified Two Functional Genes Important in Abiotic Stresses.

    Science.gov (United States)

    Feng, Zhi-Juan; He, Guan-Hua; Zheng, Wei-Jun; Lu, Pan-Pan; Chen, Ming; Gong, Ya-Ming; Ma, You-Zhi; Xu, Zhao-Shi

    2015-01-01

    It was reported that Nuclear Factor Y (NF-Y) genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica), an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA) and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC) expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam) NtERD10, NtLEA5, NtCAT, NtSOD, or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC) and contents of chlorophyll, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and malondialdehyde (MDA) in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5, and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

  12. Multivariate statistical and lead isotopic analyses approach to identify heavy metal sources in topsoil from the industrial zone of Beijing Capital Iron and Steel Factory.

    Science.gov (United States)

    Zhu, Guangxu; Guo, Qingjun; Xiao, Huayun; Chen, Tongbin; Yang, Jun

    2017-06-01

    Heavy metals are considered toxic to humans and ecosystems. In the present study, heavy metal concentration in soil was investigated using the single pollution index (PIi), the integrated Nemerow pollution index (PIN), and the geoaccumulation index (Igeo) to determine metal accumulation and its pollution status at the abandoned site of the Capital Iron and Steel Factory in Beijing and its surrounding area. Multivariate statistical (principal component analysis and correlation analysis), geostatistical analysis (ArcGIS tool), combined with stable Pb isotopic ratios, were applied to explore the characteristics of heavy metal pollution and the possible sources of pollutants. The results indicated that heavy metal elements show different degrees of accumulation in the study area, the observed trend of the enrichment factors, and the geoaccumulation index was Hg > Cd > Zn > Cr > Pb > Cu ≈ As > Ni. Hg, Cd, Zn, and Cr were the dominant elements that influenced soil quality in the study area. The Nemerow index method indicated that all of the heavy metals caused serious pollution except Ni. Multivariate statistical analysis indicated that Cd, Zn, Cu, and Pb show obvious correlation and have higher loads on the same principal component, suggesting that they had the same sources, which are related to industrial activities and vehicle emissions. The spatial distribution maps based on ordinary kriging showed that high concentrations of heavy metals were located in the local factory area and in the southeast-northwest part of the study region, corresponding with the predominant wind directions. Analyses of lead isotopes confirmed that Pb in the study soils is predominantly derived from three Pb sources: dust generated during steel production, coal combustion, and the natural background. Moreover, the ternary mixture model based on lead isotope analysis indicates that lead in the study soils originates mainly from anthropogenic sources, which contribute much more

  13. Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection.

    Directory of Open Access Journals (Sweden)

    Ari Yasunaga

    2014-02-01

    Full Text Available Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV, a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts.

  14. Identifying factors for job motivation of rural health workers in North Viet Nam.

    Science.gov (United States)

    Dieleman, Marjolein; Cuong, Pham Viet; Anh, Le Vu; Martineau, Tim

    2003-11-05

    BACKGROUND: In Viet Nam, most of the public health staff (84%) currently works in rural areas, where 80% of the people live. To provide good quality health care services, it is important to develop strategies influencing staff motivation for better performance. METHOD: An exploratory qualitative research was carried out among health workers in two provinces in North Viet Nam so as to identify entry points for developing strategies that improve staff performance in rural areas. The study aimed to determine the major motivating factors and it is the first in Viet Nam that looks at health workers' job perception and motivation. Apart from health workers, managers at national and at provincial level were interviewed as well as some community representatives. RESULTS: The study showed that motivation is influenced by both financial and non-financial incentives. The main motivating factors for health workers were appreciation by managers, colleagues and the community, a stable job and income and training. The main discouraging factors were related to low salaries and difficult working conditions. CONCLUSION: Activities associated with appreciation such as performance management are currently not optimally implemented, as health workers perceive supervision as control, selection for training as unclear and unequal, and performance appraisal as not useful. The kind of non-financial incentives identified should be taken into consideration when developing HRM strategies. Areas for further studies are identified.

  15. Identifying factors for job motivation of rural health workers in North Viet Nam

    Directory of Open Access Journals (Sweden)

    Anh Le

    2003-11-01

    Full Text Available Abstract Background In Viet Nam, most of the public health staff (84% currently works in rural areas, where 80% of the people live. To provide good quality health care services, it is important to develop strategies influencing staff motivation for better performance. Method An exploratory qualitative research was carried out among health workers in two provinces in North Viet Nam so as to identify entry points for developing strategies that improve staff performance in rural areas. The study aimed to determine the major motivating factors and it is the first in Viet Nam that looks at health workers' job perception and motivation. Apart from health workers, managers at national and at provincial level were interviewed as well as some community representatives. Results The study showed that motivation is influenced by both financial and non-financial incentives. The main motivating factors for health workers were appreciation by managers, colleagues and the community, a stable job and income and training. The main discouraging factors were related to low salaries and difficult working conditions. Conclusion Activities associated with appreciation such as performance management are currently not optimally implemented, as health workers perceive supervision as control, selection for training as unclear and unequal, and performance appraisal as not useful. The kind of non-financial incentives identified should be taken into consideration when developing HRM strategies. Areas for further studies are identified.

  16. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Saito, Kazuki; Miyado, Mami; Kobori, Yoshitomo; Tanaka, Yoko; Ishikawa, Hiromichi; Yoshida, Atsumi; Katsumi, Momori; Saito, Hidekazu; Kubota, Toshiro; Okada, Hiroshi; Ogata, Tsutomu; Fukami, Maki

    2015-03-01

    Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF) regions have been associated with the risk of spermatogenic failure (SF), the precise frequency, genomic basis and clinical consequences of these CNVs remain unclear. Here we performed multiplex ligation-dependent probe amplification (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We compared the results of MLPA with those of conventional sequence-tagged site PCR analyses. Eleven simple and complex CNVs, including three hitherto unreported variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by conventional analyses. CNVs were widely distributed in AZF regions and shared by ~60% of the patients and ~40% of the controls. Most breakpoints resided within locus-specific repeats. The majority of CNVs, including the most common gr/gr deletion, were identified in the patient and control groups at similar frequencies, whereas simple duplications were observed exclusively in the patient group. The results imply that AZF-linked CNVs are more frequent and heterogeneous than previously reported. Non-allelic homologous recombination likely underlies these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in the Japanese population. We also found a possible association between AZF-linked simple duplications and SF, which needs to be evaluated in future studies.

  17. A Bayesian Approach to Identifying New Risk Factors for Dementia: A Nationwide Population-Based Study.

    Science.gov (United States)

    Wen, Yen-Hsia; Wu, Shihn-Sheng; Lin, Chun-Hung Richard; Tsai, Jui-Hsiu; Yang, Pinchen; Chang, Yang-Pei; Tseng, Kuan-Hua

    2016-05-01

    Dementia is one of the most disabling and burdensome health conditions worldwide. In this study, we identified new potential risk factors for dementia from nationwide longitudinal population-based data by using Bayesian statistics.We first tested the consistency of the results obtained using Bayesian statistics with those obtained using classical frequentist probability for 4 recognized risk factors for dementia, namely severe head injury, depression, diabetes mellitus, and vascular diseases. Then, we used Bayesian statistics to verify 2 new potential risk factors for dementia, namely hearing loss and senile cataract, determined from the Taiwan's National Health Insurance Research Database.We included a total of 6546 (6.0%) patients diagnosed with dementia. We observed older age, female sex, and lower income as independent risk factors for dementia. Moreover, we verified the 4 recognized risk factors for dementia in the older Taiwanese population; their odds ratios (ORs) ranged from 3.469 to 1.207. Furthermore, we observed that hearing loss (OR = 1.577) and senile cataract (OR = 1.549) were associated with an increased risk of dementia.We found that the results obtained using Bayesian statistics for assessing risk factors for dementia, such as head injury, depression, DM, and vascular diseases, were consistent with those obtained using classical frequentist probability. Moreover, hearing loss and senile cataract were found to be potential risk factors for dementia in the older Taiwanese population. Bayesian statistics could help clinicians explore other potential risk factors for dementia and for developing appropriate treatment strategies for these patients.

  18. Quality assessment and factor analysis of systematic reviews and meta-analyses of endoscopic ultrasound diagnosis.

    Directory of Open Access Journals (Sweden)

    Danlu Liu

    Full Text Available Comprehensive monitoring of the quality of systematic reviews (SRs and meta-analyses (MAs of endoscopic ultrasound (EUS requires complete and accurate reporting and methodology.To assess the reporting and methodological quality of SRs/MAs on EUS diagnosis and to explore the potential factors influencing articles' quality.The quality of the reporting and methodology was evaluated in relation to the adherence of papers to the PRISMA checklist and the AMSTAR quality scale. The total scores for every criterion and for every article on the two standards were calculated. Data were evaluated and analyzed using SPSS17.0 and RevMan 5.1 in terms of publication time, category of reviews, category of journals, and funding resource.A total of 72 SRs/MAs was included, but no Cochrane Systematic Reviews (CSRs were obtained. The number of SRs/MAs ranged from 1 in 1998 to 15 in 2013; 88.1% used the QUADAS tool; the average overall scores by PRISMA statement and AMSTAR tool were 19.9 and 5.4, respectively. Scores on some items showed substantial improvement after publication of PRISMA and AMSTAR. However, no reviews followed the criterion of protocol and registration, and only 11.1% of articles fulfilled the criterion of literature search. SRs/MAs from the Science Citation Index (SCI were of better quality than non-SCI studies. Funding resource made no difference to quality. Regression analysis showed that time of publication and inclusion in the SCI were significantly correlated with total scores on the two standards.The reporting and methodological quality of SRs/MAs on EUS diagnosis has improved measurably since PRISMA and AMSTAR checklists released. It is hoped that CSR in this field will be produced. Literature searching and protocol criteria, as well as QUADAS-2 tool need to be addressed more in the future. Time of publication and SCI relate more to the overall quality of SRs/MAs than does funding resource.

  19. The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks

    Directory of Open Access Journals (Sweden)

    Yasuda Akio

    2006-02-01

    Full Text Available Abstract Background Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure. Results We developed the in vitro real-time oscillation monitoring system (IV-ROMS by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid have already been reported as the entrainment factors in vivo and in vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2, a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ, triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ2 transiently induces Cry1, Cry2, and Rorα mRNA expressions and that 15d-PGJ2-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK-independent. Conclusion Here, we identified 15d-PGJ2 as an entrainment factor in vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight

  20. Physics-based features for identifying contextual factors affecting landmine detection with ground-penetrating radar

    Science.gov (United States)

    Ratto, Christopher R.; Morton, Kenneth D., Jr.; Collins, Leslie M.; Torrione, Peter A.

    2011-06-01

    It has been established throughout the ground-penetrating radar (GPR) literature that environmental factors can severely impact the performance of GPR sensors in landmine detection applications. Over the years, electromagnetic inversion techniques have been proposed for determining these factors with the goal of mitigating performance losses. However, these techniques are often computationally expensive and require models and responses from canonical targets, and therefore may not be appropriate for real-time route-clearance applications. An alternative technique for mitigating performance changes due to environmental factors is context-dependent classification, in which decision rules are adjusted based on contextual shifts identified from the GPR data. However, analysis of the performance of context-dependent learning has been limited to qualitative comparisons of contextually-similar GPR signatures and quantitative improvement to the ROC curve, while the actual information extracted regarding soils has not been investigated thoroughly. In this work, physics-based features of GPR data used in previous context-dependent approaches were extracted from simulated GPR data generated through Finite-Difference Time-Domain (FDTD) modeling. Statistical techniques where then used to predict several potential contextual factors, including soil dielectric constant, surface roughness, amount of subsurface clutter, and the existence of subsurface layering, based on the features. Results suggest that physics-based features of the GPR background may contain informatin regarding physical properties of the environment, and contextdependent classification based on these features can exploit information regarding these potentially-important environmental factors.

  1. Identifying factors causing cost overrun of the construction projects in India

    Indian Academy of Sciences (India)

    SWAPNIL P WANJARI; GAURAV DOBARIYA

    2016-06-01

    Delay and cost overrun are common phenomena in projects worldwide. However, these are especially severe in developing countries. In India as per MOSPI report, 235 projects out of 410 were severely affected cost overrun due to certain factors. A short questionnaire was conducted with 15 prominent factorsresponsible for cost overrun and forwarded to 190 constructional professionals across India. Total 85 responses were received and it was analyzed using various statistical tools such as analysis of variance (ANOVA) and factor analysis tool using SPSS. In this study, top three factors affecting cost overruns were identified such as price escalation of raw material, delay in planned activity and lack of co-ordination between construction parties which could be significantly responsible for cost overnun of construction project in India. Factor analysismethod was also carried out to group the factors into three components of overall questionnaire. These components, such as client control component, project management component, and contractor control component,would be useful to the various parties involved in the construction activities. This paper also provides suggestive frameworks which have been framed after discussing with large number of construction professionals or expert

  2. Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses.

    Science.gov (United States)

    Chen, Yuehong; Sun, Jianhong; Yang, Yuan; Huang, Yupeng; Liu, Gang

    2016-01-01

    The objective of the study is to systematically review the malignancy risk of anti-tumor necrosis factor alpha (anti-TNFα) agents. Databases of PubMed Medline, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses of randomized control trials, observational studies, and case series that evaluated malignancy risk of anti-TNFα blockers. Search time duration was restricted from January 1st, 2000 to July 16th, 2015. Overview Quality Assessment Questionnaires were used to assess the quality of included reviews. Two methodology trained reviewers separately and repeatedly screened searched studies according to study selection criteria, collected data, and assessed quality. Totally, 42 reviews proved eligible with only one Cochrane review. Anti-TNFα antagonists were extensively used to treat various diseases; nevertheless, malignancy risks were most commonly described in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In RA patients, no increased risks of breast cancer, lymphoma, and non-melanoma skin cancer were found, but if the use of anti-TNFα agents was associated with elevated risk of overall malignancy was still uncertainty. In IBD patients, the use of anti-TNFα inhibitors was not connected with enhanced risk of overall cancer. No increased cancer risk was found in other disease conditions. Twenty-nine reviews were rated as good quality, 12 as moderate, and one as poor. There are no sufficient evidences to draw the conclusion that anti-TNFα blockers have relationship with increased malignancy risk.

  3. Identifiable risk factors for thirty-day complications following arthroscopic rotator cuff repair.

    Science.gov (United States)

    Heyer, Jessica H; Kuang, Xiangyu; Amdur, Richard L; Pandarinath, Rajeev

    2017-10-11

    Shoulder arthroscopy has increased in frequency over the past decade, with rotator cuff repair comprising the majority of cases performed. Prior studies have detailed risk factors for 30-day complications and readmission rates after arthroscopic shoulder surgery using the National Surgical Quality Improvement Program (NSQIP) database, but no study has specifically looked at arthroscopic rotator cuff repair. The purpose of the study is to evaluate the risk factors for 30-day complications following arthroscopic rotator cuff repair using the NSQIP database. The NSQIP database was queried for all patients undergoing arthroscopic rotator cuff repair from 2006-2015. Demographics and thirty-day outcomes for these patients were analyzed using univariate analyses and multivariate regression analysis to determine the risk factors for complications. 21,143 patients underwent arthroscopic rotator cuff repair, with 147 patients (0.70%) having a complication within 30-days. Univariate analysis found age >65 (p = 0.0028), male gender (p = 0.0053), elevated BMI (p = 0.0054), ASA class >2 (p 90 min (p = 0.0316) to be associated with increased risk of complications. Multivariate analysis found female sex to be protective or complication (OR 0.56, p = 0.0017), while American Society of Anesthesiology (ASA) class >2 (OR 1.51, p = 0.0335) and history of COPD (OR 2.41, p = 0.0030) and dyspnea (OR 1.89, p = 0.0359) to be risk factors for complication. The most common complication is venothromboembolic events, accounting for 36.7% of all complications. Male sex, ASA class > 2, and history of COPD and dyspnea were independent risk factors for thirty-day complications following arthroscopic rotator cuff repair. IV.

  4. Exploratory and Confirmatory Factor Analyses of the WISC-IV with Gifted Students

    Science.gov (United States)

    Rowe, Ellen W.; Dandridge, Jessica; Pawlush, Alexandra; Thompson, Dawna F.; Ferrier, David E.

    2014-01-01

    These 2 studies investigated the factor structure of the Wechsler Intelligence Scale for Children-4th edition (WISC-IV; Wechsler, 2003a) with exploratory factor analysis (EFA; Study 1) and confirmatory factor analysis (CFA; Study 2) among 2 independent samples of gifted students. The EFA sample consisted of 225 children who were referred for a…

  5. A meta-analysis to identify animal and management factors influencing gestating sow efficiency.

    Science.gov (United States)

    Douglas, S L; Szyszka, O; Stoddart, K; Edwards, S A; Kyriazakis, I

    2014-12-01

    A meta-analysis on the effects of management and animal-based factors on the reproductive efficiency of gestating sows can provide information on single-factor and interaction effects that may not have been detected in individual studies. This study analyzed the effects of such factors on the number of piglets born alive per litter (BA), piglet birth weight (BiW) and weaning weight (WW), and number of piglets born alive per kilogram of sow feed intake during gestation (BA/FI). A total of 51 papers and 7 data sources were identified for the meta-analysis, out of which 23 papers and 5 sets of production data were useable (a total of 121 treatments). The information gathered included the dependent variables as well as information regarding animal, management, and feed characteristics. While a number of factors were individually significant, the multivariate models identified significant effects only of 1) floor type (P=0.003), sow BW at the end of gestation (P=0.002), and housing (stalls vs. loose; P=0.004) on BA; as floor type and housing were confounded, they were included in 2 separate models. The BA was higher on solid (12.1) in comparison to partly slatted (11.4) and fully slatted floors (10.2); 2) sow gestation environment (P=0.017) and gestation feed allowance (P=0.046) on BiW, with BiW of pigs higher for sows kept outdoors rather than indoors (1.75 versus 1.49 kg); 3) parity number (P=0.003) and feed intake during gestation (P=0.017) on WW; in addition there was an interaction between parity number×feed ME and parity number×feed CP content of feed during gestation on WW, with the positive effects of feed ME and CP contents seen during early rather than later parities; and 4) floor type (P=0.019) and feed crude fiber (P=0.003) for BA/FI with a greater number for those kept on solid floors (5.11) versus partially and fully slatted floors (4.07 and 4.05). The meta-analysis confirmed the significant effect of several well-known factors on the efficiency of

  6. Investigation of the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV): exploratory and higher order factor analyses.

    Science.gov (United States)

    Canivez, Gary L; Watkins, Marley W

    2010-12-01

    The present study examined the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV; D. Wechsler, 2008a) standardization sample using exploratory factor analysis, multiple factor extraction criteria, and higher order exploratory factor analysis (J. Schmid & J. M. Leiman, 1957) not included in the WAIS-IV Technical and Interpretation Manual (D. Wechsler, 2008b). Results indicated that the WAIS-IV subtests were properly associated with the theoretically proposed first-order factors, but all but one factor-extraction criterion recommended extraction of one or two factors. Hierarchical exploratory analyses with the Schmid and Leiman procedure found that the second-order g factor accounted for large portions of total and common variance, whereas the four first-order factors accounted for small portions of total and common variance. It was concluded that the WAIS-IV provides strong measurement of general intelligence, and clinical interpretation should be primarily at that level.

  7. Identifying risk factors for PTSD in women seeking medical help after rape.

    Directory of Open Access Journals (Sweden)

    Anna Tiihonen Möller

    Full Text Available Rape has been found to be the trauma most commonly associated with Posttraumatic Stress Disorder (PTSD among women. It is therefore important to be able to identify those women at greatest risk of developing PTSD. The aims of the present study were to analyze the PTSD prevalence six months after sexual assaults and identify the major risk factors for developing PTSD.Participants were 317 female victims of rape who sought help at the Emergency Clinic for Raped Women at Stockholm South Hospital, Sweden. Baseline assessments of mental health were carried out and followed up after six months.Thirty-nine percent of the women had developed PTSD at the six month assessment, and 47% suffered from moderate or severe depression. The major risk factors for PTSD were having been sexually assaulted by more than one person, suffering from acute stress disorder (ASD shortly after the assault, having been exposed to several acts during the assault, having been injured, having co-morbid depression, and having a history of more than two earlier traumas. Further, ASD on its own was found to be a poor predictor of PTSD because of the substantial ceiling effect after sexual assaults.Development of PTSD is common in the aftermath of sexual assaults. Increased risk of developing PTSD is caused by a combination of victim vulnerability and the extent of the dramatic nature of the current assault. By identifying those women at greatest risk of developing PTSD appropriate therapeutic resources can be directed.

  8. Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and serum response factor activity in mice.

    Directory of Open Access Journals (Sweden)

    Twishasri Dasgupta

    Full Text Available Members of the CUG-BP, Elav-like family (CELF regulate alternative splicing in the heart. In MHC-CELFΔ transgenic mice, CELF splicing activity is inhibited postnatally in heart muscle via expression of a nuclear dominant negative CELF protein under an α-myosin heavy chain promoter. MHC-CELFΔ mice develop dilated cardiomyopathy characterized by alternative splicing defects, enlarged hearts, and severe contractile dysfunction. In this study, gene expression profiles in the hearts of wild type, high- and low-expressing lines of MHC-CELFΔ mice were compared using microarrays. Gene ontology and pathway analyses identified contraction and calcium signaling as the most affected processes. Network analysis revealed that the serum response factor (SRF network is highly affected. Downstream targets of SRF were up-regulated in MHC-CELFΔ mice compared to the wild type, suggesting an increase in SRF activity. Although SRF levels remained unchanged, known inhibitors of SRF activity were down-regulated. Conversely, we found that these inhibitors are up-regulated and downstream SRF targets are down-regulated in the hearts of MCKCUG-BP1 mice, which mildly over-express CELF1 in heart and skeletal muscle. This suggests that changes in SRF activity are a consequence of changes in CELF-mediated regulation rather than a secondary result of compensatory pathways in heart failure. In MHC-CELFΔ males, where the phenotype is only partially penetrant, both alternative splicing changes and down-regulation of inhibitors of SRF correlate with the development of cardiomyopathy. Together, these results strongly support a role for CELF-mediated alternative splicing in the regulation of contractile gene expression, achieved in part through modulating the activity of SRF, a key cardiac transcription factor.

