WorldWideScience

Sample records for association study analyses

  1. Multiple sclerosis genetics: Results from meta-analyses of candidate-gene association studies.

    Science.gov (United States)

    Tizaoui, Kalthoum

    2017-11-02

    As a complex disease, multiple sclerosis (MS) susceptibility implicates many genetic and environmental factors. Usually, individual genetic association studies have several limitations, and results are specific to the population of study. The Meta-analysis approach has been proposed to resolve these limitations and to increase the power of statistical analyses. In this review, we summarize results from meta-analyses of candidate genes of MS. Using the keywords: multiple sclerosis, genetic polymorphism and meta-analysis, we searched electronic databases (PubMed, Embase and Web of Sciences) for published meta-analyses until May 2017. Meta-analyses confirmed the association of polymorphisms in fifteen candidate genes with MS disease. However, polymorphisms in fourteen genes showed none significant association. Results outlined the importance of confirmed genes to understand signaling pathways in MS disease and shed light on their utility to develop new drugs targets. Copyright © 2017. Published by Elsevier Ltd.

  2. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer : Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    NARCIS (Netherlands)

    Khankari, Nikhil K.; Shu, Xiao Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Eeles, Rosalind A.; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J.; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos Santos Silva, Isabel; Ahsan, Habib; Whittemore, Alice; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B.; Uitterlinden, Andre G.; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare; Rahman, Nazneen; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham; Neal, David; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth; Riboli, Elio; Hunter, David; Gapstur, Susan; Berndt, Sonja; Chanock, Stephen; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Teresa Landi, Maria; Heinrich, Joachim; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.

    2016-01-01

    Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using

  3. Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.

    Science.gov (United States)

    Yashin, Anatoliy I; Fang, Fang; Kovtun, Mikhail; Wu, Deqing; Duan, Matt; Arbeev, Konstantin; Akushevich, Igor; Kulminski, Alexander; Culminskaya, Irina; Zhbannikov, Ilya; Yashkin, Arseniy; Stallard, Eric; Ukraintseva, Svetlana

    2017-10-26

    Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous health disorder with multiple alternative pathways of disease development and progression. The availability of genetic data on individuals participated in longitudinal studies of aging health and longevity, as well as on participants of cross-sectional case-control studies allow for investigating genetic and non-genetic connections with AD and to link the results of these analyses with research findings obtained in clinical, experimental, and molecular biological studies of this health disorder. The objective of this paper is to perform GWAS of AD in several study populations and investigate possible roles of detected genetic factors in developing AD hallmarks and in other health disorders. The data collected in the Framingham Heart Study (FHS), Cardiovascular Health Study (CHS), Health and Retirement Study (HRS) and Late Onset Alzheimer's Disease Family Study (LOADFS) were used in these analyses. The logistic regression and Cox's regression were used as statistical models in GWAS. The results of analyses confirmed strong associations of genetic variants from well-known genes APOE, TOMM40, PVRL2 (NECTIN2), and APOC1 with AD. Possible roles of these genes in pathological mechanisms resulting in development of hallmarks of AD are described. Many genes whose connection with AD was detected in other studies showed nominally significant associations with this health disorder in our study. The evidence on genetic connections between AD and vulnerability to infection, as well as between AD and other health disorders, such as cancer and type 2 diabetes, were investigated. The progress in uncovering hidden heterogeneity in AD would be substantially facilitated if common mechanisms involved in development of AD, its hallmarks

  4. Explorations in genome-wide association studies and network analyses with dairy cattle fertility traits.

    Science.gov (United States)

    Parker Gaddis, K L; Null, D J; Cole, J B

    2016-08-01

    The objective of this study was to identify single nucleotide polymorphisms and gene networks associated with 3 fertility traits in dairy cattle-daughter pregnancy rate, heifer conception rate, and cow conception rate-using different approaches. Deregressed predicted transmitting abilities were available for approximately 24,000 Holstein bulls and 36,000 Holstein cows sampled from the National Dairy Database with high-density genotypes. Of those, 1,732 bulls and 375 cows had been genotyped with the Illumina BovineHD Genotyping BeadChip (Illumina Inc., San Diego, CA). The remaining animals were genotyped with various chips of lower density that were imputed to high density. Univariate and trivariate genome-wide association studies (GWAS) with both medium- (60,671 markers) and high-density (312,614 markers) panels were performed for daughter pregnancy rate, heifer conception rate, and cow conception rate using GEMMA (version 0.94; http://www.xzlab.org/software.html). Analyses were conducted using bulls only, cows only, and a sample of both bulls and cows. The partial correlation and information theory algorithm was used to develop gene interaction networks. The most significant markers were further investigated to identify putatively associated genes. Little overlap in associated genes could be found between GWAS using different reference populations of bulls only, cows only, and combined bulls and cows. The partial correlation and information theory algorithm was able to identify several genes that were not identified by ordinary GWAS. The results obtained herein will aid in further dissecting the complex biology underlying fertility traits in dairy cattle, while also providing insight into the nuances of GWAS. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

    Science.gov (United States)

    Khankari, Nikhil K; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I; Easton, Douglas; Eeles, Rosalind A; Gruber, Stephen B; Haiman, Christopher A; Hunter, David J; Chanock, Stephen J; Pierce, Brandon L; Zheng, Wei

    2016-09-01

    Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

  6. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

    Directory of Open Access Journals (Sweden)

    Nikhil K Khankari

    2016-09-01

    Full Text Available Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS, to evaluate the association of adult height with these cancers.A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15, 1.07 (95% CI 1.05, 1.10, and 1.06 (95% CI 1.02, 1.11 for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18 and lung cancer (OR = 1.10, 95% CI 1.00, 1.22 associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15. Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate.Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

  7. Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

  8. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  9. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; de Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; de Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K.; Kahn, René S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Längström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-de-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W.; Muir, Walter J.; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Nöthen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutcliffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, J. C. G.; van Grootheest, Gerard; van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  10. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  11. SYSTEMS BIOLOGY ANALYSES OF GENE EXPRESSION AND GENOME WIDE ASSOCIATION STUDY DATA IN OBSTRUCTIVE SLEEP APNEA

    Science.gov (United States)

    LIU, YU; PATEL, SANJAY; NIBBE, ROD; MAXWELL, SEAN; CHOWDHURY, SALIM A.; KOYUTURK, MEHMET; ZHU, XIAOFENG; LARKIN, EMMA K.; BUXBAUM, SARAH G; PUNJABI, NARESH M.; GHARIB, SINA A.; REDLINE, SUSAN; CHANCE, MARK R.

    2015-01-01

    The precise molecular etiology of obstructive sleep apnea (OSA) is unknown; however recent research indicates that several interconnected aberrant pathways and molecular abnormalities are contributors to OSA. Identifying the genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment. Towards these goals, we have integrated relevant high dimensional data from various sources, such as genome-wide expression data (microarray), protein-protein interaction (PPI) data and results from genome-wide association studies (GWAS) in order to define sub-network elements that connect some of the known pathways related to the disease as well as define novel regulatory modules related to OSA. Two distinct approaches are applied to identify sub-networks significantly associated with OSA. In the first case we used a biased approach based on sixty genes/proteins with known associations with sleep disorders and/or metabolic disease to seed a search using commercial software to discover networks associated with disease followed by information theoretic (mutual information) scoring of the sub-networks. In the second case we used an unbiased approach and generated an interactome constructed from publicly available gene expression profiles and PPI databases, followed by scoring of the network with p-values from GWAS data derived from OSA patients to uncover sub-networks significant for the disease phenotype. A comparison of the approaches reveals a number of proteins that have been previously known to be associated with OSA or sleep. In addition, our results indicate a novel association of Phosphoinositide 3-kinase, the STAT family of proteins and its related pathways with OSA. PMID:21121029

  12. Analysing researchers’ outreach efforts and the association with publication metrics: A case study of Kudos

    Science.gov (United States)

    Aung, Htet Htet; Aw, Ashley Sara; Rapple, Charlie; Theng, Yin-Leng

    2017-01-01

    With the growth of scholarly collaboration networks and social communication platforms, members of the scholarly community are experimenting with their approach to disseminating research outputs, in an effort to increase their audience and outreach. However, from a researcher’s point of view, it is difficult to determine whether efforts to make work more visible are worthwhile (in terms of the association with publication metrics) and within that, difficult to assess which platform or network is most effective for sharing work and connecting to a wider audience. We undertook a case study of Kudos (https://www.growkudos.com), a web-based service that claims to help researchers increase the outreach of their publications, to examine the most effective tools for sharing publications online, and to investigate which actions are associated with improved metrics. We extracted a dataset from Kudos of 830,565 unique publications claimed by authors, for which 20,775 had actions taken to explain or share via Kudos, and for 4,867 of these full text download data from publishers was available. Findings show that researchers are most likely to share their work on Facebook, but links shared on Twitter are more likely to be clicked on. A Mann-Whitney U test revealed that a treatment group (publications having actions in Kudos) had a significantly higher median average of 149 full text downloads (23.1% more) per publication as compared to a control group (having no actions in Kudos) with a median average of 121 full text downloads per publication. These findings suggest that performing actions on publications, such as sharing, explaining, or enriching, could help to increase the number of full text downloads of a publication. PMID:28817627

  13. Analysing researchers' outreach efforts and the association with publication metrics: A case study of Kudos.

    Directory of Open Access Journals (Sweden)

    Mojisola Erdt

    Full Text Available With the growth of scholarly collaboration networks and social communication platforms, members of the scholarly community are experimenting with their approach to disseminating research outputs, in an effort to increase their audience and outreach. However, from a researcher's point of view, it is difficult to determine whether efforts to make work more visible are worthwhile (in terms of the association with publication metrics and within that, difficult to assess which platform or network is most effective for sharing work and connecting to a wider audience. We undertook a case study of Kudos (https://www.growkudos.com, a web-based service that claims to help researchers increase the outreach of their publications, to examine the most effective tools for sharing publications online, and to investigate which actions are associated with improved metrics. We extracted a dataset from Kudos of 830,565 unique publications claimed by authors, for which 20,775 had actions taken to explain or share via Kudos, and for 4,867 of these full text download data from publishers was available. Findings show that researchers are most likely to share their work on Facebook, but links shared on Twitter are more likely to be clicked on. A Mann-Whitney U test revealed that a treatment group (publications having actions in Kudos had a significantly higher median average of 149 full text downloads (23.1% more per publication as compared to a control group (having no actions in Kudos with a median average of 121 full text downloads per publication. These findings suggest that performing actions on publications, such as sharing, explaining, or enriching, could help to increase the number of full text downloads of a publication.

  14. Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

    Directory of Open Access Journals (Sweden)

    Kshitij Srivastava

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs. Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444 and cancer risk by using a two-sided meta-analytic approach.An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR and 95% confidence interval (95% CI were used to investigate the strength of the association.Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002. Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

  15. A clinical observational study analysing the factors associated with hyperventilation during actual cardiopulmonary resuscitation in the emergency department.

    Science.gov (United States)

    Park, Sang O; Shin, Dong Hyuk; Baek, Kwang Je; Hong, Dae Young; Kim, Eun Jung; Kim, Sang Chul; Lee, Kyeong Ryong

    2013-03-01

    This is the first study to identify the factors associated with hyperventilation during actual cardiopulmonary resuscitation (CPR) in the emergency department (ED). All CPR events in the ED were recorded by video from April 2011 to December 2011. The following variables were analysed using review of the recorded CPR data: ventilation rate (VR) during each minute and its associated factors including provider factors (experience, advanced cardiovascular life support (ACLS) certification), clinical factors (auscultation to confirm successful intubation, suctioning, and comments by the team leader) and time factors (time or day of CPR). Fifty-five adult CPR cases including a total of 673 min sectors were analysed. The higher rates of hyperventilation (VR>10/min) were delivered by inexperienced (53.3% versus 14.2%) or uncertified ACLS provider (52.2% versus 10.8%), during night time (61.0 versus 34.5%) or weekend CPR (53.1% versus 35.6%) and when auscultation to confirm successful intubation was performed (93.5% versus 52.8%) than not (all pHyperventilation during CPR was associated with inexperienced or uncertified ACLS provider, auscultation to confirm intubation, and night time or weekend CPR. And to deliver proper ventilation, comments by the team leader should be given regardless of providers' expert level. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

    Directory of Open Access Journals (Sweden)

    Wenbo Tang

    Full Text Available Genome-wide association studies (GWAS have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1 in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7. In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8 at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  17. 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

    2015-03-20

    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

  18. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

    NARCIS (Netherlands)

    Luca, G. De; Haba-Rubio, J.; Dauvilliers, Y.; Lammers, G.J.; Overeem, S.; Donjacour, C.E.; Mayer, G.; Javidi, S.; Iranzo, A.; Santamaria, J.; Peraita-Adrados, R.; Hor, H.; Kutalik, Z.; Plazzi, G.; Poli, F.; Pizza, F.; Arnulf, I.; Lecendreux, M.; Bassetti, C.; Mathis, J.; Heinzer, R.; Jennum, P.; Knudsen, S.; Geisler, P.; Wierzbicka, A.; Feketeova, E.; Pfister, C.; Khatami, R.; Baumann, C.; Tafti, M.

    2013-01-01

    The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy

  19. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

    National Research Council Canada - National Science Library

    Luca, G. De; Haba-Rubio, J; Dauvilliers, Y; Lammers, G.J; Overeem, S; Donjacour, C.E; Mayer, G; Javidi, S; Iranzo, A; Santamaria, J; Peraita-Aados, R; Hor, H; Kutalik, Z; Plazzi, G; Poli, F; Pizza, F; Arnulf, I; Leceneux, M; Bassetti, C; Mathis, J; Heinzer, R; Jennum, P; Knudsen, S; Geisler, P; Wierzbicka, A; Feketeova, E; Pfister, C; Khatami, R; Baumann, C; Tafti, M

    2013-01-01

    The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN...

  20. Methodological Standards for Meta-Analyses and Qualitative Systematic Reviews of Cardiac Prevention and Treatment Studies: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Rao, Goutham; Lopez-Jimenez, Francisco; Boyd, Jack; D'Amico, Frank; Durant, Nefertiti H; Hlatky, Mark A; Howard, George; Kirley, Katherine; Masi, Christopher; Powell-Wiley, Tiffany M; Solomonides, Anthony E; West, Colin P; Wessel, Jennifer

    2017-09-05

    Meta-analyses are becoming increasingly popular, especially in the fields of cardiovascular disease prevention and treatment. They are often considered to be a reliable source of evidence for making healthcare decisions. Unfortunately, problems among meta-analyses such as the misapplication and misinterpretation of statistical methods and tests are long-standing and widespread. The purposes of this statement are to review key steps in the development of a meta-analysis and to provide recommendations that will be useful for carrying out meta-analyses and for readers and journal editors, who must interpret the findings and gauge methodological quality. To make the statement practical and accessible, detailed descriptions of statistical methods have been omitted. Based on a survey of cardiovascular meta-analyses, published literature on methodology, expert consultation, and consensus among the writing group, key recommendations are provided. Recommendations reinforce several current practices, including protocol registration; comprehensive search strategies; methods for data extraction and abstraction; methods for identifying, measuring, and dealing with heterogeneity; and statistical methods for pooling results. Other practices should be discontinued, including the use of levels of evidence and evidence hierarchies to gauge the value and impact of different study designs (including meta-analyses) and the use of structured tools to assess the quality of studies to be included in a meta-analysis. We also recommend choosing a pooling model for conventional meta-analyses (fixed effect or random effects) on the basis of clinical and methodological similarities among studies to be included, rather than the results of a test for statistical heterogeneity. © 2017 American Heart Association, Inc.

  1. Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix™ and Narcolepsy.

    Science.gov (United States)

    Bollaerts, Kaatje; Shinde, Vivek; Dos Santos, Gaël; Ferreira, Germano; Bauchau, Vincent; Cohet, Catherine; Verstraeten, Thomas

    2016-01-01

    An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies. We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible. Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72-28.11) reduced to a median value of 6.06 (2.5th- 97.5th percentile: 2.49-15.1) and the French odds ratio of 5.43 (95% CI: 2.6-10.08) to 1.85 (2.5th-97.5th percentile: 0.85-4.08). We illustrate multiple-bias analyses using two studies on the Pandemrix™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.

  2. A critical update on endothelial nitric oxide synthase gene variations in women with idiopathic recurrent spontaneous abortion: genetic association study, systematic review and meta-analyses.

    Science.gov (United States)

    Pereza, N; Peterlin, B; Volk, M; Kapović, M; Ostojić, S

    2015-05-01

    A number of case-control studies investigated the association between idiopathic recurrent spontaneous abortion (IRSA) and variations in the gene encoding endothelial nitric oxide synthase (NOS3), but yielded contradictory results. Our aim was to test the association of the NOS3 variable number of tandem repeats (VNTR) in intron 4 and +894 G/T single-nucleotide polymorphism (SNP) with IRSA in Slovenian women (148 IRSA and 149 control women), conduct a systematic review of literature on the association between NOS3 gene variations and IRSA, and perform meta-analyses of studies that met the inclusion criteria, defined by virtue of the European Society for Human Reproduction and Embryology evidence-based guidelines for recurrent spontaneous abortion. Genotyping was performed using PCR and restriction fragment length polymorphism methods. The systematic review of literature (English language) was conducted using PubMed and Scopus databases, to 1 November 2014. We determined no association of IRSA with the VNTR in intron 4 and +894 G/T SNP in Slovenian women. Furthermore, 16 case-control studies were identified on the association between 15 NOS3 gene variations and IRSA. However, significant inconsistencies exist in the selection criteria of patients and controls between studies. The meta-analysis of VNTR in intron 4 was performed on five studies (894 patients, 944 controls), whereas the meta-analysis of +894 G/T SNP included six studies (1111 patients, 1121 controls). The association with IRSA was significant for the +894 G/T SNP under the dominant genetic model (GT+TT versus GG) based on fixed (odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.28-1.86, P = <0.01) and random effects models (OR = 1.54, 95% CI = 1.03-2.31, P = 0.03). In conclusion, the GT and TT genotypes of the +894 G/T SNP in women might contribute to a predisposition to IRSA. Additional genetic association and functional studies in different populations with larger numbers of participants and a

  3. 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

  4. 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; Amin Al Olama, Ali; 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; Edwards, Digna R Velez; 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

    2016-09-01

    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 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 cancer meta-analysis. We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932. ©2016 American Association for Cancer Research.

  5. Association between forgone care and household income among the elderly in five Western European countries – analyses based on survey data from the SHARE-study

    Science.gov (United States)

    Mielck, Andreas; Kiess, Raphael; Knesebeck, Olaf von dem; Stirbu, Irina; Kunst, Anton E

    2009-01-01

    Background Studies on the association between access to health care and household income have rarely included an assessment of 'forgone care', but this indicator could add to our understanding of the inverse care law. We hypothesize that reporting forgone care is more prevalent in low income groups. Methods The study is based on the 'Survey of Health, Ageing and Retirement in Europe (SHARE)', focusing on the non-institutionalized population aged 50 years or older. Data are included from France, Germany, Greece, Italy and Sweden. The dependent variable is assessed by the following question: During the last twelve months, did you forgo any types of care because of the costs you would have to pay, or because this care was not available or not easily accessible? The main independent variable is household income, adjusted for household size and split into quintiles, calculating the quintile limits for each country separately. Information on age, sex, self assessed health and chronic disease is included as well. Logistic regression models were used for the multivariate analyses. Results The overall level of forgone care differs considerably between the five countries (e.g. about 10 percent in Greece and 6 percent in Sweden). Low income groups report forgone care more often than high income groups. This association can also be found in analyses restricted to the subsample of persons with chronic disease. Associations between forgone care and income are particularly strong in Germany and Greece. Taking the example of Germany, forgone care in the lowest income quintile is 1.98 times (95% CI: 1.08–3.63) as high as in the highest income quintile. Conclusion Forgone care should be reduced even if it is not justified by an 'objective' need for health care, as it could be an independent stressor in its own right, and as patient satisfaction is a strong predictor of compliance. These efforts should focus on population groups with particularly high prevalence of forgone care

  6. A Robust and Powerful Set-Valued Approach to Rare Variant Association Analyses of Secondary Traits in Case-Control Sequencing Studies.

    Science.gov (United States)

    Kang, Guolian; Bi, Wenjian; Zhang, Hang; Pounds, Stanley; Cheng, Cheng; Shete, Sanjay; Zou, Fei; Zhao, Yanlong; Zhang, Ji-Feng; Yue, Weihua

    2017-03-01

    In many case-control designs of genome-wide association (GWAS) or next generation sequencing (NGS) studies, extensive data on secondary traits that may correlate and share the common genetic variants with the primary disease are available. Investigating these secondary traits can provide critical insights into the disease etiology or pathology, and enhance the GWAS or NGS results. Methods based on logistic regression (LG) were developed for this purpose. However, for the identification of rare variants (RVs), certain inadequacies in the LG models and algorithmic instability can cause severely inflated type I error, and significant loss of power, when the two traits are correlated and the RV is associated with the disease, especially at stringent significance levels. To address this issue, we propose a novel set-valued (SV) method that models a binary trait by dichotomization of an underlying continuous variable, and incorporate this into the genetic association model as a critical component. Extensive simulations and an analysis of seven secondary traits in a GWAS of benign ethnic neutropenia show that the SV method consistently controls type I error well at stringent significance levels, has larger power than the LG-based methods, and is robust in performance to effect pattern of the genetic variant (risk or protective), rare or common variants, rare or common diseases, and trait distributions. Because of the SV method's striking and profound advantage, we strongly recommend the SV method be employed instead of the LG-based methods for secondary traits analyses in case-control sequencing studies. Copyright © 2017 by the Genetics Society of America.

  7. Associations between proteasomal activator PA28γ and outcome of oral squamous cell carcinoma: Evidence from cohort studies and functional analyses

    Science.gov (United States)

    Li, Jing; Feng, Xiaodong; Sun, Chongkun; Zeng, Xin; Xie, Liang; Xu, Hao; Li, Taiwen; Wang, Ruinan; Xu, Xiaoping; Zhou, Xikun; Zhou, Min; Zhou, Yu; Dan, Hongxia; Wang, Zhiyong; Ji, Ning; Deng, Peng; Liao, Ga; Geng, Ning; Wang, Yun; Zhang, Dunfang; Lin, Yunfeng; Ye, Ling; Liang, Xinhua; Li, Longjiang; Luo, Gang; Jiang, Lu; Wang, Zhi; Chen, Qianming

    2015-01-01

    Summary Background PA28γ was suggested to play a role in malignant progression. This paper aimed to investigate the association between PA28γ and the prognosis of oral squamous cell carcinoma (OSCC) in cohort studies. Methods The PA28γ expression level was assessed by immunohistochemistry in a total of 368 OSCC patients from three independent cohorts. The Cox proportional hazards regression model was used to determine multivariate hazard ratios for Overall Survival (OS). Model discrimination was measured using C Statistic. Additionally, OS was analyzed in Head Neck Squamous Cell Carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) data set. Functional analyses were conducted both in-vitro and in-vivo. Findings The median follow-up times of patients in the three studies were 60, 52, and 51 months. High expression of PA28γ was identified in tumors from 179 of 368 patients (48.6%). Compared with low expression, high expression of PA28γ was strongly associated with worse OS, with relative risks of 5.14 (95% CI, 2.51–10.5; P < 0.001), 2.82 (95% CI, 1.73–4.61; P < 0.001), and 3.85 (95% CI, 1.59–9.37; P = 0.003). PA28γ expression was also associated with disease-free survival in all three cohorts (P < 0.005). These findings are consistent with TCGA HNSCC data (P < 0.006). The prediction of all-cause mortality was significantly improved when PA28γ was added to the traditional clinical factors (Model 3, C statistic value: 0.78 VS 0.73, P = 0.016). In functional analyses, we found that PA28γ silencing dramatically inhibited the growth, proliferation and mobility of OSCC cells in vitro and reduced tumor growth and angiogenesis in tumor-bearing mice. Interpretation PA28γ overexpression is associated with adverse prognosis in patients with OSCC. The aberrant expression of PA28γ may contribute to the pathogenesis and progression of OSCC. Research in context OSCC is one of the most common HNSCC, which have a high lethally rate. However, few

  8. Associations of indoor carbon dioxide concentrations and environmental susceptibilities with mucous membrane and lower respiratory building related symptoms in the BASE study: Analyses of the 100 building dataset

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, Christine A.; Apte, Michael G.

    2003-09-01

    Using the US EPA 100 office-building BASE Study dataset, they conducted multivariate logistic regression analyses to quantify the relationship between indoor CO{sub 2} concentrations (dCO{sub 2}) and mucous membrane (MM) and lower respiratory system (LResp) building related symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. In addition, they tested the hypothesis that certain environmentally-mediated health conditions (e.g., allergies and asthma) confer increased susceptibility to building related symptoms within office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependent associations (p < 0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100 ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average, reduce the prevalence of several building related symptoms by up to 70%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. Building occupants with certain environmentally-mediated health conditions are more likely to experience building related symptoms than those without these conditions (statistically significant ORs ranged from 2 to 11).

  9. Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

    Science.gov (United States)

    2012-01-01

    Background The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). Results The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). Conclusions In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. Trial registration ClinicalTrials.gov number NCT00154180 PMID:22587616

  10. Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

    Directory of Open Access Journals (Sweden)

    Huang Gary

    2012-07-01

    Full Text Available Abstract Background The published literature regarding the relationships between retinol-binding protein 4 (RBP4 and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT, and coronary artery calcification (CAC. Results The mean age of women was 52.9 (± 2.6 years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5 μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01, but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05. Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile. However, a squared RBP4 term in regression modeling was non-significant (P = 0.10. Conclusions In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. Trial registration ClinicalTrials.gov number NCT

  11. An omnibus permutation test on ensembles of two-locus analyses can detect pure epistasis and genetic heterogeneity in genome-wide association studies

    Science.gov (United States)

    2013-01-01

    This article presents the ability of an omnibus permutation test on ensembles of two-locus analyses (2LOmb) to detect pure epistasis in the presence of genetic heterogeneity. The performance of 2LOmb is evaluated in various simulation scenarios covering two independent causes of complex disease where each cause is governed by a purely epistatic interaction. Different scenarios are set up by varying the number of available single nucleotide polymorphisms (SNPs) in data, number of causative SNPs and ratio of case samples from two affected groups. The simulation results indicate that 2LOmb outperforms multifactor dimensionality reduction (MDR) and random forest (RF) techniques in terms of a low number of output SNPs and a high number of correctly-identified causative SNPs. Moreover, 2LOmb is capable of identifying the number of independent interactions in tractable computational time and can be used in genome-wide association studies. 2LOmb is subsequently applied to a type 1 diabetes mellitus (T1D) data set, which is collected from a UK population by the Wellcome Trust Case Control Consortium (WTCCC). After screening for SNPs that locate within or near genes and exhibit no marginal single-locus effects, the T1D data set is reduced to 95,991 SNPs from 12,146 genes. The 2LOmb search in the reduced T1D data set reveals that 12 SNPs, which can be divided into two independent sets, are associated with the disease. The first SNP set consists of three SNPs from MUC21 (mucin 21, cell surface associated), three SNPs from MUC22 (mucin 22), two SNPs from PSORS1C1 (psoriasis susceptibility 1 candidate 1) and one SNP from TCF19 (transcription factor 19). A four-locus interaction between these four genes is also detected. The second SNP set consists of three SNPs from ATAD1 (ATPase family, AAA domain containing 1). Overall, the findings indicate the detection of pure epistasis in the presence of genetic heterogeneity and provide an alternative explanation for the aetiology of T1D

  12. Association and linkage analyses of RGS4 polymorphisms in schizophrenia.

    Science.gov (United States)

    Chowdari, Kodavali V; Mirnics, Karoly; Semwal, Prachi; Wood, Joel; Lawrence, Elizabeth; Bhatia, Triptish; Deshpande, Smita N; B K, Thelma; Ferrell, Robert E; Middleton, Frank A; Devlin, Bernie; Levitt, Pat; Lewis, David A; Nimgaonkar, Vishwajit L

    2002-06-01

    Gene expression analyses of postmortem cerebral cortex suggest that transcription of the regulator of G-protein signaling 4 (RGS4) is decreased in a diagnosis-specific manner in subjects with schizophrenia. To evaluate the possible role of RGS4 in the pathogenesis of schizophrenia, we conducted genetic association and linkage studies using samples ascertained independently in Pittsburgh and New Delhi and by the NIMH Collaborative Genetics Initiative. Using the transmission disequilibrium test, significant transmission distortion was observed in the Pittsburgh and NIMH samples. Among single-nucleotide polymorphisms (SNPs) spanning approximately 300 kb, significant associations involved four SNPs localized to a 10 kb region at RGS4, but the associated haplotypes differed. A trend for transmission distortion was also present in the Indian sample for haplotypes incorporating the same SNPs. Consistent with the linkage/association observed from the family-based tests, samples with affected siblings (NIMH, India) showed higher levels of allele sharing, identical by descent, at RGS4. When the US patients were contrasted to two population-based control samples, however, no significant differences were observed. To check the specificity of the transmission bias, we therefore examined US families with bipolar I disorder (BD1) probands. This sample also showed a trend for transmission distortion, and differed significantly from the population-based controls for the four-SNP haplotypes tested in the other samples. The transmission distortion is unlikely to be due to chance, but its mechanism and specificity require further study. Our results illustrate the potential power of combining gene expression profiling and genomic analyses to identify susceptibility genes for genetically complex disorders.

  13. Meta-analyses of Blood Homocysteine Levels for Gender and Genetic Association Studies of the MTHFR C677T Polymorphism in Schizophrenia

    Science.gov (United States)

    Nishi, Akira; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Kikuchi, Kumiko; Shimodera, Shinji; Tomotake, Masahito; Ohi, Kazutaka; Hashimoto, Ryota; Imoto, Issei; Takeda, Masatoshi; Ohmori, Tetsuro

    2014-01-01

    Previous studies suggest that elevated blood homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for schizophrenia. However, the effects of gender and MTHFR C677T genotypes on blood homocysteine levels in schizophrenia have not been consistent. We first investigated whether plasma total homocysteine levels were higher in patients with schizophrenia than in controls with stratification by gender and by the MTHFR C677T genotypes in a large cohort (N = 1379). Second, we conducted a meta-analysis of association studies between blood homocysteine levels and schizophrenia separately by gender (N = 4714). Third, we performed a case-control association study between the MTHFR C677T polymorphism and schizophrenia (N = 4998) and conducted a meta-analysis of genetic association studies based on Japanese subjects (N = 10 378). Finally, we assessed the effect of plasma total homocysteine levels on schizophrenia by a mendelian randomization approach. The ANCOVA after adjustment for age demonstrated a significant effect of diagnosis on the plasma total homocysteine levels in all strata, and the subsequent meta-analysis for gender demonstrated elevated blood homocysteine levels in both male and female patients with schizophrenia although antipsychotic medication might influence the outcome. The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia. The mendelian randomization analysis in the Japanese populations yielded an OR of 1.15 for schizophrenia per 1-SD increase in plasma total homocysteine. Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia. PMID:24535549

  14. Age at natural menopause and its associated factors in Canada: cross-sectional analyses from the Canadian Longitudinal Study on Aging.

    Science.gov (United States)

    Costanian, Christy; McCague, Hugh; Tamim, Hala

    2017-10-02

    Early onset of menopause is associated with long-term disease and higher mortality risks. Research suggests that age at natural menopause (ANM) varies across populations. Little is known about factors that affect ANM in Canadian women. This study aims to estimate the median ANM and examine factors associated with earlier ANM among Canadian women. Baseline data from the Tracking cohort of the Canadian Longitudinal Study on Aging was used for this analysis. The relation of sociodemographic, lifestyle, and health-related factors with ANM was examined among 7,719 women aged 40 and above. Nonparametric Kaplan-Meier cumulative survivorship estimates were used to assess the timing of natural menopause. Univariate and multivariate Cox proportional hazard regression models were used to characterize ANM and its association with relevant covariates. Overall, median ANM was 51 years. Having no partner, low household income and education levels, current and former smoking, and cardiovascular disease were all associated with an earlier ANM, whereas current employment, alcohol consumption, and obesity were associated with later ANM. These findings provide a national estimate of ANM in Canada and show the importance of lifestyle factors and health conditions in determining menopausal age. These factors might help in risk assessment, prevention and early management of chronic disease risk during the menopausal transition.

  15. Analyse

    DEFF Research Database (Denmark)

    Greve, Bent

    2007-01-01

    Analyse i Politiken om frynsegoder med udgangspunkt i bogen Occupational Welfare - Winners and Losers publiceret på Edward Elgar......Analyse i Politiken om frynsegoder med udgangspunkt i bogen Occupational Welfare - Winners and Losers publiceret på Edward Elgar...

  16. [The maintenance of automatic analysers and associated documentation].

    Science.gov (United States)

    Adjidé, V; Fournier, P; Vassault, A

    2010-12-01

    The maintenance of automatic analysers and associated documentation taking part in the requirements of the ISO 15189 Standard and the French regulation as well have to be defined in the laboratory policy. The management of the periodic maintenance and documentation shall be implemented and fulfilled. The organisation of corrective maintenance has to be managed to avoid interruption of the task of the laboratory. The different recommendations concern the identification of materials including automatic analysers, the environmental conditions to take into account, the documentation provided by the manufacturer and documents prepared by the laboratory including procedures for maintenance.

  17. A Weighted U Statistic for Association Analyses Considering Genetic Heterogeneity

    Science.gov (United States)

    Wei, Changshuai; Elston, Robert C.; Lu, Qing

    2016-01-01

    Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments (SAGE) dataset. The genome-wide analysis of nearly one million genetic markers took 7 hours, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. PMID:26833871

  18. Exploring clinical associations using '-omics' based enrichment analyses.

    Directory of Open Access Journals (Sweden)

    David A Hanauer

    Full Text Available The vast amounts of clinical data collected in electronic health records (EHR is analogous to the data explosion from the "-omics" revolution. In the EHR clinicians often maintain patient-specific problem summary lists which are used to provide a concise overview of significant medical diagnoses. We hypothesized that by tapping into the collective wisdom generated by hundreds of physicians entering problems into the EHR we could detect significant associations among diagnoses that are not described in the literature.We employed an analytic approach original developed for detecting associations between sets of gene expression data, called Molecular Concept Map (MCM, to find significant associations among the 1.5 million clinical problem summary list entries in 327,000 patients from our institution's EHR. An odds ratio (OR and p-value was calculated for each association. A subset of the 750,000 associations found were explored using the MCM tool. Expected associations were confirmed and recently reported but poorly known associations were uncovered. Novel associations which may warrant further exploration were also found. Examples of expected associations included non-insulin dependent diabetes mellitus and various diagnoses such as retinopathy, hypertension, and coronary artery disease. A recently reported association included irritable bowel and vulvodynia (OR 2.9, p = 5.6x10(-4. Associations that are currently unknown or very poorly known included those between granuloma annulare and osteoarthritis (OR 4.3, p = 1.1x10(-4 and pyloric stenosis and ventricular septal defect (OR 12.1, p = 2.0x10(-3.Computer programs developed for analyses of "-omic" data can be successfully applied to the area of clinical medicine. The results of the analysis may be useful for hypothesis generation as well as supporting clinical care by reminding clinicians of likely problems associated with a patient's existing problems.