  9. Impact of cardiovascular risk factors on medical expenditure: evidence from epidemiological studies analysing data on health checkups and medical insurance.

    Science.gov (United States)

    Nakamura, Koshi

    2014-01-01

    Concerns have increasingly been raised about the medical economic burden in Japan, of which approximately 20% is attributable to cardiovascular disease, including coronary heart disease and stroke. Because the management of risk factors is essential for the prevention of cardiovascular disease, it is important to understand the relationship between cardiovascular risk factors and medical expenditure in the Japanese population. However, only a few Japanese epidemiological studies analysing data on health checkups and medical insurance have provided evidence on this topic. Patients with cardiovascular risk factors, including obesity, hypertension, and diabetes, may incur medical expenditures through treatment of the risk factors themselves and through procedures for associated diseases that usually require hospitalization and sometimes result in death. Untreated risk factors may cause medical expenditure surges, mainly due to long-term hospitalization, more often than risk factors preventively treated by medication. On an individual patient level, medical expenditures increase with the number of concomitant cardiovascular risk factors. For single risk factors, personal medical expenditure may increase with the severity of that factor. However, on a population level, the medical economic burden attributable to cardiovascular risk factors results largely from a single, particularly prevalent risk factor, especially from mildly-to-moderately abnormal levels of the factor. Therefore, cardiovascular risk factors require management on the basis of both a cost-effective strategy of treating high-risk patients and a population strategy for reducing both the ill health and medical economic burdens that result from cardiovascular disease.

  10. Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides: The GenSalt Study

    Science.gov (United States)

    Li, Changwei; Bazzano, Lydia A.L.; Rao, Dabeeru C.; Hixson, James E.; He, Jiang; Gu, Dongfeng; Gu, Charles C.; Shimmin, Lawrence C.; Jaquish, Cashell E.; Schwander, Karen; Liu, De-Pei; Huang, Jianfeng; Lu, Fanghong; Cao, Jie; Chong, Shen; Lu, Xiangfeng; Kelly, Tanika N.

    2016-01-01

    We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log-transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms (SNPs), single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single-marker analyses within each gene using the truncated product method (TPM). Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2–2q12.1 [maximum multipoint LOD score (MML) = 2.18 at 2q11.2] and 11q24.3–11q25 (MML = 2.29 at 11q25) for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 (CHMP3), ring finger protein 103 (RNF103), AF4/FMR2 family, member 3 (AFF3), and neurotrimin (NTM ) with triglycerides (P = 4 × 10−4, 1.00 × 10−5, 2.00 × 10−5, and 1.00 × 10−7, respectively). Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants (P = 1.00 × 10−7 and 8.00 × 10−5, respectively). Furthermore, NTM explained the linkage signal on chromosome 11. In conclusion, we identified novel genes

  11. Identifying Factors Affecting Professional Motivation of Iranian Seafarers onboard ocean Going Merchant Vessels

    Directory of Open Access Journals (Sweden)

    Asadolah Mehrara

    2016-12-01

    Full Text Available Human force employed in organizations is the main resources available to the managers. Management of human resources is perhaps the most important obligation of the manager activities and behaviors of human being are due to his needs and motivations. Since reinforcing motivations can lead to more improvements and achievements of every organization, the identification of factors affecting on motivation can help managers and supervisors to be aware of the origin of their staff’s motivations and lead their behavior towards the desired organizational aims. For this reason, this research tries to identify the most important factors affecting on professional motivation of the Iranian seafarers working on ocean-going merchant vessels (case study: National Iranian Tanker Company and to prioritize those factors in the next step. This research is of an "applied" and "descriptive-survey" type according to the goal and the methodology respectively. Statistical community of this research includes 540 of N.I.T.C. expert seafarers consisting:1- key officers (high rank officers with at least 10 years of experience, 2- low rank officers with at least 5 years of experience, 3-rating with diploma and at least 10 years of experience. Statistical sample mass based on "Kerjcie-Morgan" table includes 224 seafarers and the sampling method is the "simple random sample" method. The collecting method of data is field and library work. Further to the study of the available texts and researches about motivation and decision-making techniques and also interviewing with experts and lecturers who are masters and chief engineers of ocean-going vessels, a questionnaire has been prepared according to "Delphi method" to the scale of "Likert 5 degrees" and distributed among the statistical community. After analyzing the first questionnaire using the statistical methods and "SPSS" software, 20 affecting variables and also the final factors have been identified. Then the second

  12. Previously identified patellar tendinopathy risk factors differ between elite and sub-elite volleyball players.

    Science.gov (United States)

    Janssen, I; Steele, J R; Munro, B J; Brown, N A T

    2015-06-01

    Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub-elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub-elite male volleyball players. Nine elite and nine sub-elite male volleyball players performed a lateral stop-jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three-dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Li Min

    2017-02-01

    Full Text Available BACKGROUND: Gastric cancer (GC is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ2 = 30.71, P < .001 that exhibits better discrimination for prognosis than Lauren classification (χ2 = 12.11, P = .002. FRZB [RR (95% CI = 1.824 (1.115-2.986, P = .017] and EFEMP1 [RR (95% CI = 1.537 (0.969-2.437, P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI = 1.616 (0.938-2.785, P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.

  14. A telephone call 1 week after hospitalization can identify risk factors for vascular surgery readmission.

    Science.gov (United States)

    Hornick, John R; Balderman, Joshua A; Eugea, Ronnie; Sanchez, Luis A; Zayed, Mohamed A

    2016-09-01

    Compared with other populations, patients who undergo vascular surgery have higher 30-day hospital readmission rates of up to 25%. Postdischarge telephone call assessments have demonstrated utility in patients with significant medical comorbidities and traditionally high readmission rates. Therefore, we hypothesized that a 1-week postdischarge telephone call evaluation can identify risk factors for readmission among vascular surgery patients. Patients who underwent a vascular surgery procedure during a 1-year period by a single vascular surgeon at one hospital received a postdischarge telephone call questionnaire to review postoperative pain, surgical site, constitutional symptoms, and follow-up arrangement. The primary outcome measure was frequency of postoperative symptoms as collected on the telephone call questionnaire. The secondary outcome measure was 30-day hospital readmission rates. Among 167 patients, 131 (78%) received a telephone call after discharge. Calls identified pain relieved by prescription medication (odds ratio, 6.67; confidence interval, 0.82-53.81; P = .05) and continued dressing application (odds ratio, 9.55; confidence interval, 0.54-166.6; P = .04) as risk factors for 30-day readmission. The 30-day readmission was not statistically different in patients who were successfully and not successfully contacted with a postdischarge telephone call (8% and 17%, respectively; P = .37). Vascular surgery patients are at higher risk of 30-day readmission than are patients in other surgical subspecialties. For the majority of patients, implementing a 1-week postdischarge telephone call for short-term follow-up evaluation is feasible and can help identify potential risk factors for hospital readmission within 30 days. Published by Elsevier Inc.

  15. Identifying overlapping communities as well as hubs and outliers via nonnegative matrix factorization.

    Science.gov (United States)

    Cao, Xiaochun; Wang, Xiao; Jin, Di; Cao, Yixin; He, Dongxiao

    2013-10-21

    Community detection is important for understanding networks. Previous studies observed that communities are not necessarily disjoint and might overlap. It is also agreed that some outlier vertices participate in no community, and some hubs in a community might take more important roles than others. Each of these facts has been independently addressed in previous work. But there is no algorithm, to our knowledge, that can identify these three structures altogether. To overcome this limitation, we propose a novel model where vertices are measured by their centrality in communities, and define the identification of overlapping communities, hubs, and outliers as an optimization problem, calculated by nonnegative matrix factorization. We test this method on various real networks, and compare it with several competing algorithms. The experimental results not only demonstrate its ability of identifying overlapping communities, hubs, and outliers, but also validate its superior performance in terms of clustering quality.

  16. Identifying cooperative transcription factors by combining ChIP-chip data and knockout data

    Institute of Scientific and Technical Information of China (English)

    Yi Yang; Zili Zhang; Yixue Li; Xin-Guang Zhu; Qi Liu

    2010-01-01

    @@ Dear Editor, Eukaryotic transcriptional regulation networks are extremely complex.Usually,multiple transcription factors(TFs)bind to the promoter region of a gene and cooperate to control gene expression precisely.Identifying cooperative TFs remains a major challenge in modern biological research.Various types of data,including genomic sequences,expression profiles,ChiP-chip data and protein-protein interactions,have been used to identify mechanisms of cooperative transcriptional regulation.However,because of the noise inherent in these data and the fact that each data source only provides partial information about regulation,combining multiple types of data to improve their ability to infer cooperative TFs is advantageous[1-3].

  17. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben

    2008-01-01

    studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. METHODS: We have...... system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. CONCLUSIONS: By pathway meta-analysis many biological mechanisms beyond major......ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent...

  18. Functional Genomic Screen Identifies Klebsiella pneumoniae Factors Implicated in Blocking Nuclear Factor κB (NF-κB) Signaling.

    Science.gov (United States)

    Tomás, Anna; Lery, Leticia; Regueiro, Verónica; Pérez-Gutiérrez, Camino; Martínez, Verónica; Moranta, David; Llobet, Enrique; González-Nicolau, Mar; Insua, Jose L; Tomas, Juan M; Sansonetti, Philippe J; Tournebize, Régis; Bengoechea, José A

    2015-07-03

    Klebsiella pneumoniae is an etiologic agent of community-acquired and nosocomial pneumonia. It has been shown that K. pneumoniae infections are characterized by reduced early inflammatory response. Recently our group has shown that K. pneumoniae dampens the activation of inflammatory responses by antagonizing the activation of the NF-κB canonical pathway. Our results revealed that K. pneumoniae capsule polysaccharide (CPS) was necessary but not sufficient to attenuate inflammation. To identify additional Klebsiella factors required to dampen inflammation, we standardized and applied a high-throughput gain-of-function screen to examine a Klebsiella transposon mutant library. We identified 114 mutants that triggered the activation of NF-κB. Two gene ontology categories accounted for half of the loci identified in the screening: metabolism and transport genes (32% of the mutants) and envelope-related genes (17%). Characterization of the mutants revealed that the lack of the enterobactin siderophore was linked to a reduced CPS expression, which in turn underlined the NF-κB activation induced by the mutant. The lipopolysaccharide (LPS) O-polysaccharide and the pullulanase (PulA) type 2 secretion system (T2SS) are required for full effectiveness of the immune evasion. Importantly, these factors do not play a redundant role. The fact that LPS O-polysaccharide and T2SS mutant-induced responses were dependent on TLR2-TLR4-MyD88 activation suggested that LPS O-polysaccharide and PulA perturbed Toll-like receptor (TLR)-dependent recognition of K. pneumoniae. Finally, we demonstrate that LPS O-polysaccharide and pulA mutants are attenuated in the pneumonia mouse model. We propose that LPS O-polysaccharide and PulA T2SS could be new targets for the design of new antimicrobials. Increasing TLR-governed defense responses might provide also selective alternatives for the management of K. pneumoniae pneumonia.

  19. Identifying dietary patterns and associated health-related lifestyle factors in the adult Danish population

    DEFF Research Database (Denmark)

    Knudsen, Vibeke Kildegaard; Matthiessen, Jeppe; Biltoft-Jensen, Anja Pia

    2014-01-01

    Background/objectives:To identify and describe dietary patterns in Danish adults and to examine which demographic and health-related lifestyle factors are associated with dietary patterns.Subjects/methods:Data derived from the Danish national survey of diet and physical activity collected in 2003......, potatoes and gravy, and cake and biscuits; a 'health-conscious' pattern correlated with coarse bread, fruit, vegetables, low-fat dairy, nuts, water and tea; and a 'fast food' pattern correlated with pizza, hamburger/spring rolls, crisps, rice and pasta, sugar-sweetened soft drinks and sweets...

  20. An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors

    DEFF Research Database (Denmark)

    Finger, Monika E; Boonen, Annelies; Woodworth, Thasia G

    2017-01-01

    selection of potentially relevant CF. RESULTS: The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine......, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3...

  1. Identifying Key Factors for Introducing GPS-Based Fleet Management Systems to the Logistics Industry

    Directory of Open Access Journals (Sweden)

    Yi-Chung Hu

    2015-01-01

    Full Text Available The rise of e-commerce and globalization has changed consumption patterns. Different industries have different logistical needs. In meeting needs with different schedules logistics play a key role. Delivering a seamless service becomes a source of competitive advantage for the logistics industry. Global positioning system-based fleet management system technology provides synergy to transport companies and achieves many management goals such as monitoring and tracking commodity distribution, energy saving, safety, and quality. A case company, which is a subsidiary of a very famous food and retail conglomerate and operates the largest shipping line in Taiwan, has suffered from the nonsmooth introduction of GPS-based fleet management systems in recent years. Therefore, this study aims to identify key factors for introducing related systems to the case company. By using DEMATEL and ANP, we can find not only key factors but also causes and effects among key factors. The results showed that support from executives was the most important criterion but it has the worst performance among key factors. It is found that adequate annual budget planning, enhancement of user intention, and collaboration with consultants with high specialty could be helpful to enhance the faith of top executives for successfully introducing the systems to the case company.

  2. ESTIMATING VITICULTURAL FAVORABILITY OF COTNARI VINEYARD AREA AND IDENTIFYING LIMITING FACTORS

    Directory of Open Access Journals (Sweden)

    Cristina Chiriac

    2012-12-01

    Full Text Available For estimating the favorability of agricultural lands for vine in Cotnari vineyard area, we used 16 indicators provided in the Methodology of Soil Survey (Second part and third part - 1986. To determine the average coefficient of evaluation, respectively the class of favorability for the vine in Cotnari Vineyard, we calculated the notes of evaluation for 10 administrative units from Cotnari Vineyard: Flămânzi, Frumuşica, Deleni, Hârlău, Scobinţi, Cepleniţa, Cotnari, Cucuteni, Todireşti, Târgu Frumos. For each administrative unit were selected the territorial units of soil (U.S. within Cotnari Vineyard, from which we extracted only the ecological homogeneous territories (TEO's that are planted with vine. Among the limiting factors identified in Cotnari Vineyard we mention the geomorphologic factor (slope, landslides, the pedological factor (gleying, stagnogleying,salinization/alkalization, texture, reaction, humus content, edaphic volume and the hydrological factor (groundwater depth, excess moisture in surface, flooding by overflow.

  3. Identifying and prioritizing different factors influencing the success of advertisement during the economic depression

    Directory of Open Access Journals (Sweden)

    Aram Rashidi

    2014-04-01

    Full Text Available During the financial crisis of 2007, many businesses and banks faced unexpected circumstances and declared bankruptcy. Market mortgage crisis and the collapse of the economic system in United States created a substantial amount of damage in world economy. Within a few years, the economic downturn was transferred to developing countries such as Iran. The recession has created conditions for Iranian companies that have led them to focus more on the subject of advertising since this is the primary tool of communication and business customers business. Success and failure of many organizations and companies depend on their advertisement planning. In this study, the factors contributing to the success and effectiveness of advertising during the recession time are identified. This survey has been accomplished on investigating an Iranian dairy firm named “Kalle”. Using a questionnaire in Likert scale, the study determines the effects of various factors of advertisement on sales improvement in this firm using Pearson correlation ratio and rank them based on Freedman test. Cronbach alpha has been calculated as 0.93. According to the results, factors that contribute to the success of advertising during a recession include: Responsiveness to customers’ needs, advertising tools, content factors, the amount of money spent and availability.

  4. Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

    Science.gov (United States)

    Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

    2015-01-01

    Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (Pstroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

  5. Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.

    Science.gov (United States)

    Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching; Meschia, James F; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C; Kittner, Steven J; Rich, Stephen S; Tajuddin, Salman; Zonderman, Alan B; Evans, Michele K; Langefeld, Carl D; Gottesman, Rebecca; Mosley, Thomas H; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, Yongmei; Sale, Michèle M; Dichgans, Martin; Malik, Rainer; Longstreth, W T; Mitchell, Braxton D; Psaty, Bruce M; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B; Fornage, Myriam

    2015-08-01

    The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10(-8)) in African Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (Pstroke in COMPASS. We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. © 2015 American Heart Association, Inc.

  6. Factors for analysing and improving performance of R&D in Malaysian universities

    NARCIS (Netherlands)

    Ramli, Mohammad Shakir; de Boer, S.J.; de Bruijn, E.J.

    2004-01-01

    This paper presents a model for analysing and improving performance of R&D in Malaysian universities. There are various general models for R&D analysis, but none is specific for improving the performance of R&D in Malaysian universities. This research attempts to fill a gap in the body of knowledge

  7. Risk factors identified for owner-reported feline obesity at around one year of age: Dry diet and indoor lifestyle.

    Science.gov (United States)

    Rowe, Elizabeth; Browne, William; Casey, Rachel; Gruffydd-Jones, Tim; Murray, Jane

    2015-10-01

    Obesity is considered the second most common health problem in pet cats in developed countries. Previous studies investigating risk factors for feline obesity have been cross-sectional, where reverse causality cannot be ruled out. This study is the first to use prospective data from a large scale longitudinal study of pet cats ('Bristol Cats') to identify early-life risk factors for feline overweight/obesity at around one year of age. Data analysed were collected via three owner-completed questionnaires (for cats aged 2-4 months, 6.5-7 months and 12.5-13 months) completed between May 2010 and August 2013. Owner-reported body condition scores (BCS) of cats at age 12.5-13 months, using the 5-point system, were categorised into a dichotomous variable: overweight/obese (BCS 4-5) and not overweight (BCS 1-3) and used as the dependent variable. Cat breed, neuter status, outdoor access, type of diet, frequency of wet and dry food fed and frequency of treats fed were analysed as potential risk factors. Of the 966 cats for which data were available, 7.0% were reported by their owners to be overweight/obese at 12.5-13 months of age. Descriptive data on type of diet fed at different cat ages suggest that a dry diet is the most popular choice for UK domestic cats. Significant potential explanatory variables from univariable logistic regression models were included in multivariable logistic regression models built using stepwise forward-selection. To account for potential hierarchical clustering of data due to multi-cat households these were extended to two-level random intercept models. Models were compared using Wald test p- values. Clustering had no impact on the analysis. The final multivariable logistic regression model identified two risk factors that were independently associated with an increased risk of feline obesity developing at 12.5-13 months of age: restricted or no outdoor access and feeding dry food as the only or major (>50%) type of food in the diet at age 12

  8. Quantitative Analyses in a Multivariate Study of Language Attrition: The Impact of Extralinguistic Factors

    Science.gov (United States)

    Schmid, Monika S.; Dusseldorp, Elise

    2010-01-01

    Most linguistic processes--acquisition, change, deterioration--take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful consideration of its interplay with all other factors. The…

  9. Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization*

    Science.gov (United States)

    Stephens, Alexandre S.; Stephens, Sebastien R.; Hobbs, Carl; Hutmacher, Deitmar W.; Bacic-Welsh, Desa; Woodruff, Maria Ann; Morrison, Nigel A.

    2011-01-01

    Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem cell-mediated therapies for fracture and other orthopedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of stimulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase activity and extracellular matrix mineralization. Furthermore, similar DMSO-mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1, we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among the numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical, and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased alkaline phosphatase activity, and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. A flow on knockdown of bone-specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c, suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts. PMID:21652706

  10. Myocyte enhancer factor 2c, an osteoblast transcription factor identified by dimethyl sulfoxide (DMSO)-enhanced mineralization.

    Science.gov (United States)

    Stephens, Alexandre S; Stephens, Sebastien R; Hobbs, Carl; Hutmacher, Deitmar W; Bacic-Welsh, Desa; Woodruff, Maria Ann; Morrison, Nigel A

    2011-08-26

    Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem cell-mediated therapies for fracture and other orthopedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of stimulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase activity and extracellular matrix mineralization. Furthermore, similar DMSO-mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1, we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among the numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical, and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased alkaline phosphatase activity, and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. A flow on knockdown of bone-specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c, suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.

  11. Biomechanical approaches to identify and quantify injury mechanisms and risk factors in women's artistic gymnastics.

    Science.gov (United States)

    Bradshaw, Elizabeth J; Hume, Patria A

    2012-09-01

    Targeted injury prevention strategies, based on biomechanical analyses, have the potential to help reduce the incidence and severity of gymnastics injuries. This review outlines the potential benefits of biomechanics research to contribute to injury prevention strategies for women's artistic gymnastics by identification of mechanisms of injury and quantification of the effects of injury risk factors. One hundred and twenty-three articles were retained for review after searching electronic databases using key words, including 'gymnastic', 'biomech*', and 'inj*', and delimiting by language and relevance to the paper aim. Impact load can be measured biomechanically by the use of instrumented equipment (e.g. beatboard), instrumentation on the gymnast (accelerometers), or by landings on force plates. We need further information on injury mechanisms and risk factors in gymnastics and practical methods of monitoring training loads. We have not yet shown, beyond a theoretical approach, how biomechanical analysis of gymnastics can help reduce injury risk through injury prevention interventions. Given the high magnitude of impact load, both acute and accumulative, coaches should monitor impact loads per training session, taking into consideration training quality and quantity such as the control of rotation and the height from which the landings are executed.

  12. Identifying Stress Transcription Factors Using Gene Expression and TF-Gene Association Data.

    Science.gov (United States)

    Wu, Wei-Sheng; Chen, Bor-Sen

    2009-11-24

    Unicellular organisms such as yeasts have evolved to survive environmental stresses by rapidly reorganizing the genomic expression program to meet the challenges of harsh environments. The complex adaptation mechanisms to stress remain to be elucidated. In this study, we developed Stress Transcription Factor Identification Algorithm (STFIA), which integrates gene expression and TF-gene association data to identify the stress transcription factors (TFs) of six kinds of stresses. We identified some general stress TFs that are in response to various stresses, and some specific stress TFs that are in response to one specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs may be sufficient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the adaptation mechanisms to different stresses may have a bow-tie structure. Second, there may exist extensive regulatory cross-talk among different stress responses. In conclusion, this study proposes a network of the regulators of stress responses and their mechanism of action.

  13. Using local lexicalized rules to identify heart disease risk factors in clinical notes.

    Science.gov (United States)

    Karystianis, George; Dehghan, Azad; Kovacevic, Aleksandar; Keane, John A; Nenadic, Goran

    2015-12-01

    Heart disease is the leading cause of death globally and a significant part of the human population lives with it. A number of risk factors have been recognized as contributing to the disease, including obesity, coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, smoking, and family history of premature CAD. This paper describes and evaluates a methodology to extract mentions of such risk factors from diabetic clinical notes, which was a task of the i2b2/UTHealth 2014 Challenge in Natural Language Processing for Clinical Data. The methodology is knowledge-driven and the system implements local lexicalized rules (based on syntactical patterns observed in notes) combined with manually constructed dictionaries that characterize the domain. A part of the task was also to detect the time interval in which the risk factors were present in a patient. The system was applied to an evaluation set of 514 unseen notes and achieved a micro-average F-score of 88% (with 86% precision and 90% recall). While the identification of CAD family history, medication and some of the related disease factors (e.g. hypertension, diabetes, hyperlipidemia) showed quite good results, the identification of CAD-specific indicators proved to be more challenging (F-score of 74%). Overall, the results are encouraging and suggested that automated text mining methods can be used to process clinical notes to identify risk factors and monitor progression of heart disease on a large-scale, providing necessary data for clinical and epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Random T-DNA mutagenesis identifies a Cu-Zn-superoxide dismutase gene as a virulence factor of Sclerotinia sclerotiorum

    Science.gov (United States)

    Agrobacterium-mediated transformation (AMT) was used to identify potential virulence factors in Sclerotinia sclerotiorum. Screening AMT transformants identified two mutants showing significantly reduced virulence. The mutants showed similar growth rate, colony morphology, and sclerotial and oxalate ...

  15. Genome-wide identification, classification and functional analyses of the bHLH transcription factor family in the pig, Sus scrofa.

    Science.gov (United States)

    Liu, Wuyi

    2015-08-01

    The basic helix-loop-helix (bHLH) transcription factors are one of the largest families of gene regulatory proteins and play crucial roles in genetic, developmental and physiological processes in eukaryotes. Here, we conducted a survey of the Sus scrofa genome and identified 109 putative bHLH transcription factor members belonging to super-groups A, B, C, D, E, and F, respectively, while four members were orphan genes. We identified 6 most significantly enriched KEGG pathways and 116 most significant GO annotation categories. Further comprehensive surveys in human genome and other 12 medical databases identified 72 significantly enriched biological pathways with these 113 pig bHLH transcription factors. From the functional protein association network analysis 93 hub proteins were identified and 55 hub proteins created a tight network or a functional module within their protein families. Especially, there were 20 hub proteins found highly connected in the functional interaction network. The present study deepens our understanding and provided insights into the evolution and functional aspects of animal bHLH proteins and should serve as a solid foundation for further for analyses of specific bHLH transcription factors in the pig and other mammals.

  16. Performing statistical analyses on quantitative data in Taverna workflows: an example using R and maxdBrowse to identify differentially-expressed genes from microarray data.

    Science.gov (United States)

    Li, Peter; Castrillo, Juan I; Velarde, Giles; Wassink, Ingo; Soiland-Reyes, Stian; Owen, Stuart; Withers, David; Oinn, Tom; Pocock, Matthew R; Goble, Carole A; Oliver, Stephen G; Kell, Douglas B

    2008-08-07

    There has been a dramatic increase in the amount of quantitative data derived from the measurement of changes at different levels of biological complexity during the post-genomic era. However, there are a number of issues associated with the use of computational tools employed for the analysis of such data. For example, computational tools such as R and MATLAB require prior knowledge of their programming languages in order to implement statistical analyses on data. Combining two or more tools in an analysis may also be problematic since data may have to be manually copied and pasted between separate user interfaces for each tool. Furthermore, this transfer of data may require a reconciliation step in order for there to be interoperability between computational tools. Developments in the Taverna workflow system have enabled pipelines to be constructed and enacted for generic and ad hoc analyses of quantitative data. Here, we present an example of such a workflow involving the statistical identification of differentially-expressed genes from microarray data followed by the annotation of their relationships to cellular processes. This workflow makes use of customised maxdBrowse web services, a system that allows Taverna to query and retrieve gene expression data from the maxdLoad2 microarray database. These data are then analysed by R to identify differentially-expressed genes using the Taverna RShell processor which has been developed for invoking this tool when it has been deployed as a service using the RServe library. In addition, the workflow uses Beanshell scripts to reconcile mismatches of data between services as well as to implement a form of user interaction for selecting subsets of microarray data for analysis as part of the workflow execution. A new plugin system in the Taverna software architecture is demonstrated by the use of renderers for displaying PDF files and CSV formatted data within the Taverna workbench. Taverna can be used by data analysis

  17. Performing statistical analyses on quantitative data in Taverna workflows: An example using R and maxdBrowse to identify differentially-expressed genes from microarray data

    Directory of Open Access Journals (Sweden)

    Pocock Matthew R

    2008-08-01

    Full Text Available Abstract Background There has been a dramatic increase in the amount of quantitative data derived from the measurement of changes at different levels of biological complexity during the post-genomic era. However, there are a number of issues associated with the use of computational tools employed for the analysis of such data. For example, computational tools such as R and MATLAB require prior knowledge of their programming languages in order to implement statistical analyses on data. Combining two or more tools in an analysis may also be problematic since data may have to be manually copied and pasted between separate user interfaces for each tool. Furthermore, this transfer of data may require a reconciliation step in order for there to be interoperability between computational tools. Results Developments in the Taverna workflow system have enabled pipelines to be constructed and enacted for generic and ad hoc analyses of quantitative data. Here, we present an example of such a workflow involving the statistical identification of differentially-expressed genes from microarray data followed by the annotation of their relationships to cellular processes. This workflow makes use of customised maxdBrowse web services, a system that allows Taverna to query and retrieve gene expression data from the maxdLoad2 microarray database. These data are then analysed by R to identify differentially-expressed genes using the Taverna RShell processor which has been developed for invoking this tool when it has been deployed as a service using the RServe library. In addition, the workflow uses Beanshell scripts to reconcile mismatches of data between services as well as to implement a form of user interaction for selecting subsets of microarray data for analysis as part of the workflow execution. A new plugin system in the Taverna software architecture is demonstrated by the use of renderers for displaying PDF files and CSV formatted data within the Taverna

  18. Bioaccumulation syndrome: identifying factors that make some stream food webs prone to elevated mercury bioaccumulation.

    Science.gov (United States)

    Ward, Darren M; Nislow, Keith H; Folt, Carol L

    2010-05-01

    Mercury is a ubiquitous contaminant in aquatic ecosystems, posing a significant health risk to humans and wildlife that eat fish. Mercury accumulates in aquatic food webs as methylmercury (MeHg), a particularly toxic and persistent organic mercury compound. While mercury in the environment originates largely from anthropogenic activities, MeHg accumulation in freshwater aquatic food webs is not a simple function of local or regional mercury pollution inputs. Studies show that even sites with similar mercury inputs can produce fish with mercury concentrations ranging over an order of magnitude. While much of the foundational work to identify the drivers of variation in mercury accumulation has focused on freshwater lakes, mercury contamination in stream ecosystems is emerging as an important research area. Here, we review recent research on mercury accumulation in stream-dwelling organisms. Taking a hierarchical approach, we identify a suite of characteristics of individual consumers, food webs, streams, watersheds, and regions that are consistently associated with elevated MeHg concentrations in stream fish. We delineate a conceptual, mechanistic basis for explaining the ecological processes that underlie this vulnerability to MeHg. Key factors, including suppressed individual growth of consumers, low rates of primary and secondary production, hydrologic connection to methylation sites (e.g., wetlands), heavily forested catchments, and acidification are frequently associated with increased MeHg concentrations in fish across both streams and lakes. Hence, we propose that these interacting factors define a syndrome of characteristics that drive high MeHg production and bioaccumulation rates across these freshwater aquatic ecosystems. Finally, based on an understanding of the ecological drivers of MeHg accumulation, we identify situations when anthropogenic effects and management practices could significantly exacerbate or ameliorate MeHg accumulation in stream fish.

  19. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  20. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  1. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors

    Directory of Open Access Journals (Sweden)

    Aleem Aamer

    2010-01-01

    Full Text Available Renal involvement in patients with sickle cell disease (SCD is associated with signi-ficant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with pro-teinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients′ charts. A urine protein level of more than 0.150 grams/24 hours was consi-dered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2 years. Twenty-seven patients (40.3% had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8 g/dL and mean fetal hemoglobin (HbF level of 14.4% (± 7.3%. Majority of the patients (61 had hemoglobin SS genotype and six patients had S-β0 thala-ssemia. None of the parameters evaluated correlated with proteinuria although there was a border-line association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respec-tively. Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

  2. Who will volunteer? Analysing individual and structural factors of volunteering in Swiss sports clubs.

    Science.gov (United States)

    Schlesinger, Torsten; Nagel, Siegfried

    2013-01-01

    This article analyses the conditions influencing volunteering in sports clubs. It focuses not only on individual characteristics of volunteers but also on the corresponding structural conditions of sports clubs. It proposes a model of voluntary work in sports clubs based on economic behaviour theory. The influences of both the individual and context levels on the decision to engage in voluntary work are estimated in different multilevel models. Results of these multilevel analyses indicate that volunteering is not just an outcome of individual characteristics such as lower workloads, higher income, children belonging to the sports club, longer club memberships, or a strong commitment to the club. It is also influenced by club-specific structural conditions; volunteering is more probable in rural sports clubs whereas growth-oriented goals in clubs have a destabilising effect.

  3. Identifying critical success factors (CSFs) of implementing building information modeling (BIM) in Malaysian construction industry

    Science.gov (United States)

    Yaakob, Mazri; Ali, Wan Nur Athirah Wan; Radzuan, Kamaruddin

    2016-08-01

    Building Information Modeling (BIM) is defined as existing from the earliest concept to demolition and it involves creating and using an intelligent 3D model to inform and communicate project decisions. This research aims to identify the critical success factors (CSFs) of BIM implementation in Malaysian construction industry. A literature review was done to explore previous BIM studies on definitions and history of BIM, construction issues, application of BIM in construction projects as well as benefits of BIM. A series of interviews with multidisciplinary Malaysian construction experts will be conducted purposely for data collection process guided by the research design and methodology approach of this study. The analysis of qualitative data from the process will be combined with criteria identified in the literature review in order to identify the CSFs. Finally, the CSFs of BIM implementation will be validated by further Malaysian industrialists during a workshop. The validated CSFs can be used as a term of reference for both Malaysian practitioners and academics towards measuring BIM effectiveness level in their organizations.

  4. A systems biological approach to identify key transcription factors and their genomic neighborhoods in human sarcomas

    Institute of Scientific and Technical Information of China (English)

    Antti Ylip(a)(a); Olli Yli-Harja; Wei Zhang; Matti Nykter

    2011-01-01

    Identification of genetic signatures is the main objective for many computational oncology studies. The signature usually consists of numerous genes that are differentially expressed between two clinically distinct groups of samples, such as tumor subtypes. Prospectively, many signatures have been found to generalize poorly to other datasets and, thus, have rarely been accepted into clinical use. Recognizing the limited success of traditionally generated signatures, we developed a systems biology-based framework for robust identification of key transcription factors and their genomic regulatory neighborhoods. Application of the framework to study the differences between gastrointestinal stromal tumor (GIST) and leiomyosarcoma (LMS) resulted in the identification of nine transcription factors (SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and MYC). Functional annotations of the obtained neighborhoods identified the biological processes which the key transcription factors regulate differently between the tumor types. Analyzing the differences in the expression patterns using our approach resulted in a more robust genetic signature and more biological insight into the diseases compared to a traditional genetic signature.

  5. Genome-wide screen of Pseudomonas aeruginosa In Saccharomyces cerevisiae identifies new virulence factors

    Directory of Open Access Journals (Sweden)

    Rafat eZrieq

    2015-11-01

    Full Text Available Pseudomonas aeruginosa is a human opportunistic pathogen that causes mortality in cystic fibrosis and immunocompromised patients. While many virulence factors of this pathogen have already been identified, several remain to be discovered. In this respect we set an unprecedented genome-wide screen of a P. aeruginosa expression library based on a yeast growth phenotype. 51 candidates were selected in a three-round screening process. The robustness of the screen was validated by the selection of three well known secreted proteins including one demonstrated virulence factor, the protease LepA. Further in silico sorting of the 51 candidates highlighted three potential new Pseudomonas effector candidates (Pec. By testing the cytotoxicity of wild type P. aeruginosa vs pec mutants towards macrophages and the virulence in the Caenorhabditis elegans model, we demonstrated that the three selected Pecs are novel virulence factors of P. aeruginosa. Additional cellular localization experiments in the host revealed specific localization for Pec1 and Pec2 that could inform about their respective functions.

  6. Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

    Science.gov (United States)

    Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

    2010-03-01

    The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

  7. Identifying principal risk factors for the initiation of adolescent smoking behaviors: the significance of psychological reactance.

    Science.gov (United States)

    Miller, Claude H; Burgoon, Michael; Grandpre, Joseph R; Alvaro, Eusebio M

    2006-01-01

    An in-school youth survey for a major state anti-tobacco media campaign was conducted with 1,831 students (Grades 6-12) from 70 randomly selected classrooms throughout the state. Tobacco users accounted for nearly 25% of the sample. Pretest questionnaires assessed demographic variables, tobacco use, and various other risk factors. Several predictors of adolescents' susceptibility to tobacco use, including prior experimentation with tobacco, school performance, parental smoking status, parents' level of education, parental communication, parental relationship satisfaction, best friend's smoking status, prevalence of smokers in social environment, self-perceived potential to smoke related to peer pressure, and psychological reactance, were examined using discriminant analysis and logistic regression to identify the factors most useful in classifying adolescents as either high-risk or low-risk for smoking uptake. Results corroborate findings in the prevention literature indicating that age, prior experimentation, and having friends who smoke are among the principal predictors of smoking risk. New evidence is presented indicating that psychological reactance also should be considered as an important predictor of adolescent smoking initiation. The utility of producing antismoking messages informed by an awareness of the key risk factors-particularly psychological reactance-is discussed both in terms of the targeting and design of anti-tobacco campaigns.

  8. Identifying Major Factors Affecting Groundwater Change in the North China Plain with Grey Relational Analysis

    Directory of Open Access Journals (Sweden)

    Xue Li

    2014-06-01

    Full Text Available The North China Plain (NCP is facing a water crisis under the dual impact of natural and anthropogenic factors. Groundwater levels have declined continuously since 1960, causing a series of environmental problems that have restricted sustainable development in the region. In the present study, we first utilized a previously developed 3D groundwater model to determine changes in groundwater level in the region over the past 50 years (1961–2010. We then applied grey relational analysis (GRA to identify and ordinate major factors that have contributed to these changes. The results show an overall decreasing trend in groundwater levels in this region over the past 50 years and an increase in the water table depth at a rate of approximately 0.36 m/a. Groundwater exploitation showed the most significant correlation with the groundwater table decline, when compared with other factors including precipitation and river leakage. Therefore, human activities should be considered the primary force driving the groundwater level down. The results of this study have implications for developing criteria that consider changes in both climate and socio-economics. Furthermore, since the NCP is one of the most water-scarce and densely populated regions in the world, the analytical approach used in and the insights gained from this study are of international interest.

  9. Choosing Surgery: Identifying Factors Leading to Increased General Surgery Matriculation Rate.

    Science.gov (United States)

    Pointer, David T; Freeman, Matthew D; Korndorffer, James R; Meade, Peter C; Jaffe, Bernard M; Slakey, Douglas P

    2017-03-01

    Tulane graduates have, over the past six years, chosen general surgical residency at a rate above the national average (mean 9.6% vs 6.6%). With much of the recent career choice research focusing on disincentives and declining general surgery applicants, we sought to identify factors that positively influenced our students' decision to pursue general surgery. A 50-question survey was developed and distributed to graduates who matched into a general surgery between the years 2006 and 2014. The survey evaluated demographics, exposure to surgery, and factors affecting interest in a surgical career. We achieved a 54 per cent (61/112) response rate. Only 43 per cent considered a surgical career before medical school matriculation. Fifty-nine per cent had strongly considered a career other than surgery. Sixty-two per cent chose to pursue surgery during or immediately after their surgery clerkship. The most important factors cited for choosing general surgery were perceived career enjoyment of residents and faculty, resident/faculty relationship, and mentorship. Surgery residents and faculty were viewed as role models by 72 and 77 per cent of responders, respectively. This study demonstrated almost half of those choosing a surgical career did so as a direct result of the core rotation experience. We believe that structuring the medical student education experience to optimize the interaction of students, residents, and faculty produces a positive environment encouraging students to choose a general surgery career.

  10. GTRD: a database of transcription factor binding sites identified by ChIP-seq experiments

    Science.gov (United States)

    Yevshin, Ivan; Sharipov, Ruslan; Valeev, Tagir; Kel, Alexander; Kolpakov, Fedor

    2017-01-01

    GTRD—Gene Transcription Regulation Database (http://gtrd.biouml.org)—is a database of transcription factor binding sites (TFBSs) identified by ChIP-seq experiments for human and mouse. Raw ChIP-seq data were obtained from ENCODE and SRA and uniformly processed: (i) reads were aligned using Bowtie2; (ii) ChIP-seq peaks were called using peak callers MACS, SISSRs, GEM and PICS; (iii) peaks for the same factor and peak callers, but different experiment conditions (cell line, treatment, etc.), were merged into clusters; (iv) such clusters for different peak callers were merged into metaclusters that were considered as non-redundant sets of TFBSs. In addition to information on location in genome, the sets contain structured information about cell lines and experimental conditions extracted from descriptions of corresponding ChIP-seq experiments. A web interface to access GTRD was developed using the BioUML platform. It provides: (i) browsing and displaying information; (ii) advanced search possibilities, e.g. search of TFBSs near the specified gene or search of all genes potentially regulated by a specified transcription factor; (iii) integrated genome browser that provides visualization of the GTRD data: read alignments, peaks, clusters, metaclusters and information about gene structures from the Ensembl database and binding sites predicted using position weight matrices from the HOCOMOCO database. PMID:27924024

  11. Use of in vivo-induced antigen technology (IVIAT) to identify virulence factors of Porphyromonas gingivalis.

    Science.gov (United States)

    Wallet, Shannon M; Chung, Jin; Handfield, Martin

    2010-01-01

    Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with the initiation and progression of adult periodontal disease. The pathogenicity of P. gingivalis is multifaceted and the infection process is influenced by both microbial and host factors. It is generally accepted that genes of a pathogen that are specifically expressed during infection are likely to be important for pathogenicity. Numerous technologies have been developed to identify these genes. A novel strategy known as in vivo-induced antigen technology (IVIAT) avoids the use of animal models and utilizes serum from patients who have experienced disease caused by the pathogen of interest. While a number of putative virulence factors have been described for P. gingivalis, the identity, relevance, and mechanisms of action of virulence factors that actually provide a selective advantage to the organism in the oral cavity of diseased patients is still unclear. Here we describe the IVIAT protocol for identification of in vivo-induced genes of P. gingivalis, which can be adapted with few modifications to any microbial pathogen.

  12. Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry

    Directory of Open Access Journals (Sweden)

    Gisa Gerold

    2015-08-01

    Full Text Available Hepatitis C virus (HCV enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1, which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

  13. HPLC-MS and GC-MS analyses combined with orthogonal partial least squares to identify cytotoxic constituents from turmeric (Curcuma longa L.).

    Science.gov (United States)

    Jiang, Jianlan; Zhang, Huan; Li, Zidan; Zhang, Xiaohang; Su, Xin; Li, Yan; Qiao, Bin; Yuan, Yingjin

    2013-08-01

    We investigated the fingerprints of 48 batches of turmeric total extracts (TTE) by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively. An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we utilized orthogonal partial least squares analysis, which correlated the chemical composition of the TTE to its cytotoxic activity, to identify potential cytotoxic constituents from turmeric. The result showed that 19 constituents contributed significantly to the cytotoxicity. The obtained result was verified by canonical correlation analysis. Comparison with previous reports also indicated some interaction between the curcuminoids and sesquiterpenoids in turmeric.