  19. A Common Haplotype of the Glucokinase Gene Alters Fasting Glucose and Birth Weight: Association in Six Studies and Population-Genetics Analyses

    OpenAIRE

    Weedon, Michael N; Clark, Vanessa J; Qian, Yudong; Ben-Shlomo, Yoav; Timpson, Nicholas; Ebrahim, Shah; Lawlor, Debbie A.; Pembrey, Marcus E.; Ring, Susan; Wilkin, Terry J.; Voss, Linda D.; Jeffery, Alison N.; Metcalf, Brad; Ferrucci, Luigi; Corsi, Anna Maria

    2006-01-01

    Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK expl...

  20. Comparison of veterinary import risk analyses studies

    NARCIS (Netherlands)

    Vos-de Jong, de C.J.; Conraths, F.J.; Adkin, A.; Jones, E.M.; Hallgren, G.S.; Paisley, L.G.

    2011-01-01

    Twenty-two veterinary import risk analyses (IRAs) were audited: a) for inclusion of the main elements of risk analysis; b) between different types of IRAs; c) between reviewers' scores. No significant differences were detected between different types of IRAs, although quantitative IRAs and IRAs

  1. Association of study quality with completeness of reporting: have completeness of reporting and quality of systematic reviews and meta-analyses in major radiology journals changed since publication of the PRISMA statement?

    Science.gov (United States)

    Tunis, Adam S; McInnes, Matthew D F; Hanna, Ramez; Esmail, Kaisra

    2013-11-01

    To evaluate whether completeness of reporting of systematic reviews and meta-analyses in major radiology journals has changed since publication of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement; a secondary objective is to evaluate whether completeness of reporting (ie, PRISMA) is associated with study quality (ie, Assessing the Methodological Quality of Systematic Reviews [AMSTAR]). Systematic reviews and meta-analyses published in major radiology journals between January 2007 and December 2011 were identified by searching MEDLINE with the modified Montori method. Studies were reviewed independently by two investigators and assessed for adherence to the AMSTAR and PRISMA checklists. The average results were analyzed to assess for change in mean score before and after PRISMA publication and to assess results over time; a Pearson correlation coefficient was calculated to assess for any association between PRISMA and AMSTAR results. Included were 130 studies from 11 journals. Average PRISMA and AMSTAR results were 21.8 of 27 and 7.2 of 11, respectively. The average result was higher after publication of PRISMA, and PRISMA-reported items were 22.6 of 27 after publication of PRISMA versus 20.9 of 27 before publication of PRISMA; AMSTAR results were 7.7 of 11 after publication of PRISMA versus 6.7 of 11 before publication of PRISMA. There was a strong positive correlation (r = 0.86) between the PRISMA and AMSTAR results. There was high variability between journals. Radiology had the highest PRISMA reported items (24.7 of 27), and American Journal of Neuroradiology had the lowest (19.6 of 27). Two major areas for improvement include study protocol registration and assessment of risk of bias across studies (ie, publication bias). In major radiology journal studies, there was modest improvement in completeness of reporting of systematic reviews and meta-analyses, assessed by PRISMA, which was strongly associated with higher study

  2. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

    NARCIS (Netherlands)

    Kraja, Aldi T.; Cook, James P.; Warren, Helen R.; Surendran, Praveen; Liu, Chunyu; Evangelou, Evangelos; Manning, Alisa K.; Grarup, Niels; Drenos, Fotios; Sim, Xueling; Smith, Albert Vernon; Amin, Najaf; Blakemore, Alexandra I F; Bork-Jensen, Jette; Brandslund, Ivan; Farmaki, Aliki-Eleni; Fava, Cristiano; Ferreira, Teresa; Herzig, Karl-Heinz; Giri, Ayush; Giulianini, Franco; Grove, Megan L.; Guo, Xiuqing; Harris, Sarah E.; Have, Christian T; Havulinna, Aki S; Zhang, He; Jørgensen, Marit E; Käräjämäki, Annemari; Kooperberg, Charles; Linneberg, Allan; Little, Louis; Liu, Yongmei; Bonnycastle, Lori L.; Lu, Yingchang; Mägi, Reedik; Mahajan, Anubha; Malerba, Giovanni; Marioni, Riccardo E.; Mei, Hao; Menni, Cristina; Morrison, Alanna C.; Padmanabhan, Sandosh; Palmas, Walter R.; Poveda, Alaitz; Rauramaa, Rainer; Rayner, Nigel William; Riaz, Muhammad; Rice, Ken; Richard, Melissa A; Smith, Jennifer A.; Southam, Lorraine; Stančáková, Alena; Stirrups, Kathleen E; Tragante, Vinicius; Tuomi, Tiinamaija; Tzoulaki, Ioanna; Varga, Tibor V.; Weiss, Stefan; Yiorkas, Andrianos M; Young, Robin; Zhang, Weihua; Barnes, Michael R; Cabrera, Claudia P; Gao, He; Boehnke, Michael; Boerwinkle, Eric; Chambers, John C.; Connell, John M; Christensen, Cramer K; de Boer, Rudolf A.; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; Dominiczak, Anna F.; Dörr, Marcus; Joehanes, Roby; Edwards, Todd L.; Esko, Tõnu; Fornage, Myriam; Franceschini, Nora; Franks, Paul W.; Gambaro, Giovanni; Groop, Leif C.; Hallmans, Göran; Hansen, Torben; Hayward, Caroline; Heikki, Oksa; Ingelsson, Erik; Tuomilehto, Jaakko; Jarvelin, Marjo-Riitta; Kardia, Sharon L. R.; Karpe, Fredrik; Kooner, Jaspal S.; Lakka, Timo A.; Langenberg, Claudia; Lind, Lars; Loos, Ruth J. F.; Laakso, Markku; McCarthy, Mark I.; Melander, Olle; Mohlke, Karen L.; Morris, Andrew P.; Palmer, Colin N. A.; Pedersen, Oluf; Polasek, Ozren; Poulter, Neil R.; Province, Michael A.; Psaty, Bruce M.; Ridker, Paul M.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J.; Sever, Peter J; Skaaby, Tea; Stafford, Jeanette M; Starr, John M.; van der Harst, Pim; Van der Meer, Peter; Van Duijn, Cornelia M.; Vergnaud, Anne Claire; Gudnason, Vilmundur; Wareham, Nicholas J.; Wilson, James G.; Willer, Cristen J.; Witte, Daniel R; Zeggini, Eleftheria; Saleheen, Danish; Butterworth, Adam S.; Danesh, John; Asselbergs, Folkert W; Wain, Louise V.; Ehret, Georg B.; Chasman, Daniel I.; Caulfield, Mark J.; Elliott, Paul; Lindgren, Cecilia M.; Levy, Daniel; Newton-Cheh, Christopher; Munroe, Patricia B.; Howson, Joanna M M

    2017-01-01

    BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An

  3. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Cook, James P; Warren, Helen R

    2017-01-01

    BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data....

  4. Associations of indoor carbon dioxide concentrations, VOCS, environmental susceptibilities with mucous membrane and lower respiratory sick building syndrome symptoms in the BASE study: Analyses of the 100 building dataset

    Energy Technology Data Exchange (ETDEWEB)

    Apte, M.G.; Erdmann, C.A.

    2002-10-01

    Using the 100 office-building Building Assessment Survey and Evaluation (BASE) Study dataset, we performed multivariate logistic regression analyses to quantify the associations between indoor minus outdoor CO{sub 2} (dCO{sub 2}) concentrations and mucous membrane (MM) and lower respiratory system (Lresp) Sick Building Syndrome (SBS) symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. Using principal components analysis we identified a number of possible sources of 73 measured volatile organic compounds in the office buildings, and assessed the impact of these VOCs on the probability of presenting the SBS symptoms. Additionally we included analysis adjusting for the risks for predisposition of having SBS symptoms associated with the allergic, asthmatic, and environmentally sensitive subpopulations within the office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependant associations (p<0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100-ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average significantly reduce the prevalence of several SBS symptoms, up to 80%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. VOC sources were observed to play an role in direct association with mucous membrane and lower respiratory irritation, and possibly to be indirectly involved in indoor chemical reactions with ozone that produce irritating compounds associated with SBS symptoms. O-xylene, possibly emitted from furniture coatings was associated with shortness of breath (OR at the maximum concentration = 8, p < 0.05). The environmental sensitivities of a large subset of the office building population add to the overall risk of SBS symptoms (ORs

  5. Deep analyses of the associations of a series of biomarkers with insulin resistance, metabolic syndrome, and diabetes risk in nondiabetic middle-aged and elderly individuals: results from a Chinese community-based study

    Directory of Open Access Journals (Sweden)

    Fu S

    2016-10-01

    Full Text Available Shihui Fu,1,2,* Ping Ping,3,* Leiming Luo,1 Ping Ye1 1Department of Geriatric Cardiology, 2Department of Cardiology and Hainan Branch, 3Department of Pharmaceutical Care, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: The current study was designed to perform deep analyses of the associations of biomarkers, including high-sensitivity C-reactive protein (hs-CRP, N-terminal prohormone of brain natriuretic peptide (NT-proBNP, and homocysteine (Hcy, with insulin resistance (IR, metabolic syndrome (MetS, and diabetes risk and evaluate the abilities of biomarkers to identify IR, MetS, and diabetes risk in Chinese community-dwelling middle-aged and elderly residents.Participants and methods: A total of 396 participants older than 45 years underwent physical examinations and laboratory analyses following standardized protocol.Results: Serum hs-CRP concentrations were able to identify MetS, Chinese diabetes risk score (CDRS ≥4, high-density lipoprotein-cholesterol (HDL-c <0.9/1.0 mmol/L, and HDL-c <1.0/1.3 mmol/L (P<0.05 for all. Serum NT-proBNP concentrations were able to identify homeostasis model assessment of IR >1.5, CDRS ≥4, overweight, and blood pressure (BP ≥140/90 mmHg (P<0.05 for all. Serum Hcy concentrations were able to identify CDRS ≥4, general obesity, overweight, and BP ≥140/90 mmHg (P<0.05 for all. Serum hs-CRP concentrations were independently associated with MetS as well as HDL-c <1.0/1.3 mmol/L and HDL-c <0.9/1.0 mmol/L (P<0.05 for all. Serum NT-proBNP concentrations were independently associated with BP ≥140/90 mmHg (P<0.05. Serum Hcy concentrations were independently associated with CDRS ≥4 (P<0.05.Conclusion: Serum HDL-c levels were the major determinant of the associations between serum hs-CRP levels and MetS and the key link between inflammation and MetS. There was no other association of these biomarkers

  6. Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits

    DEFF Research Database (Denmark)

    Andreasen, Camilla Helene; Mogensen, Mette S.; Borch-Johnsen, Knut

    2008-01-01

    ,367, nNOS1AP = 8,435). RESULTS: In case-control studies we evaluated the potential association between rs3020781 and rs7538490 and type 2 diabetes and obesity. No significant associations were observed for type 2 diabetes (rs3020781: pAF = 0.49, OR = 1.02 [0.96-1.10]; rs7538490: pAF = 0.84, OR = 0.99 [0...

  7. Strategies for genetic association analyses combining unrelated case-control individuals and family trios.

    Science.gov (United States)

    Mirea, Lucia; Infante-Rivard, Claire; Sun, Lei; Bull, Shelley B

    2012-07-01

    In genetic association studies, analyses integrating data or estimates from unrelated case-control individuals and case trios (case offspring and their parents) can increase statistical power to identify disease susceptibility loci. Data on control trios may also be available, but how and when their use is advantageous is less familiar and is described here. In addition, the authors examine assumptions and properties of hybrid analyses combining association estimates from unrelated case-control individuals together with case and control family trios, focusing on low-prevalence disease. One such assumption is absence of population stratification bias (PSB), a potential source of confounding in case-control analyses. For detection of PSB, the authors discuss 4 possible tests that assess equality between individual-level and family-based estimates. Furthermore, a weighted framework is presented, in which estimates from analyses combining unrelated individuals and families (most powerful but subject to PSB) and family-based analyses (robust to PSB) are weighted according to the observed PSB test P value. In contrast to existing hybrid designs that combine individuals and families only if no significant PSB is detected, the weighted framework does not require specification of an arbitrary PSB testing level to establish significance. The statistical methods are evaluated using simulations and applied to a candidate gene study of childhood leukemia (Quebec Childhood Leukemia Study, 1980-2000).

  8. Comparison of Genome-Wide Association Methods in Analyses of Admixed Populations with Complex Familial Relationships

    DEFF Research Database (Denmark)

    Kadri, Naveen; Guldbrandtsen, Bernt; Sørensen, Peter

    2014-01-01

    ) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic......Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K...... and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships...

  9. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

    Science.gov (United States)

    Lu, Yi; Vitart, Veronique; Burdon, Kathryn P; Khor, Chiea Chuen; Bykhovskaya, Yelena; Mirshahi, Alireza; Hewitt, Alex W; Koehn, Demelza; Hysi, Pirro G; Ramdas, Wishal D; Zeller, Tanja; Vithana, Eranga N; Cornes, Belinda K; Tay, Wan-Ting; Tai, E Shyong; Cheng, Ching-Yu; Liu, Jianjun; Foo, Jia-Nee; Saw, Seang Mei; Thorleifsson, Gudmar; Stefansson, Kari; Dimasi, David P; Mills, Richard A; Mountain, Jenny; Ang, Wei; Hoehn, René; Verhoeven, Virginie J M; Grus, Franz; Wolfs, Roger; Castagne, Raphaële; Lackner, Karl J; Springelkamp, Henriët; Yang, Jian; Jonasson, Fridbert; Leung, Dexter Y L; Chen, Li J; Tham, Clement C Y; Rudan, Igor; Vatavuk, Zoran; Hayward, Caroline; Gibson, Jane; Cree, Angela J; MacLeod, Alex; Ennis, Sarah; Polasek, Ozren; Campbell, Harry; Wilson, James F; Viswanathan, Ananth C; Fleck, Brian; Li, Xiaohui; Siscovick, David; Taylor, Kent D; Rotter, Jerome I; Yazar, Seyhan; Ulmer, Megan; Li, Jun; Yaspan, Brian L; Ozel, Ayse B; Richards, Julia E; Moroi, Sayoko E; Haines, Jonathan L; Kang, Jae H; Pasquale, Louis R; Allingham, R Rand; Ashley-Koch, Allison; Mitchell, Paul; Wang, Jie Jin; Wright, Alan F; Pennell, Craig; Spector, Timothy D; Young, Terri L; Klaver, Caroline C W; Martin, Nicholas G; Montgomery, Grant W; Anderson, Michael G; Aung, Tin; Willoughby, Colin E; Wiggs, Janey L; Pang, Chi P; Thorsteinsdottir, Unnur; Lotery, Andrew J; Hammond, Christopher J; van Duijn, Cornelia M; Hauser, Michael A; Rabinowitz, Yaron S; Pfeiffer, Norbert; Mackey, David A; Craig, Jamie E; Macgregor, Stuart; Wong, Tien Y

    2013-02-01

    Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

  10. Comparison of genome-wide association methods in analyses of admixed populations with complex familial relationships.

    Directory of Open Access Journals (Sweden)

    Naveen K Kadri

    Full Text Available Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P and family (K levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic markers. Linear models that ignored K were also tested. Correction for P was performed using principal component or structured association analysis. In analyses of simulated and real data, linear mixed models that corrected for K were able to control for type-I error, regardless of whether they also corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships derived from either pedigree or from genetic markers.

  11. The MAFLA (Mississippi, Alabama, Florida) Study, Grain Size Analyses

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The MAFLA (Mississippi, Alabama, Florida) Study was funded by NOAA as part of the Outer Continental Shelf Program. Dr. L.J. Doyle produced grain size analyses in the...

  12. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

    Science.gov (United States)

    Lu, Yi; Vitart, Veronique; Burdon, Kathryn P; Khor, Chiea Chuen; Bykhovskaya, Yelena; Mirshahi, Alireza; Hewitt, Alex W; Koehn, Demelza; Hysi, Pirro G; Ramdas, Wishal D; Zeller, Tanja; Vithana, Eranga N; Cornes, Belinda K; Tay, Wan-Ting; Tai, E Shyong; Cheng, Ching-Yu; Liu, Jianjun; Foo, Jia-Nee; Saw, Seang Mei; Thorleifsson, Gudmar; Stefansson, Kari; Dimasi, David P; Mills, Richard A; Mountain, Jenny; Ang, Wei; Hoehn, René; Verhoeven, Virginie J M; Grus, Franz; Wolfs, Roger; Castagne, Raphaële; Lackner, Karl J; Springelkamp, Henriët; Yang, Jian; Jonasson, Fridbert; Leung, Dexter Y L; Chen, Li J; Tham, Clement C Y; Rudan, Igor; Vatavuk, Zoran; Hayward, Caroline; Gibson, Jane; Cree, Angela J; MacLeod, Alex; Ennis, Sarah; Polasek, Ozren; Campbell, Harry; Wilson, James F; Viswanathan, Ananth C; Fleck, Brian; Li, Xiaohui; Siscovick, David; Taylor, Kent D; Rotter, Jerome I; Yazar, Seyhan; Ulmer, Megan; Li, Jun; Yaspan, Brian L; Ozel, Ayse B; Richards, Julia E; Moroi, Sayoko E; Haines, Jonathan L; Kang, Jae H; Pasquale, Louis R; Allingham, R Rand; Ashley-Koch, Allison; Mitchell, Paul; Wang, Jie Jin; Wright, Alan F; Pennell, Craig; Spector, Timothy D; Young, Terri L; Klaver, Caroline C W; Martin, Nicholas G; Montgomery, Grant W; Anderson, Michael G; Aung, Tin; Willoughby, Colin E; Wiggs, Janey L; Pang, Chi P; Thorsteinsdottir, Unnur; Lotery, Andrew J; Hammond, Christopher J; van Duijn, Cornelia M; Hauser, Michael A; Rabinowitz, Yaron S; Pfeiffer, Norbert; Mackey, David A; Craig, Jamie E; Macgregor, Stuart; Wong, Tien Y

    2013-01-01

    Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10−8). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4–1.88, P = 2.7 × 10−10, and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29–1.68, P = 4.9 × 10−9). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10−4; tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT. PMID:23291589

  13. Quality control and conduct of genome-wide association meta-analyses

    DEFF Research Database (Denmark)

    Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C

    2014-01-01

    Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC...... a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable...

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

    Science.gov (United States)

    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; Study, LifeLines Cohort; 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; Leach, Irene Mateo; 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; Consortium, CARDIoGRAM; Consortium, DIAGRAM; Consortium, ICBP; Consortium, MAGIC; 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 serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. PMID:23263486

  15. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm

    2017-01-01

    (ACE). METHODS: In total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs......) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated......OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme...

  16. Phenotype-genotype association grid: a convenient method for summarizing multiple association analyses

    Directory of Open Access Journals (Sweden)

    O'Donnell Christopher J

    2006-05-01

    Full Text Available Abstract Background High-throughput genotyping generates vast amounts of data for analysis; results can be difficult to summarize succinctly. A single project may involve genotyping many genes with multiple variants per gene and analyzing each variant in relation to numerous phenotypes, using several genetic models and population subgroups. Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association. Results To facilitate visual display and summary of large numbers of association tests of genetic loci with multiple phenotypes, we developed a Phenotype-Genotype Association (PGA grid display. A database-backed web server was used to create PGA grids from phenotypic and genotypic data (sample sizes, means and standard errors, P-value for association. HTML pages were generated using Tcl scripts on an AOLserver platform, using an Oracle database, and the ArsDigita Community System web toolkit. The grids are interactive and permit display of summary data for individual cells by a mouse click (i.e. least squares means for a given SNP and phenotype, specified genetic model and study sample. PGA grids can be used to visually summarize results of individual SNP associations, gene-environment associations, or haplotype associations. Conclusion The PGA grid, which permits interactive exploration of large numbers of association test results, can serve as an easily adapted common and useful display format for large-scale genetic studies. Doing so would reduce the problem of publication bias, and would simplify the task of summarizing large-scale association studies.

  17. Association and interaction analyses of eight genes under asthma linkage peaks

    DEFF Research Database (Denmark)

    Ferreira, M A R; Zhao, Z Z; Thomsen, S F

    2009-01-01

    BACKGROUND: Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits. METHODS: Ninety-five single nucleotide...... polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in >5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor-diagnosed asthma, atopy, airway obstruction, total serum...... immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene-wide thresholds for significance determined through simulation. Gene-by-gene and gene-by-environment analyses were also performed. RESULTS: There was no overall evidence for association...

  18. Genome-wide association analyses identify variants in developmental genes associated with hypospadias

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Carstensen, Lisbeth

    2014-01-01

    Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1...

  19. Novel autism subtype-dependent genetic variants are revealed by quantitative trait and subphenotype association analyses of published GWAS data.

    Science.gov (United States)

    Hu, Valerie W; Addington, Anjene; Hyman, Alexander

    2011-04-27

    The heterogeneity of symptoms associated with autism spectrum disorders (ASDs) has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs). The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL), were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression) than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders.

  20. Novel autism subtype-dependent genetic variants are revealed by quantitative trait and subphenotype association analyses of published GWAS data.

    Directory of Open Access Journals (Sweden)

    Valerie W Hu

    Full Text Available The heterogeneity of symptoms associated with autism spectrum disorders (ASDs has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs. The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL, were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders.

  1. Type-based associations in grapheme-color synaesthesia revealed by response time distribution analyses.

    Science.gov (United States)

    Saiki, Jun; Yoshioka, Ayako; Yamamoto, Hiroki

    2011-12-01

    Determining the nature of binding in grapheme-color synaesthesia has consequences for understanding the neural basis of synaesthesia and visual awareness in general. We evaluated type- and token-based letter-color binding using a synaesthetic version of the object-reviewing paradigm. Although mean response times failed to reveal any significant differences between synaesthetes and control participants, RT analyses with ex-Gaussian distributions revealed that the response facilitation in the synaesthesia group reflected type representations exclusively, while response facilitation in the control group, who learned letter-color associations, was dominated by token representations. Thus, letter-color associations in associator synaesthetes are type-based, and do not involve binding to object tokens, consistent with their subjective reports. Contrary to recent studies that failed to find differences between synaesthetes and non-synaesthetes with behavioral measures, response time distribution analyses indicate that color sensations in synaesthetes are not simply the extreme form of normal letter-color associations, and cannot be attributed to demand characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies.

    Science.gov (United States)

    Buil, Alfonso; Trégouët, David-Alexandre; Souto, Juan Carlos; Saut, Noémie; Germain, Marine; Rotival, Maxime; Tiret, Laurence; Cambien, Françcois; Lathrop, Mark; Zeller, Tanja; Alessi, Marie-Christine; Rodriguez de Cordoba, Santiago; Münzel, Thomas; Wild, Philipp; Fontcuberta, Jordi; Gagnon, France; Emmerich, Joseph; Almasy, Laura; Blankenberg, Stefan; Soria, José-Manuel; Morange, Pierre-Emmanuel

    2010-06-10

    Through its binding with protein S (PS), a key element of the coagulation/fibrinolysis cascade, the C4b-binding protein (C4BP) has been hypothesized to be involved in the susceptibility to venous thrombosis (VT). To identify genetic factors that may influence the plasma levels of the 3 C4BP existing isoforms, alpha(7)beta(1), alpha(6)beta(1), and alpha(7)beta(0), we conducted a genome-wide association study by analyzing 283 437 single nucleotide polymorphisms (SNPs) in the Genetic Analysis of Idiopathic Thrombophilia (GAIT) study composed of 352 persons. Three SNPs at the C4BPB/C4BPA locus were found genome-wide significantly associated with alpha(7)beta(0) levels. One of these SNPs was further found to explain approximately 11% of the variability of mRNA C4BPA expression in the Gutenberg Heart Study composed of 1490 persons, with no effect on C4BPB mRNA expression. The allele associated with increased alpha(7)beta(0) plasma levels and increased C4BPA expression was further found associated with increased risk of VT (odds ratio [OR] = 1.24 [1.03-1.53]) in 2 independent case-control studies (MARseille THrombosis Association study [MARTHA] and FActeurs de RIsque et de récidives de la maladie thromboembolique VEineuse [FARIVE]) gathering 1706 cases and 1379 controls. This SNP was not associated with free PS or total PS. In conclusion, we observed strong evidence that the C4BPB/C4BPA locus is a new susceptibility locus for VT through a PS-independent mechanism that remains to be elucidated.

  3. No compelling positive association between ovarian hormones and wearing red clothing when using multinomial analyses.

    Science.gov (United States)

    Blake, Khandis R; Dixson, Barnaby J W; O'Dean, Siobhan M; Denson, Thomas F

    2017-04-01

    Several studies report that wearing red clothing enhances women's attractiveness and signals sexual proceptivity to men. The associated hypothesis that women will choose to wear red clothing when fertility is highest, however, has received mixed support from empirical studies. One possible cause of these mixed findings may be methodological. The current study aimed to replicate recent findings suggesting a positive association between hormonal profiles associated with high fertility (high estradiol to progesterone ratios) and the likelihood of wearing red. We compared the effect of the estradiol to progesterone ratio on the probability of wearing: red versus non-red (binary logistic regression); red versus neutral, black, blue, green, orange, multi-color, and gray (multinomial logistic regression); and each of these same colors in separate binary models (e.g., green versus non-green). Red versus non-red analyses showed a positive trend between a high estradiol to progesterone ratio and wearing red, but the effect only arose for younger women and was not robust across samples. We found no compelling evidence for ovarian hormones increasing the probability of wearing red in the other analyses. However, we did find that the probability of wearing neutral was positively associated with the estradiol to progesterone ratio, though the effect did not reach conventional levels of statistical significance. Findings suggest that although ovarian hormones may affect younger women's preference for red clothing under some conditions, the effect is not robust when differentiating amongst other colors of clothing. In addition, the effect of ovarian hormones on clothing color preference may not be specific to the color red. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Variables associated with achievement in higher education: A systematic review of meta-analyses.

    Science.gov (United States)

    Schneider, Michael; Preckel, Franzis

    2017-06-01

    The last 2 decades witnessed a surge in empirical studies on the variables associated with achievement in higher education. A number of meta-analyses synthesized these findings. In our systematic literature review, we included 38 meta-analyses investigating 105 correlates of achievement, based on 3,330 effect sizes from almost 2 million students. We provide a list of the 105 variables, ordered by the effect size, and summary statistics for central research topics. The results highlight the close relation between social interaction in courses and achievement. Achievement is also strongly associated with the stimulation of meaningful learning by presenting information in a clear way, relating it to the students, and using conceptually demanding learning tasks. Instruction and communication technology has comparably weak effect sizes, which did not increase over time. Strong moderator effects are found for almost all instructional methods, indicating that how a method is implemented in detail strongly affects achievement. Teachers with high-achieving students invest time and effort in designing the microstructure of their courses, establish clear learning goals, and employ feedback practices. This emphasizes the importance of teacher training in higher education. Students with high achievement are characterized by high self-efficacy, high prior achievement and intelligence, conscientiousness, and the goal-directed use of learning strategies. Barring the paucity of controlled experiments and the lack of meta-analyses on recent educational innovations, the variables associated with achievement in higher education are generally well investigated and well understood. By using these findings, teachers, university administrators, and policymakers can increase the effectivity of higher education. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available INTRODUCTION: Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway. METHODS: Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls. RESULTS: The TRAIL pathway achieved a significant p value (p = 0.01 for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05; the TNFSF10 (TRAIL gene obtained the most significant p value (p = 1.70×10(-4. SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706 from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3 of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415 from two genes (TNFSF10 and TNFRSF10B of the pathway had minor alleles (A that are associated with an increased risk of hip OF, with the ORs (odds ratios of 16.51 (95%CI:3.83-71.24 and 1.37 (95%CI:1.08-1.74, respectively. CONCLUSIONS: Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF.

  6. Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population.

    Science.gov (United States)

    Park, Hansoo; Lee, Seungbok; Kim, Hyun-Jin; Ju, Young Seok; Shin, Jong-Yeon; Hong, Dongwan; von Grotthuss, Marcin; Lee, Dong-Sung; Park, Changho; Kim, Jennifer Hayeon; Kim, Boram; Yoo, Yun Joo; Cho, Sung-Il; Sung, Joohon; Lee, Charles; Kim, Jong-Il; Seo, Jeong-Sun

    2012-12-01

    Musical abilities such as recognising music and singing performance serve as means for communication and are instruments in sexual selection. Specific regions of the brain have been found to be activated by musical stimuli, but these have rarely been extended to the discovery of genes and molecules associated with musical ability. A total of 1008 individuals from 73 families were enrolled and a pitch-production accuracy test was applied to determine musical ability. To identify genetic loci and variants that contribute to musical ability, we conducted family-based linkage and association analyses, and incorporated the results with data from exome sequencing and array comparative genomic hybridisation analyses. We found significant evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose supporting interval overlaps a previous study in Finnish families, and identified an intergenic single nucleotide polymorphism (SNP) (rs1251078, p = 8.4 × 10(-17)) near UGT8, a gene highly expressed in the central nervous system and known to act in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to be highly associated with musical ability (rs4148254, p = 8.0 × 10(-17)), and a 6.2 kb copy number loss near UGT8 showed a plausible association with musical ability (p = 2.9 × 10(-6)). This study provides new insight into the genetics of musical ability, exemplifying a methodology to assign functional significance to synonymous and non-coding alleles by integrating multiple experimental methods.

  7. Haplotype association analyses in resources of mixed structure using Monte Carlo testing

    Directory of Open Access Journals (Sweden)

    Thomas Alun

    2010-12-01

    Full Text Available Abstract Background Genomewide association studies have resulted in a great many genomic regions that are likely to harbor disease genes. Thorough interrogation of these specific regions is the logical next step, including regional haplotype studies to identify risk haplotypes upon which the underlying critical variants lie. Pedigrees ascertained for disease can be powerful for genetic analysis due to the cases being enriched for genetic disease. Here we present a Monte Carlo based method to perform haplotype association analysis. Our method, hapMC, allows for the analysis of full-length and sub-haplotypes, including imputation of missing data, in resources of nuclear families, general pedigrees, case-control data or mixtures thereof. Both traditional association statistics and transmission/disequilibrium statistics can be performed. The method includes a phasing algorithm that can be used in large pedigrees and optional use of pseudocontrols. Results Our new phasing algorithm substantially outperformed the standard expectation-maximization algorithm that is ignorant of pedigree structure, and hence is preferable for resources that include pedigree structure. Through simulation we show that our Monte Carlo procedure maintains the correct type 1 error rates for all resource types. Power comparisons suggest that transmission-disequilibrium statistics are superior for performing association in resources of only nuclear families. For mixed structure resources, however, the newly implemented pseudocontrol approach appears to be the best choice. Results also indicated the value of large high-risk pedigrees for association analysis, which, in the simulations considered, were comparable in power to case-control resources of the same sample size. Conclusions We propose hapMC as a valuable new tool to perform haplotype association analyses, particularly for resources of mixed structure. The availability of meta-association and haplotype-mining modules in

  8. The Association between Endometriosis, Tubal Ligation, Hysterectomy and Epithelial Ovarian Cancer: Meta-Analyses

    Directory of Open Access Journals (Sweden)

    Chunpeng Wang

    2016-11-01

    Full Text Available To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995–2016. Heterogeneity was evaluated by I2 statistic. Publication bias was tested by funnel plot and Egger’s test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28–1.57, tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60–0.81, while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81–1.14. A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer.

  9. Meta-Analyses of the Associations of Respiratory Health Effectswith Dampness and Mold in Homes

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, William J.; Lei-Gomez, Quanhong; Mendell, Mark J.

    2006-01-01

    The Institute of Medicine (IOM) of the National Academy of Sciences recently completed a critical review of the scientific literature pertaining to the association of indoor dampness and mold contamination with adverse health effects. In this paper, we report the results of quantitative meta-analysis of the studies reviewed in the IOM report. We developed point estimates and confidence intervals (CIs) to summarize the association of several respiratory and asthma-related health outcomes with the presence of dampness and mold in homes. The odds ratios and confidence intervals from the original studies were transformed to the log scale and random effect models were applied to the log odds ratios and their variance. Models were constructed both accounting for the correlation between multiple results within the studies analyzed and ignoring such potential correlation. Central estimates of ORs for the health outcomes ranged from 1.32 to 2.10, with most central estimates between 1.3 and 1.8. Confidence intervals (95%) excluded unity except in two of 28 instances, and in most cases the lower bound of the CI exceeded 1.2. In general, the two meta-analysis methods produced similar estimates for ORs and CIs. Based on the results of the meta-analyses, building dampness and mold are associated with approximately 30% to 80% increases in a variety of respiratory and asthma-related health outcomes. The results of these meta-analyses reinforce the IOM's recommendation that actions be taken to prevent and reduce building dampness problems.

  10. 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.

  11. Association and interaction analyses of eight genes under asthma linkage peaks

    DEFF Research Database (Denmark)

    Ferreira, M.A.R.; Zhao, Z.Z.; Thomsen, S.F.

    2009-01-01

    immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene-wide thresholds for significance determined through simulation. Gene-by-gene and gene-by-environment analyses were also performed. Results: There was no overall evidence for association...

  12. Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data.

    Science.gov (United States)

    Bailly, Sébastien; Leroy, Olivier; Montravers, Philippe; Constantin, Jean-Michel; Dupont, Hervé; Guillemot, Didier; Lortholary, Olivier; Mira, Jean-Paul; Perrigault, Pierre-François; Gangneux, Jean-Pierre; Azoulay, Elie; Timsit, Jean-François

    2015-11-01

    Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients. From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de-escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation. Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22%), including 48 (34%) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95% CI 0.76-1.66). In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patients.