  14. Alkaline-stress response in Glycine soja leaf identifies specific transcription factors and ABA-mediated signaling factors.

    Science.gov (United States)

    Ge, Ying; Li, Yong; Lv, De-Kang; Bai, Xi; Ji, Wei; Cai, Hua; Wang, Ao-Xue; Zhu, Yan-Ming

    2011-06-01

    Transcriptome of Glycine soja leaf tissue during a detailed time course formed a foundation for examining transcriptional processes during NaHCO(3) stress treatment. Of a total of 2,310 detected differentially expressed genes, 1,664 genes were upregulated and 1,704 genes were downregulated at various time points. The number of stress-regulated genes increased dramatically after a 6-h stress treatment. GO category gene enrichment analysis revealed that most of the differentially expressed genes were involved in cell structure, protein synthesis, energy, and secondary metabolism. Another enrichment test revealed that the response of G. soja to NaHCO(3) highlights specific transcription factors, such as the C2C2-CO-like, MYB-related, WRKY, GARP-G2-like, and ZIM families. Co-expressed genes were clustered into ten classes (P < 0.001). Intriguingly, one cluster of 188 genes displayed a unique expression pattern that increases at an early stage (0.5 and 3 h), followed by a decrease from 6 to 12 h. This group was enriched in regulation of transcription components, including AP2-EREBP, bHLH, MYB/MYB-related, C2C2-CO-like, C2C2-DOF, C2C2, C3H, and GARP-G2-like transcription factors. Analysis of the 1-kb upstream regions of transcripts displaying similar changes in abundance identified 19 conserved motifs, potential binding sites for transcription factors. The appearance of ABA-responsive elements in the upstream of co-expression genes reveals that ABA-mediated signaling participates in the signal transduction in alkaline response.

  15. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  16. A quantitative method to analyse an open-ended questionnaire: A case study about the Boltzmann Factor

    Science.gov (United States)

    Rosario Battaglia, Onofrio; Di Paola, Benedetto

    2016-05-01

    This paper describes a quantitative method to analyse an open-ended questionnaire. Student responses to a specially designed written questionnaire are quantitatively analysed by not hierarchical clustering called k -means method. Through this we can characterise behaviour students with respect their expertise to formulate explanations for phenomena or processes and/or use a given model in the different context. The physics topic is about the Boltzmann Factor, which allows the students to have a unifying view of different phenomena in different contexts.

  17. Personality Assessment Through Internet: Factor Analyses By Age Group Of The Zka Personality Questionnaire

    Directory of Open Access Journals (Sweden)

    Angel Blanch

    2013-12-01

    Full Text Available This study evaluated the psychometric properties of an on-line version of the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ by sex and age. The questionnaire was responded by 1598 people, 474 males and 1124 females, with a mean age of 32.57 (SD = 11.72. Males and females differed in their responses to all personality dimensions evaluated by this instrument, in a similar way as that reported in past research. In addition, younger people scored higher in the Aggressiveness factor, especially concerning the Physical Aggression facet, whereas older people scored higher in the Activity factor. Besides, younger people scored higher in the Neuroticism and the Sensation Seeking factors, even though there were no age differences in the Extraversion factor. The ZKA-PQ five-factor structure was clear and yielded high congruence coefficients with the original Spanish validation sample. Altogether, the findings support the validity of the online version of this instrument. The ZKAPQ online version is therefore helpful in both, basic and applied research settings about human personality and individual differences.

  18. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Directory of Open Access Journals (Sweden)

    Xiao-Jin Hou

    Full Text Available MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB. Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  19. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Science.gov (United States)

    Hou, Xiao-Jin; Li, Si-Bei; Liu, Sheng-Rui; Hu, Chun-Gen; Zhang, Jin-Zhi

    2014-01-01

    MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB) family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB). Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  20. Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

    Directory of Open Access Journals (Sweden)

    Toomas Silla

    Full Text Available Ultra-conserved genes or elements (UCGs/UCEs in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280 and Italian (n = 501 by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF5% are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

  1. An Efficient Method to Identify Conditionally Activated Transcription Factors and their Corresponding Signal Transduction Pathway Segments

    Directory of Open Access Journals (Sweden)

    Haiyan Hu

    2009-11-01

    Full Text Available A signal transduction pathway (STP is a cascade composed of a series of signal transferring steps, which often activate one or more transcription factors (TFs to control the transcription of target genes. Understanding signaling pathways is important to our understanding of the molecular mechanisms of disease. Many condition-annotated pathways have been deposited in public databases. However, condition-annotated pathways are far from complete, considering the large number of possible conditions. Computational methods to assist in the identification of conditionally activated pathways are greatly needed. In this paper, we propose an efficient method to identify conditionally activated pathway segments starting from the identification of conditionally activated TFs, by incorporating protein-DNA binding data, gene expression data and protein interaction data. Applying our methods on several microarray datasets, we have discovered many significantly activated TFs and their corresponding pathway segments, which are supported by evidence in the literature.

  2. Identifying the challenging factors in the transition from colleges of engineering to employment

    Science.gov (United States)

    Baytiyeh, Hoda; Naja, Mohamad

    2012-03-01

    The transition from university to a career in engineering is a challenging process. This study examined the perceptions of engineering graduates regarding the difficulties they encountered in their transition from the university to the workplace. Lebanese practising engineers (n=217), living around the world, were surveyed to identify their current employment situations and their attitudes toward their academic preparation. Factor analysis revealed three main challenges facing engineering graduates: communication; responsibility; self-confidence. Seventeen interviews were conducted to gather information on ways to facilitate this transition. Comments reflected the need for better collaboration between engineering schools and engineering firms. The results will provide insight for engineering colleges, faculty members and administrators into the challenges faced by graduates and their aspirations for a smoother transition into employment.

  3. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors...

  4. Identifying training deficiencies in military pilots by applying the human factors analysis and classification system.

    Science.gov (United States)

    Li, Wen-Chin; Harris, Don

    2013-01-01

    Without accurate analysis, it is difficult to identify training needs and develop the content of training programs required for preventing aviation accidents. The human factors analysis and classification system (HFACS) is based on Reason's system-wide model of human error. In this study, 523 accidents from the Republic of China Air Force were analyzed in which 1762 human errors were categorized. The results of the analysis showed that errors of judgment and poor decision-making were commonly reported amongst pilots. As a result, it was concluded that there was a need for military pilots to be trained specifically in making decisions in tactical environments. However, application of HFACS also allowed the identification of systemic training deficiencies within the organization further contributing to the accidents observed.

  5. Screening for violence risk factors identifies young adults at risk for return emergency department visit for injury.

    Science.gov (United States)

    Hankin, Abigail; Wei, Stanley; Foreman, Juron; Houry, Debra

    2014-08-01

    Homicide is the second leading cause of death among youth aged 15-24. Prior cross-sectional studies, in non-healthcare settings, have reported exposure to community violence, peer behavior, and delinquency as risk factors for violent injury. However, longitudinal cohort studies have not been performed to evaluate the temporal or predictive relationship between these risk factors and emergency department (ED) visits for injuries among at-risk youth. The objective was to assess whether self-reported exposure to violence risk factors in young adults can be used to predict future ED visits for injuries over a 1-year period. This prospective cohort study was performed in the ED of a Southeastern US Level I trauma center. Eligible participants were patients aged 18-24, presenting for any chief complaint. We excluded patients if they were critically ill, incarcerated, or could not read English. Initial recruitment occurred over a 6-month period, by a research assistant in the ED for 3-5 days per week, with shifts scheduled such that they included weekends and weekdays, over the hours from 8AM-8PM. At the time of initial contact in the ED, patients were asked to complete a written questionnaire, consisting of previously validated instruments measuring the following risk factors: a) aggression, b) perceived likelihood of violence, c) recent violent behavior, d) peer behavior, e) community exposure to violence, and f) positive future outlook. At 12 months following the initial ED visit, the participants' medical records were reviewed to identify any subsequent ED visits for injury-related complaints. We analyzed data with chi-square and logistic regression analyses. Three hundred thirty-two patients were approached, of whom 300 patients consented. Participants' average age was 21.1 years, with 60.1% female, 86.0% African American. After controlling for participant gender, ethnicity, or injury complaint at time of first visit, return visits for injuries were significantly

  6. Screening for Violence Risk Factors Identifies Young Adults at Risk for Return Emergency Department Visit for Injury

    Directory of Open Access Journals (Sweden)

    Abigail Hankin

    2014-08-01

    Full Text Available Introduction: Homicide is the second leading cause of death among youth aged 15–24. Prior crosssectional studies, in non-healthcare settings, have reported exposure to community violence, peer behavior, and delinquency as risk factors for violent injury. However, longitudinal cohort studies have not been performed to evaluate the temporal or predictive relationship between these risk factors and emergency department (ED visits for injuries among at-risk youth. The objective was to assess whether self-reported exposure to violence risk factors in young adults can be used to predict future ED visits for injuries over a 1-year period. Methods: This prospective cohort study was performed in the ED of a Southeastern US Level I trauma center. Eligible participants were patients aged 18–24, presenting for any chief complaint. We excluded patients if they were critically ill, incarcerated, or could not read English. Initial recruitment occurred over a 6-month period, by a research assistant in the ED for 3–5 days per week, with shifts scheduled such that they included weekends and weekdays, over the hours from 8AM-8PM. At the time of initial contact in the ED, patients were asked to complete a written questionnaire, consisting of previously validated instruments measuring the following risk factors: a aggression, b perceived likelihood of violence, c recent violent behavior, d peer behavior, e community exposure to violence, and f positive future outlook. At 12 months following the initial ED visit, the participants’ medical records were reviewed to identify any subsequent ED visits for injury-related complaints. We analyzed data with chisquare and logistic regression analyses. Results: Three hundred thirty-two patients were approached, of whom 300 patients consented. Participants’ average age was 21.1 years, with 60.1% female, 86.0% African American. After controlling for participant gender, ethnicity, or injury complaint at time of first

  7. Unplanned Hospital Return for Infection following Ureteroscopy-Can We Identify Modifiable Risk Factors?

    Science.gov (United States)

    Moses, Rachel A; Ghali, Fady M; Pais, Vernon M; Hyams, Elias S

    2016-04-01

    Genitourinary infection after ureteroscopy with laser lithotripsy is a clinically significant event that may lead to expensive and morbid return to the hospital. We evaluate factors associated with infection after ureteroscopy with laser lithotripsy leading to unplanned hospital return. We performed a retrospective chart review evaluating all ureteroscopy with laser lithotripsy performed at a single academic institution from April 2011 to August 2014. Data were extracted including patient demographics, comorbidities, surgical encounter characteristics, preoperative urine culture status, antibiotic type/duration and compliance with the AUA Best Practice Statement for antibiotic prophylaxis. Bivariate and multivariate analyses were performed to determine factors associated with unplanned return to the hospital. Among 550 patients undergoing ureteroscopy with laser lithotripsy 45% (248) were female with an average age of 56.8 (± 14.8) years. Overall 3.4% (19 patients) had an unplanned return for genitourinary infection, with most (78.9%, 15 of 19) requiring inpatient readmission. Overall compliance with AUA Best Practice Statement for antibiotic prophylaxis was 48.7% (268 of 550). Rates of infection related returns were higher in patients undergoing preoperative stenting (84.2% vs 58.6%, p=0.025), those with an operative time greater than 120 minutes (89.5% vs 32.6% p risk of infection, underscoring the need for locally appropriate prophylaxis strategies and further study of optimal prophylaxis regimens. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Framework of stock-recovery strategies: analyses of factors affecting success and failure

    DEFF Research Database (Denmark)

    Hammer, Cornelius; Dorrien, Christian von; Hopkins, Christopher C. E.;

    2010-01-01

    The EU FP6 UNCOVER project was aimed at producing a rational scientific basis for developing recovery strategies for some ecologically and socio-economically important fish stocks/fisheries in European seas. The immediate objectives were to identify changes experienced during stock depletion/coll...

  9. Identifying contributing factors to fatal and serious injury motorcycle collisions involving children in Malaysia.

    Science.gov (United States)

    Oxley, Jennifer; Ravi, Mano Deepa; Yuen, Jeremy; Hoareau, Effie; Hashim, Hizal Hanis

    2013-01-01

    In Malaysia, motorcycle crashes constitute approximately 60 percent of all road trauma, and a substantial proportion involve children 16 years and younger. There are, however, many gaps in our knowledge on contributing factors to crashes and injury patterns amongst children killed and seriously injured in motorcycle crashes. The aim of this study was to examine fatal and serious injury motorcycle-related collisions to identify contributing factors and injury patterns amongst child motorcyclists. All identified motorcyclist fatal crashes between 2007 and 2011 (inclusive) were extracted from the national Police-reported crash database (M-ROADS) and a range of variables were selected for examination. A total of 17,677 crashes were extracted where a rider or pillion was killed and of these crashes 2,038 involved children, equating to 12 percent. Examination of crashes involving children revealed that some crashes involved more than two children on the motorcycle, therefore, overall children constituted 9.5% of fatal and 18.4% of serious injury collisions. A high proportion of child fatal or serious injury collisions involved the child as the rider (62%), and this was most common for children aged between 10 and 16 years. The majority of collisions occurred on rural roads, in speed limit zones of 50-70km/h, and approximately one-third occurred at an intersection. Collisions involving another motorcycle or a passenger vehicle contributed to 41% and 53% of the total fatalities and severe injuries, respectively. A high proportion (43.9%) of the children (25.5% riders and 18.8% pillion) sustained head injuries with 37.7% being in the 10-16 age group. Furthermore, 52.4% of the children sustaining head injuries did not wear a helmet. The implications of these findings for countermeasures within a Safe System framework, particularly interventions aimed at reducing the rate of unlicensed riding and helmet wearing, and infrastructure countermeasures are discussed.

  10. Factors associated with onset timing, symptoms, and severity of depression identified in the postpartum period.

    Science.gov (United States)

    Fisher, Sheehan D; Wisner, Katherine L; Clark, Crystal T; Sit, Dorothy K; Luther, James F; Wisniewski, Stephen

    2016-10-01

    Unipolar and bipolar depression identified in the postpartum period have a heterogeneous etiology. The objectives of this study are to examine the risk factors that distinguish the timing of onset for unipolar and bipolar depression and the associations between depression onset by diagnosis, and general and atypical depressive symptoms. Symptoms of depression were assessed at 4- to 6-weeks postpartum by the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms in an obstetrical sample of 727 women. Data were analyzed using ANOVA, Chi-square, and linear regression. Mothers with postpartum onset of depression were more likely to be older, Caucasian, educated, married/cohabitating, have one or no previous child, and have private insurance in contrast to mothers with pre-pregnancy and prenatal onset of depression. Mothers with bipolar depression were more likely to have a pre-pregnancy onset. Three general and two atypical depressive symptoms distinguished pre-pregnancy, during pregnancy, and postpartum depression onset, and the presence of agitation distinguished between unipolar and bipolar depression. The sample was urban, which may not be generalizable to other populations. The study was cross-sectional, which excludes potential late onset of depression (after 4-6 weeks) in the first postpartum year. A collective set of factors predicted the onset of depression identified in the postpartum for mothers distinguished by episodes of unipolar versus bipolar depression, which can inform clinical interventions. Future research on the onset of major depressive episodes could inform prophylactic and early psychiatric interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Structural, functional, and genetic analyses of the actinobacterial transcription factor RbpA.

    Science.gov (United States)

    Hubin, Elizabeth A; Tabib-Salazar, Aline; Humphrey, Laurence J; Flack, Joshua E; Olinares, Paul Dominic B; Darst, Seth A; Campbell, Elizabeth A; Paget, Mark S

    2015-06-01

    Gene expression is highly regulated at the step of transcription initiation, and transcription activators play a critical role in this process. RbpA, an actinobacterial transcription activator that is essential in Mycobacterium tuberculosis (Mtb), binds selectively to group 1 and certain group 2 σ-factors. To delineate the molecular mechanism of RbpA, we show that the Mtb RbpA σ-interacting domain (SID) and basic linker are sufficient for transcription activation. We also present the crystal structure of the Mtb RbpA-SID in complex with domain 2 of the housekeeping σ-factor, σ(A). The structure explains the basis of σ-selectivity by RbpA, showing that RbpA interacts with conserved regions of σ(A) as well as the nonconserved region (NCR), which is present only in housekeeping σ-factors. Thus, the structure is the first, to our knowledge, to show a protein interacting with the NCR of a σ-factor. We confirm the basis of selectivity and the observed interactions using mutagenesis and functional studies. In addition, the structure allows for a model of the RbpA-SID in the context of a transcription initiation complex. Unexpectedly, the structural modeling suggests that RbpA contacts the promoter DNA, and we present in vivo and in vitro studies supporting this finding. Our combined data lead to a better understanding of the mechanism of RbpA function as a transcription activator.

  12. Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma

    NARCIS (Netherlands)

    Hermsen, I.G.; Haak, H.R.; Krijger, R.R. de; Kerkhofs, T.M.; Feelders, R.A.; Herder, W.W. de; Wilmink, H.; Smit, J.W.A.; Gelderblom, H.; Miranda, N.F. de; Eijk, R. van; Wezel, T. van; Morreau, H.

    2013-01-01

    BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first-line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinica

  13. Cluster and factor analyses using water quality data in the Sapkyo reservoir watershed

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chang-Soo [Chungwoon University, Hongsung(Korea); Shin, Jae-Ki [Inje University, Kimhae(Korea)

    2002-04-30

    The monthly water quality data measured at 19 stations located in the Sapkyo reservoir watershed were clustered into 2 to 7 clusters and factor analysis was conducted to characterize the water quality, using the information obtained from cluster analysis. The result of cluster analysis shows that Sapkyo reservoir and each stream (Sapkyo stream, Muhan stream and Kokkyo stream) in Sapkyo reservoir watershed have their own water quality characteristics. The result of water quality analysis indicates that the concentration of suspended solids from Sapkyo reservoir is much higher than those of other streams, and which is probably because of increment of phytoplankton biomass with rich nutrient flowing into Sapkyo reservoir from the upper stream of watershed. Furthermore, the concentrations of biochemical oxygen demand and chemical oxygen demand were 3.5 to 4.8 times and 1.7 to 2.5 times those of other streams, respectively. The overall water quality of Sapkyo reservoir watershed was considered to exceed eutrophic condition. Based on factor analysis, the water quality characteristics of Sapkyo stream and Muhan stream were closely related with farm land and residence. The water quality of Kokkyo stream was influenced by superabundant organic matter flowing from Chonan city and district wastewater treatment plant located in the upper stream of Kokkyo stream. The water quality factor influencing Sapkyo reservoir was closely related with water quality factors of other three streams. (author). 20 refs., 6 tabs., 3 figs.

  14. Meta-analyses of Big Six Interests and Big Five Personality Factors.

    Science.gov (United States)

    Larson, Lisa M.; Rottinghaus, Patrick J.; Borgen, Fred H.

    2002-01-01

    Meta-analysis of 24 samples demonstrated overlap between Holland's vocational interest domains (measured by Self Directed Search, Strong Interest Inventory, and Vocational Preference Inventory) and Big Five personality factors (measured by Revised NEO Personalty Inventory). The link is stronger for five interest-personality pairs:…

  15. Quantitative analyses in a multivariate study of language attrition : the impact of extralinguistic factors

    NARCIS (Netherlands)

    Schmid, Monika S.; Dusseldorp, Elise

    2010-01-01

    Most linguistic processes - acquisition, change, deterioration - take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful conside

  16. Quantitative analyses in a multivariate study of language attrition: The impact of extralinguistic factors

    NARCIS (Netherlands)

    Schmid, M.S.; Dusseldorp, E.

    2010-01-01

    Most linguistic processes - acquisition, change, deterioration - take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful conside

  17. Factors related to age at natural menopause: longitudinal analyses from SWAN.

    Science.gov (United States)

    Gold, Ellen B; Crawford, Sybil L; Avis, Nancy E; Crandall, Carolyn J; Matthews, Karen A; Waetjen, L Elaine; Lee, Jennifer S; Thurston, Rebecca; Vuga, Marike; Harlow, Siobán D

    2013-07-01

    Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Women's Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

  18. Comparative Factor Analyses of the Personal Attributes Questionnaire and the Bem Sex-Role Inventory.

    Science.gov (United States)

    Antill, John K.; Cunningham, John D.

    1982-01-01

    Compared the Personal Attributes Questionnaire (PAQ) and the Bem Sex Role Inventory (BSRI) as measures of androgyny. Results showed that femininty (Concern for Others) and masculinity (Dominance) accounted for most of the variance, but for PAQ, clusters of male- and female-valued items (i.e., Extroversion and Insecurity) formed subsidiary factors.…

  19. Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

    Science.gov (United States)

    Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

    2011-01-01

    Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

  20. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.

    Science.gov (United States)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E; Bolla, Manjeet K; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J; Cousminer, Diana L; Cox, Angela; Crisponi, Laura; Czene, Kamila; Davey Smith, George; de Geus, Eco J C N; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eriksson, Johan G; Fasching, Peter A; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G; Grallert, Harald; Gudbjartsson, Daniel F; Guénel, Pascal; Hall, Per; Hallberg, Emily; Hamann, Ute; Harris, Tamara B; Hartman, Catharina A; Heiss, Gerardo; Hooning, Maartje J; Hopper, John L; Hu, Frank; Hunter, David J; Ikram, M Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K; Karasik, David; Kellis, Manolis; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J; Laven, Joop S E; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A; Lindstrom, Sara; Liu, YongMei; Luan, Jian'an; Mägi, Reedik; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L; Montgomery, Grant W; Mulligan, Anna M; Nalls, Mike A; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R; Oldehinkel, Albertine J; O'Mara, Tracy A; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D P; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M; Robino, Antonietta; Rosendaal, Frits R; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F; Schmidt, Marjanka K; Scott, Robert A; Shah, Mitul; Sorice, Rossella; Southey, Melissa C; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P; Uitterlinden, André G; Edwards, Digna R Velez; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z; Boomsma, Dorret I; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A; Magnusson, Patrik K E; Martin, Nicholas G; Mook-Kanamori, Dennis O; Nohr, Ellen A; Polasek, Ozren; Porteous, David; Price, Alkes L; Ridker, Paul M; Snieder, Harold; Spector, Tim D; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A; Völzke, Henry; Wareham, Nicholas J; Wilson, James F; Spurdle, Amanda B; Thorsteindottir, Unnur; Pollard, Katherine S; Easton, Douglas F; Tung, Joyce Y; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M; Stefansson, Kari; Ong, Ken K; Perry, John R B

    2017-06-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

  1. Factor analysis is more appropriate to identify overall dietary patterns associated with diabetes when compared with treelet transform analysis

    NARCIS (Netherlands)

    Schoenaker, D.A.J.M.; Dobson, A.; Soedamah-Muthu, S.S.; Mishra, G.D.

    2013-01-01

    Treelet transform (TT) is a proposed alternative to factor analysis for deriving dietary patterns. Before applying this method to nutrition data, further analyses are required to assess its validity in nutritional epidemiology. We aimed to compare dietary patterns from factor analysis and TT and the

  2. Identifying Watershed, Landscape, and Engineering Design Factors that Influence the Biotic Condition of Restored Streams

    Directory of Open Access Journals (Sweden)

    Barbara Doll

    2016-04-01

    Full Text Available Restored stream reaches at 79 sites across North Carolina were sampled for aquatic macroinvertebrates using a rapid bioassessment protocol. Morphological design parameters and geographic factors, including watershed and landscape parameters (e.g., valley slope, substrate, were also compiled for these streams. Principal component regression analyses revealed correlations between design and landscape variables with macroinvertebrate metrics. The correlations were strengthened by adding watershed variables. Ridge regression was used to find the best-fit model for predicting dominant taxa from the “pollution sensitive” orders of Ephemeroptera (mayflies, Plecoptera (stoneflies, and Trichoptera (caddisflies, or EPT taxa, resulting in coefficient weights that were most interpretable relative to site selection and design parameters. Results indicate that larger (wider streams located in the mountains and foothills where there are steeper valleys, larger substrate, and undeveloped watersheds are expected to have higher numbers of dominant EPT taxa. In addition, EPT taxa numbers are positively correlated with accessible floodplain width and negatively correlated with width-to-depth ratio and sinuosity. This study indicates that both site selection and design should be carefully considered in order to maximize the resulting biotic condition and associated potential ecological uplift of the stream.

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

    Directory of Open Access Journals (Sweden)

    Johanna M Walz

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

  4. Identifying the Factors Leading to Success: How an Innovative Science Curriculum Cultivates Student Motivation

    Science.gov (United States)

    Scogin, Stephen C.

    2016-06-01

    PlantingScience is an award-winning program recognized for its innovation and use of computer-supported scientist mentoring. Science learners work on inquiry-based experiments in their classrooms and communicate asynchronously with practicing plant scientist-mentors about the projects. The purpose of this study was to identify specific factors contributing to the program's effectiveness in engaging students. Using multiple data sources, grounded theory (Strauss and Corbin in Basics of qualitative research. Sage, Newbury Park, 1990) was used to develop a conceptual model identifying the central phenomenon, causal conditions, intervening conditions, strategies, contexts, and student outcomes of the project. Student motivation was determined to be the central phenomenon explaining the success of the program, with student empowerment, online mentor interaction, and authenticity of the scientific experiences serving as causal conditions. Teachers contributed to student motivation by giving students more freedom, challenging students to take projects deeper, encouraging, and scaffolding. Scientists contributed to student motivation by providing explanations, asking questions, encouraging, and offering themselves as partners in the inquiry process. Several positive student outcomes of the program were uncovered and included increased positivity, greater willingness to take projects deeper, better understanding of scientific concepts, and greater commitments to collaboration. The findings of this study provide relevant information on how to develop curriculum, use technology, and train practitioners and mentors to utilize strategies and actions that improve learners' motivation to engage in authentic science in the classroom.

  5. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication.

    Science.gov (United States)

    Treffers, Emmely E; Tas, Ali; Scholte, Florine E M; Van, Myrthe N; Heemskerk, Matthias T; de Ru, Arnoud H; Snijder, Eric J; van Hemert, Martijn J; van Veelen, Peter A

    2015-07-01

    Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).

  6. Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection

    Science.gov (United States)

    de Macedo Dossin, Fernando; Choi, Seo Yeon; Kim, Nam Youl; Kim, Hi Chul; Jung, Sung Yong; Schenkman, Sergio; Almeida, Igor C.; Emans, Neil; Freitas-Junior, Lucio H.

    2011-01-01

    The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy. PMID:21625474

  7. Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection.

    Directory of Open Access Journals (Sweden)

    Auguste Genovesio

    Full Text Available The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy.

  8. Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors

    Science.gov (United States)

    Tan, Man-Wah; Rahme, Laurence G.; Sternberg, Jeffrey A.; Tompkins, Ronald G.; Ausubel, Frederick M.

    1999-01-01

    We reported recently that the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans and that many P. aeruginosa virulence factors (genes) required for maximum virulence in mouse pathogenicity are also required for maximum killing of C. elegans. Here we report that among eight P. aeruginosa PA14 TnphoA mutants isolated that exhibited reduced killing of C. elegans, at least five also exhibited reduced virulence in mice. Three of the TnphoA mutants corresponded to the known virulence-related genes lasR, gacA, and lemA. Three of the mutants corresponded to known genes (aefA from Escherichia coli, pstP from Azotobacter vinelandii, and mtrR from Neisseria gonorrhoeae) that had not been shown previously to play a role in pathogenesis, and two of the mutants contained TnphoA inserted into novel sequences. These data indicate that the killing of C. elegans by P. aeruginosa can be exploited to identify novel P. aeruginosa virulence factors important for mammalian pathogenesis. PMID:10051655

  9. Identifying environmental risk factors for human neural tube defects before and after folic acid supplementation

    Directory of Open Access Journals (Sweden)

    Li Xinhu

    2009-10-01

    Full Text Available Abstract Background Birth defects are a major cause of infant mortality and disability in many parts of the world. Neural tube defects (NTDs are one of the most common types of birth defects. In 2001, the Chinese population and family planning commission initiated a national intervention program for the prevention of birth defects. A key step in the program was the introduction of folic acid supplementation. Of interest in the present study was to determine whether folic acid supplementation has the same protective effect on NTDs under various geographical and socioeconomic conditions within the Chinese population and the nature in which the influence of environmental factors varied after folic acid supplementation. Methods In this study, Heshun was selected as the region of interest as a surrogate for helping to answer some of the questions raised in this study on the impact of the intervention program. Spatial filtering in combination with GIS software was used to detect annual potential clusters from 1998 to 2005 in Heshun, and Kruskal-wallis test and multivariate regression were applied to identify the environmental risk factors for NTDs among various regions. Results In 1998, a significant (p Conclusion This suggests that the government needs to adapt the intervention measures according to local conditions. More attention needs to be paid to the poor and to people living in areas near coal mines.

  10. Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions.

    Science.gov (United States)

    Tenor, Jennifer L; McCormick, Beth A; Ausubel, Frederick M; Aballay, Alejandro

    2004-06-01

    A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including several related to the type III secretion system (TTSS) encoded in Salmonella pathogenicity island 1 (SPI-1). Mutants corresponding to presumptive novel virulence-related genes exhibited diminished ability to invade epithelial cells and/or to induce polymorphonuclear leukocyte migration in a tissue culture model of mammalian enteropathogenesis. When expressed in C. elegans intestinal cells, the S. enterica TTSS-exported effector protein SptP inhibited a conserved p38 MAPK signaling pathway and suppressed the diminished pathogenicity phenotype of an S. enterica sptP mutant. These results show that C. elegans is an attractive model to study the interaction between Salmonella effector proteins and components of the innate immune response, in part because there is a remarkable overlap between Salmonella virulence factors required for human and nematode pathogenesis.

  11. TO STUDY THE INCIDENCE OF ANAEMIA AND IDENTIFY AS RISK FACTOR IN CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    S. Periasamy

    2016-07-01

    Full Text Available AIM AND OBJECTIVE To identify the incidence of anaemia and to identity anaemia itself as a risk factors in coronary artery disease in rural population. METHODS AND MATERIALS A prospective observational study done in patients admitted with evidence of coronary artery disease in Rajah Muthiah Medical College Hospital from January 2016 to April 2016. Patients with age more than 18 years, both gender, evidence of coronary artery disease were included and secondary case for anaemia were excluded. A detailed clinical history and examination, blood count with smear study was done. RESULT In our present study, male predominance (72% with more common in age group between (51-60 years 36%. Mean haemoglobin level in our study showed 11.70 g/dL. The incidence of anaemia was 80% with varying severity 7-9 (2%, 9-11 (32%, 11-13 (46%, >13(20% and smear showed microcytic hypochromic dominated with 52%. CONCLUSION Incidence of anaemia observed in rural population with reference to significances of role as risk factor yet to be studied with detailed study. It is important also to investigate secondary cause of anaemia.

  12. Participation of African social scientists in malaria control: identifying enabling and constraining factors

    Directory of Open Access Journals (Sweden)

    Nyamongo Isaac

    2004-12-01

    Full Text Available Abstract Objective To examine the enabling and constraining factors that influence African social scientists involvement in malaria control. Methods Convenience and snowball sampling was used to identify participants. Data collection was conducted in two phases: a mailed survey was followed by in-depth phone interviews with selected individuals chosen from the survey. Findings Most participants did not necessarily seek malaria as a career path. Having a mentor who provided research and training opportunities, and developing strong technical skills in malaria control and grant or proposal writing facilitated career opportunities in malaria. A paucity of jobs and funding and inadequate technical skills in malaria limited the type and number of opportunities available to social scientists in malaria control. Conclusion Understanding the factors that influence job satisfaction, recruitment and retention in malaria control is necessary for better integration of social scientists into malaria control. However, given the wide array of skills that social scientists have and the variety of deadly diseases competing for attention in Sub Saharan Africa, it might be more cost effective to employ social scientists to work broadly on issues common to communicable diseases in general rather than solely on malaria.

  13. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

    Science.gov (United States)

    Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

    2010-03-01

    Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

  14. Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders.

    Science.gov (United States)

    Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

    2017-06-04

    This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as "relatively low", contrasting with 21.4% rated as "relatively high". Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders.

  15. Proteomic analysis of polyribosomes identifies splicing factors as potential regulators of translation during mitosis.

    Science.gov (United States)

    Aviner, Ranen; Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo; Elroy-Stein, Orna

    2017-06-02

    Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis. Then, using a combination of pulsed SILAC, metabolic labeling and ribosome profiling, we showed that knockdown of hnRNP C affects both global and transcript-specific translation rates and found that hnRNP C is specifically important for translation of mRNAs that encode ribosomal proteins and translation factors. Taken together, our results demonstrate how proteomic analysis of polysomes can provide insight into translation regulation under various cellular conditions of interest and suggest that hnRNP C facilitates production of translation machinery components during mitosis to provide daughter cells with the ability to efficiently synthesize proteins as they enter G1 phase. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Ancestry of pink disease (infantile acrodynia) identified as a risk factor for autism spectrum disorders.

    Science.gov (United States)

    Shandley, Kerrie; Austin, David W

    2011-01-01

    Pink disease (infantile acrodynia) was especially prevalent in the first half of the 20th century. Primarily attributed to exposure to mercury (Hg) commonly found in teething powders, the condition was developed by approximately 1 in 500 exposed children. The differential risk factor was identified as an idiosyncratic sensitivity to Hg. Autism spectrum disorders (ASD) have also been postulated to be produced by Hg. Analogous to the pink disease experience, Hg exposure is widespread yet only a fraction of exposed children develop an ASD, suggesting sensitivity to Hg may also be present in children with an ASD. The objective of this study was to test the hypothesis that individuals with a known hypersensitivity to Hg (pink disease survivors) may be more likely to have descendants with an ASD. Five hundred and twenty-two participants who had previously been diagnosed with pink disease completed a survey on the health outcomes of their descendants. The prevalence rates of ASD and a variety of other clinical conditions diagnosed in childhood (attention deficit hyperactivity disorder, epilepsy, Fragile X syndrome, and Down syndrome) were compared to well-established general population prevalence rates. The results showed the prevalence rate of ASD among the grandchildren of pink disease survivors (1 in 22) to be significantly higher than the comparable general population prevalence rate (1 in 160). The results support the hypothesis that Hg sensitivity may be a heritable/genetic risk factor for ASD.

  17. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.

    Science.gov (United States)

    Cinegaglia, Naiara C; Andrade, Sonia Cristina S; Tokar, Tomas; Pinheiro, Maísa; Severino, Fábio E; Oliveira, Rogério A; Hasimoto, Erica N; Cataneo, Daniele C; Cataneo, Antônio J M; Defaveri, Júlio; Souza, Cristiano P; Marques, Márcia M C; Carvalho, Robson F; Coutinho, Luiz L; Gross, Jefferson L; Rogatto, Silvia R; Lam, Wan L; Jurisica, Igor; Reis, Patricia P

    2016-05-17

    Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

  18. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

    Directory of Open Access Journals (Sweden)

    Kandeel Amr M

    2012-11-01

    Full Text Available Abstract Background Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial to develop appropriate prevention strategies. Methods We conducted a case–control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two infectious disease hospitals in Cairo and Alexandria. Case-patients were defined as: any patient with symptoms of acute hepatitis; lab tested positive for HCV antibodies and negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of transaminase levels. Controls were selected from patients’ visitors with negative viral hepatitis markers. Subjects were interviewed about previous exposures within six months, including community-acquired and health-care associated practices. Results Case-patients were more likely than controls to have received injection with a reused syringe (OR=23.1, CI 4.7-153, to have been in prison (OR=21.5, CI 2.5-479.6, to have received IV fluids in a hospital (OR=13.8, CI 5.3-37.2, to have been an IV drug user (OR=12.1, CI 4.6-33.1, to have had minimal surgical procedures (OR=9.7, CI 4.2-22.4, to have received IV fluid as an outpatient (OR=8, CI 4–16.2, or to have been admitted to hospital (OR=7.9, CI 4.2-15 within the last 6 months. Multivariate analysis indicated that unsafe health facility practices are the main risk factors associated with transmission of HCV infection in Egypt. Conclusion In Egypt, focusing acute HCV prevention measures on health-care settings would have a beneficial impact.

  19. Factor analysis of 27Al MAS NMR spectra for identifying nanocrystalline phases in amorphous geopolymers.

    Science.gov (United States)

    Urbanova, Martina; Kobera, Libor; Brus, Jiri

    2013-11-01

    Nanostructured materials offer enhanced physicochemical properties because of the large interfacial area. Typically, geopolymers with specifically synthesized nanosized zeolites are a promising material for the sorption of pollutants. The structural characterization of these aluminosilicates, however, continues to be a challenge. To circumvent complications resulting from the amorphous character of the aluminosilicate matrix and from the low concentrations of nanosized crystallites, we have proposed a procedure based on factor analysis of (27)Al MAS NMR spectra. The capability of the proposed method was tested on geopolymers that exhibited various tendencies to crystallize (i) completely amorphous systems, (ii) X-ray amorphous systems with nanocrystalline phases, and (iii) highly crystalline systems. Although the recorded (27)Al MAS NMR spectra did not show visible differences between the amorphous systems (i) and the geopolymers with the nanocrystalline phase (ii), the applied factor analysis unambiguously distinguished these materials. The samples were separated into the well-defined clusters, and the systems with the evolving crystalline phase were identified even before any crystalline fraction was detected by X-ray powder diffraction. Reliability of the proposed procedure was verified by comparing it with (29)Si MAS NMR spectra. Factor analysis of (27)Al MAS NMR spectra thus has the ability to reveal spectroscopic features corresponding to the nanocrystalline phases. Because the measurement time of (27)Al MAS NMR spectra is significantly shorter than that of (29)Si MAS NMR data, the proposed procedure is particularly suitable for the analysis of large sets of specifically synthesized geopolymers in which the formation of the limited fractions of nanocrystalline phases is desired. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Identifying the influential aquifer heterogeneity factor on nitrate reduction processes by numerical simulation

    Science.gov (United States)

    Jang, E.; He, W.; Savoy, H.; Dietrich, P.; Kolditz, O.; Rubin, Y.; Schüth, C.; Kalbacher, T.

    2017-01-01

    Nitrate reduction reactions in groundwater systems are strongly influenced by various aquifer heterogeneity factors that affect the transport of chemical species, spatial distribution of redox reactive substances and, as a result, the overall nitrate reduction efficiency. In this study, we investigated the influence of physical and chemical aquifer heterogeneity, with a focus on nitrate transport and redox transformation processes. A numerical modeling study for simulating coupled hydrological-geochemical aquifer heterogeneity was conducted in order to improve our understanding of the influence of the aquifer heterogeneity on the nitrate reduction reactions and to identify the most influential aquifer heterogeneity factors throughout the simulation. Results show that the most influential aquifer heterogeneity factors could change over time. With abundant presence of electron donors in the high permeable zones (initial stage), physical aquifer heterogeneity significantly influences the nitrate reduction since it enables the preferential transport of nitrate to these zones and enhances mixing of reactive partners. Chemical aquifer heterogeneity plays a comparatively minor role. Increasing the spatial variability of the hydraulic conductivity also increases the nitrate removal efficiency of the system. However, ignoring chemical aquifer heterogeneity can lead to an underestimation of nitrate removals in long-term behavior. With the increase of the spatial variability of the electron donor, i.e. chemical heterogeneity, the number of the "hot spots" i.e. zones with comparably higher reactivity, should also increase. Hence, nitrate removal efficiencies will also be spatially variable but overall removal efficiency will be sustained if longer time scales are considered and nitrate fronts reach these high reactivity zones.

  1. Analysing risk factors for urinary tract infection based on automated monitoring of hospital-acquired infection.

    Science.gov (United States)

    Redder, J D; Leth, R A; Møller, J K

    2016-04-01

    Urinary tract infections account for as much as one-third of all nosocomial infections. The aim of this study was to examine previously reported characteristics of patients with hospital-acquired urinary tract infections (HA-UTI) using an automated infection monitoring system (Hospital-Acquired Infection Registry: HAIR). A matched case-control study was conducted to investigate the association of risk factors with HA-UTI. Patients with HA-UTI more frequently had indwelling urinary catheters or a disease in the genitourinary or nervous system than the controls. Automated hospital-acquired infection monitoring enables documentation of key risk factors to better evaluate infection control interventions in general or for selected groups of patients.

  2. Analyses of a Glycine max Degradome Library Identify microRNA Targets and MicroRNAs that Trigger Secondary SiRNA Biogenesis

    Institute of Scientific and Technical Information of China (English)

    Zheng Hu; Qiyan Jiang; Zhiyong Ni; Rui Chen; Shuo Xu; Hui Zhang

    2013-01-01

    Plant microRNAs (miRNAs) regulate gene expression mainly by guiding cleavage of target mRNAs.In this study,a degradome library constructed from different soybean (Glycine max (L.) Merr.) tissues was deep-sequenced.428 potential targets of small interfering RNAs and 25 novel miRNA families were identified.A total of 211 potential miRNA targets,including 174 conserved miRNA targets and 37 soybeanspecific miRNA targets,were identified.Among them,121 targets were first discovered in soybean.The signature distribution of soybean primary miRNAs (pri-miRNAs) showed that most pri-miRNAs had the characteristic pattern of Dicer processing.The biogenesis of TAS3 small interfering RNAs (siRNAs) was conserved in soybean,and nine Auxin Response Factors were identified as TAS3 siRNA targets.Twentythree miRNA targets produced secondary small interfering RNAs (siRNAs) in soybean.These targets were guided by five miRNAs:gma-miR393,gma-miR1508,gma-miR1510,gma-miR1514,and novel-11.Multiple targets of these secondary siRNAs were detected.These 23 miRNA targets may be the putative novel TAS genes in soybean.Global identification of miRNA targets and potential novel TAS genes will contribute to research on the functions of miRNAs in soybean.

  3. Analyses of a Glycine max degradome library identify microRNA targets and microRNAs that trigger secondary siRNA biogenesis.

    Science.gov (United States)

    Hu, Zheng; Jiang, Qiyan; Ni, Zhiyong; Chen, Rui; Xu, Shuo; Zhang, Hui

    2013-02-01

    Plant microRNAs (miRNAs) regulate gene expression mainly by guiding cleavage of target mRNAs. In this study, a degradome library constructed from different soybean (Glycine max (L.) Merr.) tissues was deep-sequenced. 428 potential targets of small interfering RNAs and 25 novel miRNA families were identified. A total of 211 potential miRNA targets, including 174 conserved miRNA targets and 37 soybean-specific miRNA targets, were identified. Among them, 121 targets were first discovered in soybean. The signature distribution of soybean primary miRNAs (pri-miRNAs) showed that most pri-miRNAs had the characteristic pattern of Dicer processing. The biogenesis of TAS3 small interfering RNAs (siRNAs) was conserved in soybean, and nine Auxin Response Factors were identified as TAS3 siRNA targets. Twenty-three miRNA targets produced secondary small interfering RNAs (siRNAs) in soybean. These targets were guided by five miRNAs: gma-miR393, gma-miR1508, gma-miR1510, gma-miR1514, and novel-11. Multiple targets of these secondary siRNAs were detected. These 23 miRNA targets may be the putative novel TAS genes in soybean. Global identification of miRNA targets and potential novel TAS genes will contribute to research on the functions of miRNAs in soybean.