  13. Bicycling injury hospitalisation rates in Canadian jurisdictions: analyses examining associations with helmet legislation and mode share

    Science.gov (United States)

    Teschke, Kay; Koehoorn, Mieke; Shen, Hui; Dennis, Jessica

    2015-01-01

    Objectives The purpose of this study was to calculate exposure-based bicycling hospitalisation rates in Canadian jurisdictions with different helmet legislation and bicycling mode shares, and to examine whether the rates were related to these differences. Methods Administrative data on hospital stays for bicycling injuries to 10 body region groups and national survey data on bicycling trips were used to calculate hospitalisation rates. Rates were calculated for 44 sex, age and jurisdiction strata for all injury causes and 22 age and jurisdiction strata for traffic-related injury causes. Inferential analyses examined associations between hospitalisation rates and sex, age group, helmet legislation and bicycling mode share. Results In Canada, over the study period 2006–2011, there was an average of 3690 hospitalisations per year and an estimated 593 million annual trips by bicycle among people 12 years of age and older, for a cycling hospitalisation rate of 622 per 100 million trips (95% CI 611 to 633). Hospitalisation rates varied substantially across the jurisdiction, age and sex strata, but only two characteristics explained this variability. For all injury causes, sex was associated with hospitalisation rates; females had rates consistently lower than males. For traffic-related injury causes, higher cycling mode share was consistently associated with lower hospitalisation rates. Helmet legislation was not associated with hospitalisation rates for brain, head, scalp, skull, face or neck injuries. Conclusions These results suggest that transportation and health policymakers who aim to reduce bicycling injury rates in the population should focus on factors related to increased cycling mode share and female cycling choices. Bicycling routes designed to be physically separated from traffic or along quiet streets fit both these criteria and are associated with lower relative risks of injury. PMID:26525719

  14. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    2011-02-01

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  15. Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index

    Science.gov (United States)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian’an; Mägi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segré, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F.; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Åsa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R.B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I.F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N.M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J.C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Gräßler, Jürgen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; König, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O’Donnell, Christopher J.; O’Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Paré, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H.; Platou, Carl G.P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B.J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kähönen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Grönberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E.H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, André; Valle, Timo T.; Wabitsch, Martin; Waeber, Gérard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O’Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H.-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Gonçalo R.; Barroso, Inês; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J.F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (P<5×10−8), one of which includes a copy number variant near GPRC5B. Some loci (MC4R, POMC, SH2B1, BDNF) map near key hypothalamic regulators of energy balance, and one is near GIPR, an incretin receptor. Furthermore, genes in other newly-associated loci may provide novel insights into human body weight regulation. PMID:20935630

  16. CVD diamond Brewster window: feasibility study by FEM analyses

    Directory of Open Access Journals (Sweden)

    Vaccaro A.

    2012-09-01

    Full Text Available Chemical vapor deposition (CVD diamond windows are a crucial component in heating and current drive (H&CD applications. In order to minimize the amount of reflected power from the diamond disc, its thickness must match the desired beam wavelength, thus proper targeting of the plasma requires movable beam reflectors. This is the case, for instance, of the ITER electron cyclotron H&CD system. However, looking at DEMO, the higher heat loads and neutron fluxes could make the use of movable parts close to the plasma difficult. The issue might be solved by using gyrotrons able to tune the beam frequency to the desired resonance, but this concept requires transmission windows that work in a given frequency range, such as the Brewster window. It consists of a CVD diamond disc brazed to two copper cuffs at the Brewster angle. The brazing process is carried out at about 800°C and then the temperature is decreased down to room temperature. Diamond and copper have very different thermal expansion coefficients, therefore high stresses build up during the cool down phase that might lead to failure of the disc. Considering also the complex geometry of the window with the skewed position of the disc, analyses are required in the first place to check its feasibility. The cool down phase was simulated by FEM structural analyses for several geometric and constraint configurations of the window. A study of indirect cooling of the window by water was also performed considering a HE11 mode beam. The results are here reported.

  17. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian'an; Maegi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segre, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelaenen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F.; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R. B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I. F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proenca, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N. M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J. C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Graessler, Juergen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; Koenig, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimaeki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Pare, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietilaeinen, Kirsi H.; Platou, Carl G. P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstrale, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Toenjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B. J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kaehoenen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Greonberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E. H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre; Valle, Timo T.; Wabitsch, Martin; Waeber, Gerard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Goncalo R.; Barroso, Ines; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J. F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of

  18. 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

  19. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SN...

  20. Integrated metagenomics and metatranscriptomics analyses of root-associated soil from transgenic switchgrass.

    Science.gov (United States)

    Chauhan, Archana; Smartt, Abby; Wang, Jun; Utturkar, Sagar; Frank, Ashley; Bi, Meng; Liu, Jiang; Williams, Daniel; Xu, Tingting; Eldridge, Melanie; Arreaza, Andres; Rogers, Alexandra; Gonzalez, Hector Castro; Layton, Alice C; Baxter, Holly L; Mazarei, Mitra; DeBruyn, Jennifer M; Stewart, C Neal; Brown, Steven D; Hauser, Loren J; Sayler, Gary S

    2014-08-14

    The benefits of using transgenic switchgrass with decreased levels of caffeic acid 3-O-methyltransferase (COMT) as biomass feedstock have been clearly demonstrated. However, its effect on the soil microbial community has not been assessed. Here we report metagenomic and metatranscriptomic analyses of root-associated soil from COMT switchgrass compared with nontransgenic counterparts. Copyright © 2014 Chauhan et al.

  1. Study of the Microbiological Analyses Carried Out at the Laboratory ...

    African Journals Online (AJOL)

    ... Candida albicans, Pseudomonas, Syphilis, hepatitis viruses and HIV) in deferens samples (Urine, Pus, saddle, like and Serum) in patients in relation with total analyses carried out for 3 years. Then we follow their development during this period with the analysis of the results. Keywords: Microbiological analyses; Germs; ...

  2. 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.

  3. Meta-analyses of studies of the human microbiota.

    Science.gov (United States)

    Lozupone, Catherine A; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vázquez-Baeza, Yoshiki; Jansson, Janet K; Gordon, Jeffrey I; Knight, Rob

    2013-10-01

    Our body habitat-associated microbial communities are of intense research interest because of their influence on human health. Because many studies of the microbiota are based on the same bacterial 16S ribosomal RNA (rRNA) gene target, they can, in principle, be compared to determine the relative importance of different disease/physiologic/developmental states. However, differences in experimental protocols used may produce variation that outweighs biological differences. By comparing 16S rRNA gene sequences generated from diverse studies of the human microbiota using the QIIME database, we found that variation in composition of the microbiota across different body sites was consistently larger than technical variability across studies. However, samples from different studies of the Western adult fecal microbiota generally clustered by study, and the 16S rRNA target region, DNA extraction technique, and sequencing platform produced systematic biases in observed diversity that could obscure biologically meaningful compositional differences. In contrast, systematic compositional differences in the fecal microbiota that occurred with age and between Western and more agrarian cultures were great enough to outweigh technical variation. Furthermore, individuals with ileal Crohn's disease and in their third trimester of pregnancy often resembled infants from different studies more than controls from the same study, indicating parallel compositional attributes of these distinct developmental/physiological/disease states. Together, these results show that cross-study comparisons of human microbiota are valuable when the studied parameter has a large effect size, but studies of more subtle effects on the human microbiota require carefully selected control populations and standardized protocols.

  4. Comparison of different anticoagulant associations on haemostasis and biochemical analyses in feline blood specimens.

    Science.gov (United States)

    Granat, Fanny; Monzali, Céline; Jeunesse, Elisabeth; Guerlin, Maud; Trumel, Catherine; Geffré, Anne; Bourgès-Abella, Nathalie

    2017-04-01

    Objectives Universal anticoagulant could be an alternative to the multiple blood sampling required for clinical pathology investigations in cats. An association of citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to be a good substitute for EDTA for haematology analysis in cats, limiting platelet clumping, and has also been shown to be valid for haematology, secondary haemostasis and some biochemical variables in humans. The aim of the study was therefore to investigate the effects of CTAD on in vitro platelet aggregation and compare results of secondary haemostasis and biochemistry tests, excluding a priori those variables not reliably measured in CTAD, such as sodium, chloride and divalent cations, in feline blood specimens collected in CTAD and paired citrate and heparin tubes. Methods Thirty blood specimens sampled in citrate and CTAD were analysed for in vitro platelet aggregation, and 60 blood specimens sampled in citrate or heparin and CTAD were analysed for plasma coagulation and a biochemistry panel. Results In vitro platelet aggregation was inhibited in CTAD compared with citrate specimens. Prothrombin time, activated partial thromboplastin time, antithrombin and fibrinogen results were similar, despite some significant differences. Measurements of triglycerides, cholesterol, glucose, urea, creatinine, phosphate, total proteins and alanine aminotransferase activity were similar and well correlated in CTAD and heparin plasmas, despite some significant differences and moderate biases. Albumin showed a marked positive proportional bias, and creatine kinase and alkaline phosphatase activities a moderate and marked negative mixed bias, respectively, but could be measured in CTAD if new reference intervals were calculated. Aspartate aminotransferase activity showed a marked negative proportional bias, along with a poor correlation and some clinical misclassifications just like the potassium concentration, and thus cannot be recommended

  5. Distinguishing Mediational Models and Analyses in Clinical Psychology: Atemporal Associations Do Not Imply Causation.

    Science.gov (United States)

    Winer, E Samuel; Cervone, Daniel; Bryant, Jessica; McKinney, Cliff; Liu, Richard T; Nadorff, Michael R

    2016-09-01

    A popular way to attempt to discern causality in clinical psychology is through mediation analysis. However, mediation analysis is sometimes applied to research questions in clinical psychology when inferring causality is impossible. This practice may soon increase with new, readily available, and easy-to-use statistical advances. Thus, we here provide a heuristic to remind clinical psychological scientists of the assumptions of mediation analyses. We describe recent statistical advances and unpack assumptions of causality in mediation, underscoring the importance of time in understanding mediational hypotheses and analyses in clinical psychology. Example analyses demonstrate that statistical mediation can occur despite theoretical mediation being improbable. We propose a delineation of mediational effects derived from cross-sectional designs into the terms temporal and atemporal associations to emphasize time in conceptualizing process models in clinical psychology. The general implications for mediational hypotheses and the temporal frameworks from within which they may be drawn are discussed. © 2016 Wiley Periodicals, Inc.

  6. Case-Study Inverse Thermal Analyses of Al2139 and Al2198 Electron Beam Welds

    Science.gov (United States)

    Zervaki, A. D.; Stergiou, V.; Lambrakos, S. G.

    2013-11-01

    Case study inverse thermal analyses of A12139 and Al2198 electron beam welds are presented. These analyses represent a continuation of previous studies using laser beam welds, but provide accessibility to different regions of the parameter space for temperature histories than achievable using laser beams. For these analyses, a numerical methodology is employed, which is in terms of analytic functions for inverse thermal analysis of steady-state energy deposition in plate structures. The results of the case studies presented provide parametric representations of weld temperature histories, which can be adopted as input data to various types of computational procedures, such as those for prediction of solid-state phase transformations and their associated software implementations. In addition, these weld temperature histories can be used for construction of numerical basis functions that can be adopted for inverse analysis of welds corresponding to other process parameters or welding processes process conditions of which are within similar regimes.

  7. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

    2011-01-01

    and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...

  8. Proteomic and phosphoproteomic analyses of chromatin-associated proteins from Arabidopsis thaliana

    KAUST Repository

    Bigeard, Jean

    2014-07-10

    The nucleus is the organelle where basically all DNA-related processes take place in eukaryotes, such as replication, transcription, and splicing as well as epigenetic regulation. The identification and description of the nuclear proteins is one of the requisites toward a comprehensive understanding of the biological functions accomplished in the nucleus. Many of the regulatory mechanisms of protein functions rely on their PTMs among which phosphorylation is probably one of the most important properties affecting enzymatic activity, interaction with other molecules, localization, or stability. So far, the nuclear and subnuclear proteome and phosphoproteome of the model plant Arabidopsis thaliana have been the subject of very few studies. In this work, we developed a purification protocol of Arabidopsis chromatin-associated proteins and performed proteomic and phosphoproteomic analyses identifying a total of 879 proteins of which 198 were phosphoproteins that were mainly involved in chromatin remodeling, transcriptional regulation, and RNA processing. From 230 precisely localized phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified sites. This protocol and data thereby obtained should be a valuable resource for many domains of plant research.

  9. nmr spectroscopic study and dft calculations of vibrational analyses ...

    African Journals Online (AJOL)

    Preferred Customer

    ANALYSES, GIAO NMR SHIELDINGS AND 1JCH, 1JCC SPIN-SPIN COUPLING. CONSTANTS ... proton coupled and uncoupled 13C, 15N, DEPT, COSY, HETCOR, INADEQUATE NMR spectra and the magnitude ... methodology an interesting variety of spin-spin coupling constants can be calculated with good accuracy in ...

  10. Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

    Science.gov (United States)

    Rucker, James J H; Tansey, Katherine E; Rivera, Margarita; Pinto, Dalila; Cohen-Woods, Sarah; Uher, Rudolf; Aitchison, Katherine J; Craddock, Nick; Owen, Michael J; Jones, Lisa; Jones, Ian; Korszun, Ania; Barnes, Michael R; Preisig, Martin; Mors, Ole; Maier, Wolfgang; Rice, John; Rietschel, Marcella; Holsboer, Florian; Farmer, Anne E; Craig, Ian W; Scherer, Stephen W; McGuffin, Peter; Breen, Gerome

    2016-02-15

    Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; 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; Pourcain, Beate St; 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, Tönu; 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; Müller-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, Göran; 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; Lindström, 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; Körner, 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, Josée; 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, Inês

    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 raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  12. Heritability and Genome-Wide Association Analyses of Sleep Duration in Children : The EAGLE Consortium

    NARCIS (Netherlands)

    Marinelli, Marcella; Pappa, Irene; Bustamante, Mariona; Bonilla, Carolina; Suarez, Anna; Tiesler, Carla M; Vilor-Tejedor, Natalia; Zafarmand, Mohammad Hadi; Alvarez-Pedrerol, Mar; Andersson, Sture; Bakermans-Kranenburg, Marian J; Estivill, Xavier; Evans, David M; Flexeder, Claudia; Fons, Joan; Gonzalez, Juan R; Guxens, Monica; Huss, Anke; van IJzendoorn, Marinus H; Jaddoe, Vincent W V; Julvez, Jordi; Lahti, Jari; López-Vicente, Mónica; Lopez-Espinosa, Maria-Jose; Manz, Judith; Mileva-Seitz, Viara R; Perola, Markus; Pesonen, Anu-Katriina; Rivadeneira, Fernando; Salo, Perttu P; Shahand, Shayan; Schulz, Holger; Standl, Marie; Thiering, Elisabeth; Timpson, Nicholas J; Torrent, Maties; Uitterlinden, André G; Smith, George Davey; Estarlich, Marisa; Heinrich, Joachim; Räikkönen, Katri; Vrijkotte, Tanja G M; Tiemeier, Henning; Sunyer, Jordi

    2016-01-01

    STUDY OBJECTIVES: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration

  13. Heritability and genome-wide association analyses of sleep duration in children: The EAGLE consortium

    NARCIS (Netherlands)

    A.W. Marinelli (Andreas); M. Pappa (Magda); M. Bustamante (Mariona); C. Bonilla (Carolina); Suarez, A. (Anna); C. Tiesler (Carla); N. Vilor-Tejedor (Natàlia); M.H. Zafarmand (Mohammad Hadi); M. Alvarez-Pedrerol (Mar); Andersson, S. (Sture); M.J. Bakermans-Kranenburg (Marian); X. Estivill (Xavier); D.M. Evans (David); C. Flexeder (Claudia); J. Forns (Joan); J.R. Gonzalez (Juan); M. Guxens (Mònica ); A. Huss (Anke); M.H. van IJzendoorn (Rien); V.W.V. Jaddoe (Vincent); J. Julvez (Jordi); J. Lahti (Jari); M. López-Vicente (Mònica); M.-J. Lopez-Espinosa (Maria-Jose); Manz, J. (Judith); V. Mileva-Seitz; M. Perola (Markus); A.-K. Pesonen (Anu-Katriina); F. Rivadeneira Ramirez (Fernando); P. Salo (Perttu); Shahand, S. (Shayan); H. Schulz (Holger); E. Standl (Eberhard); E. Thiering (Eelisabeth); N.J. Timpson (Nicholas); M. Torrent (Maties); A.G. Uitterlinden (André); G.D. Smith; M. Estarlich (Marisa); J. Heinrich (Joachim); K. Räikkönen (Katri); T.G.M. Vrijkotte (Tanja); H.W. Tiemeier (Henning); J. Sunyer (Jordi)

    2016-01-01

    textabstractStudy Objectives: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of

  14. Environmental risk factors of pregnancy outcomes: a summary of recent meta-analyses of epidemiological studies

    Directory of Open Access Journals (Sweden)

    Nieuwenhuijsen Mark J

    2013-01-01

    Full Text Available Abstract Background Various epidemiological studies have suggested associations between environmental exposures and pregnancy outcomes. Some studies have tempted to combine information from various epidemiological studies using meta-analysis. We aimed to describe the methodologies used in these recent meta-analyses of environmental exposures and pregnancy outcomes. Furthermore, we aimed to report their main findings. Methods We conducted a bibliographic search with relevant search terms. We obtained and evaluated 16 recent meta-analyses. Results The number of studies included in each reported meta-analysis varied greatly, with the largest number of studies available for environmental tobacco smoke. Only a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating system. Generally they tested for heterogeneity and publication bias. Publication bias did not occur frequently. The meta-analyses found statistically significant negative associations between environmental tobacco smoke and stillbirth, birth weight and any congenital anomalies; PM2.5 and preterm birth; outdoor air pollution and some congenital anomalies; indoor air pollution from solid fuel use and stillbirth and birth weight; polychlorinated biphenyls (PCB exposure and birth weight; disinfection by-products in water and stillbirth, small for gestational age and some congenital anomalies; occupational exposure to pesticides and solvents and some congenital anomalies; and agent orange and some congenital anomalies. Conclusions The number of meta-analyses of environmental exposures and pregnancy outcomes is small and they vary in methodology. They reported statistically significant associations between environmental exposures such as environmental tobacco smoke, air pollution and chemicals and pregnancy outcomes.

  15. Neuroimaging genetic analyses of novel candidate genes associated with reading and language.

    Science.gov (United States)

    Gialluisi, Alessandro; Guadalupe, Tulio; Francks, Clyde; Fisher, Simon E

    2017-09-01

    Neuroimaging measures provide useful endophenotypes for tracing genetic effects on reading and language. A recent Genome-Wide Association Scan Meta-Analysis (GWASMA) of reading and language skills (N=1862) identified strongest associations with the genes CCDC136/FLNC and RBFOX2. Here, we follow up the top findings from this GWASMA, through neuroimaging genetics in an independent sample of 1275 healthy adults. To minimize multiple-testing, we used a multivariate approach, focusing on cortical regions consistently implicated in prior literature on developmental dyslexia and language impairment. Specifically, we investigated grey matter surface area and thickness of five regions selected a priori: middle temporal gyrus (MTG); pars opercularis and pars triangularis in the inferior frontal gyrus (IFG-PO and IFG-PT); postcentral parietal gyrus (PPG) and superior temporal gyrus (STG). First, we analysed the top associated polymorphisms from the reading/language GWASMA: rs59197085 (CCDC136/FLNC) and rs5995177 (RBFOX2). There was significant multivariate association of rs5995177 with cortical thickness, driven by effects on left PPG, right MTG, right IFG (both PO and PT), and STG bilaterally. The minor allele, previously associated with reduced reading-language performance, showed negative effects on grey matter thickness. Next, we performed exploratory gene-wide analysis of CCDC136/FLNC and RBFOX2; no other associations surpassed significance thresholds. RBFOX2 encodes an important neuronal regulator of alternative splicing. Thus, the prior reported association of rs5995177 with reading/language performance could potentially be mediated by reduced thickness in associated cortical regions. In future, this hypothesis could be tested using sufficiently large samples containing both neuroimaging data and quantitative reading/language scores from the same individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Ecogeographical associations between climate and human body composition: analyses based on anthropometry and skinfolds.

    Science.gov (United States)

    Wells, Jonathan C K

    2012-02-01

    In the 19th century, two "ecogeographical rules" were proposed hypothesizing associations of climate with mammalian body size and proportions. Data on human body weight and relative leg length support these rules; however, it is unknown whether such associations are attributable to lean tissue (the heat-producing component) or fat (energy stores). Data on weight, height, and two skinfold thickness were obtained from the literature for 137 nonindustrialized populations, providing 145 male and 115 female individual samples. A variety of indices of adiposity and lean mass were analyzed. Preliminary analyses indicated secular increases in skinfolds in men but not women, and associations of age and height with lean mass in both sexes. Decreasing annual temperature was associated with increasing body mass index (BMI), and increasing triceps but not subscapular skinfold. After adjusting for skinfolds, decreasing temperature remained associated with increasing BMI. These results indicate that colder environments favor both greater peripheral energy stores, and greater lean mass. Contrasting results for triceps and subscapular skinfolds might be due to adaptive strategies either constraining central adiposity in cold environments to reduce cardiovascular risk, or favoring central adiposity in warmer environments to maintain energetic support of the immune system. Polynesian populations were analyzed separately and contradicted all of the climate trends, indicating support for the hypothesis that they are cold-adapted despite occupying a tropical region. It is unclear whether such associations emerge through natural selection or through trans-generational and life-course plasticity. These findings nevertheless aid understanding of the wide variability in human physique and adiposity. Copyright © 2011 Wiley Periodicals, Inc.

  17. Association and expression analyses of the Ucp2 and Ucp3 gene ...

    Indian Academy of Sciences (India)

    2016-12-02

    Dec 2, 2016 ... Genetic studies have demonstrated that Ucp2 and Ucp3 gene variants are involved in obesity and metabolic syndrome. The aim of this study was to identify associations between polymorphisms of Ucp2 and Ucp3 genes and economically-important traits in Qinchuan cattle. In the present study, one ...

  18. Meta-analyses of studies of the human microbiota

    National Research Council Canada - National Science Library

    Lozupone, Catherine A; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vázquez-Baeza, Yoshiki; Jansson, Janet K; Gordon, Jeffrey I; Knight, Rob

    2013-01-01

    .... By comparing 16S rRNA gene sequences generated from diverse studies of the human microbiota using the QIIME database, we found that variation in composition of the microbiota across different body...

  19. Impact of random safety analyses on structure, process and outcome indicators: multicentre study.

    Science.gov (United States)

    Bodí, María; Oliva, Iban; Martín, Maria Cruz; Gilavert, Maria Carmen; Muñoz, Carlos; Olona, Montserrat; Sirgo, Gonzalo

    2017-12-01

    To assess the impact of a real-time random safety tool on structure, process and outcome indicators. Prospective study conducted over a period of 12 months in two adult patient intensive care units. Safety rounds were conducted three days a week ascertaining 37 safety measures (grouped into 10 blocks). In each round, 50% of the patients and 50% of the measures were randomized. The impact of this safety tool was analysed on indicators of structure (safety culture, healthcare protocols), process (improvement proportion related to tool application, IPR) and outcome (mortality, average stay, rate of catheter-related bacteraemias and rate of ventilator-associated pneumonia, VAP). A total of 1214 patient-days were analysed. Structure indicators: the use of the safety tool was associated with an increase in the safety climate and the creation/modification of healthcare protocols (sedation/analgesia and weaning). Process indicators: Twelve of the 37 measures had an IPR > 10%; six showed a progressive decrease in the IPR over the study period. Nursing workloads and patient severity on the day of analysis were independently associated with a higher IPR in half of the blocks of variables. Outcome indicators: A significant decrease in the rate of VAP was observed. The real-time random safety tool improved the care process and adherence to clinical practice guidelines and was associated with an improvement in structure, process and outcome indicators.

  20. Quantile regression analyses of associated factors for body mass index in Korean adolescents.

    Science.gov (United States)

    Kim, T H; Lee, E K; Han, E

    2015-05-01

    This study examined the influence of home and school environments, and individual health-risk behaviours on body weight outcomes in Korean adolescents. This was a cross-sectional observational study. Quantile regression models to explore heterogeneity in the association of specific factors with body mass index (BMI) over the entire conditional BMI distribution was used. A nationally representative web-based survey for youths was used. Paternal education level of college or more education was associated with lower BMI for girls, whereas college or more education of mothers was associated with higher BMI for boys; for both, the magnitude of association became larger at the upper quantiles of the conditional BMI distribution. Girls with good family economic status were more likely to have higher BMIs than those with average family economic status, particularly at the upper quantile of the conditional BMI distribution. Attending a co-ed school was associated with lower BMI for both genders with a larger association at the upper quantiles. Substantial screen time for TV watching, video games, or internet surfing was associated with a higher BMI with a larger association at the upper quantiles for both girls and boys. Dental prevention was negatively associated with BMI, whereas suicide consideration was positively associated with BMIs of both genders with a larger association at a higher quantile. These findings suggest that interventions aimed at behavioural changes and positive parental roles are needed to effectively address high adolescent BMI. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  1. Associations between sleep duration, sedentary time, physical activity, and health indicators among Canadian children and youth using compositional analyses.

    Science.gov (United States)

    Carson, Valerie; Tremblay, Mark S; Chaput, Jean-Philippe; Chastin, Sebastien F M

    2016-06-01

    The purpose of this study was to examine the relationships between movement behaviours (sleep duration, sedentary time, physical activity) and health indicators in a representative sample of children and youth using compositional analyses. Cross-sectional findings are based on 4169 children and youth (aged 6-17 years) from cycles 1 to 3 of the Canadian Health Measures Survey. Sedentary time (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were accelerometer-derived. Sleep duration was subjectively measured. Body mass index z scores, waist circumference, blood pressure, behavioural strengths and difficulties, and aerobic fitness were measured in the full sample. Triglycerides, high-density lipoprotein-cholesterol, C-reactive protein, and insulin were measured in a fasting subsample. The composition of movement behaviours was entered into linear regression models via an isometric log ratio transformation and was found to be associated with all health indicators (p < 0.01). Relative to other movement behaviours, time spent in SB or LPA was positively associated (p < 0.04) and time spent in MVPA or sleep was negatively associated (p < 0.02) with obesity risk markers. Similarly, LPA was positively associated (p < 0.005) and sleep was negatively associated (p < 0.03) with unfavourable behavioural strengths and difficulties scores and systolic blood pressure. Relative to other movement behaviours, time spent in SB was negatively associated (p < 0.001) and time spent in MVPA (p < 0.001) was positively associated with aerobic fitness. Likewise, MVPA was also negatively associated with several cardiometabolic risk markers (p < 0.008). Compositional data analyses provide novel insights into collective health implications of 24-h movement behaviours and can facilitate interesting avenues for future investigations.

  2. Confidence Levels in Statistical Analyses. Analysis of Variances. Case Study.

    Directory of Open Access Journals (Sweden)

    Ileana Brudiu

    2010-05-01

    Full Text Available Applying a statistical test to check statistical assumptions offers a positive or negative response regarding the veracity of the issued hypothesis. In case of variance analysis it’s necessary to apply a post hoc test to determine differences within the group. Statistical estimation using confidence levels provides more information than a statistical test, it shows the high degree of uncertainty resulting from small samples and builds conclusions in terms of "marginally significant" or "almost significant (p being close to 0,05 . The case study shows how the statistical estimation completes the application form the analysis of variance test and Tukey test.

  3. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

    NARCIS (Netherlands)

    Jin, Ying; Birlea, Stanca A.; Fain, Pamela R.; Ferrara, Tracey M.; Ben, Songtao; Riccardi, Sheri L.; Cole, Joanne B.; Gowan, Katherine; Holland, Paulene J.; Bennett, Dorothy C.; Luiten, Rosalie M.; Wolkerstorfer, Albert; van der Veen, J. P. Wietze; Hartmann, Anke; Eichner, Saskia; Schuler, Gerold; van Geel, Nanja; Lambert, Jo; Kemp, E. Helen; Gawkrodger, David J.; Weetman, Anthony P.; Taïeb, Alain; Jouary, Thomas; Ezzedine, Khaled; Wallace, Margaret R.; McCormack, Wayne T.; Picardo, Mauro; Leone, Giovanni; Overbeck, Andreas; Silverberg, Nanette B.; Spritz, Richard A.

    2012-01-01

    We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis

  4. Multicollinearity in Regression Analyses Conducted in Epidemiologic Studies.

    Science.gov (United States)

    Vatcheva, Kristina P; Lee, MinJae; McCormick, Joseph B; Rahbar, Mohammad H

    2016-04-01

    The adverse impact of ignoring multicollinearity on findings and data interpretation in regression analysis is very well documented in the statistical literature. The failure to identify and report multicollinearity could result in misleading interpretations of the results. A review of epidemiological literature in PubMed from January 2004 to December 2013, illustrated the need for a greater attention to identifying and minimizing the effect of multicollinearity in analysis of data from epidemiologic studies. We used simulated datasets and real life data from the Cameron County Hispanic Cohort to demonstrate the adverse effects of multicollinearity in the regression analysis and encourage researchers to consider the diagnostic for multicollinearity as one of the steps in regression analysis.

  5. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes

    Science.gov (United States)

    Todd, John A; Walker, Neil M; Cooper, Jason D; Smyth, Deborah J; Downes, Kate; Plagnol, Vincent; Bailey, Rebecca; Nejentsev, Sergey; Field, Sarah F; Payne, Felicity; Lowe, Christopher E; Szeszko, Jeffrey S; Hafler, Jason P; Zeitels, Lauren; Yang, Jennie H M; Vella, Adrian; Nutland, Sarah; Stevens, Helen E; Schuilenburg, Helen; Coleman, Gillian; Maisuria, Meeta; Meadows, William; Smink, Luc J; Healy, Barry; Burren, Oliver S; Lam, Alex A C; Ovington, Nigel R; Allen, James; Adlem, Ellen; Leung, Hin-Tak; Wallace, Chris; Howson, Joanna M M; Guja, Cristian; Ionescu-Tirgoviste, Constantin; Simmonds, Matthew J; Heward, Joanne M; Gough, Stephen CL; Dunger, David B; Wicker, Linda S; Clayton, David G

    2007-01-01

    The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan1 on seven diseases, including the multifactorial, autoimmune disease, type 1 diabetes (T1D), shows significant association (P < 5 × 10−7 between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios that were independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (Pfollow-up ≤ 1.35 × 10−9; Poverall ≤ 1.15 × 10−14), leaving eight regions with small effects or false-positive associations with T1D. We also obtained evidence for chromosome 18q22 (Poverall = 1.38 × 10−8) from a genome-wide association study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten. PMID:17554260

  6. 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.

  7. 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

  8. Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses

    Directory of Open Access Journals (Sweden)

    Ruth H. Keogh

    2016-01-01

    Full Text Available Abstract Background Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Methods Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. Results The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Conclusions Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

  9. Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studies

    Science.gov (United States)

    Ranjan, Subham; Devarapalli, Ramesh; Kundu, Sudeshna; Vangala, Venu R.; Ghosh, Animesh; Reddy, C. Malla

    2017-04-01

    Hydrochlorothiazide (HCT) is a diuretic BCS class IV drug with poor aqueous solubility and low permeability leading to poor oral absorption. The present work explores the cocrystallization technique to enhance the aqueous solubility of HCT. Three new cocrystals of HCT with water soluble coformers phenazine (PHEN), 4-dimethylaminopyridine (DMAP) and picolinamide (PICA) were prepared successfully by solution crystallization method and characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), fourier transform -infraredspectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Structural characterization revealed that the cocrystals with PHEN, DMAP and PICA exists in P21/n, P21/c and P21/n space groups, respectively. The improved solubility of HCT-DMAP (4 fold) and HCT-PHEN (1.4 fold) cocrystals whereas decreased solubility of HCT-PICA (0.5 fold) as compared to the free drug were determined after 4 h in phosphate buffer, pH 7.4, at 25 °C by using shaking flask method. HCT-DMAP showed a significant increase in solubility than all previously reported cocrystals of HCT suggest the role of a coformer. The study demonstrates that the selection of coformer could have pronounced impact on the physicochemical properties of HCT and cocrystallization can be a promising approach to improve aqueous solubility of drugs.

  10. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

    Science.gov (United States)

    Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A; Low, Siew-Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurman, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

    2017-01-01

    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8 PMID:28416818

  11. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Luca, Gianina; Haba-Rubio, José; Dauvilliers, Yves

    2013-01-01

    The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy...... diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women...

  12. Coordinated Analyses of Mineral-organic Matter Associations in Interplanetary Dust Particles

    Science.gov (United States)

    Nakamura-Messenger, K.; Herzog, G. F.; Smith, T.; Keller, L. P.; Flynn, G. J.; Khodja, H.; Taylor, S.; Wirick, S.; Messenger, S.

    2012-01-01

    Little is known about the timing and processes involved in the incorporation of organic matter with inorganic materials in early Solar System bodies. Recently, X-ray absorption near-edge spectroscopy (XANES) studies showed carbon-rich rims surrounding individual mineral grains in anhydrous IDPs [1,2]. These carbonaceous rims are believed to have formed prior to parent body formation and likely served to bond mineral grains during accretion into larger aggregates. We are exploring the nature of these carbonaceous rims through coordinated analyses of their chemistry, mineralogy, spectroscopy and isotopic characteristics. Here we report our preliminary mineralogical observations.

  13. Results of Chemical Analyses in Support of Yucca Mountain Studies

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Jeanette

    2007-12-11

    Ground water monitoring for the Nye County Early Warning Drilling Program (NCEWDP) was established to monitor underground water sources of the area and to protect communities surrounding the Nevada Test Site (NTS) from potential radionuclide contamination of these water sources. It provides hydrological information pertaining to groundwater flow patterns and recharge issues in the vicinity of Yucca Mountain. The Harry Reid Center for Environmental Studies (HRC) obtained groundwater samples from select NCEWDP wells shown in Figure 1. These samples were analyzed for major cations, major anions, trace elements, rare earth elements, alkalinity, pH and conductivity. These geochemical results can be used to evaluate the degree of interaction between the aquifers sampled, leading to a thorough mapping of the aquifer system. With increased analysis down gradient of the Yucca Mountain area, evaluations can identify viable groundwater flow paths and establish mixing of the groundwater systems. Tracer tests provide insight into groundwater flow characteristics and transport processes of potential contaminants. These tests are important for contaminant migration issues including safe disposal of hazardous and radioactive materials and remediation of potentially released contaminants. At a minimum, two conservative (non-sorbing) tracers with different diffusion coefficients are used for each tracer test. The tracer test performed under this cooperative agreement utilized fluorinated benzoic acids and halides as conservative tracers. The tracers are of differing size and have differing rates of diffusion into the rock. Larger molecules can not enter the pore spaces that are penetrated by the smaller molecules, therefore larger tracers will travel faster through thegroundwater system. Identical responses of the two tracers indicate no appreciable diffusion into pores of the aquifer system tuff. For the Nye County Tracer Tests, the HRC provided chemical analysis for the tracer

  14. Study on analyses of experimental data at DCA

    Energy Technology Data Exchange (ETDEWEB)

    Min, Byung Joo; Suk, Ho Chun; Hazama, T. [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-11-01

    In this report, the lattice characteristics of DCA are calculated to validate WIMS-AECL code for the lattice analysis of CANDU core by using experimental data of DCA and JNC. These results are compared with those of WIMS-ATR code. Analytical studies of some critical experiments had been performed to analyze the effects of fuel composition and lattice pitch. Different items of reactor physics such as local power peaking factor (LPF), effective multiplication factor (Keff) and coolant void reactivity were calculated for two coolant void fractions (0% and 100%). LPFs calculated by WIMS-ATR code are in close agreement with the experimental results. LPFs calculated by WIMS-AECL code with WINFRITH and ENDF/B-V libraries have similar values for both libraries but the differences between experimental data and results of WIMS-AECL code are larger than those of WIMS-ATR code. The maximum difference between the values calculated by WIMS-ATR and experimental values of LPFs are within 1.3%. LPF of Pu fuel cluster is found to be higher than that of the uranium fuel cluster. The coupled code systems WIMS-ATR and CITATION used in this analysis predict Keff within 1% {delta}K and coolant void reactivity within 4%{delta}K/K in all cases. The coolant void reactivity of uranium fuel is found to be positive for two lattice pitches (25.0 and 28.3 cm). Presence of plutonium fuel makes it more negative compare to uranium fuel. To validate WIMS-AECL code, the core characteristics of DCA shall be calculated by WIMS-AECL and CITATION codes in the future. 8 refs., 8 figs., 12 tabs. (Author)

  15. Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses.

    Science.gov (United States)

    Bianchi-Jassir, Fiorella; Seale, Anna C; Kohli-Lynch, Maya; Lawn, Joy E; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Rubens, Craig E

    2017-11-06

    Preterm birth complications are the leading cause of deaths among children preterm delivery. This article is the fifth of 11 in a series. We aimed to assess the association between GBS maternal colonization and preterm birth in order to inform estimates of the burden of GBS. We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on the association of preterm birth (preterm birth with maternal GBS colonization to be 1.21 (95% confidence interval [CI], .99-1.48; P = .061) in cohort and cross-sectional studies, and the odds ratio to be 1.85 (95% CI, 1.24-2.77; P = .003) in case-control studies. Preterm birth was associated with GBS bacteriuria in cohort studies (RR, 1.98 [95% CI, 1.45-2.69]; P preterm birth is associated with maternal GBS colonization, especially where there is evidence of ascending infection (bacteriuria). Several biases reduce the chance of detecting an effect. Equally, however, results, including evidence for the association, may be due to confounding, which is rarely addressed in studies. Assessment of any effect on preterm delivery should be included in future maternal GBS vaccine trials.

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

    Science.gov (United States)

    Jones, Samuel E; Tyrrell, Jessica; Wood, Andrew R; Beaumont, Robin N; Ruth, Katherine S; Tuke, Marcus A; Yaghootkar, Hanieh; Hu, Youna; Teder-Laving, Maris; Hayward, Caroline; Roenneberg, Till; Wilson, James F; Del Greco, Fabiola; Hicks, Andrew A; Shin, Chol; Yun, Chang-Ho; Lee, Seung Ku; Metspalu, Andres; Byrne, Enda M; Gehrman, Philip R; Tiemeier, Henning; Allebrandt, Karla V; Freathy, Rachel M; Murray, Anna; Hinds, David A; Frayling, Timothy M; Weedon, Michael N

    2016-08-01

    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 (P23andMe participants; thirteen of the chronotype signals remained associated at P23andMe 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 circadian rhythms in humans.

  17. Mouse and human genetic analyses associate kalirin with ventral striatal activation during impulsivity and with alcohol misuse

    Directory of Open Access Journals (Sweden)

    Yolanda ePeña-Oliver

    2016-04-01

    Full Text Available Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behaviour in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioural data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org, to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of <0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologues of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol-experience. There was a significant overall association between the human homologues of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.

  18. Atopic asthma and TNF-308 alleles: linkage disequilibrium and association analyses.

    Science.gov (United States)

    Di Somma, Carmela; Charron, Dominique; Deichmann, Klaus; Buono, Catello; Ruffilli, Anna

    2003-03-01

    The association of a tumor necrosis factor -308 allele (TNF2) to asthma has been reported in some studies but not in others. The aim of this study was to test this association in a population recruited on the basis of allergy to Parietaria. In the study population, asthma was positively associated to HLA-DRB1*03 (p = 0.01) and to the haplotype TNF2/DRB1*03 (p = 0.02). In the parent subgroup, the proportion of asthmatics was increased in patients with TNF2 (p = 0.01), but the primary association of asthma was to the haplotype TNF2/DRB1*1104 (p = 0.005). The study population was subdivided according to prick skin test (ST) positivity to Lolium, Parietaria, and D. pteronyssinus. Asthma was associated to HLA-DRB1*03 and to the haplotype TNF2/DRB1*03 (p = 0.0015 and 0.0001, respectively) in patients ST positive to Lolium, and to the haplotype TNF2/DRB1*1104 (p = 0.025) in patients ST positive to Parietaria. The transmission disequilibrium test detected excess transmission of HLA-DRB1*03 and of the haplotype TNF2/DRB1*03 (p = 0.03 and 0.04, respectively) to siblings with asthma and ST positivity to Lolium and of HLA-DRB1*1104 and of the haplotype TNF2/DRB1*1104 (p = 0.04 and 0.015, respectively) to siblings with asthma and ST positivity to Parietaria. Taken together, these observations indicate that the haplotypes TNF2/DRB1*03 and TNF2/*B1*1104 contain alleles controlling atopic asthma in patients with sensitization to Lolium and Parietaria, respectively. This suggests that the association of asthma to TNF2 reflects linkage disequilibrium with genes influencing specific immune response.

  19. Genome-Wide Association Meta-Analyses to Identify Common Genetic Variants Associated with Hallux Valgus in Caucasian and African Americans

    Science.gov (United States)

    Hsu, Yi-Hsiang; Liu, Youfang; Hannan, Marian T.; Maixner, William; Smith, Shad B.; Diatchenko, Luda; Golightly, Yvonne M.; Menz, Hylton B.; Kraus, Virginia B.; Doherty, Michael; Wilson, A.G.; Jordan, Joanne M.

    2016-01-01

    Objective Hallux valgus (HV) affects ~36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV. Methods HV was assessed in 3 Caucasian cohorts (n=2,263, n=915, and n=1,231 participants, respectively). In each cohort, a GWAS was conducted using 2.5M imputed single nucleotide polymorphisms (SNPs). Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV was sex-specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=5.46×10−7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=7.21×10−7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p-value =4.1×10−9). The association signals diminished when combining men and women. Conclusion Findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation. PMID:26337638

  20. Multivariate analyses for determining the association of field porcine fertility with sperm motion traits analysed by computer-assisted semen analysis and with sperm morphology.

    Science.gov (United States)

    Kummer, A B H P; Gaggini, T S; Bernardi, M L; McManus, C; Gonçales, E M; Wentz, I; Bortolozzo, F P

    2013-10-01

    This study investigates the association of semen traits with boar fertility. The fertility outcome (farrowing rate - FR and total piglets born - TB) of 14 boars was obtained from a field trial conducted during 10 week of breeding period on a commercial farm using multiparous sows (n = 948) through single-sire mating with 2 × 10(9) motile sperm cells per artificial insemination (AI) dose. Sperm motion parameters, evaluated with computer-assisted semen analysis system in raw and stored semen at 17°C for 240 h, in addition to morphological sperm defects, measured on the collection day, were included in the analysis to determine which semen traits were important to discriminate the fertility potential of ejaculates from these boars. The data underwent multivariate cluster, canonical and discriminant analyses. Four clusters of boars were formed based on fertility outcome. One boar, with the lowest FR and TB values (89.7% and 11.98), and two boars, with the highest FR and TB values (97.8% and 14.16), were placed in different clusters. The other boars were separated in two distinct clusters (four and seven boars), including boars with intermediate TB (12.64 and 13.22) but divergent values for FR (95.9% vs 91.8%). Semen traits with higher discriminatory power included total motility, progressive motility, amplitude of lateral head displacement and cytoplasmatic droplets. Through multivariate discriminant analysis, more than 80% of the 140 ejaculates were correctly classified into their own group, showing that this analysis may be an efficient statistical tool to improve the discrimination of potential fertility of boars. Nevertheless, the validation of the relationship between fertility and semen traits using this statistical approach needs to be performed on a larger number of farms and with a greater number of boars. © 2013 Blackwell Verlag GmbH.

  1. Multivariate analyses with end-member mixing to characterize groundwater flow: Wind Cave and associated aquifers

    Science.gov (United States)

    Long, Andrew J.; Valder, Joshua F.

    2011-01-01

    Principal component analysis (PCA) applied to hydrochemical data has been used with end-member mixing to characterize groundwater flow to a limited extent, but aspects of this approach are unresolved. Previous similar approaches typically have assumed that the extreme-value samples identified by PCA represent end members. The method presented herein is different from previous work in that (1) end members were not assumed to have been sampled but rather were estimated and constrained by prior knowledge; (2) end-member mixing was quantified in relation to hydrogeologic domains, which focuses model results on major hydrologic processes; (3) a method to select an appropriate number of end members using a series of cluster analyses is presented; and (4) conservative tracers were weighted preferentially in model calibration, which distributed model errors of optimized values, or residuals, more appropriately than would otherwise be the case. The latter item also provides an estimate of the relative influence of geochemical evolution along flow paths in comparison to mixing. This method was applied to groundwater in Wind Cave and the associated karst aquifer in the Black Hills of South Dakota, USA. The end-member mixing model was used to test a hypothesis that five different end-member waters are mixed in the groundwater system comprising five hydrogeologic domains. The model estimated that Wind Cave received most of its groundwater inflow from local surface recharge with an additional 33% from an upgradient aquifer. Artesian springs in the vicinity of Wind Cave primarily received water from regional groundwater flow.

  2. Associations between sleep hygiene and insomnia severity in college students: cross-sectional and prospective analyses.

    Science.gov (United States)

    Gellis, Les A; Park, Aesoon; Stotsky, Miriam T; Taylor, Daniel J

    2014-11-01

    Although a small number of studies characterized cross-sectional associations between sleep hygiene and insomnia severity, no prior study has examined their relationships prospectively. Further, the relationship between sleep hygiene and insomnia severity among college students has rarely been examined. This study examined the prevalence of diverse sleep hygiene behaviors and their associations with insomnia severity in two independent samples of college students from a cross-sectional (N=548; mean age=19; 59% female; 71% White) and a two-wave short-term prospective (N=157; mean age=19; 71% female; 76% White) study. A total of 12% to 13% of students reported clinically significant insomnia. On average, students reported frequent engagement in inconsistent sleep-wake schedules and lounging and worrying/thinking about important matters in the bed. Improper sleep scheduling, behaviors that promote arousal near bedtime, and uncomfortable sleeping environments were positively associated with cross-sectional insomnia severity. After controlling for other well-established risk factors, only improper sleep scheduling remained significant. Prospectively, baseline improper sleep scheduling predicted insomnia severity at a 2-month follow-up after controlling for baseline insomnia severity and other well-established risk factors. Together, findings suggest a potential unique role of improper sleep scheduling in insomnia among college students. Copyright © 2014. Published by Elsevier Ltd.

  3. Comparison of analyses of the QTLMAS XII common dataset. II: genome-wide association and fine mapping

    Directory of Open Access Journals (Sweden)

    Crooks Lucy

    2009-02-01

    Full Text Available Abstract As part of the QTLMAS XII workshop, a simulated dataset was distributed and participants were invited to submit analyses of the data based on genome-wide association, fine mapping and genomic selection. We have evaluated the findings from the groups that reported fine mapping and genome-wide association (GWA efforts to map quantitative trait loci (QTL. Generally the power to detect QTL was high and the Type 1 error was low. Estimates of QTL locations were generally very accurate. Some methods were much better than others at estimating QTL effects, and with some the accuracy depended on simulated effect size or minor allele frequency. There were also indications of bias in the effect estimates. No epistasis was simulated, but the two studies that included searches for epistasis reported several interacting loci, indicating a problem with controlling the Type I error rate in these analyses. Although this study is based on a single dataset, it indicates that there is a need to improve fine mapping and GWA methods with respect to estimation of genetic effects, appropriate choice of significance thresholds and analysis of epistasis.

  4. Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.

    Science.gov (United States)

    Sørensen, Louise Bergmann; Damsgaard, Camilla Trab; Dalskov, Stine-Mathilde; Petersen, Rikke Agnete; Egelund, Niels; Dyssegaard, Camilla Brørup; Stark, Ken D; Andersen, Rikke; Tetens, Inge; Astrup, Arne; Michaelsen, Kim Fleisher; Lauritzen, Lotte

    2015-11-28

    Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (Pschool performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

  5. Association analyses of porcine SERPINE1 reveal sex-specific effects on muscling, growth, fat accretion and meat quality.

    Science.gov (United States)

    Weisz, F; Bartenschlager, H; Knoll, A; Mileham, A; Deeb, N; Geldermann, H; Cepica, S

    2012-10-01

    The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1) gene encodes plasminogen activator inhibitor type 1 (PAI), which is the major physiological inhibitor of tissue-type and urokinase-type plasminogen activators and plays a role in obesity and insulin resistance in women but not in men. We detected SNP FN396538:g.566G>A in intron 3 and a non-synonymous substitution NM_213910:c.612A>G in exon 3 (p.Ile159Val) and mapped the gene to position 8.4 cM on the linkage map of chromosome 3. Association analyses were conducted on the 12th-15th generation of the Meishan × Large White (MLW) cross (n = 565), with records for weight at the end of test, lifetime daily gain, test time daily gain, loin depth and backfat depth, as well as on a European wild boar × Meishan (W × M) F(2) population (n = 333) with 47 traits recorded for carcass composition and meat quality. Analyses performed across the entire MLW population or in the male animals did not show any trait significantly associated with the loci studied. In female animals, both SNPs were associated with loin depth at nominal P < 0.05 with adjusted P values equal to 0.051 (g.566) and 0.057 (c.612). Differences between homozygotes were up to 0.65 SD. In the entire W × M population and female animals, SERPINE1 was significantly associated at adjusted P < 0.05 in descending order with muscling, growth and fat accretion and in male animals with meat quality (R-value). In the studied populations, allele effects were in opposite directions, which implies that the SNPs are markers that are in linkage disequilibrium with a causative mutation. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

  6. Application of Fuzzy Association Rule Mining for Analysing Students Academic Performance

    OpenAIRE

    Olufunke O. Oladipupo; Olanrewaju. J. Oyelade; Dada. O. Aborisade

    2012-01-01

    This study examines the relationship between students preadmission academic profile and academic performance. Data sample of students in the Department of Computer Science in one of Nigeria private Universities was used. The preadmission academic profile considered includes 'O' level grades, University Matriculation Examination (UME) scores, and Post-UME scores. The academic performance is defined using students Grade Point Average (GPA) at the end of a particular session. Fuzzy Association R...

  7. Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium.

    Science.gov (United States)

    Marinelli, Marcella; Pappa, Irene; Bustamante, Mariona; Bonilla, Carolina; Suarez, Anna; Tiesler, Carla M; Vilor-Tejedor, Natalia; Zafarmand, Mohammad Hadi; Alvarez-Pedrerol, Mar; Andersson, Sture; Bakermans-Kranenburg, Marian J; Estivill, Xavier; Evans, David M; Flexeder, Claudia; Forns, Joan; Gonzalez, Juan R; Guxens, Monica; Huss, Anke; van IJzendoorn, Marinus H; Jaddoe, Vincent W V; Julvez, Jordi; Lahti, Jari; López-Vicente, Mónica; Lopez-Espinosa, Maria-Jose; Manz, Judith; Mileva-Seitz, Viara R; Perola, Markus; Pesonen, Anu-Katriina; Rivadeneira, Fernando; Salo, Perttu P; Shahand, Shayan; Schulz, Holger; Standl, Marie; Thiering, Elisabeth; Timpson, Nicholas J; Torrent, Maties; Uitterlinden, André G; Smith, George Davey; Estarlich, Marisa; Heinrich, Joachim; Räikkönen, Katri; Vrijkotte, Tanja G M; Tiemeier, Henning; Sunyer, Jordi

    2016-10-01

    Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits. We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase. We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h(2) 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found (rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism. The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.

  8. Genomewide linkage and peakwide association analyses of carotid plaque in Caribbean Hispanics.

    Science.gov (United States)

    Dong, Chuanhui; Beecham, Ashley; Slifer, Susan; Wang, Liyong; Blanton, Susan H; Wright, Clinton B; Rundek, Tatjana; Sacco, Ralph L

    2010-12-01

    Atherosclerosis is a complex subclinical cardiovascular disorder with a substantial genetic component. This study sought to identify genetic loci influencing carotid plaque in 2 independent samples. B-mode ultrasound was performed to determine the presence and area of carotid plaque. Variance components analysis was used to test for linkage using 383 autosomal microsatellite markers in 1308 subjects from 100 Dominican families. Multiple linear and logistic regression models were used to investigate the association between plaque traits and 18,904 single nucleotide polymorphisms under the 1-logarithm of odds unit down regions of linkage peaks in an independent community-based data set (N = 941, 41% Dominicans) from the Northern Manhattan Study. After adjustment for age, hypertension, diabetes mellitus, cigarette pack-years, body mass index, and waist-to-hip ratio, significant heritability was detected for plaque presence (h² = 0.50 ± 0.14, P identified 4 regions with multipoint logarithm of odds scores ≥ 2.00 on 7q36, 11p15, 14q32, and 15q23. In the association analysis of the 4 linkage peaks, several single nucleotide polymorphisms in or near SOX6, FSD2, AP3S2, EFTUD1, and MYOD1 were associated with carotid plaque traits with a nominal P ≤ 0.0005 in the Northern Manhattan Study data set and with a P ≤ 0.01 in Northern Manhattan Study Dominican subset. Carotid plaque has considerable heritability and may be influenced by loci on chromosomes 11p15, 14q32, and 15q23. The SOX6 gene within the bone morphogenic protein pathway could be a candidate for carotid plaque. Larger independent studies are needed to validate these findings.

  9. Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia

    DEFF Research Database (Denmark)

    Severinsen, J E; Als, T D; Binderup, H

    2006-01-01

    M segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample...... comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample......(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge...

  10. Association analyses of the MAS-QTL data set using grammar, principal components and Bayesian network methodologies

    Directory of Open Access Journals (Sweden)

    Karacaören Burak

    2011-05-01

    Full Text Available Abstract Background It has been shown that if genetic relationships among individuals are not taken into account for genome wide association studies, this may lead to false positives. To address this problem, we used Genome-wide Rapid Association using Mixed Model and Regression and principal component stratification analyses. To account for linkage disequilibrium among the significant markers, principal components loadings obtained from top markers can be included as covariates. Estimation of Bayesian networks may also be useful to investigate linkage disequilibrium among SNPs and their relation with environmental variables. For the quantitative trait we first estimated residuals while taking polygenic effects into account. We then used a single SNP approach to detect the most significant SNPs based on the residuals and applied principal component regression to take linkage disequilibrium among these SNPs into account. For the categorical trait we used principal component stratification methodology to account for background effects. For correction of linkage disequilibrium we used principal component logit regression. Bayesian networks were estimated to investigate relationship among SNPs. Results Using the Genome-wide Rapid Association using Mixed Model and Regression and principal component stratification approach we detected around 100 significant SNPs for the quantitative trait (p Conclusions GRAMMAR could efficiently incorporate the information regarding random genetic effects. Principal component stratification should be cautiously used with stringent multiple hypothesis testing correction to correct for ancestral stratification and association analyses for binary traits when there are systematic genetic effects such as half sib family structures. Bayesian networks are useful to investigate relationships among SNPs and environmental variables.

  11. Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.

    Science.gov (United States)

    Yang, J; Li, M D

    2016-08-01

    Experimental approaches to genetic studies of complex traits evolve with technological advances. How do discoveries using different approaches advance our knowledge of the genetic architecture underlying complex diseases/traits? Do most of the findings of newer techniques, such as genome-wide association study (GWAS), provide more information than older ones, for example, genome-wide linkage study? In this review, we address these issues by developing a nicotine dependence (ND) genetic susceptibility map based on the results obtained by the approaches commonly used in recent years, namely, genome-wide linkage, candidate gene association, GWAS and targeted sequencing. Converging and diverging results from these empirical approaches have elucidated a preliminary genetic architecture of this intractable psychiatric disorder and yielded new hypotheses on ND etiology. The insights we obtained by putting together results from diverse approaches can be applied to other complex diseases/traits. In sum, developing a genetic susceptibility map and keeping it updated are effective ways to keep track of what we know about a disease/trait and what the next steps may be with new approaches.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Genome-wide association analyses reveal complex genetic architecture underlying natural variation for flowering time in canola.

    Science.gov (United States)

    Raman, H; Raman, R; Coombes, N; Song, J; Prangnell, R; Bandaranayake, C; Tahira, R; Sundaramoorthi, V; Killian, A; Meng, J; Dennis, E S; Balasubramanian, S

    2016-06-01

    Optimum flowering time is the key to maximize canola production in order to meet global demand of vegetable oil, biodiesel and canola-meal. We reveal extensive variation in flowering time across diverse genotypes of canola under field, glasshouse and controlled environmental conditions. We conduct a genome-wide association study and identify 69 single nucleotide polymorphism (SNP) markers associated with flowering time, which are repeatedly detected across experiments. Several associated SNPs occur in clusters across the canola genome; seven of them were detected within 20 Kb regions of a priori candidate genes; FLOWERING LOCUS T, FRUITFUL, FLOWERING LOCUS C, CONSTANS, FRIGIDA, PHYTOCHROME B and an additional five SNPs were localized within 14 Kb of a previously identified quantitative trait loci for flowering time. Expression analyses showed that among FLC paralogs, BnFLC.A2 accounts for ~23% of natural variation in diverse accessions. Genome-wide association analysis for FLC expression levels mapped not only BnFLC.C2 but also other loci that contribute to variation in FLC expression. In addition to revealing the complex genetic architecture of flowering time variation, we demonstrate that the identified SNPs can be modelled to predict flowering time in diverse canola germplasm accurately and hence are suitable for genomic selection of adaptative traits in canola improvement programmes. ©2015 The Authors. Plant, Cell & Environment published by JohnWiley & Sons Ltd.

  14. Structural characterisation and transdermal delivery studies on sugar microneedles: experimental and finite element modelling analyses.

    Science.gov (United States)

    Loizidou, Eriketi Z; Williams, Nicholas A; Barrow, David A; Eaton, Mark J; McCrory, John; Evans, Sam L; Allender, Chris J

    2015-01-01

    Dissolving microneedles are especially attractive for transdermal drug delivery as they are associated with improved patient compliance and safety. Furthermore, microneedles made of sugars offer the added benefit of biomolecule stabilisation making them ideal candidates for delivering biological agents such as proteins, peptides and nucleic acids. In this study, we performed experimental and finite element analyses to study the mechanical properties of sugar microneedles and evaluate the effect of sugar composition on microneedle ability to penetrate and deliver drug to the skin. Results showed that microneedles made of carboxymethylcellulose/maltose are superior to those made of carboxymethylcellulose/trehalose and carboxymethylcellulose/sucrose in terms of mechanical strength and the ability to deliver drug. Buckling was predicted to be the main mode of microneedle failure and the order of buckling was positively correlated to the Young's modulus values of the sugar constituents of each microneedle. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 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.

  16. Cystatin C and Risk of Diabetes and the Metabolic Syndrome - Biomarker and Genotype Association Analyses.

    Directory of Open Access Journals (Sweden)

    Martin Magnusson

    Full Text Available We recently reported a relationship between plasma levels of cystatin C and incidence of the metabolic syndrome (MetS among the first 2,369 subjects who participated in the re-examination study of the population-based Malmö and Diet Cancer Cardiovascular cohort (MDC-CC-re-exam. In this study we aimed to replicate these results and also investigate if cystatin C was causally associated with MetS and diabetes.We estimated the effect size of the strongest GWAS derived cystatin C SNP (major allele of rs13038305 on plasma cystatin C in the now completed MDC-CC-re-exam (n = 3,734 and thereafter examined the association between plasma cystatin C (403 cases of diabetes and 2665 controls as well as rs13038305 (235 cases and 2425 controls with incident diabetes. The association of rs13038305 and incident MetS (511 cases of MetS and 1980 controls was similarly investigated in the whole MDC-CC-re-exam. We also attempted to replicate our previously shown association of cystatin C with incident MetS in subjects from the MDC-CC-re-exam (147 cases and 711 controls that were not included in our previous report.In the entire MDC-CC-re-exam, each copy of the major allele of rs13038305 was associated with approximately 0.30 standard deviation (SD higher plasma concentration of cystatin C (β = 0.33, p = 4.2E-28 in age and sex adjusted analysis. Cystatin C in plasma was not associated with incident diabetes after adjustment for known diabetes risk factors (OR per 1 SD increment 0.99 (0.86-1.13, p = 0.842. In the replication cohort of MDC-CC-re-exam, the OR (95% CI for incident MetS in subjects belonging to quartiles 1, 2, 3 and 4 of plasma cystatin C levels was 1.00 (reference, 1.21 (0.70-2.07, 1.62 (0.95-2.78 and 1.72 (1.01-2.93 (ptrend = 0.026 in age and sex adjusted analysis. In the entire MDC-CC-re-exam the odds ratio for incident MetS and diabetes per copy of the major rs13038305 allele was 1.13, (0.95-1.34, p = 0.160 and 1.07, 95% CI 0.89-1.30, p = 0

  17. 45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Studies, exhibits, analyses, engineering reports, tests and projects. 13.7 Section 13.7 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT IN AGENCY PROCEEDINGS General Provisions § 13.7 Studies, exhibits, analyses,...

  18. An approach to analyse the specific impact of rapamycin on mRNA-ribosome association

    Directory of Open Access Journals (Sweden)

    Jaquier-Gubler Pascale

    2008-08-01

    Full Text Available Abstract Background Recent work, using both cell culture model systems and tumour derived cell lines, suggests that the differential recruitment into polysomes of mRNA populations may be sufficient to initiate and maintain tumour formation. Consequently, a major effort is underway to use high density microarray profiles to establish molecular fingerprints for cells exposed to defined drug regimes. The aim of these pharmacogenomic approaches is to provide new information on how drugs can impact on the translational read-out within a defined cellular background. Methods We describe an approach that permits the analysis of de-novo mRNA-ribosome association in-vivo during short drug exposures. It combines hypertonic shock, polysome fractionation and high-throughput analysis to provide a molecular phenotype of translationally responsive transcripts. Compared to previous translational profiling studies, the procedure offers increased specificity due to the elimination of the drugs secondary effects (e.g. on the transcriptional read-out. For this pilot "proof-of-principle" assay we selected the drug rapamycin because of its extensively studied impact on translation initiation. Results High throughput analysis on both the light and heavy polysomal fractions has identified mRNAs whose re-recruitment onto free ribosomes responded to short exposure to the drug rapamycin. The results of the microarray have been confirmed using real-time RT-PCR. The selective down-regulation of TOP transcripts is also consistent with previous translational profiling studies using this drug. Conclusion The technical advance outlined in this manuscript offers the possibility of new insights into mRNA features that impact on translation initiation and provides a molecular fingerprint for transcript-ribosome association in any cell type and in the presence of a range of drugs of interest. Such molecular phenotypes defined pre-clinically may ultimately impact on the evaluation of

  19. Small-study effects and time trends in diagnostic test accuracy meta-analyses : a meta-epidemiological study

    NARCIS (Netherlands)

    van Enst, Wynanda Annefloor; Naaktgeboren, Christiana A; Ochodo, Eleanor A; de Groot, Joris A.H.; Leeflang, Mariska M; Reitsma, Johannes B; Scholten, Rob J P M; Moons, Karel G M; Zwinderman, Aeilko H; Bossuyt, Patrick M M; Hooft, Lotty

    2015-01-01

    BACKGROUND: Small-study effects and time trends have been identified in meta-analyses of randomized trials. We evaluated whether these effects are also present in meta-analyses of diagnostic test accuracy studies. METHODS: A systematic search identified test accuracy meta-analyses published between

  20. EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study

    Directory of Open Access Journals (Sweden)

    Phillips Evelyn

    2010-03-01

    Full Text Available Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital. Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may

  1. Storage and shipping of tissue samples for DNA analyses: A case study on earthworms ?

    OpenAIRE

    Straube, Daniela; Juen, Anita

    2013-01-01

    Nowadays, molecular analyses play an important role in studies of soil dwelling animals, for example in taxonomy, phylogeography or food web analyses. The quality of the DNA, used for later molecular analyses, is an important factor and depends on collection and preservation of samples prior to DNA extraction. Ideally, DNA samples are frozen immediately upon collection, but if samples are collected in the field, suitable preservation methods might be limited due to unavailability of resources...

  2. Retrospective analyses of complications associated with transcutaneous replacement of percutaneous gastrostomy and jejunostomy feeding devices.

    Science.gov (United States)

    Nishiwaki, Shinji; Araki, Hiroshi; Fang, John C; Hayashi, Motoshi; Takada, Jun; Iwashita, Masahide; Tagami, Atsushi; Hatakeyama, Hiroo; Hayashi, Takao; Maeda, Teruo; Saito, Koshiro

    2011-10-01

    Feeding device replacement is often required for long-term maintenance after initial percutaneous endoscopic gastrostomy or jejunostomy placement. Although there are several case reports on serious complications of gastrostomy device replacement, there are few reports of an overall analysis of the complications associated with feeding device replacement. To evaluate the frequency and variety of complications of transcutaneous replacement of feeding devices. A retrospective study. Single center: Nishimino Kosei Hospital. This study involved 363 consecutive patients undergoing a total of 1265 percutaneous gastrostomy or jejunostomy device replacements from March 2000 to September 2010. A new replacement device was inserted through the ostomy tract by using an obturator after traction removal of the previous device. Endoscopic treatments were performed in the cases of fistula disruption or hemorrhage. Complications and their outcomes. Gastrostomy and jejunostomy devices were replaced 1126 and 139 times, respectively. There were 16 complications (1.3% of total replacements) consisting of 10 cases of fistula disruption caused by misplacement of replacement devices into the peritoneal cavity, 4 cases of hemorrhage, and 1 case each of colocutaneous fistula and device breakage. Anticoagulation or antiplatelet medications were continued in all 4 hemorrhage cases but in only 27 of 347 (7.7%) complication-free cases (P < .0001). There were no replacement-related adverse events that required surgical repair. A single center, retrospective analysis. Fistula disruption and hemorrhage were the most common complications associated with device replacement. In patients on anticoagulants, caution is necessary to avoid hemorrhage after replacement. It is also important to verify that the replaced device is located in the GI tract lumen before feeding. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  3. Genome-Wide Association and Transcriptome Analyses Reveal Candidate Genes Underlying Yield-determining Traits in Brassica napus.

    Science.gov (United States)

    Lu, Kun; Peng, Liu; Zhang, Chao; Lu, Junhua; Yang, Bo; Xiao, Zhongchun; Liang, Ying; Xu, Xingfu; Qu, Cunmin; Zhang, Kai; Liu, Liezhao; Zhu, Qinlong; Fu, Minglian; Yuan, Xiaoyan; Li, Jiana

    2017-01-01

    Yield is one of the most important yet complex crop traits. To improve our understanding of the genetic basis of yield establishment, and to identify candidate genes responsible for yield improvement in Brassica napus, we performed genome-wide association studies (GWAS) for seven yield-determining traits [main inflorescence pod number (MIPN), branch pod number (BPN), pod number per plant (PNP), seed number per pod (SPP), thousand seed weight, main inflorescence yield (MIY), and branch yield], using data from 520 diverse B. napus accessions from two different yield environments. In total, we detected 128 significant single nucleotide polymorphisms (SNPs), 93 of which were revealed as novel by integrative analysis. A combination of GWAS and transcriptome sequencing on 21 haplotype blocks from samples pooled by four extremely high-yielding or low-yielding accessions revealed the differential expression of 14 crucial candiate genes (such as Bna.MYB83, Bna.SPL5, and Bna.ROP3) associated with multiple traits or containing multiple SNPs associated with the same trait. Functional annotation and expression pattern analyses further demonstrated that these 14 candiate genes might be important in developmental processes and biomass accumulation, thus affecting the yield establishment of B. napus. These results provide valuable information for understanding the genetic mechanisms underlying the establishment of high yield in B. napus, and lay the foundation for developing high-yielding B. napus varieties.

  4. Mental retirement and health selection: Analyses from the U.S. Health and Retirement Study.

    Science.gov (United States)

    Clouston, Sean A P; Denier, Nicole

    2017-04-01

    Research has recently suggested that retirement may decrease cognitive engagement, resulting in cognitive aging. Few studies have systematically documented whether or how selectivity into retirement shapes the relationship between retirement and cognitive aging. We draw on data from the Health and Retirement Study (1998-2012) to examine the relationship between cognition and retirement for 18,575 labor force participants. Longitudinal regression discontinuity modeling was used to examine performance and decline in episodic memory. Models differentiated three forms of selection bias: indirect and direct selection as well as reverse causation. To further interrogate the disuse hypothesis, we adjust for confounding from health and socioeconomic sources. Results revealed that individuals who retired over the course of the panel were substantially different in terms of health, wealth and cognition when compared to those who remained employed. However, accounting for observed selection biases, significant associations were found linking longer retirement with more rapid cognitive decline. This study examined respondents who were in the labor force at baseline and transitioned into retirement. Analyses suggested that those who retired over the course of the panel had worse overall functioning, but also experienced more rapid declines after retirement that increased the rate of aging by two-fold, resulting in yearly losses of 3.7% (95% CI = [3.5, 4.0]) of one standard deviation in functioning attributable to retirement. Results are supportive of the view that retirement is associated with more rapid cognitive aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locus.

    Directory of Open Access Journals (Sweden)

    André Scherag

    Full Text Available BACKGROUND: Independent genome-wide association studies (GWAS showed an obesogenic effect of two single nucleotide polymorphisms (SNP; rs12970134 and rs17782313 more than 150 kb downstream of the melanocortin 4 receptor gene (MC4R. It is unclear if the SNPs directly influence MC4R function or expression, or if the SNPs are on a haplotype that predisposes to obesity or includes functionally relevant genetic variation (synthetic association. As both exist, functionally relevant mutations and polymorphisms in the MC4R coding region and a robust association downstream of the gene, MC4R is an ideal model to explore synthetic association. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed a genomic region (364.9 kb encompassing the MC4R in GWAS data of 424 obesity trios (extremely obese child/adolescent and both parents. SNP rs12970134 showed the lowest p-value (p = 0.004; relative risk for the obesity effect allele: 1.37; conditional analyses on this SNP revealed that 7 of 78 analyzed SNPs provided independent signals (p≤0.05. These 8 SNPs were used to derive two-marker haplotypes. The three best (according to p-value haplotype combinations were chosen for confirmation in 363 independent obesity trios. The confirmed obesity effect haplotype includes SNPs 3' and 5' of the MC4R. Including MC4R coding variants in a joint model had almost no impact on the effect size estimators expected under synthetic association. CONCLUSIONS/SIGNIFICANCE: A haplotype reaching from a region 5' of the MC4R to a region at least 150 kb from the 3' end of the gene showed a stronger association to obesity than single SNPs. Synthetic association analyses revealed that MC4R coding variants had almost no impact on the association signal. Carriers of the haplotype should be enriched for relevant mutations outside the MC4R coding region and could thus be used for re-sequencing approaches. Our data also underscore the problems underlying the identification of relevant mutations

  6. Study design and sampling intensity for demographic analyses of bear populations

    Science.gov (United States)

    Harris, R.B.; Schwartz, C.C.; Mace, R.D.; Haroldson, M.A.