  4. Analysing a Numerical Calculation Adequacy of the Recovery Factor for Various Problem Statement Options

    Directory of Open Access Journals (Sweden)

    A. D. Kliukvin

    2016-01-01

    Full Text Available The paper studies a recovery temperature distribution in a turbulent boundary layer of the compressible gas in a rectangular heat-insulated channel in supersonic flow mode using the numerical methods of gas dynamics. The software package ANSYS Fluent was used for calculation.In the numerical simulation were used SST and k-epsilon turbulence models with two types of thermal boundary conditions on the channel wall: the standard adiabatic condition, provided by the software package, as well as the user boundary condition (UDF based on the empirical dependence of the recovery factor in a turbulent boundary layer on the Prandtl number of the medium.A data analysis showed that an application of the standard boundary condition of a heatinsulated wall, in some cases, results in recovery factor values on the wall, corresponding to the laminar rather than turbulent boundary layer.For all options of the numerical model under consideration was found a non-zero value of the heat flow to the adiabatic wall. In the case of setting the user boundary conditions, this fact is due to the approximate nature of the dependence of the recovery factor on the Prandtl number.For standard boundary condition of an adiabatic wall the most likely explanation for this result is a feature of the numerical solution scheme, according to which, to set the zero heat flow, is used a number of ghost cells, which can lead to the heat pattern distortion in the computational domain in the vicinity of the wall.Correction of boundary conditions using an empirical relationship for the recovery factor enabled us to reduce the heat flows and have a better approximation of the adiabatic boundary condition.Thus, it follows from the data obtained that the calculation of heat exchange in a turbulent boundary layer by means of ANSYS Fluent software physically yet does not provide the adequate results, and for its update at the moment the third party experimental data are required.

  5. Factors predicting the development of pressure ulcers in an at-risk population who receive standardized preventive care: secondary analyses of a multicentre randomised controlled trial.

    Science.gov (United States)

    Demarre, Liesbet; Verhaeghe, Sofie; Van Hecke, Ann; Clays, Els; Grypdonck, Maria; Beeckman, Dimitri

    2015-02-01

    To identify predictive factors associated with the development of pressure ulcers in patients at risk who receive standardized preventive care. Numerous studies have examined factors that predict risk for pressure ulcer development. Only a few studies identified risk factors associated with pressure ulcer development in hospitalized patients receiving standardized preventive care. Secondary analyses of data collected in a multicentre randomized controlled trial. The sample consisted of 610 consecutive patients at risk for pressure ulcer development (Braden Score Pressure ulcers in category II-IV were significantly associated with non-blanchable erythema, urogenital disorders and higher body temperature. Predictive factors significantly associated with superficial pressure ulcers were admission to an internal medicine ward, incontinence-associated dermatitis, non-blanchable erythema and a lower Braden score. Superficial sacral pressure ulcers were significantly associated with incontinence-associated dermatitis. Despite the standardized preventive measures they received, hospitalized patients with non-blanchable erythema, urogenital disorders and a higher body temperature were at increased risk for developing pressure ulcers. Improved identification of at-risk patients can be achieved by taking into account specific predictive factors. Even if preventive measures are in place, continuous assessment and tailoring of interventions is necessary in all patients at risk. Daily skin observation can be used to continuously monitor the effectiveness of the intervention. © 2014 John Wiley & Sons Ltd.

  6. Analyses of mode filling factor of a laser end-pumped by a LD with high-order transverse modes

    Science.gov (United States)

    Han, Juhong; Wang, You; An, Guofei; Rong, Kepeng; Yu, Hang; Wang, Shunyan; Zhang, Wei; Cai, He; Xue, Liangping; Wang, Hongyuan; Zhou, Jie

    2017-05-01

    Although the concept of the mode filling factor (also named as "mode-matching efficiency") has been well discussed decades before, the concept of so-called overlap coefficient is often confused by the laser technicians because there are several different formulae for various engineering purposes. Furthermore, the LD-pumped configurations have become the mainstream of solid-state lasers since their compact size, high optical-to-optical efficiency, low heat generation, etc. As the beam quality of LDs are usually very unsatisfactory, it is necessary to investigate how the mode filling factor of a laser system is affected by a high-powered LD pump source. In this paper, theoretical analyses of an end-pumped laser are carried out based on the normalized overlap coefficient formalism. The study provides a convenient tool to describe the intrinsically complex issue of mode interaction corresponding to a laser and an end-pumped source. The mode filling factor has been studied for many cases in which the pump mode and the laser mode have been considered together in the calculation based on analyses of the rate equations. The results should be applied for analyses of any other types of lasers with the similar optical geometry.

  7. Sustainability Efficiency Factor: Measuring Sustainability in Advanced Energy Systems through Exergy, Exergoeconomic, Life Cycle, and Economic Analyses

    Science.gov (United States)

    Boldon, Lauren

    (NHES) reference case studies to (1) introduce sustainability metrics, such as life cycle assessment, (2) demonstrate the methods behind exergy and exergoeconomic analyses, (3) provide an economic analysis of the potential for SMR development from first-of-a-kind (FOAK) to nth-of-a-kind (NOAK), thereby illustrating possible cost reductions and deployment flexibility for SMRs over large conventional nuclear reactors, (4) assess the competitive potential for incorporation of storage and hydrogen production in NHES and in regulated and deregulated electricity markets, (5) compare an SMR-hydrogen production plant to a natural gas steam methane reforming plant using the SEF, and (6) identify and review the social considerations which would support future nuclear development domestically and abroad, such as public and political/regulatory needs and challenges. The Global Warming Potential (GWP) for the SMR (300 MWth)-wind (60 MWe)-high temperature steam electrolysis (200 tons Hydrogen per day) system was calculated as approximately 874 g CO2-equivalent as part of the life cycle assessment. This is 92.6% less than the GWP estimated for steam methane reforming production of hydrogen by Spath and Mann. The unit exergetic and exergoeconomic costs were determined for each flow within the NHES system as part of the exergy/exergoeconomic cost analyses. The unit exergetic cost is lower for components yielding more meaningful work like the one exiting the SMR with a unit exergetic cost of 1.075 MW/MW. In comparison, the flow exiting the turbine has a very high unit exergetic cost of 15.31, as most of the useful work was already removed through the turning of the generator/compressor shaft. In a similar manner, the high unit exergoeconomic cost of 12.45/MW*sec is observed for the return flow to the reactors, because there is very little exergy present. The first and second law efficiencies and the exergoeconomic factors were also determined over several cases. For the first or base SMR

  8. Identifying erosive periods by using RUSLE factors in mountain fields of the Central Spanish Pyrenees

    Directory of Open Access Journals (Sweden)

    M. López-Vicente

    2008-03-01

    Full Text Available The Mediterranean environment is characterized by strong temporal variations in rainfall volume and intensity, soil moisture and vegetation cover along the year. These factors play a key role on soil erosion. The aim of this work is to identify different erosive periods in function of the temporal changes in rainfall and runoff characteristics (erosivity, maximum intensity and number of erosive events, soil properties (soil erodibility in relation to freeze-thaw processes and soil moisture content and current tillage practices in a set of agricultural fields in a mountainous area of the Central Pyrenees in NE Spain. To this purpose the rainfall and runoff erosivity (R, the soil erodibility (K and the cover-management (C factors of the empirical RUSLE soil loss model were used. The R, K and C factors were calculated at monthly scale. The first erosive period extends from July to October and presents the highest values of erosivity (87.8 MJ mm ha−1 h−1, maximum rainfall intensity (22.3 mm h−1 and monthly soil erosion (0.25 Mg ha−1 month−1 with the minimum values of duration of erosive storms, freeze-thaw cycles, soil moisture content and soil erodibility (0.007 Mg h MJ−1 mm−1. This period includes the harvesting and the plowing tillage practices. The second erosive period has a duration of two months, from May to June, and presents the lowest total and monthly soil losses (0.10 Mg ha−1 month−1 that correspond to the maximum protection of the soil by the crop-cover ($C$ factor = 0.05 due to the maximum stage of the growing season and intermediate values of rainfall and runoff erosivity, maximum rainfall intensity and soil erodibility. The third erosive period extends from November to April and has the minimum values of rainfall erosivity (17.5 MJ mm ha−1 h−1 and

  9. Identifying erosive periods by using RUSLE factors in mountain fields of the Central Spanish Pyrenees

    Directory of Open Access Journals (Sweden)

    M. López-Vicente

    2007-07-01

    Full Text Available The Mediterranean environment is characterized by strong temporal variations in rainfall volume and intensity, soil moisture and vegetation cover along the year. These factors play a key role on soil erosion. The aim of this work is to identify different erosive periods in function of the temporal changes in rainfall and runoff characteristics (erosivity, maximum intensity and number of erosive events, soil properties (soil erodibility in relation to freeze-thaw processes and soil moisture content and current tillage practices in a set of agricultural fields in a mountainous area of the Central Pyrenees in NE Spain. To this purpose the rainfall and runoff erosivity (R, the soil erodibility (K and the cover-management (C factors of the empirical RUSLE soil loss model were used. The R, K and C factors were calculated at monthly scale. The first erosive period extends from July to October and presents the highest values of erosivity (87.8 MJ mm ha−1 h−1, maximum rainfall intensity (22.3 mm h−1 and monthly soil erosion (0.10 Mg ha−1 month−1 with the minimum values of duration of erosive storms, freeze-thaw cycles, soil moisture content and soil erodibility (0.007 Mg h MJ−1 mm−1. This period includes the harvesting and the plowing tillage practices. The second erosive period has a duration of two months, from May to June, and presents the lowest total and monthly soil losses (0.04 Mg ha−1 month−1 that correspond to the maximum protection of the soil by the crop-cover (C factor = 0.05 due to the maximum stage of the growing season and intermediate values of rainfall and runoff erosivity, maximum rainfall intensity and soil erodibility. The third erosive period extends from November to April and has the minimum values of rainfall erosivity (17.5 MJ mm ha−1 h−1 and maximum rainfall intensity (6.0 mm h−1

  10. Demographic, clinical and psychosocial factors identify a high-risk group for depression screening among predominantly Hispanic patients with Type 2 diabetes in safety net care.

    Science.gov (United States)

    Ell, Kathleen; Katon, Wayne; Lee, Pey-Jiuan; Guterman, Jeffrey; Wu, Shinyi

    2015-01-01

    Identify biopsychosocial factors associated with depression for patients with Type 2 diabetes. A quasi-experimental clinical trial of 1293 patients was predominantly Hispanic (91%) female (62%), mean age 53 and average diabetes duration 10 years; 373 (29%) patients were depressed and assessed by Patient Health Questionnaire-9. Demographic, baseline clinical and psychosocial variables were compared between depressed and nondepressed patients. Bivariate analyses found depression significantly associated (pidentified six key risk factors: greater disability, diabetes symptoms and regimen distress, female gender, less diabetes self-care and lack of A1C. In addition, after controlling for identified six factors, the number of psychosocial stressors significantly associated with increased risk of depression (adjusted odds ratio=1.37, 95% confidence intervals: 1.18-1.58, pidentify a high-risk group of patients needing depression screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Identifying factors to improve oral cancer screening uptake: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Fatemeh Vida Zohoori

    Full Text Available AIMS: To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake. METHODS: Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week, irregular dental attenders living in economically deprived areas of Teesside. RESULTS: There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer. CONCLUSIONS: The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.

  12. Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors.

    Directory of Open Access Journals (Sweden)

    Lionel Rigottier-Gois

    Full Text Available Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence. For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i resistance to oxidative stress, ii antibiotic resistance, iii resistance to opsonophagocytosis, iv adherence to the human colon carcinoma Caco-2 epithelial cells and v virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence.

  13. Using focus groups to identify factors affecting healthy weight maintenance in college men.

    Science.gov (United States)

    Walsh, Jennifer R; White, Adrienne A; Greaney, Mary L

    2009-06-01

    Healthful eating and physical activity are important for healthy weight maintenance. The hypothesis for this study was that college-aged men would perceive factors affecting eating and physical activity as both contributing to and inhibiting healthy weight maintenance. The overall objective was to explore how men view weight maintenance in the context of these aspects. Subjects (n = 47, mean age = 20.3 +/- 1.7 years) completed an online survey, including the 51-item Three-Factor Eating Questionnaire, and participated in 1 of 6 focus groups. Three face-to-face and 3 online synchronous groups were conducted using a 15-question discussion guide to identify weight maintenance issues around eating, physical activity, and body perceptions. Weight satisfaction decreased with increase in both dietary restraint and disinhibition. Number of attempts to lose weight was positively associated with BMI (r [44] = .465, P = .01) and dietary restraint (r [44] = .515, P = .01). Findings from both focus group formats were similar. Motivators (sports performance/fitness, self-esteem, attractiveness, long-term health) were similar for eating healthfully and being physically active; however, more motivators to be physically active than to eat healthfully emerged. Enablers for eating healthfully included liking the taste, availability of healthful foods, using food rules to guide intake, having a habit of healthful eating, and internal drive/will. Barriers to healthful eating included fat in dairy foods, fruit and vegetable taste, and quick spoilage. Barriers to being physically active included lack of time/time management, obligations, being lazy, and girlfriends. Results may be used to inform future obesity prevention interventions.

  14. On applying safety archetypes to the Fukushima accident to identify nonlinear influencing factors

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, A.L., E-mail: alsousa@cnen.gov.br [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil); Ribeiro, A.C.O., E-mail: antonio.ribeiro@bayer.com [Bayer Crop Science Brasil S.A., Belford Roxo, RJ (Brazil); Duarte, J.P., E-mail: julianapduarte@poli.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Escola Politecnica. Departamento de Engenharia Nuclear; Frutuoso e Melo, P.F., E-mail: frutuoso@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COOPE/UFRJ), RJ (Brazil). Programa de Engenharia Nuclear

    2013-07-01

    Nuclear power plants are typically characterized as high reliable organizations. In other words, they are organizations defined as relatively error free over a long period of time. Another relevant characteristic of the nuclear industry is that safety efforts are credited to design. However, major accidents, like the Fukushima accident, have shown that new tools are needed to identify latent deficiencies and help improve their safety level. Safety archetypes proposed elsewhere (e. g., safety issues stalled in the face of technological advances and eroding safety) consonant with International Atomic Energy Agency (IAEA) efforts are used to examine different aspects of accidents in a systemic perspective of the interaction between individuals, technology and organizational factors. Safety archetypes can help consider nonlinear interactions. Effects are rarely proportional to causes and what happens locally in a system (near the current operating point) often does not apply to distant regions (other system states), so that one has to consider the so-called nonlinear interactions. This is the case, for instance, with human probability failure estimates and safety level identification. In this paper, we discuss the Fukushima accident in order to show how archetypes can highlight nonlinear interactions of factors that influenced it and how to maintain safety levels in order to prevent other accidents. The initial evaluation of the set of archetypes suggested in the literature showed that at least four of them are applicable to the Fukushima accident, as is inferred from official reports on the accident. These are: complacency (that is, the effects of complacency on safety), decreased safety awareness, fixing on symptoms and not the real causes and eroding safety. (author)

  15. Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population.

    Science.gov (United States)

    Ellis, Justine A; Scurrah, Katrina J; Duncan, Anna E; Lamantia, Angela; Byrnes, Graham B; Harrap, Stephen B

    2007-04-01

    There have been a number of genome-wide linkage studies for adult height in recent years. These studies have yielded few well-replicated loci, and none have been further confirmed by the identification of associated gene variants. The inconsistent results may be attributable to the fact that few studies have combined accurate phenotype measures with informative statistical modelling in healthy populations. We have performed a multi-stage genome-wide linkage analysis for height in 275 adult sibling pairs drawn randomly from the Victorian Family Heart Study (VFHS), a healthy population-based Caucasian cohort. Height was carefully measured in a standardised fashion on regularly calibrated equipment. Following genome-wide identification of a peak Z-score of 3.14 on chromosome 3 at 69 cM, we performed a fine-mapping analysis of this region in an extended sample of 392 two-generation families. We used a number of variance components models that incorporated assortative mating and shared environment effects, and we observed a peak LOD score of approximately 3.5 at 78 cM in four of the five models tested. We also demonstrated that the most prevalent model in the literature gave the worst fit, and the lowest LOD score (2.9) demonstrating the importance of appropriate modelling. The region identified in this study replicates the results of other genome-wide scans of height and bone-related phenotypes, strongly suggesting the presence of a gene important in bone growth on chromosome 3p. Association analyses of relevant candidate genes should identify the genetic variants responsible for the chromosome 3p linkage signal in our population.

  16. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

    Directory of Open Access Journals (Sweden)

    Thomas Nebl

    2011-09-01

    Full Text Available Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.

  17. Kernel principal component and maximum autocorrelation factor analyses for change detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Canty, Morton John

    2009-01-01

    in Nevada acquired on successive passes of the Landsat-5 satellite in August-September 1991. The six-band images (the thermal band is omitted) with 1,000 by 1,000 28.5 m pixels were first processed with the iteratively re-weighted MAD (IR-MAD) algorithm in order to discriminate change. Then the MAD image......Principal component analysis (PCA) has often been used to detect change over time in remotely sensed images. A commonly used technique consists of finding the projections along the eigenvectors for data consisting of pair-wise (perhaps generalized) differences between corresponding spectral bands...... covering the same geographical region acquired at two different time points. In this paper kernel versions of the principal component and maximum autocorrelation factor (MAF) transformations are used to carry out the analysis. An example is based on bi-temporal Landsat-5 TM imagery over irrigation fields...

  18. Microarray hybridization analysis of light-dependent gene expression in Penicillium chrysogenum identifies bZIP transcription factor PcAtfA.

    Science.gov (United States)

    Wolfers, Simon; Kamerewerd, Jens; Nowrousian, Minou; Sigl, Claudia; Zadra, Ivo; Kürnsteiner, Hubert; Kück, Ulrich; Bloemendal, Sandra

    2015-04-01

    The fungal velvet complex is a light-dependent master regulator of secondary metabolism and development in the major penicillin producer, Penicillium chrysogenum. However, the light-dependent mechanism is unclear. To identify velvet-dependent transcriptional regulators that show light-regulated expression, we performed microarray hybridizations with RNA isolated from P. chrysogenum ΔPcku70 cultures grown under 13 different long-term, light-dependent growth conditions. We compared these expression data to data from two velvet complex deletion mutants; one lacked a subunit of the velvet complex (ΔPcvelA), and the other lacked a velvet-associated protein (ΔPclaeA). We sought to identify genes that were up-regulated in light, but down-regulated in ΔPcvelA and ΔPclaeA. We identified 148 co-regulated genes that displayed this regulatory pattern. In silico analyses of the co-regulated genes identified six proteins with fungal-specific transcription factor domains. Among these, we selected the bZIP transcription factor, PcAtfA, for functional characterization in deletion and complementation strains. Our data clearly indicates that PcAtfA governs spore germination. This comparative analysis of different microarray hybridization data sets provided results that may be useful for identifying genes for future functional analyses.

  19. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. PMID:27432226

  20. Description of first germinal mosaic mutation identified in dominant skeletal mutation experiments and considerations about how to deal with this kind of spontaneous mutation in analyses

    Energy Technology Data Exchange (ETDEWEB)

    Selby, Paul B.; Earhart, Vicki S.; Garrison, Edna M.; Raymer, G. Douglas

    2004-01-12

    Germinal mosaicism is a well-established mechanism by which new spontaneous mutations enter the human population, but it is only rather recently that clusters of mutations arising in that way have been acknowledged and dealt with in specific-locus experiments on male mice. This paper reports the first cluster of germinal mosaic mutations to have been identified in experiments on the induction of dominant skeletal mutations. The mutation was detected in six offspring of a control male from the radiation part of an Assessment-of-Dominant-Damage (ADD) experiment. Reasons are provided to explain why this one litter of six mutants was excluded from the analysis of induction of dominant mutations causing the more common skeletal anomalies, which is reported in another paper. The effects of excluding this litter from that analysis are fully described. There is discussion of why such clusters should be included in some analyses but omitted in others. They should certainly always be reported because, in some cases, they can have a major impact on conclusions. Details on this one cluster of FCGM mutations provide numerous examples of how a dominant skeletal mutation that causes rare effects can also cause many of the more common anomalies.

  1. Identifying the factors governing attitude towards the e-Agriservice among dairy farmers in Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Sagar Kisan Wadkar

    2016-01-01

    Full Text Available Information and communication technology (ICT projects have a great potential to revolutionise the information delivery system by bridging the gap between farmers and extension personnel. aAQUA (Almost All Questions Answered portal was launched by the Developmental Informatics Laboratory (DIL at Indian Institute of Technology (IIT Mumbai, Maharashtra, India in 2003 as an information providing system to deliver technology options and tailored information for the problems and queries raised by Indian dairy farmers. To measure the effectiveness of this service the attitudinal dimensions of the users of aAQUA e-Agriservice were investigated using a 22 item scale. A simple random sampling technique was used to select 120 dairy farmers from which data were collected and subjected to factor analysis to identify the underlying constructs in this research. From the attitude items, four components were extracted and named as the pessimistic, utility, technical and efficacy perspective, which influenced the development of varied level of attitudinal inclination towards the e-Agriservice. These components explained 64.40 per cent of variation in the attitude of the users towards the aAQUA e-Agriservice. This study provides a framework for technically efficient service provision that might help to reduce the pessimistic attitude of target population to adopt e-Agriservice in their farming system. The results should also be helpful for researchers, academics, ICT based service providers and policy makers to consider these perspectives while planning and implementing ICT projects.