    2011-01-01

    The rate of population change through time (??) is a fundamental element of a wildlife population's conservation status, yet estimating it with acceptable precision for bears is difficult. For studies that follow known (usually marked) bears, ?? can be estimated during some defined time by applying either life-table or matrix projection methods to estimates of individual vital rates. Usually however, confidence intervals surrounding the estimate are broader than one would like. Using an estimator suggested by Doak et al. (2005), we explored the precision to be expected in ?? from demographic analyses of typical grizzly (Ursus arctos) and American black (U. americanus) bear data sets. We also evaluated some trade-offs among vital rates in sampling strategies. Confidence intervals around ?? were more sensitive to adding to the duration of a short (e.g., 3 yrs) than a long (e.g., 10 yrs) study, and more sensitive to adding additional bears to studies with small (e.g., 10 adult females/yr) than large (e.g., 30 adult females/yr) sample sizes. Confidence intervals of ?? projected using process-only variance of vital rates were only slightly smaller than those projected using total variances of vital rates. Under sampling constraints typical of most bear studies, it may be more efficient to invest additional resources into monitoring recruitment and juvenile survival rates of females already a part of the study, than to simply increase the sample size of study females. ?? 2011 International Association for Bear Research and Management.

  7. BioSMACK: a linux live CD for genome-wide association analyses.

    Science.gov (United States)

    Hong, Chang Bum; Kim, Young Jin; Moon, Sanghoon; Shin, Young-Ah; Go, Min Jin; Kim, Dong-Joon; Lee, Jong-Young; Cho, Yoon Shin

    2012-01-01

    Recent advances in high-throughput genotyping technologies have enabled us to conduct a genome-wide association study (GWAS) on a large cohort. However, analyzing millions of single nucleotide polymorphisms (SNPs) is still a difficult task for researchers conducting a GWAS. Several difficulties such as compatibilities and dependencies are often encountered by researchers using analytical tools, during the installation of software. This is a huge obstacle to any research institute without computing facilities and specialists. Therefore, a proper research environment is an urgent need for researchers working on GWAS. We developed BioSMACK to provide a research environment for GWAS that requires no configuration and is easy to use. BioSMACK is based on the Ubuntu Live CD that offers a complete Linux-based operating system environment without installation. Moreover, we provide users with a GWAS manual consisting of a series of guidelines for GWAS and useful examples. BioSMACK is freely available at http://ksnp.cdc. go.kr/biosmack.

  8. Microwave power transmission system studies. Volume 2: Introduction, organization, environmental and spaceborne systems analyses

    Science.gov (United States)

    Maynard, O. E.; Brown, W. C.; Edwards, A.; Haley, J. T.; Meltz, G.; Howell, J. M.; Nathan, A.

    1975-01-01

    Introduction, organization, analyses, conclusions, and recommendations for each of the spaceborne subsystems are presented. Environmental effects - propagation analyses are presented with appendices covering radio wave diffraction by random ionospheric irregularities, self-focusing plasma instabilities and ohmic heating of the D-region. Analyses of dc to rf conversion subsystems and system considerations for both the amplitron and the klystron are included with appendices for the klystron covering cavity circuit calculations, output power of the solenoid-focused klystron, thermal control system, and confined flow focusing of a relativistic beam. The photovoltaic power source characteristics are discussed as they apply to interfacing with the power distribution flow paths, magnetic field interaction, dc to rf converter protection, power distribution including estimates for the power budget, weights, and costs. Analyses for the transmitting antenna consider the aperture illumination and size, with associated efficiencies and ground power distributions. Analyses of subarray types and dimensions, attitude error, flatness, phase error, subarray layout, frequency tolerance, attenuation, waveguide dimensional tolerances, mechanical including thermal considerations are included. Implications associated with transportation, assembly and packaging, attitude control and alignment are discussed. The phase front control subsystem, including both ground based pilot signal driven adaptive and ground command approaches with their associated phase errors, are analyzed.

  9. Efficacy and safety of tadalafil 5 mg once daily in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in men aged ≥75 years: integrated analyses of pooled data from multinational, randomized, placebo-controlled clinical studies.

    Science.gov (United States)

    Oelke, Matthias; Wagg, Adrian; Takita, Yasushi; Büttner, Hartwig; Viktrup, Lars

    2017-05-01

    To assess efficacy and safety of tadalafil in men aged ≥75 years with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) and additional safety in men aged ≥75 years with erectile dysfunction (ED). We conducted an integrated analysis of 12 phase II-III randomized, double-blind and/or open-label extension studies to evaluate short-term (12-26 weeks) efficacy and short- and longer-term (42-52 weeks) safety in men aged aged ≥75 years. All men received once-daily tadalafil 5 mg or placebo. The efficacy outcome was International Prostate Symptom Score (IPSS). Safety measurements included treatment-emergent adverse events (TEAEs), adverse events (AEs) leading to discontinuation, serious AEs (SAEs), and cardiovascular AEs. All analyses were intention-to-treat. Changes from baseline to efficacy endpoint and differences in changes between treatment groups were estimated as least-squares means using analysis of covariance models. Change in the mean IPSS was significantly different in men aged aged ≥75 years across tadalafil and placebo groups (treatment-by-age interaction P = 0.034). Tadalafil was not statistically significantly better than placebo in men aged ≥75 years, but effect size varied between studies. Maintenance of efficacy with tadalafil was observed across age groups. Short-term tadalafil safety findings for men aged age groups. Limitations include exclusion of men with serious co-existing conditions and limited sample sizes of men aged ≥75 years. Efficacy with once-daily tadalafil 5 mg in the treatment of LUTS/BPH differed between men aged age group. The older age group had more concomitant diseases and used more drugs, which may have reduced efficacy. The small sample size precluded uni-/multivariate analyses to assess plausible interference from confounding factors. Tadalafil had a reassuring safety profile and no evidence of increased cardiovascular AEs in aging men. © 2016 The Authors BJU International © 2016

  10. 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; Mägi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loïc; 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.; Pourcain, Beate St; 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, Tõnu; 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; Müller-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, Göran; 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; Lindström, 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.; Körner, 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, Josée; 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, Inês

    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

  11. 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

  12. 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...

  13. Brain responses to social norms: Meta-analyses of fMRI studies.

    Science.gov (United States)

    Zinchenko, Oksana; Arsalidou, Marie

    2017-11-21

    Social norms have a critical role in everyday decision-making, as frequent interaction with others regulates our behavior. Neuroimaging studies show that social-based and fairness-related decision-making activates an inconsistent set of areas, which sometimes includes the anterior insula, anterior cingulate cortex, and others lateral prefrontal cortices. Social-based decision-making is complex and variability in findings may be driven by socio-cognitive activities related to social norms. To distinguish among social-cognitive activities related to social norms, we identified 36 eligible articles in the functional magnetic resonance imaging (fMRI) literature, which we separate into two categories (a) social norm representation and (b) norm violations. The majority of original articles (>60%) used tasks associated with fairness norms and decision-making, such as ultimatum game, dictator game, or prisoner's dilemma; the rest used tasks associated to violation of moral norms, such as scenarios and sentences of moral depravity ratings. Using quantitative meta-analyses, we report common and distinct brain areas that show concordance as a function of category. Specifically, concordance in ventromedial prefrontal regions is distinct to social norm representation processing, whereas concordance in right insula, dorsolateral prefrontal, and dorsal cingulate cortices is distinct to norm violation processing. We propose a neurocognitive model of social norms for healthy adults, which could help guide future research in social norm compliance and mechanisms of its enforcement. © 2017 Wiley Periodicals, Inc.

  14. JUPITER and satellites: Clinical implications of the JUPITER study and its secondary analyses.

    Science.gov (United States)

    Kostapanos, Michael S; Elisaf, Moses S

    2011-07-26

    THE JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION: an intervention trial evaluating rosuvastatin (JUPITER) study was a real breakthrough in primary cardiovascular disease prevention with statins, since it was conducted in apparently healthy individuals with normal levels of low-density lipoprotein cholesterol (LDL-C JUPITER, rosuvastatin was associated with significant reductions in cardiovascular outcomes as well as in overall mortality compared with placebo. In this paper the most important secondary analyses of the JUPITER trial are discussed, by focusing on their novel findings regarding the role of statins in primary prevention. Also, the characteristics of otherwise healthy normocholesterolemic subjects who are anticipated to benefit more from statin treatment in the clinical setting are discussed. Subjects at "intermediate" or "high" 10-year risk according to the Framingham score, those who exhibit low post-treatment levels of both LDL-C (JUPITER added to our knowledge that statins may be effective drugs in the primary prevention of cardiovascular disease in normocholesterolemic individuals at moderate-to-high risk. Also, statin treatment may reduce the risk of venous thromboembolism and preserve renal function. An increase in physician-reported diabetes represents a major safety concern associated with the use of the most potent statins.

  15. Predicting associations between microRNAs and target genes in breast cancer by bioinformatics analyses.

    Science.gov (United States)

    Zheng, Tianying; Zhang, Xing; Wang, Yonggang; Yu, Xiucui

    2016-08-01

    Breast cancer is the leading type of cancer among females. However, the association between microRNAs (miRNAs) and target genes in breast tumorigenesis is poorly studied. The original data set GSE26659 was downloaded from the Gene Expression Omnibus, and then the differentially expressed miRNAs among 77 breast cancer patients and 17 controls were identified using the Limma package in R software. Furthermore, breast cancer-related differentially expressed miRNAs were selected from a human miRNA disease database and their target genes were selected from five miRNA databases. Then, functional analysis was performed for the target genes followed by construction of a miRNA-target gene network. A total of 34 differentially expressed miRNAs were identified, including 13 breast cancer-related miRNAs. Moreover, the target genes of the 13 miRNAs were significantly enriched in regulation of transcription (P=7.43E-09) and pathways related to cancer (P=3.33E-11). Finally, eight upregulated miRNAs (including hsa-miR-425) and five downregulated miRNAs (including hsa-miR-143, hsa-miR-145 and hsa-miR-125b) were identified in the miRNA-target gene network. In conclusion, using bioinformatics approaches, we demonstrate that the changes in regulation of transcription and cancer pathways may play significant roles in the process of breast cancerogenesis. Differentially expressed miRNAs and their target genes may be new targets for breast cancer therapy.

  16. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. METHODOLOGY/PRINCIPAL FINDINGS: We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. CONCLUSIONS/SIGNIFICANCE: We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help

  17. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Science.gov (United States)

    Heimesaat, Markus M; Boelke, Silvia; Fischer, André; Haag, Lea-Maxie; Loddenkemper, Christoph; Kühl, Anja A; Göbel, Ulf B; Bereswill, Stefan

    2012-01-01

    Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa) applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help to distinguish between relevant bacteria and secondary contaminants thus providing

  18. The association between Colombian medical students' healthy personal habits and a positive attitude toward preventive counseling: cross-sectional analyses

    Directory of Open Access Journals (Sweden)

    Sarmiento Francisco

    2009-07-01

    Full Text Available Abstract Background Physician-delivered preventive counseling is important for the prevention and management of chronic diseases. Data from the U.S. indicates that medical students with healthy personal habits have a better attitude towards preventive counseling. However, this association and its correlates have not been addressed in rapidly urbanized settings where chronic disease prevention strategies constitute a top public health priority. This study examines the association between personal health practices and attitudes toward preventive counseling among first and fifth-year students from 8 medical schools in Bogotá, Colombia. Methods During 2006, a total of 661 first- and fifth-year medical students completed a culturally adapted Spanish version of the "Healthy Doctor = Healthy Patient" survey (response rate = 78%. Logistic regression analyses were used to assess the association between overall personal practices on physical activity, nutrition, weight control, smoking, alcohol use (main exposure variable and student attitudes toward preventive counseling on these issues (main outcome variable, stratified by year of training and adjusting by gender and medical training-related factors (basic knowledge, perceived adequacy of training and perception of the school's promotion on each healthy habit. Results The median age and percentage of females for the first- and fifth-year students were 21 years and 59.5% and 25 years and 65%, respectively. After controlling for gender and medical training-related factors, consumption of ≥ 5 daily servings of fruits and/or vegetables, not being a smoker or binge drinker were associated with a positive attitude toward counseling on nutrition (OR = 4.71; CI = 1.6–14.1; p = 0.006 smoking (OR = 2.62; CI = 1.1–5.9; p = 0.022, and alcohol consumption (OR = 2.61; CI = 1.3–5.4; p = 0.009, respectively. Conclusion As for U.S. physician and medical students, a positive association was found between the

  19. The association between Colombian medical students' healthy personal habits and a positive attitude toward preventive counseling: cross-sectional analyses

    Science.gov (United States)

    Duperly, John; Lobelo, Felipe; Segura, Carolina; Sarmiento, Francisco; Herrera, Deisy; Sarmiento, Olga L; Frank, Erica

    2009-01-01

    Background Physician-delivered preventive counseling is important for the prevention and management of chronic diseases. Data from the U.S. indicates that medical students with healthy personal habits have a better attitude towards preventive counseling. However, this association and its correlates have not been addressed in rapidly urbanized settings where chronic disease prevention strategies constitute a top public health priority. This study examines the association between personal health practices and attitudes toward preventive counseling among first and fifth-year students from 8 medical schools in Bogotá, Colombia. Methods During 2006, a total of 661 first- and fifth-year medical students completed a culturally adapted Spanish version of the "Healthy Doctor = Healthy Patient" survey (response rate = 78%). Logistic regression analyses were used to assess the association between overall personal practices on physical activity, nutrition, weight control, smoking, alcohol use (main exposure variable) and student attitudes toward preventive counseling on these issues (main outcome variable), stratified by year of training and adjusting by gender and medical training-related factors (basic knowledge, perceived adequacy of training and perception of the school's promotion on each healthy habit). Results The median age and percentage of females for the first- and fifth-year students were 21 years and 59.5% and 25 years and 65%, respectively. After controlling for gender and medical training-related factors, consumption of ≥ 5 daily servings of fruits and/or vegetables, not being a smoker or binge drinker were associated with a positive attitude toward counseling on nutrition (OR = 4.71; CI = 1.6–14.1; p = 0.006 smoking (OR = 2.62; CI = 1.1–5.9; p = 0.022), and alcohol consumption (OR = 2.61; CI = 1.3–5.4; p = 0.009), respectively. Conclusion As for U.S. physician and medical students, a positive association was found between the personal health habits of

  20. Comprehensive Metaproteomic Analyses of Urine in the Presence and Absence of Neutrophil-Associated Inflammation in the Urinary Tract

    Science.gov (United States)

    Yu, Yanbao; Sikorski, Patricia; Smith, Madeline; Bowman-Gholston, Cynthia; Cacciabeve, Nicolas; Nelson, Karen E.; Pieper, Rembert

    2017-01-01

    Inflammation in the urinary tract results in a urinary proteome characterized by a high dynamic range of protein concentrations and high variability in protein content. This proteome encompasses plasma proteins not resorbed by renal tubular uptake, renal secretion products, proteins of immune cells and erythrocytes derived from trans-urothelial migration and vascular leakage, respectively, and exfoliating urothelial and squamous epithelial cells. We examined how such proteins partition into soluble urine (SU) and urinary pellet (UP) fractions by analyzing 33 urine specimens 12 of which were associated with a urinary tract infection (UTI). Using mass spectrometry-based metaproteomic approaches, we identified 5,327 non-redundant human proteins, 2,638 and 4,379 of which were associated with SU and UP fractions, respectively, and 1,206 non-redundant protein orthology groups derived from pathogenic and commensal organisms of the urogenital tract. Differences between the SU and UP proteomes were influenced by local inflammation, supported by respective comparisons with 12 healthy control urine proteomes. Clustering analyses showed that SU and UP fractions had proteomic signatures discerning UTIs, vascular injury, and epithelial cell exfoliation from the control group to varying degrees. Cases of UTI revealed clusters of proteins produced by activated neutrophils. Network analysis supported the central role of neutrophil effector proteins in the defense against invading pathogens associated with subsequent coagulation and wound repair processes. Our study expands the existing knowledge of the urinary proteome under perturbed conditions, and should be useful as reference dataset in the search of biomarkers. PMID:28042331

  1. Genome wide association analyses based on a multiple trait approach for modeling feed efficiency

    Science.gov (United States)

    Genome wide association (GWA) of feed efficiency (FE) could help target important genomic regions influencing FE. Data provided by an international dairy FE research consortium consisted of phenotypic records on dry matter intakes (DMI), milk energy (MILKE), and metabolic body weight (MBW) on 6,937 ...

  2. Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy.

    Science.gov (United States)

    Seo, Jeong-Sun; Lee, Seungbok; Shin, Jong-Yeon; Hwang, Yu Jin; Cho, Hyesun; Yoo, Seong-Keun; Kim, Yunha; Lim, Sungsu; Kim, Yun Kyung; Hwang, Eun Mi; Kim, Su Hyun; Kim, Chong-Hyun; Hyeon, Seung Jae; Yun, Ji-Young; Kim, Jihye; Kim, Yona; Alvarez, Victor E; Stein, Thor D; Lee, Junghee; Kim, Dong Jin; Kim, Jong-Il; Kowall, Neil W; Ryu, Hoon; McKee, Ann C

    2017-05-19

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.

  3. Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

    Science.gov (United States)

    Seo, Jeong-Sun; Lee, Seungbok; Shin, Jong-Yeon; Hwang, Yu Jin; Cho, Hyesun; Yoo, Seong-Keun; Kim, Yunha; Lim, Sungsu; Kim, Yun Kyung; Hwang, Eun Mi; Kim, Su Hyun; Kim, Chong-Hyun; Hyeon, Seung Jae; Yun, Ji-Young; Kim, Jihye; Kim, Yona; Alvarez, Victor E; Stein, Thor D; Lee, Junghee; Kim, Dong Jin; Kim, Jong-Il; Kowall, Neil W; Ryu, Hoon; McKee, Ann C

    2017-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE. PMID:28524178

  4. Medication-wide association studies

    NARCIS (Netherlands)

    P.B. Ryan (Patrick); D. Madigan (David); P.E. Stang (Paul); M.J. Schuemie (Martijn); G. Hripcsak (G.)

    2013-01-01

    textabstractUndiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate

  5. Sensitivity Study of Poisson's Ratio Used in Soil Structure Interaction (SSI) Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seung-ju [KHNP CRI, Daejeon (Korea, Republic of); You, Dong-Hyun [KEPCO Engineering and Construction, Gimcheon (Korea, Republic of); Jang, Jung-bum; Yun, Kwan-hee [KEPCO Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    The preliminary review for Design Certification (DC) of APR1400 was accepted by NRC on March 4, 2015. After the acceptance of the application for standard DC of APR1400, KHNP has responded the Request for Additional Information (RAI) raised by NRC to undertake a full design certification review. Design certification is achieved through the NRC's rulemaking process, and is founded on the staff's review of the application, which addresses the various safety issues associated with the proposed nuclear power plant design, independent of a specific site. The USNRC issued RAIs pertain to Design Control Document (DCD) Ch.3.7 'Seismic Design' is DCD Tables 3.7A-1 and 3.7A-2 show Poisson’s ratios in the S1 and S2 soil profiles used for SSI analysis as great as 0.47 and 0.48 respectively. Based on staff experience, use of Poisson's ratio approaching these values may result in numerical instability of the SSI analysis results. Sensitivity study is performed using the ACS SASSI NI model of APR1400 with S1 and S2 soil profiles to demonstrate that the Poisson’s ratio values used in the SSI analyses of S1 and S2 soil profile cases do not produce numerical instabilities in the SSI analysis results. No abrupt changes or spurious peaks, which tend to indicate existence of numerical sensitivities in the SASSI solutions, appear in the computed transfer functions of the original SSI analyses that have the maximum dynamic Poisson’s ratio values of 0.47 and 0.48 as well as in the re-computed transfer functions that have the maximum dynamic Poisson’s ratio values limited to 0.42 and 0.45.

  6. Methodological quality of meta-analyses of single-case experimental studies.

    Science.gov (United States)

    Jamshidi, Laleh; Heyvaert, Mieke; Declercq, Lies; Fernández-Castilla, Belén; Ferron, John M; Moeyaert, Mariola; Beretvas, S Natasha; Onghena, Patrick; Van den Noortgate, Wim

    2017-12-28

    Methodological rigor is a fundamental factor in the validity and credibility of the results of a meta-analysis. Following an increasing interest in single-case experimental design (SCED) meta-analyses, the current study investigates the methodological quality of SCED meta-analyses. We assessed the methodological quality of 178 SCED meta-analyses published between 1985 and 2015 through the modified Revised-Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. The main finding of the current review is that the methodological quality of the SCED meta-analyses has increased over time, but is still low according to the R-AMSTAR checklist. A remarkable percentage of the studies (93.80% of the included SCED meta-analyses) did not even reach the midpoint score (22, on a scale of 0-44). The mean and median methodological quality scores were 15.57 and 16, respectively. Relatively high scores were observed for "providing the characteristics of the included studies" and "doing comprehensive literature search". The key areas of deficiency were "reporting an assessment of the likelihood of publication bias" and "using the methods appropriately to combine the findings of studies". Although the results of the current review reveal that the methodological quality of the SCED meta-analyses has increased over time, still more efforts are needed to improve their methodological quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Association and expression analyses of the Ucp2 and Ucp3 gene ...

    Indian Academy of Sciences (India)

    YANING WANG

    Abstract. The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. Genetic studies have demonstrated that Ucp2 and Ucp3 gene variants are involved in obesity and metabolic syndrome. The aim of this study was to identify ...

  8. Association and expression analyses of the Ucp2 and Ucp3 gene ...

    Indian Academy of Sciences (India)

    2016-12-02

    Dec 2, 2016 ... Abstract. The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. Genetic studies have demonstrated that Ucp2 and Ucp3 gene variants are involved in obesity and metabolic syndrome. The aim of this study ...

  9. Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare

    Science.gov (United States)

    Hooijmans, Carlijn R.; IntHout, Joanna; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.

    2014-01-01

    In research aimed at improving human health care, animal studies still play a crucial role, despite political and scientific efforts to reduce preclinical experimentation in laboratory animals. In animal studies, the results and their interpretation are not always straightforward, as no single study is executed perfectly in all steps. There are several possible sources of bias, and many animal studies are replicates of studies conducted previously. Use of meta-analysis to combine the results of studies may lead to more reliable conclusions and a reduction of unnecessary duplication of animal studies. In addition, due to the more exploratory nature of animal studies as compared to clinical trials, meta-analyses of animal studies have greater potential in exploring possible sources of heterogeneity. There is an abundance of literature on how to perform meta-analyses on clinical data. Animal studies, however, differ from clinical studies in some aspects, such as the diversity of animal species studied, experimental design, and study characteristics. In this paper, we will discuss the main principles and practices for meta-analyses of experimental animal studies. PMID:25541544

  10. Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance.

    Science.gov (United States)

    Harrison, Odile B; Clemence, Marianne; Dillard, Joseph P; Tang, Christoph M; Trees, David; Grad, Yonatan H; Maiden, Martin C J

    2016-12-01

    Antimicrobial resistance (AMR) threatens our ability to treat the sexually transmitted bacterial infection gonorrhoea. The increasing availability of whole genome sequence (WGS) data from Neisseria gonorrhoeae isolates, however, provides us with an opportunity in which WGS can be mined for AMR determinants. Chromosomal and plasmid genes implicated in AMR were catalogued on the PubMLST Neisseria database (http://pubmlst.org/neisseria). AMR genotypes were identified in WGS from 289 gonococci for which MICs against several antimicrobial compounds had been determined. Whole genome comparisons were undertaken using whole genome MLST (wgMLST). Clusters of isolates with distinct AMR genotypes were apparent following wgMLST analysis consistent with the occurrence of genome wide genetic variation. This included the presence of the gonococcal genetic island (GGI), a type 4 secretion system shown to increase recombination and for which possession was significantly associated with AMR to multiple antimicrobials. Evolution of the gonococcal genome occurs in response to antimicrobial selective pressure resulting in the formation of distinct N. gonorrhoeae populations evidenced by the wgMLST clusters seen here. Genomic islands offer selective advantages to host bacteria and possession of the GGI may, not only facilitate the spread of AMR in gonococcal populations, but may also confer fitness advantages. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. HLA-DRB1* and allergy to Parietaria: linkage and association analyses.

    Science.gov (United States)

    D'Amato, M; Picardi, A; Menna, T; Di Somma, C; Ariano, R; di Pietro, A; Charron, D; Maggi, E; Matricardi, P; Plebani, A; Poto, S; Testa, G; Sacerdoti, G; Ruffilli, A

    1999-12-01

    In this study, we used the affected sibling-pairs approach to investigate the linkage of HLA (human leukocyte antigen)-DRB* with phenotypes related to allergy to Parietaria, the most common pollinosis in Mediterranean countries. The study population consisted of 51 nuclear families (235 subjects). Linkage was detected with Parietaria skin test positivity (p or =125 IU/ml and Parietaria allergy and that total IgE levels can discriminate population subsets where different alleles (at the HLA region or at loci in linkage disequilibrium) contribute to control allergen-specific IgE synthesis.

  12. Laboratory analyses of the potential toxicity of sediment-associated polydimethylsiloxane to benthic macroinvertebrates

    NARCIS (Netherlands)

    Henry, K.S.; Wieland, W.H.; Powell, D.E.; Giesy, J.P.

    2001-01-01

    Polydimethylsiloxane (PDMS) is widely used in a number of industrial processes and consumer products that result in down-the-drain disposal. The log p value for the PDMS used in the present study was 10, and the vapor pressure and water solubility values were below detection limits. These

  13. Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance.

    Science.gov (United States)

    Höti, Naseruddin; Shah, Punit; Hu, Yingwei; Yang, Shuang; Zhang, Hui

    2017-03-01

    While significant advances have been made in the diagnosis and treatment of prostate cancer, each year tens of thousands of men still die from prostate cancer in the United States. Thus, greater understanding of cellular pathways and molecular basis of prostate cancer progression in the development of androgen resistance is needed to treat these lethal phenotypes. To dissect the mechanism of androgen resistance, we utilize a proteomics approach to study the development of androgen resistance in LNCaP prostate cancer cells. Our results showed the predominant involvement of metabolic pathways that were elevated in androgen resistance phenotype. We further found the amplification of PI3K/AKT pathway and the overexpression of proteasome proteins while the mitochondrial oxidation phosphorylation was severely hampered in castration-resistant LNCaP-95 cells compared to LNCaP cells. Interestingly, we also found the induction of Dicer, a cytoplasmic endoribonuclease microRNA regulator in the androgen-ablated LNCaP-95 prostate cancer cells. We verified some of these data by orthogonal methods including Western blot analysis and in castrated animal xenograft studies. To our knowledge, this is the first report showing induced expression of proteasome proteins in androgen ablation prostate cancer cells. If validated in clinical studies, the findings will have significant implications in understanding the complexity of biochemical recurrence in prostate cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

    Science.gov (United States)

    Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama-Jr, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2017-04-21

    Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA2s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA2s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not efficiently

  15. Long-term results of cabergoline therapy for macroprolactinomas and analyses of factors associated with remission after withdrawal.

    Science.gov (United States)

    Watanabe, Shinya; Akutsu, Hiroyoshi; Takano, Shingo; Yamamoto, Tetsuya; Ishikawa, Eiichi; Suzuki, Hiroaki; Matsumura, Akira

    2017-02-01

    Withdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal. This was an institutional review board-approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal. Median follow-up after the initiation of cabergoline therapy was 54·3 (range 5·3 to 137·2) months. Recurrences of hyperprolactinaemia were observed in 3 of 11 (27%) postwithdrawal patients at a median time of 3·0 (range; 2·9-11·2) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analysed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, the absence of cavernous sinus invasion on pretreatment MRI (≥3/4 tumour encasement of the intracavernous internal carotid artery) (HR; 21·94, 95% CI; 2·06-1071·0, P = 0·006), initial PRL cabergoline therapy (HR; 5·14, 95% CI; 1·10-39·02, P = 0·04) showed statistically significant correlations with remission after withdrawal. Cabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. The absence of cavernous sinus invasion, serum PRL level lower than 132·7 ng/ml before cabergoline therapy or nadir serum PRL below 1·9 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years. © 2016 John Wiley

  16. Are Early-Life Socioeconomic Conditions Directly Related to Birth Outcomes? Grandmaternal Education, Grandchild Birth Weight, and Associated Bias Analyses.

    Science.gov (United States)

    Huang, Jonathan Y; Gavin, Amelia R; Richardson, Thomas S; Rowhani-Rahbar, Ali; Siscovick, David S; Enquobahrie, Daniel A

    2015-10-01

    Grandmaternal education may be related to grandchild birth weight (GBW) through maternal early-life development; however, conventional regression models may be endogenously confounded. Alternative models employing explicit structural assumptions may provide incrementally clearer evidence. We used data from the US National Longitudinal Study of Adolescent to Adult Health (1995-2009; 1,681 mother-child pairs) to estimate "direct effects" of grandmaternal educational level (less than high school, high school diploma or equivalent, or college degree) at the time of the mother's birth on GBW, adjusted for maternal life-course factors: maltreatment as a child, education and income as an adult, prepregnancy overweight, and prenatal smoking. Using conventional and marginal structural model (MSM) approaches, we estimated 54-g (95% confidence interval: -14.0, 122.1) and 87-g (95% confidence interval: 10.9, 162.5) higher GBWs per increase in educational level, respectively. The MSM allowed simultaneous mediation by and adjustment for prepregnancy overweight. Estimates were insensitive to alternate structural assumptions and mediator parameterizations. Bias analysis suggested that a single unmeasured confounder would have to have a strong influence on GBW (approximately 150 g) or be greatly imbalanced across exposure groups (approximately 25%) to completely explain the findings. Coupling an MSM with sensitivity analyses provides some evidence that maternal early-life socioeconomic environment is directly associated with offspring birth weight. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. A Discovery Genome-Wide Association Study of Entrepreneurship

    Science.gov (United States)

    Quaye, Lydia; Nicolaou, Nicos; Shane, Scott; Mangino, Massimo

    2012-01-01

    To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association…

  18. Is bilingualism associated with a lower risk of dementia in community-living older adults? Cross-sectional and prospective analyses.

    Science.gov (United States)

    Yeung, Caleb M; St John, Philip D; Menec, Verena; Tyas, Suzanne L

    2014-01-01

    The aim of this study was to determine whether bilingualism is associated with dementia in cross-sectional or prospective analyses of older adults. In 1991, 1616 community-living older adults were assessed and were followed 5 years later. Measures included age, sex, education, subjective memory loss (SML), and the modified Mini-mental State Examination (3MS). Dementia was determined by clinical examination in those who scored below the cut point on the 3MS. Language status was categorized based upon self-report into 3 groups: English as a first language (monolingual English, bilingual English) and English as a Second Language (ESL). The ESL category had lower education, lower 3MS scores, more SML, and were more likely to be diagnosed with cognitive impairment, no dementia at both time 1 and time 2 compared with those speaking English as a first language. There was no association between being bilingual (ESL and bilingual English vs. monolingual) and having dementia at time 1 in bivariate or multivariate analyses. In those who were cognitively intact at time 1, there was no association between being bilingual and having dementia at time 2 in bivariate or multivariate analyses. We did not find any association between speaking >1 language and dementia.

  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. Trend analyses in the health behaviour in school-aged children study

    DEFF Research Database (Denmark)

    Schnohr, Christina W; Molcho, Michal; Rasmussen, Mette

    2015-01-01

    BACKGROUND: This article presents the scope and development of the Health Behaviour in School-aged Children (HBSC) study, reviews trend papers published on international HBSC data up to 2012 and discusses the efforts made to produce reliable trend analyses. METHODS: The major goal of this article....... CONCLUSION: The article present recommendations to take a number of the considerations into account. The considerations imply methodological challenges, which are core issues in undertaking trend analyses....... collecting data from adolescents aged 11-15 years, on a broad variety of health determinants and health behaviours. RESULTS: A number of methodological challenges have stemmed from the growth of the HBSC-study, in particular given that the study has a focus on monitoring trends. Some of those challenges...

  1. Comparative phylogenomics and multi-gene cluster analyses of the Citrus Huanglongbing (HLB)-associated bacterium Candidatus Liberibacter.

    Science.gov (United States)

    Doddapaneni, Harshavardhan; Liao, Huihong; Lin, Hong; Bai, Xianjin; Zhao, Xiaolong; Civerolo, Edwin L; Irey, Michael; Coletta-Filho, Helvecio; Pietersen, Gerhard

    2008-08-28

    Huanglongbing (HLB, previously known as citrus greening), is associated with Candidatus Liberibacter species and is a serious threat to citrus production world-wide. The pathogen is a Gram negative, unculturable, phloem-limited bacterium with limited known genomic information. Expanding the genetic knowledge of this organism may provide better understanding of the pathogen and possibly develop effective strategies for control and management of HLB. Here, we report cloning and characterization of an additional 14.7 Kb of new genomic sequences from three different genomic regions of the Candidatus Liberibacter asiaticus (Las). Sequence variation analyses among the available Ca. Liberibacter species sequences as well as the newly cloned 1.5 Kb of rpoB gene from different Ca. Liberibacter strains have identified INDELs and SNPs. Phylogenetic analysis of the deduced protein sequences from the cloned regions characterizes the HLB-associated Candidatus Liberibacter as a new clade in the sub-division of the alpha-proteobacteria. Comparative analyses of the cloned gene regions of Candidatus Liberibacter with members of the order Rhizobiales suggest overall gene structure and order conservation, albeit with minor variations including gene decay due to the identified pseudogenes. The newly cloned gene regions contribute to our understanding of the molecular aspects of genomic evolution of Ca. Liberibacter.

  2. Comparative phylogenomics and multi-gene cluster analyses of the Citrus Huanglongbing (HLB-associated bacterium Candidatus Liberibacter

    Directory of Open Access Journals (Sweden)

    Civerolo Edwin L

    2008-08-01

    Full Text Available Abstract Background Huanglongbing (HLB, previously known as citrus greening, is associated with Candidatus Liberibacter species and is a serious threat to citrus production world-wide. The pathogen is a Gram negative, unculturable, phloem-limited bacterium with limited known genomic information. Expanding the genetic knowledge of this organism may provide better understanding of the pathogen and possibly develop effective strategies for control and management of HLB. Results Here, we report cloning and characterization of an additional 14.7 Kb of new genomic sequences from three different genomic regions of the Candidatus Liberibacter asiaticus (Las. Sequence variation analyses among the available Ca. Liberibacter species sequences as well as the newly cloned 1.5 Kb of rpoB gene from different Ca. Liberibacter strains have identified INDELs and SNPs. Phylogenetic analysis of the deduced protein sequences from the cloned regions characterizes the HLB-associated Candidatus Liberibacter as a new clade in the sub-division of the α-proteobacteria. Conclusion Comparative analyses of the cloned gene regions of Candidatus Liberibacter with members of the order Rhizobiales suggest overall gene structure and order conservation, albeit with minor variations including gene decay due to the identified pseudogenes. The newly cloned gene regions contribute to our understanding of the molecular aspects of genomic evolution of Ca. Liberibacter.