  2. Conceptual and Operational Considerations in Identifying Socioenvironmental Factors Associated with Disability among Community-Dwelling Adults

    Directory of Open Access Journals (Sweden)

    Mathieu Philibert

    2015-04-01

    Full Text Available Disability is conceived as a person–context interaction. Physical and social environments are identified as intervention targets for improving social participation and independence. In comparison to the body of research on place and health, relatively few reports have been published on residential environments and disability in the health sciences literature. We reviewed studies evaluating the socioenvironmental correlates of disability. Searches were conducted in Medline, Embase and CINAHL databases for peer-reviewed articles published between 1997 and 2014. We found many environmental factors to be associated with disability, particularly area-level socioeconomic status and rurality. However, diversity in conceptual and methodological approaches to such research yields a limited basis for comparing studies. Conceptual inconsistencies in operational measures of disability and conceptual disagreement between studies potentially affect understanding of socioenvironmental influences. Similarly, greater precision in socioenvironmental measures and in study designs are likely to improve inference. Consistent and generalisable support for socioenvironmental influences on disability in the general adult population is scarce.

  3. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

    Directory of Open Access Journals (Sweden)

    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  4. Identifying Risk Factors of Boot Procurement: A Case Study of Stadium Australia

    Directory of Open Access Journals (Sweden)

    Marcus Jefferies

    2012-11-01

    Full Text Available Private sector input into the procurement of public works and services is continuing to increase. This has partly arisen out of a requirement for infrastructure development to be undertaken at a rate that maintains and allows growth. This has become a major challange for the construction industry that cannot be met by government alone. The emergence of Build-Own-Operate-Transfer (BOOT schemes as a response to this challange provides a means for developing the infrastructure of a country without directly impacting on the governments budgetary constraints. The concepts of BOOT are without doubt extremely complex arrangements, which bring to the construction sector risks not experienced previously. Many of the infrastructure partnerships between public and private sector in the pastare yet to provide evidence of successful completion, since few of the concession periods have expired. This paper provides an identified list of risk factors to a case study of Stadium Australia. The most significant risk associated with Stadium Australia include the bidding process, the high level of public scrutiny, post-Olympic Games facility revenue and the complicated nature of the consortium structure.  

  5. Identifying Risk Factors of Boot Procurement: A Case Study of Stadium Australia

    Directory of Open Access Journals (Sweden)

    Marcus Jefferies

    2012-11-01

    Full Text Available Private sector input into the procurement of public works and services is continuing to increase. This has partly arisen out of a requirement for infrastructure development to be undertaken at a rate that maintains and allows growth. This has become a major challange for the construction industry that cannot be met by government alone. The emergence of Build-Own-Operate-Transfer (BOOT schemes as a response to this challange provides a means for developing the infrastructure of a country without directly impacting on the governments budgetary constraints. The concepts of BOOT are without doubt extremely complex arrangements, which bring to the construction sector risks not experienced previously. Many of the infrastructure partnerships between public and private sector in the pastare yet to provide evidence of successful completion, since few of the concession periods have expired. This paper provides an identified list of risk factors to a case study of Stadium Australia. The most significant risk associated with Stadium Australia include the bidding process, the high level of public scrutiny, post-Olympic Games facility revenue and the complicated nature of the consortium structure.

  6. Factors Identified with Higher Levels of Career Satisfaction of Physicians in Andalusia, Spain.

    Science.gov (United States)

    Peña-Sánchez, Juan Nicolás; Lepnurm, Rein; Morales-Asencio, José Miguel; Delgado, Ana; Domagała, Alicja; Górkiewicz, Maciej

    2014-04-26

    The satisfaction of physicians is a worldwide issue linked with the quality of health services; their satisfaction needs to be studied from a multi-dimensional perspective, considering lower- and higher-order needs. The objectives of this study were to: i) measure the career satisfaction of physicians; ii) identify differences in the dimensions of career satisfaction; and iii) test factors that affect higher- and lower-order needs of satisfaction among physicians working in Andalusian hospitals (Spain). Forty-one percent of 299 eligible physicians participated in a study conducted in six selected hospitals. Physicians reported higher professional, inherent, and performance satisfaction than personal satisfaction. Foreign physicians reported higher levels of personal and performance satisfaction than local physicians, and those who received non-monetary incentives had higher professional and performance satisfaction. In conclusion, physicians in the selected Andalusian hospitals reported low levels of personal satisfaction. Non-monetary incentives were more relevant to influence their career satisfaction. Further investigations are recommended to study differences in the career satisfaction between foreign and local physicians.

  7. siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection.

    Science.gov (United States)

    Radoshitzky, Sheli R; Pegoraro, Gianluca; Chī, Xi Olì; D Ng, Lián; Chiang, Chih-Yuan; Jozwick, Lucas; Clester, Jeremiah C; Cooper, Christopher L; Courier, Duane; Langan, David P; Underwood, Knashka; Kuehl, Kathleen A; Sun, Mei G; Caì, Yíngyún; Yú, Shu Qìng; Burk, Robin; Zamani, Rouzbeh; Kota, Krishna; Kuhn, Jens H; Bavari, Sina

    2016-03-01

    Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2) expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1-PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling.

  8. siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection.

    Directory of Open Access Journals (Sweden)

    Sheli R Radoshitzky

    2016-03-01

    Full Text Available Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2 expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1-PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling.

  9. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    Science.gov (United States)

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  10. Epidermal growth factor gene is a newly identified candidate gene for gout

    Science.gov (United States)

    Han, Lin; Cao, Chunwei; Jia, Zhaotong; Liu, Shiguo; Liu, Zhen; Xin, Ruosai; Wang, Can; Li, Xinde; Ren, Wei; Wang, Xuefeng; Li, Changgui

    2016-01-01

    Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67–0.88, Padjusted = 6.42 × 10−3). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations. PMID:27506295

  11. Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor.

    Science.gov (United States)

    Frullanti, Elisa; Berking, Carola; Harbeck, Nadia; Jézéquel, Pascal; Haugen, Aage; Mawrin, Christian; Parise, Orlando; Sasaki, Hidefumi; Tsuchiya, Norihiko; Dragani, Tommaso A

    2011-07-01

    Fibroblast growth factor receptor 4 (FGFR4) contains a Gly388Arg functional polymorphism (rs351855) that has shown contrasting results in association studies. In this study, we assessed the association between the FGFR4 Gly388Arg polymorphism and cancer prognosis. Meta-analysis and pooled analysis of 6817 and 2537 cancer cases, respectively, were carried out by nodal status and overall survival. The study included the following types of cancer: brain, breast, colorectal, head and neck, larynx, lung, melanoma, prostate, sarcomas. A statistically significant association between the Arg388Arg genotype and nodal involvement was found in the meta-analysis (odds ratio=1.33, 95% confidence interval 1.01-1.74). In the pooled analysis, the Arg388 allele carriers showed an increased hazard of poor overall survival compared with homozygous carriers of the common Gly388 allele, even after adjusting for nodal status (hazard ratio=1.21, 95% confidence interval 1.05-1.40). These results provide evidence of a role for the FGFR4 Gly388Arg polymorphism in modulating patients' outcome in different types of cancer, thus offering to clinicians a new marker to predict predisposition to poor survival in cancer patients.

  12. Expression and functional analyses of Krüppel-like factor 3 in chicken adipose tissue.

    Science.gov (United States)

    Zhang, Zhi-Wei; Wu, Chun-Yan; Li, Hui; Wang, Ning

    2014-01-01

    Studies in mammalian species showed that Krüppel-like factor 3 (KLF3) regulated adipose tissue development. However, it was not reported in chicken. In the current study, we found that during the growth and development of abdominal fat tissue, chicken KLF3 (Gallus gallus KLF3, gKLF3) was consecutively expressed, and its transcripts were higher at 7 weeks of age and lower at 10 weeks of age in lean broilers than in fat broilers. In addition, gKLF3 overexpression suppressed chicken CCAAT/enhancer binding protein alpha (C/EBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN), and lipoprotein lipase (LPL) promoter activities, but increased chicken peroxisome proliferator-activated receptor gamma (PPARγ) promoter activity. Additionally, point mutagenesis analysis showed that the substitution of Asp by Gly within the Pro-Val-Asp-Leu-Thr (PVDLT) motif of gKLF3 significantly reduced the ability of gKLF3 to regulate the promoter activities of FABP4, FASN, LPL, C/EBPα, and PPARγ.

  13. Stress analyses coupled with damage laws to determine biomechanical risk factors for deep tissue injury during sitting.

    Science.gov (United States)

    Linder-Ganz, Eran; Gefen, Amit

    2009-01-01

    Deep tissue injury (DTI) is a potentially life-threatening form of pressure ulcer that onsets in muscle tissue overlying bony prominences and progresses unnoticeably to more superficial tissues. To minimize DTI, the efficacy of wheelchair cushions should be evaluated not only based on their performance in redistributing interface pressures but also according to their effects on stress concentrations in deep tissues, particularly muscles. However, a standard bioengineering approach for such analyses is missing in literature. The goals of this study were to develop an algorithm to couple finite element (FE) modeling of the buttocks with an injury threshold for skeletal muscle and with a damage-stiffening law for injured muscle tissue, from previous animal experiments, to predict DTI onset and progression for different patient anatomies and wheelchair cushions. The algorithm was also employed for identifying intrinsic (anatomical) biomechanical risk factors for DTI onset. A set of three-dimensional FE models of seated human buttocks was developed, representing different severities of pathoanatomical changes observed in chronically sitting patients: muscle atrophy and "flattening" of the ischial tuberosity (IT). These models were then tested with cushions of different stiffnesses representing products available on the market and semirigid supports. Outcome measures were the percentage of damaged muscle tissue volumes after 90 min and 110 min of simulated continuous immobilized sitting as well as muscle injury rates post-60 min, -90 min, and -110 min of continuous sitting. Damaged muscle volumes grew exponentially with the level of muscle atrophy. For example, simulation of a subject with 70% muscle atrophy sitting on a soft cushion showed damage to 33% of the muscle volume after 90 min of immobilized sitting, whereas a comparable simulation with a nonatrophied muscle yielded only 0.4% damaged tissue volume. The rates of DTI progression also increased substantially with

  14. Factor analyses for the Örebro Musculoskeletal Pain Questionnaire for working and nonworking patients with chronic low back pain.

    Science.gov (United States)

    Soer, Remko; Vroomen, Patrick; Stewart, Roy; Coppes, Maarten; Stegeman, Patrick; Dijkstra, Pieter; Reneman, Michiel

    2017-04-01

    The Örebro Musculoskeletal Pain Questionnaire (ÖMPQ) has good psychometric properties to predict return to work in patients with acute low back pain. Although it is used in patients with chronic back pain and nonworkers, there is no evidence on the factor structure of the ÖMPQ in these populations. This is deemed an important prerequisite for future prediction studies. This study aimed to analyze the factor structure of the ÖMPQ in working and nonworking patients with chronic back pain. This is a cross-sectional study in a university-based spine center. The patient sample consists two cohorts of working and nonworking adult patients (>18 years) with specific and nonspecific chronic back pain. The Örebro Musculoskeletal Pain Questionnaire. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed in working (N=557) and nonworking (N=266) patients for three, four, five, and six factors identified in literature. A goodness of fit index was calculated by a chi-square. Root mean square error of approximation (RMSEA) was calculated, and the number of factors identified was based on RMSEA values 0.90 are considered to indicate acceptable fit. In working patients, a five-factor solution had the best fit (RMSEA0.90), but substantial adaptations should be made to get proper fit (removal of the work-related items). In nonworking patients, a four-factor analysis had the best fit (RMSEAback pain. Substantial adaptations should be made to obtain a factor structure with acceptable fit. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative.

    Science.gov (United States)

    Gangwisch, James E; Hale, Lauren; Garcia, Lorena; Malaspina, Dolores; Opler, Mark G; Payne, Martha E; Rossom, Rebecca C; Lane, Dorothy

    2015-08-01

    The consumption of sweetened beverages, refined foods, and pastries has been shown to be associated with an increased risk of depression in longitudinal studies. However, any influence that refined carbohydrates has on mood could be commensurate with their proportion in the overall diet; studies are therefore needed that measure overall intakes of carbohydrate and sugar, glycemic index (GI), and glycemic load. We hypothesized that higher dietary GI and glycemic load would be associated with greater odds of the prevalence and incidence of depression. This was a prospective cohort study to investigate the relations between dietary GI, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in postmenopausal women who participated in the Women's Health Initiative Observational Study at baseline between 1994 and 1998 (n = 87,618) and at the 3-y follow-up (n = 69,954). We found a progressively higher dietary GI to be associated with increasing odds of incident depression in fully adjusted models (OR for the fifth compared with first quintile: 1.22; 95% CI: 1.09, 1.37), with the trend being statistically significant (P = 0.0032). Progressively higher consumption of dietary added sugars was also associated with increasing odds of incident depression (OR for the fifth compared with first quintile: 1.23; 95% CI: 1.07, 1.41; P-trend = 0.0029). Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression, and nonwhole/refined grain consumption was associated with increased odds of depression. The results from this study suggest that high-GI diets could be a risk factor for depression in postmenopausal women. Randomized trials should be undertaken to examine the question of whether diets rich in low-GI foods could serve as treatments and primary preventive measures for depression in postmenopausal women.

  16. Validating the European Health Literacy Survey Questionnaire in people with type 2 diabetes: Latent trait analyses applying multidimensional Rasch modelling and confirmatory factor analysis.

    Science.gov (United States)

    Finbråten, Hanne Søberg; Pettersen, Kjell Sverre; Wilde-Larsson, Bodil; Nordström, Gun; Trollvik, Anne; Guttersrud, Øystein

    2017-11-01

    To validate the European Health Literacy Survey Questionnaire (HLS-EU-Q47) in people with type 2 diabetes mellitus. The HLS-EU-Q47 latent variable is outlined in a framework with four cognitive domains integrated in three health domains, implying 12 theoretically defined subscales. Valid and reliable health literacy measurers are crucial to effectively adapt health communication and education to individuals and groups of patients. Cross-sectional study applying confirmatory latent trait analyses. Using a paper-and-pencil self-administered approach, 388 adults responded in March 2015. The data were analysed using the Rasch methodology and confirmatory factor analysis. Response violation (response dependency) and trait violation (multidimensionality) of local independence were identified. Fitting the "multidimensional random coefficients multinomial logit" model, 1-, 3- and 12-dimensional Rasch models were applied and compared. Poor model fit and differential item functioning were present in some items, and several subscales suffered from poor targeting and low reliability. Despite multidimensional data, we did not observe any unordered response categories. Interpreting the domains as distinct but related latent dimensions, the data fit a 12-dimensional Rasch model and a 12-factor confirmatory factor model best. Therefore, the analyses did not support the estimation of one overall "health literacy score." To support the plausibility of claims based on the HLS-EU score(s), we suggest: removing the health care aspect to reduce the magnitude of multidimensionality; rejecting redundant items to avoid response dependency; adding "harder" items and applying a six-point rating scale to improve subscale targeting and reliability; and revising items to improve model fit and avoid bias owing to person factors. © 2017 John Wiley & Sons Ltd.

  17. Confirmatory factor analyses of the full and short versions of the Marlowe-Crowne Social Desirability Scale.

    Science.gov (United States)

    Loo, R; Thorpe, K

    2000-10-01

    Over the years, researchers have developed various short versions of the Marlowe-Crowne Social Desirability Scale (D. P. Crowne & D. Marlowe, 1960). The authors used confirmatory factor analyses (J. L. Arbuckle, 1997) as well as item and scale analyses to evaluate the adequacy of the full version and various short versions. Overall, the results from 232 Canadian undergraduates showed (a) that all the short versions in the present study are a significant improvement in fit over the 33-item full scale and (b) that W. M. Reynolds's (1982) Forms A and B are the best fitting short versions. No gender differences were found for the full scale or any of the short versions. The results show that the full scale could be improved psychometrically and that the psychometrically sound short versions should be available because they require less administration time than the full scale.

  18. Identifying key processes in the hydrochemistry of a basin through the combined use of factor and regression models

    Indian Academy of Sciences (India)

    Sandow Mark Yidana; Bruce Banoeng-Yakubo; Patrick Asamoah Sakyi

    2012-04-01

    An innovative technique of measuring the intensities of major sources of variation in the hydrochemistry of (ground) water in a basin has been developed. This technique, which is based on the combination of R-mode factor and multiple regression analyses, can be used to measure the degrees of influence of the major sources of variation in the hydrochemistry without measuring the concentrations of the entire set of physico-chemical parameters which are often used to characterize water systems. R-mode factor analysis was applied to the data of 13 physico-chemical parameters and 50 samples in order to determine the major sources of variation in the hydrochemistry of some aquifers in the western region of Ghana. In this study, three sources of variation in the hydrochemistry were distinguished: the dissolution of chlorides and sulfates of the major cations, carbonate mineral dissolution, and silicate mineral weathering. Two key parameters were identified with each of the processes and multiple regression models were developed for each process. These models were tested and found to predict these processes quite accurately, and can be applied anywhere within the terrain. This technique can be reliably applied in areas where logistical constraints limit water sampling for whole basin hydrochemical characterization. Q-mode hierarchical cluster analysis (HCA) applied to the data revealed three major groundwater associations distinguished on the basis of the major causes of variation in the hydrochemistry. The three groundwater types represent Na–HCO3, Ca–HCO3, and Na–Cl groundwater types. Silicate stability diagrams suggest that all these groundwater types are mainly stable in the kaolinite and montmorillonite fields suggesting moderately restricted flow conditions.

  19. Identifying Factors Influencing the Establishment of a Health System Reform Plan in Iran's Public Hospitals

    Directory of Open Access Journals (Sweden)

    Rasul Fani khiavi

    2016-09-01

    Full Text Available In today's world, health views have found a wider perspective in which non-medical expectations are particularly catered to. The health system reform plan seeks to improve society's health, decrease treatment costs, and increase patient satisfaction. This study investigated factors affecting the successful establishment of a health system reform plan. A mixed qualitative – quantitative approach was applied to conduct to explore influential factors associated with the establishment of a health system reform plan in Iran's public hospitals. The health systems and approaches to improving them in other countries have been studied. A Likert-based five-point questionnaire was the measurement instrument, and its content validity based on content validity ratio (CVR was 0.87. The construct validity, calculated using the factorial analysis and Kaiser Mayer Olkin (KMO techniques, was 0.964, which is a high level and suggests a correlation between the scale items. To complete the questionnaire, 185 experts, specialists, and executives of Iran’s health reform plan were selected using the Purposive Stratified Non Random Sampling and snowball methods. The data was then analyzed using exploratory factorial analysis and SPSS and LISREL software applications. The results of this research imply the existence of a pattern with a significant and direct relationship between the identified independent variables and the dependent variable of the establishment of a health system reform plan. The most important indices of establishing a health system reform plan, in the order of priority, were political support; suitable proportion and coverage of services presented in the society; management of resources; existence of necessary infrastructures; commitment of senior managers; constant planning, monitoring, and evaluation; and presentation of feedback to the plan's executives, intrasector/extrasector cooperation, and the plan’s guiding committee. Considering the

  20. Identifying risk factors of avian infectious diseases at household level in Poyang Lake region, China.

    Science.gov (United States)

    Jiang, Qian; Zhou, Jieting; Jiang, Zhiben; Xu, Bing

    2014-09-01

    Poultry kept in backyard farms are susceptible to acquiring and spreading infectious diseases because of free ranging and poor biosecurity measures. Since some of these diseases are zoonoses, this is also a significant health concern to breeders and their families. Backyard farms are common in rural regions of China. However, there is lack of knowledge of backyard poultry in the country. To obtain first-hand information of backyard poultry and identify risk factors of avian infectious diseases, a cross-sectional study was carried out at household level in rural regions around Poyang Lake. A door-to-door survey was conducted to collect data on husbandry practices, trading practices of backyard farmers, and surrounding environments of backyard farms. Farms were categorized into cases and controls based on their history of poultry death. Data were collected for 137 farms, and the association with occurrence of poultry death event was explored by chi-square tests. Results showed that vaccination implementation was a protective factor (odds ratio OR=0.40, 95% confidence interval CI: 0.20-0.80, p=0.01), while contact with other backyard flocks increased risk (OR=1.72, 95% CI: 0.79-3.74, p=0.16). A concept of "farm connectivity" characterized by the density of particular land-use types in the vicinity of the farm was proposed to characterize the degree of contact between poultry in one household farm and those in other household farms. It was found that housing density in a 20-m buffer zone of the farmhouse was most significantly associated with poultry death occurrence (OR=1.08, 95% CI: 1.02-1.17, p=0.03), and was in agreement with observation of villagers. Binary logistic regression was applied to evaluate the relationship between poultry death event and density of land-use types in all buffer zones. When integrated with vaccination implementation for poultry, prediction accuracy of poultry death event reached 72.0%. Results combining questionnaire survey with

  1. Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Wang, Ying; Huang, Lu; Wu, Shuqiang; Jia, Yongshi; Yang, Yunmei; Luo, Limin; Bi, Aihong; Fang, Min

    2015-01-01

    This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to explore its potential correlation with the progression of NSCLC. Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs). Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis. Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation. EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

  2. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses.