  3. Characterization of rainfall distribution and flooding associated with U.S. landfalling tropical cyclones: Analyses of Hurricanes Frances, Ivan, and Jeanne (2004)

    Science.gov (United States)

    Villarini, Gabriele; Smith, James A.; Baeck, Mary Lynn; Marchok, Timothy; Vecchi, Gabriel A.

    2011-12-01

    Rainfall and flooding associated with landfalling tropical cyclones are examined through empirical analyses of three hurricanes (Frances, Ivan, and Jeanne) that affected large portions of the eastern U.S. during September 2004. Three rainfall products are considered for the analyses: NLDAS, Stage IV, and TMPA. Each of these products has strengths and weaknesses related to their spatio-temporal resolution and accuracy in estimating rainfall. Based on our analyses, we recommend using the Stage IV product when studying rainfall distribution in landfalling tropical cyclones due to its fine spatial and temporal resolutions (about 4-km and hourly) and accuracy, and the capability of estimating rainfall up to 150 km from the coast. Lagrangian analyses of rainfall distribution relative to the track of the storm are developed to represent evolution of the temporal and spatial structure of rainfall. Analyses highlight the profound changes in rainfall distribution near landfall, the changing contributions to the rainfall field from eyewall convection, inner rain bands and outer rain bands, and the key role of orographic amplification of rainfall. We also present new methods for examining spatial extreme of flooding from tropical cyclones and illustrate the links between evolving rainfall structure and spatial extent of flooding.

  4. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

    Science.gov (United States)

    Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-01-01

    Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to

  5. The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses

    Directory of Open Access Journals (Sweden)

    Judith Schmitz

    2017-07-01

    Full Text Available Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.

  6. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials.

    Science.gov (United States)

    Citrome, Leslie; Durgam, Suresh; Lu, Kaifeng; Ferguson, Paul; Laszlovszky, István

    2016-01-01

    Although most patients with schizophrenia are not aggressive, individuals with the disorder have increased risk of hostile behavior. Cariprazine, a dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, was evaluated for antihostility effects in patients with schizophrenia. Post hoc analyses were conducted using pooled data from 3 positive randomized, placebo-controlled, phase 2/3 studies in inpatients (18-60 years) with acute exacerbation of schizophrenia according to DSM-IV-TR criteria; data were collected between 2008 and 2011. The principal post hoc outcome was mean change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) hostility item (P7); separate analyses adjusted for certain PANSS positive symptoms and sedation covariates. Analyses were based on the pooled intent-to-treat population (N = 1,466) using a mixed-effects model for repeated measures approach; separate analyses were conducted in subgroups categorized by baseline hostility item scores (P7: ≥ 2, ≥ 3, ≥ 4). The least squares mean difference (LSMD) in change from baseline to week 6 was statistically significant on all PANSS hostility item analyses in favor of cariprazine versus placebo: unadjusted (-0.28; P < .0001), adjusted for PANSS positive symptoms (-0.12; P < .05), adjusted for positive symptoms plus sedation (-0.12; P < .05). The magnitude of change for cariprazine increased with greater baseline hostility (LSMD vs placebo for ≥ 2, ≥ 3, ≥ 4 subgroups: -0.32, -0.37, -0.51, respectively; P < .01 all). Significant improvement on the hostility item was seen in cariprazine- versus placebo-treated patients with schizophrenia; the effect of cariprazine increased with greater levels of baseline hostility. ClinicalTrials.gov identifiers: NCT00694707, NCT01104766, and NCT01104779. © Copyright 2016 Physicians Postgraduate Press, Inc.

  7. Systematic evaluation of the associations between environmental risk factors and dementia: An umbrella review of systematic reviews and meta-analyses.

    Science.gov (United States)

    Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Middleton, Lefkos T; Ioannidis, John P A; Evangelou, Evangelos

    2017-04-01

    Dementia is a heterogeneous neurodegenerative disease, whose etiology results from a complex interplay between environmental and genetic factors. We searched PubMed to identify meta-analyses of observational studies that examined associations between nongenetic factors and dementia. We estimated the summary effect size using random-effects and fixed-effects model, the 95% CI, and the 95% prediction interval. We assessed the between-study heterogeneity (I-square), evidence of small-study effects, and excess significance. A total of 76 unique associations were examined. By applying standardized criteria, seven associations presented convincing evidence. These associations pertained to benzodiazepines use, depression at any age, late-life depression, and frequency of social contacts for all types of dementia; late-life depression for Alzheimer's disease; and type 2 diabetes mellitus for vascular dementia and Alzheimer's disease. Several risk factors present substantial evidence for association with dementia and should be assessed as potential targets for interventions, but these associations may not necessarily be causal. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  8. Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses.

    Science.gov (United States)

    Vukovic, Vladimir; Ianuale, Carolina; Leoncini, Emanuele; Pastorino, Roberta; Gualano, Maria Rosaria; Amore, Rosarita; Boccia, Stefania

    2016-02-10

    Polymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer. We searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95% confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site. Seventy case-control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95% CI, 0.96-1.12) for overall cancer (P for heterogeneity cancer for those homozygous mutant of rs762551. An OR of 0.79 (95% CI, 0.65-0.95; P for heterogeneity = 0.09, I(2) = 58.1%) was obtained for the bladder cancer from the hospital-based studies and on Caucasians. This large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95% CI, 0.70-1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed

  9. Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis

    OpenAIRE

    Masterson, Liam; Winder, David M; Ball, Siolian L. R.; Vaughan, Katie; Lehmann, Martin; Scholtz, Lars-Uwe; Sterling, Jane C; Sudhoff, Holger H; Goon, Peter K C

    2016-01-01

    Background Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. Methods HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with pat...

  10. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    OpenAIRE

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; KO, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C.

    2015-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies...

  11. Multicenter prospective study analysing the role of rotavirus on acute gastroenteritis in Spain.

    Science.gov (United States)

    Gimenez-Sanchez, F; Delgado-Rubio, A; Martinon-Torres, F; Bernaola-Iturbe, E

    2010-05-01

    Paediatric rotavirus gastroenteritis is the most frequent cause of acute gastroenteritis (AGE) in children up to 5 years of age worldwide. To analyse the clinical characteristics of AGE caused by rotavirus comparing to AGE caused by other agents. The study was conducted in 30 health-care centers in Spain (25 hospitals and five primary centers) between January and March 2006. Children with AGE up to 2 years of age were included. Stool samples were analysed using immunochromatographic test to identify rotavirus infection. Clinical and epidemiological data were analysed. A total of 1192 children were enrolled (mean age: 11.2 months). Fever, Vomiting, weakness and dehydration were more frequent in rotavirus-positive AGE cases. Severity score was higher and hospitalization was likely in AGE caused by rotavirus. Family AGE illness was more frequent in children with rotavirus-positive AGE. Breastfeeding was found as a protective factor against Rotavirus AGE. Rotavirus is the primary causal agent of AGE in children under 2 years of age in Spain, causing more severe symptoms and more hospital admissions than other causal agents. Our data support the interest of the introduction of the available rotavirus vaccines in the Spanish immunization schedule.

  12. Analysing the impacts of air quality policies on ecosystem services; a case study for Telemark, Norway.

    Science.gov (United States)

    Hein, L; White, L; Miles, A; Roberts, P

    2018-01-15

    There is an increasing interest in considering the effects of air pollution on ecosystem services supply in order to enhance cost-benefit analyses of air pollution policies. This paper presents a generic, conceptual approach that can be used to link atmospheric deposition of air pollutants to ecosystem services supply and societal benefits. The approach is applied in a case study in the Telemark county of Norway. First, we examine the potential effects of four European air quality policy scenarios on N deposition in the ecosystems of this county. Second, we analyse the subsequent impacts on the supply of three ecosystem services: carbon sequestration, timber production and biodiversity. Changes in the supply of the first two services are analysed in both physical and monetary units, biodiversity effects are only analysed in physical terms. The scenarios derive from work conducted in the context of the European National Emissions Ceilings Directive. In the 2010 base case the benefits of carbon sequestration are estimated at 13 million euro per year and the value of timber harvesting at 2.9 million euro per year. Under the examined policy scenarios aiming to reduce nitrogen emissions the societal benefits resulting from these two ecosystem services in Telemark are found to be reduced; the scenarios have little effect on terrestrial biodiversity. Such results cannot be scaled up, individual ecosystem services respond differently to changes in air pollution depending upon type of pollutant, type of ecosystem, type of service, and the magnitude of change. The paper further presents an analysis of the uncertainties that need to be considered in linking air pollution and ecosystem services including those in deposition rates, ecosystem responses, human responses and in the values of ecosystem services. Our conceptual approach is also useful for larger scale analysis of air pollution effects on ecosystem services, for example at national or potentially European scale

  13. Pathways from fertility history to later life health: Results from analyses of the English Longitudinal Study of Ageing

    Directory of Open Access Journals (Sweden)

    Emily Grundy

    2015-01-01

    Full Text Available Background: Previous research shows associations between fertility histories and later life health. The childless, those with large families, and those with a young age at entry to parenthood generally have higher mortality and worse health than parents of two or three children. These associations are hypothesised to reflect a range of biosocial influences, but underlying mechanisms are poorly understood. Objective: To identify pathways from fertility histories to later life health by examining mediation through health-related behaviours, social support and strain, and wealth. Additionally to examine mediation through allostatic load - an indicator of multisystem physical dysregulation, hypothesised to be an outcome of chronic stress. Methods: Associations between fertility histories, mediators, and outcomes were analysed using path models. Data were drawn from the English Longitudinal Study of Ageing. Outcomes studied were a measure of allostatic load based on 9 biomarkers and self-reported long-term illness which limited activities. Results: Early parenthood (Conclusions: In England early parenthood and larger family size are associated with less wealth and poorer health behaviours and this accounts for much of the association with health. At least part of this operates through stress-related physiological dysfunction (allostatic load.

  14. Association of atopic diseases and attention-deficit/hyperactivity disorder : A systematic review and meta-analyses

    NARCIS (Netherlands)

    van der Schans, Jurjen; Cicek, Rukiye; de Vries, Tjalling W.; Hak, Eelko; Hoekstra, Pieter J.

    Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention-deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross-sectional and longitudinal studies that assessed the association between atopic

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

    Science.gov (United States)

    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 ...

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

    NARCIS (Netherlands)

    A. Okbay (Aysu); Baselmans, B.M.L. (Bart M.L.); J.E. de Neve (Jan-Emmanuel); P. Turley (Patrick); M. Nivard (Michel); Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); J. Derringer; J. Gratten (Jacob); J.J. Lee (James J.); Liu, J.Z. (Jimmy Z); R. de Vlaming (Ronald); SAhluwalia, T. (Tarunveer); Buchwald, J. (Jadwiga); A. Cavadino (Alana); A.C. Frazier-Wood (Alexis C.); Furlotte, N.A. (Nicholas A); Garfield, V. (Victoria); Geisel, M.H. (Marie Henrike); J.R. Gonzalez (Juan R.); Haitjema, S. (Saskia); R. Karlsson (Robert); Der Laan, S.W. (Sander Wvan); K.-H. Ladwig (Karl-Heinz); J. Lahti (Jari); S.J. van der Lee (Sven); P.A. Lind (Penelope); Liu, T. (Tian); Matteson, L. (Lindsay); E. Mihailov (Evelin); M. Miller (Mike); CMinica, C. (Camelia); MNolte, I. (Ilja); D.O. Mook-Kanamori (Dennis); P.J. van der Most (Peter); C. Oldmeadow (Christopher); Y. Qian (Yong); O. Raitakari (Olli); R. Rawal (R.); A. Realo; Rueedi, R. (Rico); Schmidt, B. (Börge); A.V. Smith (Albert Vernon); E. Stergiakouli (Evangelia); T. Tanaka (Toshiko); K.D. Taylor (Kent); Wedenoja, J. (Juho); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); MWillems, S. (Sara); Zhao, W. (Wei); L.C. Study (LifeLines Cohort); N. Amin (Najaf); Bakshi, A. (Andrew); P.A. Boyle (Patricia); Cherney, S. (Samantha); Cox, S.R. (Simon R); G. Davies (Gail); O.S.P. Davis (Oliver S.); J. Ding (Jun); N. Direk (Nese); Eibich, P. (Peter); R. Emeny (Rebecca); Fatemifar, G. (Ghazaleh); J.D. Faul; L. Ferrucci (Luigi); A.J. Forstner (Andreas); C. Gieger (Christian); Gupta, R. (Richa); T.B. Harris (Tamara B.); J.M. Harris (Juliette); E.G. Holliday (Elizabeth); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); M. Kaakinen (Marika); E. Kajantie (Eero); Karhunen, V. (Ville); I. Kolcic (Ivana); M. Kumari (Meena); L.J. Launer (Lenore); L. Franke (Lude); Li-Gao, R. (Ruifang); Koini, M. (Marisa); A. Loukola (Anu); P. Marques-Vidal; G.W. Montgomery (Grant); M. Mosing (Miriam); L. Paternoster (Lavinia); A. Pattie (Alison); K. Petrovic (Katja); Pulkki-R'back, L. (Laura); L. Quaye (Lydia); R'ikkönen, K. (Katri); I. Rudan (Igor); R. Scott (Rodney); J.A. Smith (Jennifer A); A.R. Sutin; Trzaskowski, M. (Maciej); Vinkhuyze, A.E. (Anna E.); L. Yu (Lei); D. Zabaneh (Delilah); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); D.I. Boomsma (Dorret); H. Snieder (Harold); Chang, S.-C. (Shun-Chiao); F. Cucca (Francesco); I.J. Deary (Ian J.); C.M. van Duijn (Cornelia); K. Hagen (Knut); U. Bültmann (Ute); E.J. Geus (Eeco); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); T. Hansen (T.); Hartman, C.A. (Catharine A); C.M.A. Haworth (Claire M.); C. Hayward (Caroline); A.C. Heath (Andrew C.); D.A. Hinds (David A.); E. Hypponen (Elina); W.G. Iacono (William); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); Keltikangas-J'rvinen, L. (Liisa); P. Kraft (Peter); Kubzansky, L.D. (Laura D.); Lehtim'ki, T. (Terho); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); M. Mills (Melinda); R. de Mutsert (Reneé); A.J. Oldehinkel (Albertine); G. Pasterkamp (Gerard); N.L. Pedersen (Nancy); R. Plomin (Robert); O. Polasek (Ozren); C. Power (Christopher); S.S. Rich (Stephen); F.R. Rosendaal (Frits); H.M. den Ruijter (Hester ); Schlessinger, D. (David); R. Schmidt (Reinhold); R. Svento (Rauli); R. Schmidt (Reinhold); B.Z. Alizadeh (Behrooz); T.I.A. Sørensen (Thorkild); DSpector, T. (Tim); Steptoe, A. (Andrew); A. Terracciano; A.R. Thurik (Roy); N.J. Timpson (Nicholas); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Vollenweider (Peter); Wagner, G.G. (Gert G.); D.R. Weir (David); J. Yang (Joanna); Conley, D.C. (Dalton C.); G.D. Smith; Hofman, A. (Albert); M. Johannesson (Magnus); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); Pickrell, J.K. (Joseph K.); Esko, T. (T'nu); R.F. Krueger; J.P. Beauchamp (Jonathan); Ph.D. Koellinger (Philipp); D.J. Benjamin (Daniel J.); M. Bartels (Meike); D. Cesarini (David)

    2016-01-01

    textabstractVery 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.

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

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; 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; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; 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; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; 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; 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; Steptoe, Andrew; Terracciano, Antonio; 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

    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

  18. 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 conduct...

  19. Chemical and geotechnical analyses of soil samples from Olkiluoto for studies on sorption in soils

    Energy Technology Data Exchange (ETDEWEB)

    Lusa, M.; Aemmaelae, K.; Hakanen, M.; Lehto, J. (Helsinki Univ., Dept. of Chemistry, Lab. of Radiochemistry (Finland)); Lahdenperae, A.-M. (Poeyry Environment Oy, Vantaa (Finland))

    2009-05-15

    The safety assessment of disposal of spent nuclear fuel will include an estimate on the behavior of nuclear waste nuclides in the biosphere. As a part of this estimate also the transfer of nuclear waste nuclides in the soil and sediments is to be considered. In this study soil samples were collected from three excavator pits in Olkiluoto and the geotechnical and chemical characteristics of the samples were determined. In later stage these results will be used in sorption tests. Aim of these tests is to determine the Kd-values for Cs, Tc and I and later for Mo, Nb and Cl. Results of these sorption tests will be reported later. The geotechnical characteristics studied included dry weight and organic matter content as well as grain size distribution and mineralogy analyses. Selective extractions were carried out to study the sorption of cations into different mineral types. The extractions included five steps in which the cations bound to exchangeable, carbonate, oxides of Fe and Mn, organic matter and residual fractions were determined. For all fractions ICPMS analyses were carried out. In these analyses Li, Na, Mg, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Cs and Pb were determined. In addition six profiles were taken from the surroundings of two excavator pits for the 137Cs determination. Besides the samples taken for the characterization of soil, supplement samples were taken from the same layers for the separation of soil water. From the soil water pH, DOC, anions (F, Cl, NO{sub 3}, SO{sub 4}) and cations (Na, Mg, K, Ca, Al, Cr, Mn, Fe, Ni, Cu, Zn, As, S, Cd, Cs, Pb, U) were determined. (orig.)

  20. Association Between Hypertonic Saline and Hospital Length of Stay in Acute Viral Bronchiolitis: A Reanalysis of 2 Meta-analyses.

    Science.gov (United States)

    Brooks, Corinne G; Harrison, Wade N; Ralston, Shawn L

    2016-06-01

    Two previous meta-analyses of nebulized hypertonic saline (HS) on hospital length of stay (LOS) in acute viral bronchiolitis have suggested benefit. Neither study fully addressed the issue of excessive heterogeneity in the cohort of studies, indicating that it may be inappropriate to combine such dissimilar studies to estimate a common treatment effect. To reanalyze the existing data set for sources of heterogeneity to delineate the population most likely to benefit from HS. We used the previously analyzed cohort of randomized trials from 2 published meta-analyses comparing HS with normal saline (or, in 1 case, with standard of care) in infants hospitalized for bronchiolitis. We also repeated the search strategy used by the most recent Cochrane Review in the Medline database through September 2015. Eighteen randomized clinical trials of HS in infants with bronchiolitis reporting LOS as an outcome measure were included. The guidelines used for abstracting data included LOS, study year, setting, sample size, type of control, admission/discharge criteria, adjunct medications, treatment frequency, mean day of illness at study enrollment, mean severity of illness scores, and mean age. Weighted mean difference in LOS and study heterogeneity as measured by the I2 statistic. There were 18 studies included of 2063 infants (63% male), with a mean age of 4.2 months. The mean LOS was 3.6 days. Two main sources of heterogeneity were identified. First, the effect of HS on LOS was entirely sensitive to the removal of one study population, noted to have a widely divergent definition of the primary outcome. Second, there was a baseline imbalance in mean day of illness at presentation between treatment groups. Controlling for either of these factors resolved the heterogeneity (I2 = reduced from 78% to 45% and 0%, respectively) and produced summary estimates in support of the null hypothesis (that HS does not affect LOS). There was a weighted mean difference in LOS of -0.21 days

  1. The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes.

    Science.gov (United States)

    Thissen, Andrieke J A M; Bralten, Janita; Rommelse, Nanda N J; Arias-Vasquez, Alejandro; Greven, Corina U; Heslenfeld, Dirk; Luman, Marjolein; Oosterlaan, Jaap; Hoekstra, Pieter J; Hartman, Catharina; Franke, Barbara; Buitelaar, Jan K

    2015-09-01

    Elucidating genetic mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD) has been challenging. Relatively unexplored is the fact that genetic mechanisms can differ with age. The current study explored the association between dopaminergic and serotonergic genes, ADHD symptoms, and neurocognitive functioning in relation to age. Associations of three genetic ADHD risk factors, DAT1, DRD4, and 5-HTT with symptoms and six neurocognitive measures were explored in two samples of the NeuroIMAGE study: 756 children, adolescents, and young adults with ADHD, their siblings, and controls (M age 17 years, SD 3.2), and 393 parents with and without ADHD (M age 48 years, SD 4.8). Association analyses were performed in both samples, and effects were compared to address dichotomous age effects. Gene*age interactions were examined to address continuous age effects. Moderating effects of age were found for DRD4-7R carriership and ADHD symptoms in the adult group only; in the adolescents the 5-HTT LL genotype was differentially associated with inhibition and with motor timing at different ages, and to inhibition in adults; DAT1 10-6 haplotype carriership showed differential working memory performance depending on age. None of our effects survived correction for multiple comparisons. Our results are preliminary, but may point to differential genotype-phenotype associations at different ages. This can be seen as a proof of concept for the importance of age in dopaminergic and serotonergic genetic association analyses. Our findings are consistent with the idea that genetic and neurocognitive mechanisms underlying ADHD may change throughout life. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  2. Parametric analyses of summative scores may lead to conflicting inferences when comparing groups: A simulation study.

    Science.gov (United States)

    Khan, Asaduzzaman; Chien, Chi-Wen; Bagraith, Karl S

    2015-04-01

    To investigate whether using a parametric statistic in comparing groups leads to different conclusions when using summative scores from rating scales compared with using their corresponding Rasch-based measures. A Monte Carlo simulation study was designed to examine between-group differences in the change scores derived from summative scores from rating scales, and those derived from their corresponding Rasch-based measures, using 1-way analysis of variance. The degree of inconsistency between the 2 scoring approaches (i.e. summative and Rasch-based) was examined, using varying sample sizes, scale difficulties and person ability conditions. This simulation study revealed scaling artefacts that could arise from using summative scores rather than Rasch-based measures for determining the changes between groups. The group differences in the change scores were statistically significant for summative scores under all test conditions and sample size scenarios. However, none of the group differences in the change scores were significant when using the corresponding Rasch-based measures. This study raises questions about the validity of the inference on group differences of summative score changes in parametric analyses. Moreover, it provides a rationale for the use of Rasch-based measures, which can allow valid parametric analyses of rating scale data.

  3. Intelligence and handedness: Meta-analyses of studies on intellectually disabled, typically developing, and gifted individuals.

    Science.gov (United States)

    Papadatou-Pastou, Marietta; Tomprou, Dimitra-Maria

    2015-09-01

    Understanding the relationship between cerebral laterality and intelligence is important in elucidating the neurological underpinnings of individual differences in cognitive abilities. A widely used, behavioral indicator for cerebral laterality, mainly of language, is handedness. A number of studies have compared cognitive abilities between groups of left- and right-handers, while others have investigated the handedness prevalence between groups of different cognitive abilities. The present study comprises five meta-analyses of studies that have assessed the handedness prevalence in (a) individuals with intellectual disability (ID) of unknown/idiopathic nature compared to typically developing (TD) individuals, and (b) individuals with intellectual giftedness (IG) compared to TD individuals. Nineteen data sets totaling 16,076 participants (5795 ID, 8312 TD, and 1969 IG) were included in the analyses. Elevated levels of atypical handedness were found to be robust only for the ID to TD comparison. Findings constrain the range of acceptable theories on the handedness distribution for different intelligence levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

    Science.gov (United States)

    Theodoratou, Evropi; Tzoulaki, Ioanna; Zgaga, Lina; Ioannidis, John P A

    2014-04-01

    To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Medline, Embase, and screening of citations and references. Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of

  5. Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Qing Zhang

    2016-02-01

    Full Text Available Background/Aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs were calculated to assess the relationship between clinicopathological features and BRAFV600E mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Results: Of 25,241 cases with PTC, 15,290 (60.6% were positive for BRAF mutation and 9,951 (39.4% were tested negative for BRAF mutation. Negative status of BRAFV600E mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97 and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64. By contrast, positive status of BRAFV600E mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32, extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63, TNM stage (OR = 1.67; 95%CI = 1.53-1.81, lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93, vascular invasion (OR = 1.47; 95%CI = 1.22-1.79 and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18. However, there was no significant association between BRAFV600E mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07, tumor size (OR = 0.84; 95%CI = 0.64-1.09 and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27. Conclusion: This meta-analysis confirmed significant associations between BRAFV600E mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence

  6. Short Sleep Duration as a Risk Factor for Hypercholesterolemia: Analyses of the National Longitudinal Study of Adolescent Health

    Science.gov (United States)

    Gangwisch, James E.; Malaspina, Dolores; Babiss, Lindsay A.; Opler, Mark G.; Posner, Kelly; Shen, Sa; Turner, J. Blake; Zammit, Gary K.; Ginsberg, Henry N.

    2010-01-01

    Study Objectives: To explore the relationship between sleep duration in adolescence and hypercholesterolemia in young adulthood. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in women. Short sleep duration has been found in cross sectional studies to be associated with higher total cholesterol and lower HDL cholesterol levels. Sleep deprivation could increase the risk for hypercholesterolemia by increasing appetite and dietary consumption of saturated fats, decreasing motivation to engage in regular physical activity, and increasing stress and resultant catecholamine induced lipolysis. No previous published population studies have examined the longitudinal relationship between sleep duration and high cholesterol. Design: Multivariate longitudinal analyses stratified by sex of the ADD Health using logistic regression. Setting: United States nationally representative, school-based, probability-based sample. Participants: Adolescents (n = 14,257) in grades 7 to 12 at baseline (1994-95) and ages 18 to 26 at follow-up (2001-02). Measurements and Results: Among females, each additional hour of sleep was associated with a significantly decreased odds of being diagnosed with high cholesterol in young adulthood (OR = 0.85, 95% CI 0.75-0.96) after controlling for covariates. Additional sleep was associated with decreased, yet not statistically significant, odds ratios for hypercholesterolemia in males (OR = 0.91, 95% CI 0.79-1.05). Conclusions: Short sleep durations in adolescent women could be a significant risk factor for high cholesterol. Interventions that lengthen sleep could potentially serve as treatments and as primary preventative measures for hypercholesterolemia. Citation: Gangwisch JE; Malaspina D; Babiss LA; Opler MG; Posner K; Shen S; Turner JB; Zammit GK; Ginsberg HN. Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent

  7. Analyse - technologies; Analyse - technologies

    Energy Technology Data Exchange (ETDEWEB)

    Roudil, D.; Chevalier, M.; Cormont, Ph.; Viala, F.; Kopp, Ch.; Peillet, O.; Chatroux, D.; Lausenaz, Y.; Villard, J.F.; Bruel, L.; Berhouet, F.; Chartier, F.; Aubert, M.; Blanchet, P.; Steiner, F.; Puech, M.H.; Bienvenu, Ph.; Noire, M.H.; Bouzon, C.; Schrive, L

    1999-07-01

    In this chapter of the DCC 1999 scientific report, the following theoretical studies are detailed: emulsions characterization by ultrasonics, high resolution wavelength meter, optimization methodology for diffractive and hybrid optic system, reliability for fast switches in power electronics, study of cesium isolation in irradiated fuels, chemical optodes based on evanescent wave absorption, radionuclides (Zirconium 93 and molybdenum 93) determination in irradiated fuels processing effluents, study of viscous liquid ultrafiltration using supercritical CO{sub 2} fluid. (A.L.B.)

  8. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  9. Mid-latitude ozone changes: studies with a 3-D CTM forced by ERA-40 analyses

    Directory of Open Access Journals (Sweden)

    W. Feng

    2007-01-01

    Full Text Available We have used an off-line three-dimensional (3-D chemical transport model (CTM to study long-term changes in stratospheric O3. The model was run from 1977–2004 and forced by ECMWF ERA-40 and operational analyses. Model runs were performed to examine the impact of increasing halogens and additional stratospheric bromine from short-lived source gases. The analyses capture much of the observed interannual variability in column ozone, but there are also unrealistic features. In particular the ERA-40 analyses cause a large positive anomaly in northern hemisphere (NH column O3 in the late 1980s. Also, the change from ERA-40 to operational winds at the start of 2002 introduces abrupt changes in some model fields (e.g. temperature, ozone which affect analysis of trends. The model reproduces the observed column increase in NH mid-latitudes from the mid 1990s. Analysis of a run with fixed halogens shows that this increase is not due to a significant decrease in halogen-induced loss, i.e. is not an indication of recovery. The model predicts only a small decrease in halogen-induced loss after 1999. In the upper stratosphere, despite the modelled turnover of chlorine around 1999, O3 does not increase because of the effects of increasing ECMWF temperatures, decreasing modelled CH4 at this altitude, and abrupt changes in the SH temperatures at the end of the ERA-40 period. The impact of an additional 5 pptv stratospheric bromine from short-lived species decreases mid-latitude column O3 by about 10 DU. However, the impact on the modelled relative O3 anomaly is generally small except during periods of large volcanic loading.

  10. Family based association analyses between the serotonin transporter gene polymorphism (5-HTTLPR) and neuroticism, anxiety and depression

    NARCIS (Netherlands)

    Middeldorp, Christel M.; de Geus, Eco J. C.; Beem, A. Leo; Lakenberg, Nico; Hottenga, Jouke-Jan; Slagboom, P. Eline; Boomsma, Dorret I.

    2007-01-01

    We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring).

  11. Association analyses of porcine SERPINE1 reveal sex-specific effects on muscling, growth, fat accretion and meat quality

    Czech Academy of Sciences Publication Activity Database

    Weisz, Filip; Bartenschlager, H.; Knoll, Aleš; Mileham, A.; Deeb, N.; Geldermann, H.; Čepica, Stanislav

    2012-01-01

    Roč. 43, č. 5 (2012), s. 614-619 ISSN 0268-9146 R&D Projects: GA ČR GAP502/10/1216 Institutional research plan: CEZ:AV0Z50450515 Keywords : association study * fat deposition * meat quality Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 2.584, year: 2012

  12. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

    NARCIS (Netherlands)

    Direk, Nese; Williams, Stephanie; Smith, Jennifer A; Ripke, Stephan; Air, Tracy; Amare, Azmeraw T; Amin, Najaf; Baune, Bernhard T; Bennett, David A; Blackwood, Douglas H R; Boomsma, Dorret; Breen, Gerome; Buttenschøn, Henriette Nørmølle; Byrne, Enda M; Børglum, Anders D; Castelao, Enrique; Cichon, Sven; Clarke, Toni-Kim; Cornelis, Marilyn C; Dannlowski, Udo; De Jager, Philip L; Demirkan, Ayse; Domenici, Enrico; van Duijn, Cornelia M; Dunn, Erin C; Eriksson, Johan G; Esko, Tonu; Faul, Jessica D; Ferrucci, Luigi; Fornage, Myriam; de Geus, Eco; Gill, Michael; Gordon, Scott D; Grabe, Hans-Jörgen; van Grootheest, Gerard; Hamilton, Steven P; Hartman, Catharina A; Heath, Andrew C; Hek, Karin; Hofman, Albert; Homuth, Georg; Horn, Carsten; Jan Hottenga, Jouke; Kardia, Sharon L R; Kloiber, Stefan; Koenen, Karestan; Kutalik, Zoltán; Ladwig, Karl-Heinz; Lahti, Jari; Levinson, Douglas F; Lewis, Cathryn M; Lewis, Glyn; Li, Qingqin S; Llewellyn, David J; Lucae, Susanne; Lunetta, Kathryn L; MacIntyre, Donald J; Madden, Pamela A F; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Mosley, Thomas H; Murabito, Joanne M; Müller-Myhsok, Bertram; Nöthen, Markus M; Nyholt, Dale R; O'Donovan, Michael C; Penninx, Brenda W; Pergadia, Michele L.; Perlis, Roy; Potash, James B; Preisig, Martin; Purcell, Shaun M; Quiroz, Jorge A; Räikkönen, Katri; Rice, John P; Rietschel, Marcella; Rivera, Margarita; Schulze, Thomas G; Shi, Jianxin; Shyn, Stanley I; Sinnamon, Grant C; Smit, Johannes H; Smoller, Jordan W; Snieder, Harold; Tanaka, Toshiko; Tansey, Katherine E; Teumer, Alexander; Uher, Rudolf; Umbricht, Daniel; Van der Auwera, Sandra; Ware, Erin B; Weir, David R; Weissman, Myrna M; Willemsen, Gonneke; Yang, Jingyun; Zhao, Wei; Tiemeier, Henning; Sullivan, Patrick F

    2017-01-01

    BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide

  13. Medicinal plants recommended by the world health organization: DNA barcode identification associated with chemical analyses guarantees their quality.

    Directory of Open Access Journals (Sweden)

    Rafael Melo Palhares

    Full Text Available Medicinal plants are used throughout the world, and the regulations defining their proper use, such as identification of the correct species and verification of the presence, purity and concentration of the required chemical compounds, are widely recognized. Herbal medicines are made from vegetal drugs, the processed products of medicinal species. These processed materials present a number of challenges in terms of botanical identification, and according to the World Health Organization (WHO, the use of incorrect species is a threat to consumer safety. The samples used in this study consisted of the dried leaves, flowers and roots of 257 samples from 8 distinct species approved by the WHO for the production of medicinal herbs and sold in Brazilian markets. Identification of the samples in this study using DNA barcoding (matK, rbcL and ITS2 regions revealed that the level of substitutions may be as high as 71%. Using qualitative and quantitative chemical analyses, this study identified situations in which the correct species was being sold, but the chemical compounds were not present. Even more troubling, some samples identified as substitutions using DNA barcoding contained the chemical compounds from the correct species at the minimum required concentration. This last situation may lead to the use of unknown species or species whose safety for human consumption remains unknown. This study concludes that DNA barcoding should be used in a complementary manner for species identification with chemical analyses to detect and quantify the required chemical compounds, thus improving the quality of this class of medicines.

  14. Medicinal Plants Recommended by the World Health Organization: DNA Barcode Identification Associated with Chemical Analyses Guarantees Their Quality

    Science.gov (United States)

    Palhares, Rafael Melo; Gonçalves Drummond, Marcela; dos Santos Alves Figueiredo Brasil, Bruno; Pereira Cosenza, Gustavo; das Graças Lins Brandão, Maria; Oliveira, Guilherme

    2015-01-01

    Medicinal plants are used throughout the world, and the regulations defining their proper use, such as identification of the correct species and verification of the presence, purity and concentration of the required chemical compounds, are widely recognized. Herbal medicines are made from vegetal drugs, the processed products of medicinal species. These processed materials present a number of challenges in terms of botanical identification, and according to the World Health Organization (WHO), the use of incorrect species is a threat to consumer safety. The samples used in this study consisted of the dried leaves, flowers and roots of 257 samples from 8 distinct species approved by the WHO for the production of medicinal herbs and sold in Brazilian markets. Identification of the samples in this study using DNA barcoding (matK, rbcL and ITS2 regions) revealed that the level of substitutions may be as high as 71%. Using qualitative and quantitative chemical analyses, this study identified situations in which the correct species was being sold, but the chemical compounds were not present. Even more troubling, some samples identified as substitutions using DNA barcoding contained the chemical compounds from the correct species at the minimum required concentration. This last situation may lead to the use of unknown species or species whose safety for human consumption remains unknown. This study concludes that DNA barcoding should be used in a complementary manner for species identification with chemical analyses to detect and quantify the required chemical compounds, thus improving the quality of this class of medicines. PMID:25978064

  15. Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

    NARCIS (Netherlands)

    Franke, B.; Buitelaar, J.K.; Cichon, S.; Craddock, N.; Daly, M.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.; Sklar, P.; Sullivan, P.F.

    2009-01-01

    OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues

  16. A HuGE Review and Meta-Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Katherine Angela Benson

    Full Text Available New onset diabetes after transplantation (NODAT is a serious complication following solid organ transplantation. There is a genetic contribution to NODAT and we have conducted comprehensive meta-analysis of available genetic data in kidney transplant populations.Relevant articles investigating the association between genetic markers and NODAT were identified by searching PubMed, Web of Science and Google Scholar. SNPs described in a minimum of three studies were included for analysis using a random effects model. The association between identified variants and NODAT was calculated at the per-study level to generate overall significance values and effect sizes.Searching the literature returned 4,147 citations. Within the 36 eligible articles identified, 18 genetic variants from 12 genes were considered for analysis. Of these, three were significantly associated with NODAT by meta-analysis at the 5% level of significance; CDKAL1 rs10946398 p = 0.006 OR = 1.43, 95% CI = 1.11-1.85 (n = 696 individuals, KCNQ1 rs2237892 p = 0.007 OR = 1.43, 95% CI = 1.10-1.86 (n = 1,270 individuals, and TCF7L2 rs7903146 p = 0.01 OR = 1.41, 95% CI = 1.07-1.85 (n = 2,967 individuals.Evaluating cumulative evidence for SNPs associated with NODAT in kidney transplant recipients has revealed three SNPs associated with NODAT. An adequately powered, dense genome-wide association study will provide more information using a carefully defined NODAT phenotype.

  17. A case study of discordant overlapping meta-analyses: vitamin d supplements and fracture.

    Science.gov (United States)

    Bolland, Mark J; Grey, Andrew

    2014-01-01

    Overlapping meta-analyses on the same topic are now very common, and discordant results often occur. To explore why discordant results arise, we examined a common topic for overlapping meta-analyses- vitamin D supplements and fracture. We identified 24 meta-analyses of vitamin D (with or without calcium) and fracture in a PubMed search in October 2013, and analysed a sample of 7 meta-analyses in the highest ranking general medicine journals. We used the AMSTAR tool to assess the quality of the meta-analyses, and compared their methodologies, analytic techniques and results. Applying the AMSTAR tool suggested the meta-analyses were generally of high quality. Despite this, there were important differences in trial selection, data extraction, and analytical methods that were only apparent after detailed assessment. 25 trials were included in at least one meta-analysis. Four meta-analyses included all eligible trials according to the stated inclusion and exclusion criteria, but the other 3 meta-analyses "missed" between 3 and 8 trials, and 2 meta-analyses included apparently ineligible trials. The relative risks used for individual trials differed between meta-analyses for total fracture in 10 of 15 trials, and for hip fracture in 6 of 12 trials, because of different outcome definitions and analytic approaches. The majority of differences (11/16) led to more favourable estimates of vitamin D efficacy compared to estimates derived from unadjusted intention-to-treat analyses using all randomised participants. The conclusions of the meta-analyses were discordant, ranging from strong statements that vitamin D prevents fractures to equally strong statements that vitamin D without calcium does not prevent fractures. Substantial differences in trial selection, outcome definition and analytic methods between overlapping meta-analyses led to discordant estimates of the efficacy of vitamin D for fracture prevention. Strategies for conducting and reporting overlapping meta-analyses

  18. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

    Science.gov (United States)

    Graham, Deborah S Cunninghame; Pinder, Christopher L; Tombleson, Philip; Behrens, Timothy W; Martín, Javier; Fairfax, Benjamin P; Knight, Julian C; Chen, Lingyan; Replogle, Joseph; Syvänen, Ann-Christine; Rönnblom, Lars; Graham, Robert R; Wither, Joan E; Rioux, John D; Alarcón-Riquelme, Marta E; Vyse, Timothy J

    2015-01-01

    Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n=16) of transcription factors among SLE susceptibility genes. This supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE. PMID:26502338

  19. The Small and the Dead: A Review of Ancient DNA Studies Analysing Micromammal Species.

    Science.gov (United States)

    Woods, Roseina; Marr, Melissa M; Brace, Selina; Barnes, Ian

    2017-11-08

    The field of ancient DNA (aDNA) has recently been in a state of exponential growth, largely driven by the uptake of Next Generation Sequencing (NGS) techniques. Much of this work has focused on the mammalian megafauna and ancient humans, with comparatively less studies looking at micromammal fauna, despite the potential of these species in testing evolutionary, environmental and taxonomic theories. Several factors make micromammal fauna ideally suited for aDNA extraction and sequencing. Micromammal subfossil assemblages often include the large number of individuals appropriate for population level analyses, and, furthermore, the assemblages are frequently found in cave sites where the constant temperature and sheltered environment provide favourable conditions for DNA preservation. This review looks at studies that include the use of aDNA in molecular analysis of micromammal fauna, in order to examine the wide array of questions that can be answered in the study of small mammals using new palaeogenetic techniques. This study highlights the bias in current aDNA studies and assesses the future use of aDNA as a tool for the study of micromammal fauna.

  20. Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival.

    Science.gov (United States)

    Sveen, Anita; Agesen, Trude H; Nesbakken, Arild; Rognum, Torleiv O; Lothe, Ragnhild A; Skotheim, Rolf I

    2011-05-27

    Colorectal cancer (CRC) is a heterogeneous disease that, on the molecular level, can be characterized by inherent genomic instabilities; chromosome instability and microsatellite instability. In the present study we analyze genome-wide disruption of pre-mRNA splicing, and propose transcriptome instability as a characteristic that is analogous to genomic instability on the transcriptome level. Exon microarray profiles from two independent series including a total of 160 CRCs were investigated for their relative amounts of exon usage differences. Each exon in each sample was assigned an alternative splicing score calculated by the FIRMA algorithm. Amounts of deviating exon usage per sample were derived from exons with extreme splicing scores. There was great heterogeneity within both series in terms of sample-wise amounts of deviating exon usage. This was strongly associated with the expression levels of approximately half of 280 splicing factors (54% and 48% of splicing factors were significantly correlated to deviating exon usage amounts in the two series). Samples with high or low amounts of deviating exon usage, associated with overall transcriptome instability, were almost completely separated into their respective groups by hierarchical clustering analysis of splicing factor expression levels in both sample series. Samples showing a preferential tendency towards deviating exon skipping or inclusion were associated with skewed transcriptome instability. There were significant associations between transcriptome instability and reduced patient survival in both sample series. In the test series, patients with skewed transcriptome instability showed the strongest prognostic association (P = 0.001), while a combination of the two characteristics showed the strongest association with poor survival in the validation series (P = 0.03). We have described transcriptome instability as a characteristic of CRC. This transcriptome instability has associations with splicing

  1. Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines.

    Science.gov (United States)

    Eng, Lawson; Ibrahim-zada, Irada; Jarjanazi, Hamdi; Savas, Sevtap; Meschian, Mehran; Pritchard, Kathleen I; Ozcelik, Hilmi

    2011-02-11

    Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel. 43 SNPs were found significantly associated (FDRlines. Haplotypes found in GRIK1, SGCD, ROBO1, LPHN2, and PTPRD were more strongly associated with response than their individual SNPs. Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel.

  2. Event-level relationship between methamphetamine use significantly associated with non-adherence to pharmacologic trial medications in event-level analyses.

    Science.gov (United States)

    Hermanstyne, Keith A; Santos, Glenn-Milo; Vittinghoff, Eric; Santos, Deirdre; Colfax, Grant; Coffin, Phillip

    2014-10-01

    Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49-0.98). In addition, age (AOR: 1.07; 95% CI: 1.02-1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64-0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Publication bias & small-study effects in pediatric dentistry meta-analyses.

    Science.gov (United States)

    Papageorgiou, Spyridon N; Dimitraki, Dionysia; Coolidge, Trilby; Kotsanos, Nikolaos

    2015-03-01

    The aim of this study was to examine the presence and extent of publication bias and small-study effects in meta-analyses (MAs) investigating pediatric dentistry-related subjects. Following a literature search, 46 MAs including 882 studies were analyzed qualitatively. Of these, 39 provided enough data to be re-analyzed. Publication bias was assessed with the following methods: contour-enhanced funnel plots, Begg and Mazumdar's rank correlation and Egger's linear regression tests, Rosenthal's failsafe N, and Duval and Tweedie's "trim and fill" procedure. Only a few MAs adequately assessed the existence and effect of publication bias. Inspection of the funnel plots indicated asymmetry, which was confirmed by Begg-Mazumdar's test in 18% and by Egger's test in 33% of the MAs. According to Rosenthal's criterion, 80% of the MAs were robust, while adjusted effects with unpublished studies differed from little to great from the unadjusted ones. Pooling of the Egger's intercepts indicated that evidence of asymmetry was found in the pediatric dental literature, which was accentuated in dental journals and in diagnostic MAs. Since indications of small-study effects and publication bias in pediatric dentistry were found, the influence of small or missing trials on estimated treatment effects should be routinely assessed in future MAs. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Storage and shipping of tissue samples for DNA analyses: A case study on earthworms☆

    Science.gov (United States)

    Straube, Daniela; Juen, Anita

    2013-01-01

    Nowadays, molecular analyses play an important role in studies of soil dwelling animals, for example in taxonomy, phylogeography or food web analyses. The quality of the DNA, used for later molecular analyses, is an important factor and depends on collection and preservation of samples prior to DNA extraction. Ideally, DNA samples are frozen immediately upon collection, but if samples are collected in the field, suitable preservation methods might be limited due to unavailability of resources or remote field sites. Moreover, shipping samples over long distances can cause loss of DNA quality e.g. by thawing or leaking of preservation liquid. In this study we use earthworms, a key organism in soil research, to compare three different DNA preservation methods – freezing at −20 °C, storing in 75% ethanol, and freeze drying. Samples were shipped from the United States of America to Austria. The DNA of the samples was extracted using two different extraction methods, peqGOLD™ and Chelex® 100. The DNA amplification success was determined by amplifying four DNA fragments of different length. The PCR amplification success is significantly influenced by preservation method and extraction method and differed significantly depending on the length of the DNA fragment. Freeze drying samples was the best preservation method when samples were extracted using the silica based extraction method peqGOLD™. For samples that were extracted with Chelex® 100, storage in ethanol was the best preservation method. However, the overall amplification success was significantly lower for the extraction procedure based on Chelex® 100. The detection of the small DNA fragments was higher and independent from the extraction method, while the amplification success was significantly reduced for the longer DNA fragments. We recommend freeze drying of DNA samples, especially when they have to be shipped for longer distances. No special packaging or declaration is needed for freeze dried

  5. Storage and shipping of tissue samples for DNA analyses: A case study on earthworms.

    Science.gov (United States)

    Straube, Daniela; Juen, Anita

    2013-07-01

    Nowadays, molecular analyses play an important role in studies of soil dwelling animals, for example in taxonomy, phylogeography or food web analyses. The quality of the DNA, used for later molecular analyses, is an important factor and depends on collection and preservation of samples prior to DNA extraction. Ideally, DNA samples are frozen immediately upon collection, but if samples are collected in the field, suitable preservation methods might be limited due to unavailability of resources or remote field sites. Moreover, shipping samples over long distances can cause loss of DNA quality e.g. by thawing or leaking of preservation liquid. In this study we use earthworms, a key organism in soil research, to compare three different DNA preservation methods - freezing at -20 °C, storing in 75% ethanol, and freeze drying. Samples were shipped from the United States of America to Austria. The DNA of the samples was extracted using two different extraction methods, peqGOLD™ and Chelex® 100. The DNA amplification success was determined by amplifying four DNA fragments of different length. The PCR amplification success is significantly influenced by preservation method and extraction method and differed significantly depending on the length of the DNA fragment. Freeze drying samples was the best preservation method when samples were extracted using the silica based extraction method peqGOLD™. For samples that were extracted with Chelex® 100, storage in ethanol was the best preservation method. However, the overall amplification success was significantly lower for the extraction procedure based on Chelex® 100. The detection of the small DNA fragments was higher and independent from the extraction method, while the amplification success was significantly reduced for the longer DNA fragments. We recommend freeze drying of DNA samples, especially when they have to be shipped for longer distances. No special packaging or declaration is needed for freeze dried

  6. Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study

    DEFF Research Database (Denmark)

    Singh, Jatinder; Minster, Ryan L; Schupf, Nicole

    2017-01-01

    Background: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Methods: Using data from the Long Life Family Study, we performed genomewide association analyses...

  7. Prospective association of childhood receptive vocabulary and conduct problems with self-reported adolescent delinquency: tests of mediation and moderation in sibling-comparison analyses.

    Science.gov (United States)

    Lahey, Benjamin B; D'Onofrio, Brian M; Van Hulle, Carol A; Rathouz, Paul J

    2014-11-01

    Associations among receptive vocabulary measured at 4-9 years, mother-reported childhood conduct problems at 4-9 years, and self-reported adolescent delinquency at 14-17 years were assessed using data from a prospective study of the offspring of a large U.S. nationally representative sample of women. A novel quasi-experimental strategy was used to rule out family-level confounding by estimating path-analytic associations within families in a sibling comparison design. This allowed simultaneous tests of the direct and indirect effects of receptive vocabulary and childhood conduct problems, and of their joint moderation, on adolescent delinquency without family-level environmental confounding. The significant association of receptive vocabulary with later adolescent delinquency was indirect, mediated by childhood conduct problems. Furthermore, a significant interaction between receptive vocabulary and childhood conduct problems reflected a steeper slope for the predictive association between childhood conduct problems and adolescent delinquency when receptive vocabulary scores were higher. These findings of significant indirect association were qualitatively identical in both population-level and within-family analyses, suggesting that they are not the result of family-level confounds.

  8. Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent Health.

    Science.gov (United States)

    Gangwisch, James E; Malaspina, Dolores; Babiss, Lindsay A; Opler, Mark G; Posner, Kelly; Shen, Sa; Turner, J Blake; Zammit, Gary K; Ginsberg, Henry N

    2010-07-01

    To explore the relationship between sleep duration in adolescence and hypercholesterolemia in young adulthood. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in women. Short sleep duration has been found in cross sectional studies to be associated with higher total cholesterol and lower HDL cholesterol levels. Sleep deprivation could increase the risk for hypercholesterolemia by increasing appetite and dietary consumption of saturated fats, decreasing motivation to engage in regular physical activity, and increasing stress and resultant catecholamine induced lipolysis. No previous published population studies have examined the longitudinal relationship between sleep duration and high cholesterol. Multivariate longitudinal analyses stratified by sex of the ADD Health using logistic regression. United States nationally representative, school-based, probability-based sample. Adolescents (n = 14,257) in grades 7 to 12 at baseline (1994-95) and ages 18 to 26 at follow-up (2001-02). Among females, each additional hour of sleep was associated with a significantly decreased odds of being diagnosed with high cholesterol in young adulthood (OR = 0.85, 95% CI 0.75-0.96) after controlling for covariates. Additional sleep was associated with decreased, yet not statistically significant, odds ratios for hypercholesterolemia in males (OR = 0.91, 95% CI 0.79-1.05). Short sleep durations in adolescent women could be a significant risk factor for high cholesterol. Interventions that lengthen sleep could potentially serve as treatments and as primary preventative measures for hypercholesterolemia.

  9. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

    Science.gov (United States)

    Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-07-13

    To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living

  10. Anonymisation of address coordinates for microlevel analyses of the built environment: a simulation study.

    Science.gov (United States)

    Buck, Christoph; Dreger, Steffen; Pigeot, Iris

    2015-03-09

    Data privacy is a major concern in spatial epidemiology because exact residential locations or parts of participants' addresses such as street or zip codes are used to perform geospatial analyses. To overcome this concern, different levels of aggregation such as census districts or zip code areas are mainly used, though any spatial aggregation leads to a loss of spatial variability. For the assessment of urban opportunities for physical activity that was conducted in the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study, macrolevel analyses were performed, but the use of exact residential addresses for micro-level analyses was not permitted by the responsible office for data protection. We therefore implemented a spatial blurring to anonymise address coordinates depending on the underlying population density. We added a standard Gaussian distributed error to individual address coordinates with the variance σ² depending on the population density and on the chosen k-anonymity. 1000 random point locations were generated and repeatedly blurred 100 times to obtain anonymised locations. For each location 1 km network-dependent neighbourhoods were used to calculate walkability indices. Indices of blurred locations were compared to indices based on their sampling origins to determine the effect of spatial blurring on the assessment of the built environment. Spatial blurring decreased with increasing population density. Similarly, mean differences in walkability indices also decreased with increasing population density. In particular for densely-populated areas with at least 1500 residents per km², differences between blurred locations and their sampling origins were small and did not affect the assessment of the built environment after spatial blurring. This approach allowed the investigation of the built environment at a microlevel using individual network-dependent neighbourhoods, while ensuring

  11. A case study of discordant overlapping meta-analyses: vitamin d supplements and fracture.

    Directory of Open Access Journals (Sweden)

    Mark J Bolland

    Full Text Available BACKGROUND: Overlapping meta-analyses on the same topic are now very common, and discordant results often occur. To explore why discordant results arise, we examined a common topic for overlapping meta-analyses- vitamin D supplements and fracture. METHODS AND FINDINGS: We identified 24 meta-analyses of vitamin D (with or without calcium and fracture in a PubMed search in October 2013, and analysed a sample of 7 meta-analyses in the highest ranking general medicine journals. We used the AMSTAR tool to assess the quality of the meta-analyses, and compared their methodologies, analytic techniques and results. Applying the AMSTAR tool suggested the meta-analyses were generally of high quality. Despite this, there were important differences in trial selection, data extraction, and analytical methods that were only apparent after detailed assessment. 25 trials were included in at least one meta-analysis. Four meta-analyses included all eligible trials according to the stated inclusion and exclusion criteria, but the other 3 meta-analyses "missed" between 3 and 8 trials, and 2 meta-analyses included apparently ineligible trials. The relative risks used for individual trials differed between meta-analyses for total fracture in 10 of 15 trials, and for hip fracture in 6 of 12 trials, because of different outcome definitions and analytic approaches. The majority of differences (11/16 led to more favourable estimates of vitamin D efficacy compared to estimates derived from unadjusted intention-to-treat analyses using all randomised participants. The conclusions of the meta-analyses were discordant, ranging from strong statements that vitamin D prevents fractures to equally strong statements that vitamin D without calcium does not prevent fractures. CONCLUSIONS: Substantial differences in trial selection, outcome definition and analytic methods between overlapping meta-analyses led to discordant estimates of the efficacy of vitamin D for fracture prevention

  12. 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.

  13. Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines

    Directory of Open Access Journals (Sweden)

    Jarjanazi Hamdi

    2011-02-01

    Full Text Available Abstract Background Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel. Results 43 SNPs were found significantly associated (FDR CFTR, ROBO1, PTPRD, BTBD12, DCT, SNTG1, SGCD, LPHN2, GRIK1, ZNF607. SNPs in GRIK1, DCT, SGCD and CFTR were predicted to be intronic enhancers, altering gene expression, while SNPs in ZNF607 and BTBD12 cause conservative missense mutations. mRNA expression analysis supported these findings as GRIK1, DCT, SNTG1, SGCD and CFTR showed significantly (p GRIK1, SGCD, ROBO1, LPHN2, and PTPRD were more strongly associated with response than their individual SNPs. Conclusions Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely

  14. Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males.

    Science.gov (United States)

    Liu, Yao-Zhong; Pei, Yu-Fang; Liu, Jian-Feng; Yang, Fang; Guo, Yan; Zhang, Lei; Liu, Xiao-Gang; Yan, Han; Wang, Liang; Zhang, Yin-Ping; Levy, Shawn; Recker, Robert R; Deng, Hong-Wen

    2009-08-28

    Current genome-wide association studies (GWAS) are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI), with the osteoporosis risk phenotype, hip bone mineral density (BMD), scanning approximately 380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6) gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82x10(-7) and 1.47x10(-6), respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the approximately 380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS) cohort containing 3,355 Caucasians (1,370 males and 1,985 females) from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis.

  15. Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.

    Science.gov (United States)

    Masterson, Liam; Winder, David M; Ball, Siolian L R; Vaughan, Katie; Lehmann, Martin; Scholtz, Lars-Uwe; Sterling, Jane C; Sudhoff, Holger H; Goon, Peter K C

    2016-06-13

    Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival. HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04). Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.

  16. Ozone therapy as an adjuvant for endondontic protocols: microbiological - ex vivo study and citotoxicity analyses.

    Science.gov (United States)

    Nogales, Carlos Goes; Ferreira, Marina Beloti; Montemor, Antonio Fernando; Rodrigues, Maria Filomena de Andrade; Lage-Marques, José Luiz; Antoniazzi, João Humberto

    2016-01-01

    This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I - control; Group II - standard protocol; Group III - standard protocol + ozone gas at 40 µg/mL; and Group IV - standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) - broth medium; Group II - aqueous ozone at 2 µg/mL; Group III - aqueous ozone at 5 µg/mL; and Group IV - aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  17. Family structure and posttraumatic stress reactions: a longitudinal study using multilevel analyses

    Directory of Open Access Journals (Sweden)

    Nygaard Egil

    2011-12-01

    Full Text Available Abstract Background There is limited research on the relevance of family structures to the development and maintenance of posttraumatic stress following disasters. We longitudinally studied the effects of marital and parental statuses on posttraumatic stress reactions after the 2004 Southeast Asian tsunami and whether persons in the same households had more shared stress reactions than others. Method The study included a tourist population of 641 Norwegian adult citizens, many of them from families with children. We measured posttraumatic stress symptoms with the Impact of Event Scale-Revised at 6 months and 2 years post-disaster. Analyses included multilevel methods with mixed effects models. Results Results showed that neither marital nor parental status was significantly related to posttraumatic stress. At both assessments, adults living in the same household reported levels of posttraumatic stress that were more similar to one another than adults who were not living together. Between households, disaster experiences were closely related to the variance in posttraumatic stress symptom levels at both assessments. Within households, however, disaster experiences were less related to the variance in symptom level at 2 years than at 6 months. Conclusions These results indicate that adult household members may influence one another's posttraumatic stress reactions as well as their interpretations of the disaster experiences over time. Our findings suggest that multilevel methods may provide important information about family processes after disasters.

  18. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Science.gov (United States)

    NOGALES, Carlos Goes; FERREIRA, Marina Beloti; MONTEMOR, Antonio Fernando; RODRIGUES, Maria Filomena de Andrade; Lage-MARQUES, José Luiz; ANTONIAZZI, João Humberto

    2016-01-01

    ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results. PMID:28076466

  19. Who runs public health? A mixed-methods study combining qualitative and network analyses.

    Science.gov (United States)

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

    2013-09-01

    Persistent health inequalities encourage researchers to identify new ways of understanding the policy process. Informal relationships are implicated in finding evidence and making decisions for public health policy (PHP), but few studies use specialized methods to identify key actors in the policy process. We combined network and qualitative data to identify the most influential individuals in PHP in a UK conurbation and describe their strategies to influence policy. Network data were collected by asking for nominations of powerful and influential people in PHP (n = 152, response rate 80%), and 23 semi-structured interviews were analysed using a framework approach. The most influential PHP makers in this conurbation were mid-level managers in the National Health Service and local government, characterized by managerial skills: controlling policy processes through gate keeping key organizations, providing policy content and managing selected experts and executives to lead on policies. Public health professionals and academics are indirectly connected to policy via managers. The most powerful individuals in public health are managers, not usually considered targets for research. As we show, they are highly influential through all stages of the policy process. This study shows the importance of understanding the daily activities of influential policy individuals.

  20. Correcting for multivariate measurement error by regression calibration in meta-analyses of epidemiological studies

    DEFF Research Database (Denmark)

    Tybjærg-Hansen, Anne

    2009-01-01

    Within-person variability in measured values of multiple risk factors can bias their associations with disease. The multivariate regression calibration (RC) approach can correct for such measurement error and has been applied to studies in which true values or independent repeat measurements......-specific, averaged and empirical Bayes estimates of RC parameters. Additionally, we allow for binary covariates (e.g. smoking status) and for uncertainty and time trends in the measurement error corrections. Our methods are illustrated using a subset of individual participant data from prospective long-term studies...... in the Fibrinogen Studies Collaboration to assess the relationship between usual levels of plasma fibrinogen and the risk of coronary heart disease, allowing for measurement error in plasma fibrinogen and several confounders Udgivelsesdato: 2009/3/30...

  1. 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.

  2. Associations between food and beverage groups and major diet-related chronic diseases: an exhaustive review of pooled/meta-analyses and systematic reviews.

    Science.gov (United States)

    Fardet, Anthony; Boirie, Yves

    2014-12-01

    Associations between food and beverage groups and the risk of diet-related chronic disease (DRCD) have been the subject of intensive research in preventive nutrition. Pooled/meta-analyses and systematic reviews (PMASRs) aim to better characterize these associations. To date, however, there has been no attempt to synthesize all PMASRs that have assessed the relationship between food and beverage groups and DRCDs. The objectives of this review were to aggregate PMASRs to obtain an overview of the associations between food and beverage groups (n = 17) and DRCDs (n = 10) and to establish new directions for future research needs. The present review of 304 PMASRs published between 1950 and 2013 confirmed that plant food groups are more protective than animal food groups against DRCDs. Within plant food groups, grain products are more protective than fruits and vegetables. Among animal food groups, dairy/milk products have a neutral effect on the risk of DRCDs, while red/processed meats tend to increase the risk. Among beverages, tea was the most protective and soft drinks the least protective against DRCDs. For two of the DRCDs examined, sarcopenia and kidney disease, no PMASR was found. Overweight/obesity, type 2 diabetes, and various types of cardiovascular disease and cancer accounted for 289 of the PMASRs. There is a crucial need to further study the associations between food and beverage groups and mental health, skeletal health, digestive diseases, liver diseases, kidney diseases, obesity, and type 2 diabetes. © 2014 International Life Sciences Institute.

  3. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Directory of Open Access Journals (Sweden)

    Carlos Goes NOGALES

    Full Text Available ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (p<0.05%. Results The results revealed antimicrobial efficacy by Group IV with no CFU count. The cytotoxicity assay showed Groups III and IV to be the most aggressive, providing a decrease in cell viability at hour 0 from 100% to 77.3% and 68.6%, respectively. Such a decrease in cell viability was reverted, and after 72 hours Groups III and IV provided the greatest increase in cell viability, being statistically different from Groups I and II. Conclusion According to the applied methodology and the limitations of this study, it was possible to conclude that ozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  4. Multi-Criteria Analyses of Urban Planning for City Expansion: A Case Study of Zamora, Spain

    Directory of Open Access Journals (Sweden)

    Marco Criado

    2017-10-01

    Full Text Available This study has established a methodology to determine the most environmentally suitable area for the expansion of Zamora (Spain using geographic information system (GIS technology. The objective was to develop a GIS-based methodology for the identification of urban peripheral areas that are suitable for the accommodation of new buildings and services, that are compliant with environmental criteria, and that guarantee an adequate quality of life for the future population such that extra construction costs are avoided. The methodological core is based on two multi-criteria analyses (MCAs: MCA-1 determines areas suitable for building—the most environmentally sustainable areas that do not present risks or discomforts to the population—by analyzing the restrictive factors; MCA-2 takes the sectors that received a favorable evaluation in MCA-1, determines which of those have a lower economic overhead for construction, and analyzes the different conditioning criteria related to their pre-existing infrastructures. Finally, the location of the sectors is determined by a decision factor that satisfies some strategic need of the municipality.

  5. a Comparative Study of Alto Saxophone Reeds Through Spectral and Subjective Analyses.

    Science.gov (United States)

    Henderson, Caroline Blythe

    The purpose of this study was to analyze six brands of cane reeds and five brands of synthetic reeds to determine the differences in tone quality produced by each. Spectral analysis was used to determine the individual reed which conformed most closely to the average profile of each brand. A panel of seven saxophone performers then presented their opinions of the each reed's tone quality upon hearing a live performance of an excerpt from Eugene Bozza's Aria for alto saxophone and piano performed on the reeds most representative of each brand. The evaluation form used by the judges included ten sets of bipolar adjectives: good-bad, harmonious-dissonant, clean-dirty, light-dark, pleasurable-painful, beautiful-ugly, strong-weak, complex -simple, masculine-feminine, and interesting-boring. The results indicated that the primary factors influencing the tone quality of a given reed were the strength of the overtones present regardless of their order and the dominance of either the fundamental or the first overtone. Although professional musicians normally hand-select their reeds for performance, this research based on both spectral and subjective analyses provides clear evidence for both musicians and music educators to refine and improve their reed selection process.

  6. Sensitivity studies for 3-D rod ejection analyses on axial power shape

    Energy Technology Data Exchange (ETDEWEB)

    Park, Min-Ho; Park, Jin-Woo; Park, Guen-Tae; Ryu, Seok-Hee; Um, Kil-Sup; Lee, Jae-Il [KEPCO NF, Daejeon (Korea, Republic of)

    2015-10-15

    The current safety analysis methodology using the point kinetics model combined with numerous conservative assumptions result in unrealistic prediction of the transient behavior wasting huge margin for safety analyses while the safety regulation criteria for the reactivity initiated accident are going strict. To deal with this, KNF is developing a 3-D rod ejection analysis methodology using the multi-dimensional code coupling system CHASER. The CHASER system couples three-dimensional core neutron kinetics code ASTRA, sub-channel analysis code THALES, and fuel performance analysis code FROST using message passing interface (MPI). A sensitivity study for 3-D rod ejection analysis on axial power shape (APS) is carried out to survey the tendency of safety parameters by power distributions and to build up a realistic safety analysis methodology while maintaining conservatism. The currently developing 3-D rod ejection analysis methodology using the multi-dimensional core transient analysis code system, CHASER was shown to reasonably reflect the conservative assumptions by tuning up kinetic parameters.

  7. Genome-Wide Association Analyses Based on Broadly Different Specifications for Prior Distributions, Genomic Windows, and Estimation Methods.

    Science.gov (United States)

    Chen, Chunyu; Steibel, Juan P; Tempelman, Robert J

    2017-08-01

    A currently popular strategy (EMMAX) for genome-wide association (GWA) analysis infers association for the specific marker of interest by treating its effect as fixed while treating all other marker effects as classical Gaussian random effects. It may be more statistically coherent to specify all markers as sharing the same prior distribution, whether that distribution is Gaussian, heavy-tailed (BayesA), or has variable selection specifications based on a mixture of, say, two Gaussian distributions [stochastic search and variable selection (SSVS)]. Furthermore, all such GWA inference should be formally based on posterior probabilities or test statistics as we present here, rather than merely being based on point estimates. We compared these three broad categories of priors within a simulation study to investigate the effects of different degrees of skewness for quantitative trait loci (QTL) effects and numbers of QTL using 43,266 SNP marker genotypes from 922 Duroc-Pietrain F2-cross pigs. Genomic regions were based either on single SNP associations, on nonoverlapping windows of various fixed sizes (0.5-3 Mb), or on adaptively determined windows that cluster the genome into blocks based on linkage disequilibrium. We found that SSVS and BayesA lead to the best receiver operating curve properties in almost all cases. We also evaluated approximate maximum a posteriori (MAP) approaches to BayesA and SSVS as potential computationally feasible alternatives; however, MAP inferences were not promising, particularly due to their sensitivity to starting values. We determined that it is advantageous to use variable selection specifications based on adaptively constructed genomic window lengths for GWA studies. Copyright © 2017 by the Genetics Society of America.

  8. Tri-level study of the causes of traffic accidents, volume 2 : special analyses.

    Science.gov (United States)

    1979-05-01

    This final report is comprised of two volumes. Volume I provides causal result tabulations and related analyses. Volume II presents several special analysis reports dealing with driver vision knowledge, psychological make-up, etc. Human, environmenta...

  9. Assessing the relationship between farming practices, laboratory analyses and post-mortem findings: a case study in pig fattening.

    Science.gov (United States)

    Langkabel, N; Fries, R

    2013-12-01

    European Union legislation on animal production associated with food safety requires the collection and management of information and data about the farm, the herd and the individual animal. This paper describes the technical steps of the generation, collection and interpretation of data from 296 pig-fattening farms, belonging to two farming associations and using indoor production systems (56 management parameters). The paper also describes post-mortem findings and the results of enzyme-linked immunosorbent assays (ELISA) for antibodies to salmonellae, Trichinella spp. and Yersinia spp. A total of nearly 30 million data points were collected and analysed for this study. The results of the ELISA were negative for Trichinella spp.; for salmonellae and Yersinia spp., both negative and positive results were obtained. Analysis of the farm management parameters showed no significant differences; therefore, the cut-off levels for salmonellae and Yersinia spp. were increased, in order to identify farms with a greater hygiene burden. Post-mortem findings, possibly related to 'farm hygiene', were used in the analysis. As a result, three farms with particular management decisions were identified as potentially having contributed to the high burden of pathogens detected using ELISA. A relationship between laboratory results and farm management parameters assessed from yes/no answers could not be established in this study without further work on the available data set.

  10. Association of HOXA10, ZFPM2, and MMP2 genes with scrotal hernias evaluated via biological candidate gene analyses in pigs.

    Science.gov (United States)

    Zhao, Xia; Du, Zhi-Qiang; Vukasinovic, Natascha; Rodriguez, Fernanda; Clutter, Archie C; Rothschild, Max F

    2009-08-01

    To evaluate the associations between 14 biological candidate genes and scrotal hernias in pigs. 1,534 Pietrain-based pigs, including 692 individuals from 298 pig families and 842 male pigs without family information. Pigs were classified as affected or unaffected for scrotal hernias. Single nucleotide polymorphisms of candidate genes were analyzed via PCR assays and genotyped. Statistical analyses were performed on the family-trio and the case-control data. 2 genes involved in collagen metabolism (homeobox A10 [HOXA10] and matrix metalloproteinases 2 [MMP2]) and 1 gene encoding zinc finger protein multitype 2 (ZFPM2, important in the development of diaphragmatic hernia) were significantly associated with hernias. Pigs with these genotypes had high odds of developing scrotal hernias in the case and control groups (2 ZFPM2 variants: odds ratio, 4.3 [95% confidence interval, 2.78 to 6.64] and 4.45[95%confidenceinterval,2.88to6.88]). Anothergene, collagentypeII A 1(COL2A1),was potentially involved in hernia development. HOXA10, ZFPM2, MMP2, and COL2A1 could have important roles in pig hernia development and potentially be useful for marker-assisted selection in the pig industry. Pigs are used for the study of many human diseases because of their physiologic similarities. Genes associated with scrotal hernias in this study may be directly used in understanding the molecular mechanisms underlying this defect in humans.