    Science.gov (United States)

    Abd El-Rehim, Dalia M; Ball, Graham; Pinder, Sarah E; Rakha, Emad; Paish, Claire; Robertson, John F R; Macmillan, Douglas; Blamey, Roger W; Ellis, Ian O

    2005-09-01

    Recent studies on gene molecular profiling using cDNA microarray in a relatively small series of breast cancer have identified biologically distinct groups with apparent clinical and prognostic relevance. The validation of such new taxonomies should be confirmed on larger series of cases prior to acceptance in clinical practice. The development of tissue microarray (TMA) technology provides methodology for high-throughput concomitant analyses of multiple proteins on large numbers of archival tumour samples. In our study, we have used immunohistochemistry techniques applied to TMA preparations of 1,076 cases of invasive breast cancer to study the combined protein expression profiles of a large panel of well-characterized commercially available biomarkers related to epithelial cell lineage, differentiation, hormone and growth factor receptors and gene products known to be altered in some forms of breast cancer. Using hierarchical clustering methodology, 5 groups with distinct patterns of protein expression were identified. A sixth group of only 4 cases was also identified but deemed too small for further detailed assessment. Further analysis of these clusters was performed using multiple layer perceptron (MLP)-artificial neural network (ANN) with a back propagation algorithm to identify key biomarkers driving the membership of each group. We have identified 2 large groups by their expression of luminal epithelial cell phenotypic characteristics, hormone receptors positivity, absence of basal epithelial phenotype characteristics and lack of c-erbB-2 protein overexpression. Two additional groups were characterized by high c-erbB-2 positivity and negative or weak hormone receptors expression but showed differences in MUC1 and E-cadherin expression. The final group was characterized by strong basal epithelial characteristics, p53 positivity, absent hormone receptors and weak to low luminal epithelial cytokeratin expression. In addition, we have identified significant

  3. A review of the use of human factors classification frameworks that identify causal factors for adverse events in the hospital setting.

    Science.gov (United States)

    Mitchell, R J; Williamson, A M; Molesworth, B; Chung, A Z Q

    2014-01-01

    Various human factors classification frameworks have been used to identified causal factors for clinical adverse events. A systematic review was conducted to identify human factors classification frameworks that identified the causal factors (including human error) of adverse events in a hospital setting. Six electronic databases were searched, identifying 1997 articles and 38 of these met inclusion criteria. Most studies included causal contributing factors as well as error and error type, but the nature of coding varied considerably between studies. The ability of human factors classification frameworks to provide information on specific causal factors for an adverse event enables the focus of preventive attention on areas where improvements are most needed. This review highlighted some areas needing considerable improvement in order to meet this need, including better definition of terms, more emphasis on assessing reliability of coding and greater sophistication in analysis of results of the classification. Practitioner Summary: Human factors classification frameworks can be used to identify causal factors of clinical adverse events. However, this review suggests that existing frameworks are diverse, limited in their identification of the context of human error and have poor reliability when used by different individuals.

  4. Identifying the factors influencing minority language use in health care education settings: a European perspective.

    Science.gov (United States)

    Roberts, G W; Paden, L

    2000-07-01

    The recent enhanced status of many minority languages across the European Community has led to increasing demands for their use within the public sector. This is particularly evident in health care, where, in circumstances of stress and vulnerability, denying opportunities for clients to communicate in their preferred language may place them at a personal disadvantage and compromise their health chances. In view of the exclusion of many minority languages from the public domain over the years, their re-introduction demands adaptations to health care education programmes in order to promote language sensitivity in practice. Before embarking on developments which establish such languages within the professional sphere, valuable insight may be gained by examining their current use in practice education. Furthermore, comparing their use across language communities enables the sharing of common experiences and furthers opportunities for developing networks across Europe. This paper describes an ethnographic study of the use, within midwifery education, of the Welsh language in north Wales, the Catalan language in Barcelona and the Irish language in Western Ireland. Semi-structured interviews were conducted with key lecturers, clinical mentors and students across the three communities in order to determine patterns of language use within a range of learning environments. Focus groups were also held in order to confirm the findings. The data reveal many commonalities in terms of language use across the three settings and important factors are identified which support the use of minority languages in practice education. The findings are invaluable for guiding future bilingual initiatives across health care education programmes.

  5. Clinical incidents involving students on placement: an analysis of incident reports to identify potential risk factors.

    Science.gov (United States)

    Gaida, J E; Maloney, S; Lo, K; Morgan, P

    2015-06-01

    Students are sometimes involved in incidents during clinical training. To the authors' knowledge, no quantitative studies of incidents specifically involving physiotherapy students on clinical placement are available in the literature. A retrospective audit (2008 to 2011) of incident reports involving physiotherapy students was conducted to identify the nature and features of incidents. The study aimed to determine if injuries to a student or patient were more or less likely when the supervisor was in close proximity, and whether students with lower academic performance in their preclinical semester were more likely to be involved in an incident. There were 19 care-delivery-related and three equipment-related incidents. There were no incidents of violent, aggressive or demeaning behaviour towards students. The incident rate was 9.0/100,000 student-hours for third-year students and 6.8/100,000 student-hours for fourth-year students. The majority of incidents (55%) occurred from 11 am to 12-noon and from 3 pm to 3.30 pm. Incidents more often resulted in patient or student injury when the supervisor was not in close proximity (approximately 50% vs approximately 20%), although the difference was not significant (P=0.336). The academic results of students involved in incidents were equivalent to the whole cohort in their preclinical semester {mean 75 [standard deviation (SD) 6] vs 76 (SD 7); P=0.488}. The unexpected temporal clustering of incidents warrants further investigation. Student fatigue may warrant attention as a potential contributor; however, contextual factors, such as staff workload, along with organisational systems, structures and procedures may be more relevant. The potential relationship between supervisor proximity and injury also warrants further exploration. The findings of the present study should be integrated into clinical education curricula and communicated to clinical educators. Copyright © 2014 Chartered Society of Physiotherapy. Published by

  6. Identifying factors associated with concordance with the American College of Rheumatology rheumatoid arthritis treatment recommendations.

    Science.gov (United States)

    Harrold, Leslie R; Reed, George W; Kremer, Joel M; Curtis, Jeffrey R; Solomon, Daniel H; Hochberg, Marc C; Kavanaugh, Arthur; Saunders, Katherine C; Shan, Ying; Spruill, Tanya M; Pappas, Dimitrios A; Greenberg, Jeffrey D

    2016-04-26

    Factors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown. We identified a national cohort of biologic-naive patients with RA with visits between December 2008 and February 2013. Treatment acceleration (initiation or dose escalation of biologic and nonbiologic DMARDs) in response to moderate to high disease activity (using the Clinical Disease Activity Index) was assessed. The population was divided into two subcohorts: (1) methotrexate (MTX)-only users and (2) multiple nonbiologic DMARD users. In both subcohorts, we compared the characteristics of patients who received care consistent with the ACR recommendations (e.g., prescriptions for treatment acceleration) and their providers with the characteristics of those who did not at the conclusion of one visit and over two visits, using logistic regression and adjusting for clustering of patients by rheumatologist. Our study included 741 MTX monotherapy and 995 multiple nonbiologic DMARD users cared for by 139 providers. Only 36.2 % of MTX monotherapy users and 39.6 % of multiple nonbiologic DMARD users received care consistent with the recommendations after one visit, which increased over two visits to 78.3 % and 76.2 %, respectively (25-30 % achieved low disease activity by the second visit without DMARD acceleration). Increasing time since the ACR publication on RA treatment recommendations was not associated with improved adherence. Allowing two encounters for treatment acceleration was associated with an increase in care concordant with the recommendations; however, time since publication was not.

  7. Three different anti-lipopolysaccharide factors identified from giant freshwater prawn, Macrobrachium rosenbergii.

    Science.gov (United States)

    Ren, Qian; Zhang, Zhao; Li, Xin-Chang; Jie-Du; Hui, Kai-Min; Zhang, Chi-Yu; Wang, Wen

    2012-10-01

    Anti-lipopolysaccharide factor (ALF) is a type of basic protein and an important antimicrobial peptide that can bind and neutralize lipopolysaccharides (LPS). This protein shows a broad spectrum of antimicrobial activity. In this study, three forms of ALF designated as MrALF5, MrALF6, and MrALF7 were identified from giant freshwater prawn, Macrobrachium rosenbergii. MrALF5, MrALF6, and MrALF7 genes encode 133, 121, and 120 amino acids of the corresponding proteins, respectively. All these ALF proteins contain LPS-binding domain with two conserved cysteine residues. The genomic sequences of MrALF5 and MrALF7 were amplified. The genomic structures of MrALF5 and MrALF7 comprise three exons interrupted by two introns. Phylogenetic analysis showed that MrALF5, MrALF6, and MrALF7 were clustered into clade II. Evolutionary analysis showed that ALF genes from M. rosenbergii may suffer a rapid evolution. MrALF5 was expressed mainly in the hepatopancreas, gills, and heart. MrALF6 was mainly distributed in the intestine and hepatopancreas. The highest expression level of MrALF7 was detected in the hepatopancreas. MrALF6, as well as MrALF7, was downregulated by Escherichia coli challenge, and all three ALF genes were upregulated by Vibrio or white spot syndrome virus challenge. MrALF6 was also upregulated by Staphylococcus aureus challenge. In summary, the three isoforms of ALF genes may participate in the innate immune response against bacteria and virus infecting the giant fresh water prawn.

  8. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  9. Identification of humic-like substances (HULIS in oxygenated organic aerosols using NMR and AMS factor analyses and liquid chromatographic techniques

    Directory of Open Access Journals (Sweden)

    M. Paglione

    2013-06-01

    Full Text Available The atmospheric organic aerosol composition is characterized by a great diversity of functional groups and chemical species challenging simple classification schemes. Traditional off-line chemical methods identified chemical classes based on the retention behavior on chromatographic columns and absorbing beds. Such approach led to the isolation of complex mixtures of compounds such as the humic-like substances (HULIS. More recently, on-line aerosol mass spectrometry (AMS was employed to identify chemical classes by extracting fragmentation patterns from experimental data series using statistical methods (factor analysis, providing simplified schemes for oxygenated organic aerosols (OOAs classification on the basis of the distribution of oxygen-containing functionalities. The analysis of numerous AMS datasets suggested the occurrence of very oxidized OOAs which were postulated to correspond to the HULIS. However, only a few efforts were made to test the correspondence of the AMS classes of OOAs with the traditional classification from the off-line methods. In this paper, we consider a case study representative for polluted continental regional background environments. We examine the AMS factors for OOAs identified by positive matrix factorization (PMF and compare to chemical classes of water-soluble organic carbon (WSOC analysed off-line on a set of filters collected in parallel. WSOC fractionation was performed by means of factor analysis applied to H-NMR spectroscopic data, and by applying an ion-exchange chromatographic method for direct quantification of HULIS. Results show that the very oxidized low-volatility OOAs from AMS correlate with the NMR factor showing HULIS features and also with true "chromatographic" HULIS. On the other hand, UV/VIS-absorbing polyacids (or HULIS sensu stricto isolated on ion-exchange beds were only a fraction of the AMS and NMR organic carbon fractions showing functional groups attributable to highly substituted

  10. Identification of humic-like substances (HULIS) in oxygenated organic aerosols using NMR and AMS factor analyses and liquid chromatographic techniques

    Science.gov (United States)

    Paglione, M.; Kiendler-Scharr, A.; Mensah, A. A.; Finessi, E.; Giulianelli, L.; Sandrini, S.; Facchini, M. C.; Fuzzi, S.; Schlag, P.; Piazzalunga, A.; Tagliavini, E.; Henzing, J. S.; Decesari, S.

    2014-01-01

    The atmospheric organic aerosol composition is characterized by a great diversity of functional groups and chemical species, challenging simple classification schemes. Traditional offline chemical methods identify chemical classes based on the retention behaviour on chromatographic columns and absorbing beds. Such an approach led to the isolation of complex mixtures of compounds such as the humic-like substances (HULIS). More recently, online aerosol mass spectrometry (AMS) was employed to identify chemical classes by extracting fragmentation patterns from experimental data series using statistical methods (factor analysis), providing simplified schemes for the classification of oxygenated organic aerosols (OOAs) on the basis of the distribution of oxygen-containing functionalities. The analysis of numerous AMS data sets suggested the occurrence of very oxidized OOAs which were postulated to correspond to HULIS. However, only a few efforts were made to test the correspondence of the AMS classes of OOAs with the traditional classifications from the offline methods. In this paper, we consider a case study representative of polluted continental regional background environments. We examine the AMS factors for OOAs identified by positive matrix factorization (PMF) and compare them to chemical classes of water-soluble organic carbon (WSOC) analysed offline on a set of filters collected in parallel. WSOC fractionation was performed by means of factor analysis applied to proton nuclear magnetic resonance (NMR) spectroscopic data, and by applying an ion-exchange chromatographic method for direct quantification of HULIS. Results show that the very oxidized low-volatility OOAs from AMS correlate with the NMR factor showing HULIS features and also with true "chromatographic" HULIS. On the other hand, UV/VIS-absorbing polyacids (or HULIS {sensu stricto}) isolated on ion-exchange beds were only a fraction of the AMS and NMR organic carbon fractions showing functional groups

  11. Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Jennifer L Bolton

    Full Text Available OBJECTIVE: We examined whether a panel of SNPs, systematically selected from genome-wide association studies (GWAS, could improve risk prediction of coronary heart disease (CHD, over-and-above conventional risk factors. These SNPs have already demonstrated reproducible associations with CHD; here we examined their use in long-term risk prediction. STUDY DESIGN AND SETTING: SNPs identified from meta-analyses of GWAS of CHD were tested in 840 men and women aged 55-75 from the Edinburgh Artery Study, a prospective, population-based study with 15 years of follow-up. Cox proportional hazards models were used to evaluate the addition of SNPs to conventional risk factors in prediction of CHD risk. CHD was classified as myocardial infarction (MI, coronary intervention (angioplasty, or coronary artery bypass surgery, angina and/or unspecified ischaemic heart disease as a cause of death; additional analyses were limited to MI or coronary intervention. Model performance was assessed by changes in discrimination and net reclassification improvement (NRI. RESULTS: There were significant improvements with addition of 27 SNPs to conventional risk factors for prediction of CHD (NRI of 54%, P<0.001; C-index 0.671 to 0.740, P = 0.001, as well as MI or coronary intervention, (NRI of 44%, P<0.001; C-index 0.717 to 0.750, P = 0.256. ROC curves showed that addition of SNPs better improved discrimination when the sensitivity of conventional risk factors was low for prediction of MI or coronary intervention. CONCLUSION: There was significant improvement in risk prediction of CHD over 15 years when SNPs identified from GWAS were added to conventional risk factors. This effect may be particularly useful for identifying individuals with a low prognostic index who are in fact at increased risk of disease than indicated by conventional risk factors alone.

  12. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik;

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...

  13. Linkage and association analyses identify a candidate region for apoB level on chromosome 4q32.3 in FCHL families.

    Science.gov (United States)

    Wijsman, Ellen M; Rothstein, Joseph H; Igo, Robert P; Brunzell, John D; Motulsky, Arno G; Jarvik, Gail P

    2010-06-01

    Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1 with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance, with heterozygotes for this SNP having a trait value that was approximately 30% higher than that of the high-frequency homozygote, thus identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals segregating otherwise-rare single variants leads to high power to implicate such variants.

  14. Identifying Factors Associated with Changes in CD4+ Count in HIV-Infected Adults in Saskatoon, Saskatchewan

    Directory of Open Access Journals (Sweden)

    Kelsey Hunt

    2015-01-01

    Full Text Available OBJECTIVE: To assess the impact of clinical and social factors unique to HIV-infected adults in Saskatoon, Saskatchewan, regarding the rate of CD4+ count change, and to identify factors associated with a risk of CD4+ count decline.

  15. Identifying factors that influence customer retention in a South African retail bank

    OpenAIRE

    Gouws, Nadia

    2012-01-01

    Customer retention plays a pivotal role in contributing to the profitability of retail banks. Within this extremely competitive market it necessitates retails banks to follow a structured, data-driven approach to identify “at risk” customers and to launch proactive retention campaigns based on identified drivers of customer attrition. The following main drivers of customer attrition were identified in the retail bank:  Attrition decrease as Vertical Sales Index increase.  Attrition...

  16. Exploratory and Higher-Order Factor Analyses of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Adolescent Subsample

    Science.gov (United States)

    Canivez, Gary L.; Watkins, Marley W.

    2010-01-01

    The factor structure of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV; Wechsler, 2008a) with the adolescent participants (ages 16-19 years; N = 400) in the standardization sample was assessed using exploratory factor analysis, multiple factor extraction criteria, and higher-order exploratory factor analyses. Results from…

  17. Exploratory and Higher-Order Factor Analyses of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Adolescent Subsample

    Science.gov (United States)

    Canivez, Gary L.; Watkins, Marley W.

    2010-01-01

    The factor structure of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV; Wechsler, 2008a) with the adolescent participants (ages 16-19 years; N = 400) in the standardization sample was assessed using exploratory factor analysis, multiple factor extraction criteria, and higher-order exploratory factor analyses. Results from…

  18. Localization and transcriptional responses of Chrysoporthe austroafricana in Eucalyptus grandis identify putative pathogenicity factors

    Directory of Open Access Journals (Sweden)

    Ronishree Mangwanda

    2016-12-01

    Full Text Available Chrysoporthe austroafricana is a fungal pathogen that causes the development of stem cankers on susceptible Eucalyptus grandis trees. Clones of E. grandis that are partially resistant and highly susceptible have been identified based on the extent of lesion formation on the stem upon inoculation with C. austroafricana. These interactions have been used as a model pathosystem to enhance our understanding of interactions between pathogenic fungi and woody hosts, which may be different to herbaceous hosts. In previous research, transcriptomics of host responses in these two clones to C. austroafricana suggested roles for salicylic acid and gibberellic acid phytohormone signalling in defense. However, it is unclear how the pathogen infiltrates host tissue and which pathogenicity factors facilitate its spread in the two host genotypes. The aim of this study was to investigate these two aspects of the E. grandis-C. austroafricana interaction and to test the hypothesis that the pathogen possesses mechanisms to modulate the tree phytohormone-mediated defenses. Light microscopy showed that the pathogen occurred in most cell types and structures within infected E. grandis stem tissue. Notably, the fungus appeared to spread through the stem by penetrating cell wall pits. In order to understand the molecular interaction between these organisms and predict putative pathogenicity mechanisms of C. austroafricana, fungal gene expression was studied in vitro and in planta. Fungal genes associated with cell wall degradation, carbohydrate metabolism and phytohormone manipulation were expressed in planta by C. austroafricana. These genes could be involved in fungal spread by facilitating cell wall pit degradation and manipulating phytohormone mediated defense in each host environment, respectively. Specifically, the in planta expression of an ent-kaurene oxidase and salicylate hydroxylase in C. austroafricana suggests putative mechanisms by which the pathogen can

  19. Identifying the sources of nitrate contamination of groundwater in an agricultural area (Haean basin, Korea) using isotope and microbial community analyses

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heejung [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of); Kaown, Dugin, E-mail: dugin1@snu.ac.kr [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of); Mayer, Bernhard [Department of Geoscience, University of Calgary, 2500 University Drive NW, Calgary T2N 1N4, Alberta (Canada); Lee, Jin-Yong [Department of Geology, Kangwon National University, Chuncheon 200–701 (Korea, Republic of); Hyun, Yunjung [Planning and Management Group, Korea Environment Institute, Sejong 339-007 (Korea, Republic of); Lee, Kang-Kun [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of)

    2015-11-15

    } and SO{sub 4}{sup 2−} in groundwater in areas with intensive agricultural land use. - Highlights: • Dual isotope analyses identified contaminant sources. • Aquifer contamination was affected by land use. • Microbial community in groundwater reflects land use. • Approach is promising for managing water quality in agricultural areas.

  20. A modified reverse one-hybrid screen identifies transcriptional activation in Phyochrome-Interacting Factor 3

    Science.gov (United States)

    Transcriptional activation domains (TAD) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput...

  1. Identifying the most critical project complexity factors using Delphi method: the Iranian construction industry

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Mozaffari

    2012-09-01

    Full Text Available Complexity is one of the most important issues influencing success of any construction project and there are literally different studies devoted to detect important factors increasing complexity of projects. During the past few years, there have been growing interests in developing mass construction projects in Iran. The proposed study of this paper uses Delphi technique to find out about important factors as barriers of construction projects in Iran. The results show that among 47 project complexity factors, 19 factors are more important than others are. The study groups different factors into seven categories including environmental, organizational, objectives, tasks, stakeholders, technological, information systems and determines the relative importance of each. In each group, many other sub group activities are determined and they are carefully investigated. The study provides some detailed suggestions on each category to reduce the complexity of construction project.

  2. An empirical study on identifying critical success factors on chaos management

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2012-08-01

    Full Text Available Chaos management is one of the most necessary efforts on managing business units. Many organizations fail to cope with undesirable circumstances, which may happen without any prior notice and as a result, they may face with significant financial losses. In this paper, we present an empirical study to determine critical success factors, which could help handle any possible chaos in organizations. The proposed study of this paper is implemented for a set of travel agencies located in Tehran, Iran. Chronbach alpha is calculated as 0.821, which is well above the minimum desirable level. In addition, we have also performed factor analysis, which yields a KMO value of 0.576 with the level of significance of 0.000. The results indicate that there are six important factors including effective management strategy, internal environmental factors, creative and innovative attitudes, external environmental factors and top level management tho