  11. Associations between Sleep Duration and Indicators of Cardiometabolic Disease in Canadian Children and Adolescents: Analyses of the 2007-2009 Canadian Health Measures Survey.

    Science.gov (United States)

    Sluggett, Larine; Wagner, Shannon L; Hardy, Cindy; Harris, R Luke

    2016-10-01

    Indicators of cardiometabolic disease-including obesity, hyperinsulinemia, and dyslipidemia-are associated with an increased risk of cardiovascular disease and type 2 diabetes. Rates of obesity and type 2 diabetes in Canadian children and adolescents have increased rapidly in recent years; research exploring modifiable risk factors is critical. Experimental and epidemiological research demonstrates that partial sleep loss is linked with deteriorations in indicators of cardiometabolic health. The objectives of this study are (1) to examine associations between short sleep duration and indicators of cardiometabolic disease in Canadian children and adolescents and (2) to identify determinants of short sleep duration in this population. Logistic regression models were developed to examine associations between sleep duration and indicators of cardiometabolic disease and to identify predictors of short sleep duration. Compared with longer sleepers, children and adolescents with short sleep duration had greater odds of being overweight or obese. Sex- and age-stratified analyses indicated that short sleep duration was linked with greater odds of overweight/obesity in boys and adolescents only. Short sleepers did not have greater odds of having hyperinsulinemia, low HDL cholesterol, or high triglycerides. Age was a strong predictor of inadequate sleep duration. Future studies should include longitudinal designs that address whether short sleep duration in boys and in adolescents contributes directly to the development of overweight and obesity.

  12. Analyses of 1100 supernumerary teeth in a nonsyndromic Turkish population: A retrospective multicenter study.

    Science.gov (United States)

    Bereket, C; Çakır-Özkan, N; Şener, İ; Bulut, E; Baştan, A İ

    2015-01-01

    The aim of this study was to analyze the clinical and radiological features of supernumerary teeth (ST), record the related complications, and discuss different forms of treatment. A total of 111,293 patients were examined over a 3-year period. The patients' ages and genders, in addition to the number, morphology, location, position, shape, developmental stage, and eruption status of ST and associated complications, were recorded. Among the 111,293 patients, there were 851 (0.76%) patients with 1100 ST. Of these patients, 478 (56.2%) were males, and 373 (43.8%) were females, with a mean age of 22.71. Most of the 1100 ST were located in the maxilla, 437 (39.72%) were a conical shape, with 82.81% of these including a fully developed tooth. A mesiodens was the most common type of supernumerary tooth (n=284, 33.37%), followed by distomolars (n=204, 23.97%) and parapremolars (n=146, 17.16%). Among the 1100 ST, 422 (38.36%) were associated with complications. No previous studies in the literature have examined in detail so many cases with ST. The demographic profile of the patients with ST presented herein provides useful additional epidemiological information.

  13. Correlation analyses revealed global microRNA-mRNA expression associations in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Wang, Lan; Zhu, Jiang; Deng, Fei-Yan; Wu, Long-Fei; Mo, Xing-Bo; Zhu, Xiao-Wei; Xia, Wei; Xie, Fang-Fei; He, Pei; Bing, Peng-Fei; Qiu, Ying-Hua; Lin, Xiang; Lu, Xin; Zhang, Lei; Yi, Neng-Jun; Zhang, Yong-Hong; Lei, Shu-Feng

    2017-09-06

    MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3'-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA-mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA-mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA-mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA-mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA-mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases.

  14. First fungal community analyses of endophytic ascomycetes associated with Viscum album ssp. austriacum and its host Pinus sylvestris.

    Science.gov (United States)

    Peršoh, Derek; Melcher, Martina; Flessa, Fabienne; Rambold, Gerhard

    2010-07-01

    The endophytic fungal communities in the hemi-parasitic epiphyte Viscum album and in its phorophyte Pinus sylvestris were compared to reveal the fungal distribution patterns in their hosts. The ITS nrDNA of 208 multiple-isolated fungal strains was sequenced and a newly designed process was applied for assigning taxon names to the obtained sequences. Furthermore, the isolates were grouped as clusters, by subjecting a sequence similarity matrix to various cluster analyses, the results of which were compared and verified by data from phylogenetic reconstructions. In contrast to a previously reported dominance of Leotiomycetes among Pinus inhabiting fungi, the endophytic communities of the two host plant species studied here were dominated by Xylariaceae (Sordariomycetes). This is in accordance with the finding that host selectivity was only a minor factor in explaining the distribution patterns of the endophytic fungi in Viscum and Pinus. Organ and, probably, tissue selectivity had a more pronounced effect. The composition and condition of the woods in the surrounding, however, are concluded to be the major determinants, due to the following circumstantial evidence: The highest similarities in fungal community compositions were found for the leaves of the two host plant species, especially when considering only the older leaves. The finding that the inhabitants of matured or senescent organs are less host-selective is in accordance with decreasing defence capabilities of ageing host plant tissue and an increased nutrient supply for saprobic taxa. Therefore, the composition of the fungal communities in ageing leaves seems to be predominantly ascribed to contagious spread and to depend on the spectrum of nearby sporulating fungal taxa. We suggest that because a broad range of suitable substrates for Xylariaceae was present in immediate vicinity of the study sites, these fungi also dominated among the recorded endophytic taxa. Copyright © 2010 The British Mycological

  15. Scientometric analyses of studies on the role of innate variation in athletic performance.

    Science.gov (United States)

    Lombardo, Michael P; Emiah, Shadie

    2014-01-01

    Historical events have produced an ideologically charged atmosphere in the USA surrounding the potential influences of innate variation on athletic performance. We tested the hypothesis that scientific studies of the role of innate variation in athletic performance were less likely to have authors with USA addresses than addresses elsewhere because of this cultural milieu. Using scientometric data collected from 290 scientific papers published in peer-reviewed journals from 2000-2012, we compared the proportions of authors with USA addresses with those that listed addresses elsewhere that studied the relationships between athletic performance and (a) prenatal exposure to androgens, as indicated by the ratio between digits 2 and 4, and (b) the genotypes for angiotensin converting enzyme, α-actinin-3, and myostatin; traits often associated with athletic performance. Authors with USA addresses were disproportionately underrepresented on papers about the role of innate variation in athletic performance. We searched NIH and NSF databases for grant proposals solicited or funded from 2000-2012 to determine if the proportion of authors that listed USA addresses was associated with funding patterns. NIH did not solicit grant proposals designed to examine these factors in the context of athletic performance and neither NIH nor NSF funded grants designed to study these topics. We think the combined effects of a lack of government funding and the avoidance of studying controversial or non-fundable topics by USA based scientists are responsible for the observation that authors with USA addresses were underrepresented on scientific papers examining the relationships between athletic performance and innate variation.

  16. Serum concentrations of mood stabilizers are associated with memory, but not other cognitive domains in psychosis spectrum disorders; explorative analyses in a naturalistic setting.

    Science.gov (United States)

    Steen, Nils Eiel; Aas, Monica; Simonsen, Carmen; Dieset, Ingrid; Tesli, Martin; Nerhus, Mari; Gardsjord, Erlend; Mørch, Ragni; Agartz, Ingrid; Melle, Ingrid; Vaskinn, Anja; Spigset, Olav; Andreassen, Ole A

    2016-12-01

    Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. There is a lack of knowledge of the relationship of these medications and cognition in the psychosis spectrum. We studied the association between serum concentration of mood stabilizers and cognitive performance in a well-characterized sample of bipolar and schizophrenia spectrum disorders. Serum concentrations of valproate, lamotrigine, and lithium were analyzed for associations to performance on neuropsychological tests in six cognitive domains in individuals with bipolar disorder (n = 167) and in a combined sample of individuals with bipolar or schizophrenia spectrum disorders (n = 217). Linear regression with adjustments for gender, age, and symptom levels of depression, mania, and psychosis were applied for the association analyses. There were negative associations between serum levels of valproate and short term delayed recall (bipolar: p = 0.043; combined: p = 0.044) and working memory (bipolar: p = 0.043). A positive association was suggested between serum level of lithium and working memory (bipolar: p = 0.039). There were no other significant relationships between serum levels of valproate, lamotrigine, or lithium and neuropsychological test performance in neither the bipolar disorder nor the combined group. Serum levels of mood stabilizers were unrelated to cognitive performance in most domains, indicating that higher dose does not lead to broader cognitive impairments in bipolar and related psychotic disorder patients. However, worsened memory with increasing levels of valproate suggests cautious dosing of anticonvulsants, while increasing lithium level seems to be associated with improved memory. The findings should be interpreted with caution due to the explorative, naturalistic design.

  17. Partial correlation analyses of global diffusion tensor imaging-derived metrics in glioblastoma multiforme: Pilot study

    Science.gov (United States)

    Cortez-Conradis, David; Rios, Camilo; Moreno-Jimenez, Sergio; Roldan-Valadez, Ernesto

    2015-01-01

    AIM: To determine existing correlates among diffusion tensor imaging (DTI)-derived metrics in healthy brains and brains with glioblastoma multiforme (GBM). METHODS: Case-control study using DTI data from brain magnetic resonance imaging of 34 controls (mean, 41.47; SD, ± 21.94 years; range, 21-80 years) and 27 patients with GBM (mean, SD; 48.41 ± 15.18 years; range, 18-78 years). Image postprocessing using FSL software calculated eleven tensor metrics: fractional (FA) and relative anisotropy; pure isotropic (p) and anisotropic diffusions (q), total magnitude of diffusion (L); linear (Cl), planar (Cp) and spherical tensors (Cs); mean (MD), axial (AD) and radial diffusivities (RD). Partial correlation analyses (controlling the effect of age and gender) and multivariate Mancova were performed. RESULTS: There was a normal distribution for all metrics. Comparing healthy brains vs brains with GBM, there were significant very strong bivariate correlations only depicted in GBM: [FA↔Cl (+)], [FA↔q (+)], [p↔AD (+)], [AD↔MD (+)], and [MD↔RD (+)]. Among 56 pairs of bivariate correlations, only seven were significantly different. The diagnosis variable depicted a main effect [F-value (11, 23) = 11.842, P ≤ 0.001], with partial eta squared = 0.850, meaning a large effect size; age showed a similar result. The age also had a significant influence as a covariate [F (11, 23) = 10.523, P < 0.001], with a large effect size (partial eta squared = 0.834). CONCLUSION: DTI-derived metrics depict significant differences between healthy brains and brains with GBM, with specific magnitudes and correlations. This study provides reference data and makes a contribution to decrease the underlying empiricism in the use of DTI parameters in brain imaging. PMID:26644826

  18. Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males.

    Directory of Open Access Journals (Sweden)

    Yao-Zhong Liu

    2009-08-01

    Full Text Available Current genome-wide association studies (GWAS are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically.To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI, with the osteoporosis risk phenotype, hip bone mineral density (BMD, scanning approximately 380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6 gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82x10(-7 and 1.47x10(-6, respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the approximately 380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS cohort containing 3,355 Caucasians (1,370 males and 1,985 females from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat.Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis.

  19. Host-dependent differences in resource use associated with Anilocra spp. parasitism in two coral reef fishes, as revealed by stable carbon and nitrogen isotope analyses

    Science.gov (United States)

    Welicky, Rachel; Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2017-01-01

    The role of parasites in trophic ecology is poorly understood in marine ecosystems. Stable isotope analyses (SIA) have been widely used in studies of trophic ecology, but have rarely been applied to study the role of parasites. Considering that some parasites are associated with altered host foraging patterns, SIA can help elucidate whether parasitism influences host trophic interactions. French grunt (Haemulon flavolineatum), an abundant Caribbean coral reef fish, contributes greatly to trophic connectivity. They typically depart the reef at dusk, feed overnight in seagrass beds, and return to the reef at dawn. The large parasitic isopod Anilocra haemuli commonly infects French grunt, and infected fish are less likely to complete their diel migration, and are in poorer condition than uninfected conspecifics. Brown chromis (Chromis multilineata) are diurnally feeding planktivores and infection by Anilocra chromis does not influence host condition. To determine if Anilocra infection influences host diet and foraging locality, we conducted stable carbon and nitrogen isotope analyses on scale, muscle, heart and gill tissues of infected and uninfected French grunt and brown chromis. We determined that all French grunt had δ13C values representative of seagrass habitats, but infected French grunt were significantly enriched in 13C and 15N compared to uninfected conspecifics. This suggests that compared to uninfected conspecifics, infected French grunt forage in seagrass, but on isotopically enriched prey, and/or are in poorer condition, which can elevate δ13C and δ15N values. For brown chromis, infection did not significantly influence any δ13C and δ15N values; hence they all foraged in the same environment and on similar prey. This is the first study to use SIA to examine differences in resource use by Caribbean coral reef fishes associated with parasitism and to evaluate how closely related parasites might have host-dependent effects on host trophic ecology.

  20. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration

    DEFF Research Database (Denmark)

    Liberati, Alessandro; Altman, Douglas G; Tetzlaff, Jennifer

    2009-01-01

    and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic...... reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential....... The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses....

  1. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  2. Lateral preferences for hand clasping and arm folding are associated with handedness in two large-sample latent variable analyses.

    Science.gov (United States)

    Tran, Ulrich S; Koller, Ingrid; Nader, Ingo W; Pietschnig, Jakob; Schild, Anne H E; Stieger, Stefan; Zeilinger, Elisabeth L; Voracek, Martin

    2014-01-01

    Hand clasping (HC) and arm folding (AF) are bilateral limb postures which are subject to lateral preferences. Previous research suggested that left HC and left AF are "canonical" among European populations, i.e., generally preferred by right-handers. However, evidence on the associations of handedness with HC and AF to date is sparse and inconsistent, with studies mostly relying on relatively small sample sizes and arbitrary classifications of handedness. Utilizing latent class analysis for handedness classification, we present data from two large and independent middle-European samples, a discovery (n = 7,658) and replication (n = 5,062) sample. Our results indicate that right HC, not left HC, is overall preferred and that right-handedness is associated with right HC/left AF, and left- and mixed-handedness with left HC/right AF. Moreover, lateral preferences increased with age, and men had a higher preference of right HC, independent of handedness. We discuss our findings with regard to the generalizability of previous results.

  3. A study of atypical APTT derivative curves on the ACL TOP coagulation analyser.

    Science.gov (United States)

    Solano, C; Zerafa, P; Bird, R

    2011-02-01

    The graphical representation of clotting data can provide useful information. A novel feature of the ACL TOP software allows display of clot reaction curves with superimposed first and second derivative curves. We noted atypical derivative plots associated with normal 'S'-shaped clot reaction curves in some abnormal activated partial thromboplastin time (APTT). We tested 179 citrate plasmas with four different APTT reagents on the ACL TOP. We documented the prevalence and utility of these APTT atypical derivative curves in these patients. Ellagic acid APTT reagents commonly produce atypical derivative curves despite normal 'S'-shaped clot reaction curves. Occasionally, these atypical second derivative curves may cause incorrect APTT results. With silica activator APTT reagents, atypical derivative curves were associated with genuine coagulation abnormalities such as single factor deficiencies and lupus anticoagulants (LAs). To our knowledge, this novel finding has not been reported. Atypical derivative curves seen in ellagic acid APTTs are of limited diagnostic use because of the frequency with which they occur. This may be related to the need to optimize the data reduction utilized on the ACL TOP for these reagents. With silica activator APTTs, the presence of atypical derivative curves proved to be a very simple tool when troubleshooting unexpected abnormal APTT results, commonly predicting a factor deficiency or LA that would warrant further investigation. The cause of these aberrant derivative curves is probably related to abnormal thrombin generation in the APTT test and warrants further study. © 2010 Blackwell Publishing Ltd.

  4. Analysing Regional Land Surface Temperature Changes by Satellite Data, a Case Study of Zonguldak, Turkey

    Science.gov (United States)

    Sekertekin, A.; Kutoglu, S.; Kaya, S.; Marangoz, A. M.

    2014-12-01

    In recent years, climate change is one of the most important problems that the ecological system of the world has been encountering. Global warming and climate change have been studied frequently by all disciplines all over the world and Geomatics Engineering also contributes to such studies by means of remote sensing, global positioning system etc. Monitoring Land Surface Temperature (LST) via remote sensing satellites is one of the most important contributions to climatology. LST is an important parameter governing the energy balance on the Earth and there are lots of algorithms to obtain LST by remote sensing techniques. The most commonly used algorithms are split-window algorithm, temperature/emissivity separation method, mono-window algorithm and single channel method. Generally three algorithms are used to obtain LST by using Landsat 5 TM data. These algorithms are radiative transfer equation method, single channel method and mono-window algorithm. Radiative transfer equation method is not applicable because during the satellite pass, atmospheric parameters must be measured in-situ. In this research, mono window algorithm was implemented to Landsat 5 TM image. Besides, meteorological data such as humidity and temperature are used in the algorithm. Acquisition date of the image is 28.08.2011 and our study area is Zonguldak, Turkey. High resolution images are used to investigate the relationships between LST and land cover type. As a result of these analyses, area with vegetation cover has approximately 5 ºC lower temperature than the city center and arid land. Because different surface properties like reinforced concrete construction, green zones and sandbank are all together in city center, LST differs about 10 ºC in the city center. The temperature around some places in thermal power plant region Çatalağzı, is about 5 ºC higher than city center. Sandbank and agricultural areas have highest temperature because of land cover structure. Thanks to this

  5. Analysing Health Professionals' Learning Interactions in an Online Social Network: A Longitudinal Study.

    Science.gov (United States)

    Li, Xin; Verspoor, Karin; Gray, Kathleen; Barnett, Stephen

    2016-01-01

    This paper summarises a longitudinal analysis of learning interactions occurring over three years among health professionals in an online social network. The study employs the techniques of Social Network Analysis (SNA) and statistical modeling to identify the changes in patterns of interaction over time and test associated structural network effects. SNA results indicate overall low participation in the network, although some participants became active over time and even led discussions. In particular, the analysis has shown that a change of lead contributor results in a change in learning interaction and network structure. The analysis of structural network effects demonstrates that the interaction dynamics slow down over time, indicating that interactions in the network are more stable. The health professionals may be reluctant to share knowledge and collaborate in groups but were interested in building personal learning networks or simply seeking information.

  6. Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

    Directory of Open Access Journals (Sweden)

    Valerie Carson

    2017-11-01

    Full Text Available Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1 the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA, and moderate- to vigorous-intensity physical activity (MVPA with adiposity indicators; and (2 the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA, and sleep duration was parental reported. Adiposity indicators included waist circumference (WC and body mass index (BMI z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006 but not with WC (p = 0.718. Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285, sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614, LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902, or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288 relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first

  7. Meta-Analyses of QTLs Associated with Protein and Oil Contents and Compositions in Soybean [Glycine max (L.) Merr.] Seed.

    Science.gov (United States)

    Van, Kyujung; McHale, Leah K

    2017-06-01

    Soybean [Glycine max (L.) Merr.] is a valuable and nutritious crop in part due to the high protein meal and vegetable oil produced from its seed. Soybean producers desire cultivars with both elevated seed protein and oil concentrations as well as specific amino acid and fatty acid profiles. Numerous studies have identified quantitative trait loci (QTLs) associated with seed composition traits, but validation of these QTLs has rarely been carried out. In this study, we have collected information, including genetic location and additive effects, on each QTL for seed contents of protein and oil, as well as amino acid and fatty acid compositions from over 80 studies. Using BioMercator V. 4.2, a meta-QTL analysis was performed with genetic information comprised of 175 QTLs for protein, 205 QTLs for oil, 156 QTLs for amino acids, and 113 QTLs for fatty acids. A total of 55 meta-QTL for seed composition were detected on 6 out of 20 chromosomes. Meta-QTL possessed narrower confidence intervals than the original QTL and candidate genes were identified within each meta-QTL. These candidate genes elucidate potential natural genetic variation in genes contributing to protein and oil biosynthesis and accumulation, providing meaningful information to further soybean breeding programs.

  8. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies

    DEFF Research Database (Denmark)

    NN, NN; Whitlock, Gary; Lewington, Sarah

    2009-01-01

    /m(2)). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070...... diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. FINDINGS: In both sexes, mortality was lowest at about 22.5-25 kg/m(2). Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI...... disease and is probably largely causal. At 30-35 kg/m(2), median survival is reduced by 2-4 years; at 40-45 kg/m(2), it is reduced by 8-10 years (which is comparable with the effects of smoking). The definite excess mortality below 22.5 kg/m(2) is due mainly to smoking-related diseases, and is not fully...

  9. Incorporating Concomitant Medications into Genome-Wide Analyses for the Study of Complex Disease and Drug Response

    Directory of Open Access Journals (Sweden)

    Daniel Rotroff

    2016-08-01

    Full Text Available Given the high costs of conducting a drug-response trial, researchers are now aiming to use retrospective analyses to conduct genome-wide association studies (GWAS to identify underlying genetic contributions to drug-response variation. To prevent confounding results from a GWAS to investigate drug response, it is necessary to account for concomitant medications, defined as any medication taken concurrently with the primary medication being investigated. We use data from the Action to Control Cardiovascular Disease (ACCORD trial in order to implement a novel scoring procedure for incorporating concomitant medication information into a linear regression model in preparation for GWAS. In order to accomplish this, two primary medications were selected: thiazolidinediones and metformin because of the wide-spread use of these medications and large sample sizes available within the ACCORD trial. A third medication, fenofibrate, along with a known confounding medication, statin, were chosen as a proof-of-principle for the scoring procedure. Previous studies have identified SNP rs7412 as being associated with statin response. Here we hypothesize that including the score for statin as a covariate in the GWAS model will correct for confounding of statin and yield a change in association at rs7412. The response of the confounded signal was successfully diminished from p=3.19*10-7 to p=1.76*10-5, by accounting for statin using the scoring procedure presented here. This approach provides the ability for researchers to account for concomitant medications in complex trial designs where monotherapy treatment regimens are not available.

  10. Applying fMRI complexity analyses to the single subject: a case study for proposed neurodiagnostics.

    Science.gov (United States)

    Rădulescu, Anca R; Hannon, Emily R

    2017-04-01

    Nonlinear dynamic tools have been statistically validated at the group level to identify subtle differences in system wide regulation of brain meso-circuits, often increasing clinical sensitivity over conventional analyses alone. We explored the feasibility of extracting information at the single-subject level, illustrating two pairs of healthy individuals with psychological differences in stress reactivity. We applied statistical and nonlinear dynamic tools to capture key characteristics of the prefrontal-limbic loop. We compared single subject results with statistical results for the larger group. We concluded that complexity analyses may identify important differences at the single-subject level, supporting their potential towards neurodiagnostic applications.

  11. Municipal solid waste composition: Sampling methodology, statistical analyses, and case study evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Edjabou, Maklawe Essonanawe, E-mail: vine@env.dtu.dk [Department of Environmental Engineering, Technical University of Denmark, 2800 Kgs. Lyngby (Denmark); Jensen, Morten Bang; Götze, Ramona; Pivnenko, Kostyantyn [Department of Environmental Engineering, Technical University of Denmark, 2800 Kgs. Lyngby (Denmark); Petersen, Claus [Econet AS, Omøgade 8, 2.sal, 2100 Copenhagen (Denmark); Scheutz, Charlotte; Astrup, Thomas Fruergaard [Department of Environmental Engineering, Technical University of Denmark, 2800 Kgs. Lyngby (Denmark)

    2015-02-15

    Highlights: • Tiered approach to waste sorting ensures flexibility and facilitates comparison of solid waste composition data. • Food and miscellaneous wastes are the main fractions contributing to the residual household waste. • Separation of food packaging from food leftovers during sorting is not critical for determination of the solid waste composition. - Abstract: Sound waste management and optimisation of resource recovery require reliable data on solid waste generation and composition. In the absence of standardised and commonly accepted waste characterisation methodologies, various approaches have been reported in literature. This limits both comparability and applicability of the results. In this study, a waste sampling and sorting methodology for efficient and statistically robust characterisation of solid waste was introduced. The methodology was applied to residual waste collected from 1442 households distributed among 10 individual sub-areas in three Danish municipalities (both single and multi-family house areas). In total 17 tonnes of waste were sorted into 10–50 waste fractions, organised according to a three-level (tiered approach) facilitating comparison of the waste data between individual sub-areas with different fractionation (waste from one municipality was sorted at “Level III”, e.g. detailed, while the two others were sorted only at “Level I”). The results showed that residual household waste mainly contained food waste (42 ± 5%, mass per wet basis) and miscellaneous combustibles (18 ± 3%, mass per wet basis). The residual household waste generation rate in the study areas was 3–4 kg per person per week. Statistical analyses revealed that the waste composition was independent of variations in the waste generation rate. Both, waste composition and waste generation rates were statistically similar for each of the three municipalities. While the waste generation rates were similar for each of the two housing types (single

  12. Transethnic Meta-Analysis of Genomewide Association Studies

    OpenAIRE

    Morris, Andrew P.

    2011-01-01

    The detection of loci contributing effects to complex human traits, and their subsequent fine-mapping for the location of causal variants, remains a considerable challenge for the genetics research community. Meta-analyses of genomewide association studies, primarily ascertained from European-descent populations, have made considerable advances in our understanding of complex trait genetics, although much of their heritability is still unexplained. With the increasing availability of genomewi...

  13. Analysing the impacts of air quality policies on ecosystem services; a case study for Telemark, Norway

    NARCIS (Netherlands)

    Hein, L.; White, L.; Miles, A.; Roberts, P.

    2018-01-01

    There is an increasing interest in considering the effects of air pollution on ecosystem services supply in order to enhance cost-benefit analyses of air pollution policies. This paper presents a generic, conceptual approach that can be used to link atmospheric deposition of air pollutants to

  14. Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy.

    Science.gov (United States)

    Shyng, S L; Ferrigni, T; Shepard, J B; Nestorowicz, A; Glaser, B; Permutt, M A; Nichols, C G

    1998-07-01

    The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas. Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia. We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. With the exception of N188S and H125Q, all mutants had reduced response to stimulation by MgADP. These results indicate that lack of, or reduction of, K(ATP) channel sensitivity to MgADP is a common molecular defect associated with the disease. The mutant channels also showed varied response to activation by the potassium channel opener diazoxide. Because these mutations are distributed throughout the molecule, our data have new implications for structure-function relationships of the K(ATP) channel, suggesting that structural elements in SUR1 outside of the two nucleotide-binding folds are also important in regulating channel activity.

  15. A Study for Visual Realism of Designed Pictures on Computer Screens by Investigation and Brain-Wave Analyses.

    Science.gov (United States)

    Wang, Lan-Ting; Lee, Kun-Chou

    2016-08-01

    In this article, the visual realism of designed pictures on computer screens is studied by investigation and brain-wave analyses. The practical electroencephalogram (EEG) measurement is always time-varying and fluctuating so that conventional statistical techniques are not adequate for analyses. This study proposes a new scheme based on "fingerprinting" to analyze the EEG. Fingerprinting is a technique of probabilistic pattern recognition used in electrical engineering, very like the identification of human fingerprinting in a criminal investigation. The goal of this study was to assess whether subjective preference for pictures could be manifested physiologically by EEG fingerprinting analyses. The most important advantage of the fingerprinting technique is that it does not require accurate measurement. Instead, it uses probabilistic classification. Participants' preference for pictures can be assessed using fingerprinting analyses of physiological EEG measurements. © The Author(s) 2016.

  16. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  17. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and ... Polymorphisms in the POMC gene locus are associated with obesity phenotypes. Aim: To ... Keywords: Childhood obesity; POMC gene; Metabolic syndrome ...

  18. Is quality and completeness of reporting of systematic reviews and meta-analyses published in high impact radiology journals associated with citation rates?

    Science.gov (United States)

    van der Pol, Christian B; McInnes, Matthew D F; Petrcich, William; Tunis, Adam S; Hanna, Ramez

    2015-01-01

    The purpose of this study is to determine whether study quality and completeness of reporting of systematic reviews (SR) and meta-analyses (MA) published in high impact factor (IF) radiology journals is associated with citation rates. All SR and MA published in English between Jan 2007-Dec 2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE. The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist for study quality, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR & MA. Each SR & MA was then searched in Google Scholar to yield a citation rate. Spearman correlation coefficients were used to assess the relationship between AMSTAR and PRISMA results with citation rate. Multivariate analyses were performed to account for the effect of journal IF and journal 5-year IF on correlation with citation rate. Values were reported as medians with interquartile range (IQR) provided. 129 studies from 11 journals were included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5-9) and median PRISMA result was 23.0/27 (IQR: 21-25). The median citation rate for SR & MA was 0.73 citations/month post-publication (IQR: 0.40-1.17). There was a positive correlation between both AMSTAR and PRISMA results and SR & MA citation rate; ρ=0.323 (P=0.0002) and ρ=0.327 (P=0.0002) respectively. Positive correlation persisted for AMSTAR and PRISMA results after journal IF was partialed out; ρ=0.243 (P=0.006) and ρ=0.256 (P=0.004), and after journal 5-year IF was partialed out; ρ=0.235 (P=0.008) and ρ=0.243 (P=0.006) respectively. There is a positive correlation between the quality and the completeness of a reported SR or MA with citation rate which persists when adjusted for journal IF and journal 5-year IF.

  19. Manned systems utilization analysis (study 2.1). Volume 3: LOVES computer simulations, results, and analyses

    Science.gov (United States)

    Stricker, L. T.

    1975-01-01

    The LOVES computer program was employed to analyze the geosynchronous portion of the NASA's 1973 automated satellite mission model from 1980 to 1990. The objectives of the analyses were: (1) to demonstrate the capability of the LOVES code to provide the depth and accuracy of data required to support the analyses; and (2) to tradeoff the concept of space servicing automated satellites composed of replaceable modules against the concept of replacing expendable satellites upon failure. The computer code proved to be an invaluable tool in analyzing the logistic requirements of the various test cases required in the tradeoff. It is indicated that the concept of space servicing offers the potential for substantial savings in the cost of operating automated satellite systems.

  20. Deep Space Mission Trend Analyses: A Briefing to the Next Generation EBRE Study Team

    Science.gov (United States)

    Abraham, Douglas S.

    2012-01-01

    Determination of stakeholder needs for next generation implementations necessitates a multi ]pronged approach. . Future mission set analyses provide a lower gbound h for some of these needs. . Earth ]based analogies provide an upper gbound h for some of these needs. . Interpreting the results requires being mindful of both the near ]term contextual factors and long ]term factors that are in play. . In the context of last year fs analyses, the current budget environment, the potential Pu ]238 shortage, and SMD fs gsingle 34m only h policy may, collectively, create a future deep space mission set that, from a capacity and end ]to ]end link difficulty standpoint, is no more challenging than it is today. . Nonetheless, data rates and volumes continue to increase, suggesting capability and spectrum challenges ahead. These results agree with the results from the Earthbased analogies. . Emerging developments such as smallsats and distributed spacecraft could significantly change the capacity and end ]to ]end link difficulty picture.

  1. Multigenic control of pod shattering resistance in Chinese rapeseed germplasm revealed by genome-wide association and linkage analyses

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2016-07-01

    Full Text Available Majority of rapeseed cultivars shatter seeds upon maturity especially under hot-dry and windy conditions, reducing yield and gross margin return to growers. Here, we identified quantitative trait loci (QTL for resistance to pod shatter in unstructured diverse panel of 143 rapeseed accessions, and two structured populations derived from bi-parental doubled haploid (DH and inter-mated (IF2 crosses derived from R1 (resistant to pod shattering and R2 (prone to pod shattering accessions. Genome-wide association analysis identified six significant QTL for resistance to pod shatter located on chromosomes A01, A06, A07, A09, C02 and C05. Two of the QTL, qSRI.A09 delimited with the SNP marker Bn-A09-p30171993 (A09 and qSRI.A06 delimited with the SNP marker Bn-A06-p115948 (A06 could be repeatedly detected across environments in diversity panel, DH and IF2 populations, suggesting that at least two loci on chromosomes A06 and A09 were the main contributors to pod shatter resistance in Chinese germplasm. Significant SNP markers identified in this study especially those appeared repeatedly across environments provide a cost-effective and an efficient method for introgression and pyramiding of favorable alleles for pod shatter resistance via marker-assisted selection in rapeseed improvement programs.

  2. 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. Copyright © 2016 Anderson et al.

  3. Analysing the sustainability performance and critical improvement factors of urban municipal waste systems - Case study Trondheim

    OpenAIRE

    Unander, Silje Madalena Oliveira

    2017-01-01

    The management of the natural output of consumption, waste, has to become more sustainable. Ideally this would mean that it simply ceased to exist, but as unrealistic that may be, the current discourse in waste legislation and management is on increasing the material recycling rate. This is a part of the circular economy. Analysing waste management systems is crucial to know what effect different measures might have on the actual recycling rate. In turn, these measures might impact the energ...

  4. Genome-wide sequential, evolutionary, organizational and expression analyses of phenylpropanoid biosynthesis associated MYB domain transcription factors in Arabidopsis.

    Science.gov (United States)

    Mondal, Sunil Kanti; Roy, Sujit

    2017-06-02

    The MYB gene family represents one of the largest groups of transcription factors in plants. Recent evidences have also demonstrated key role of MYB transcription factors in regulating the expression of major genes involved in the biosynthesis of phenylpropanoid compounds which confer biotic and abiotic stress tolerance in plant species. However, no comprehensive genome-wide analysis of the phenylpropanoid pathway-associated MYB transcription factors has been reported thus far. In this study, 11 Arabidopsis MYB proteins, such as MYB3, MYB4, MYB7, MYB11, MYB12, MYB32, MYB75, MYB90, MYB111, MYB113, and MYB114 were initially identified considering their reported regulatory function in phenylpropanoid biosynthesis pathway. Subsequent genome-wide analysis have identified the corresponding homologues from Glycine max, Vigna radiata, Oryza sativa, and Zea mays, while homologous of Arabidopsis MYB75, MYB90, MYB113, and MYB114 were not detected in rice and maize genomes. The identified MYB proteins were classified into three groups (I-III) based on phylogeny. Sequence and domain analysis revealed presence of two conserved DNA binding MYB domains in the selected MYB proteins. Promoter analysis indicated presence of cis-regulatory elements related to light signaling, development, and stress response. Expression analysis of selected Arabidopsis MYB genes revealed their function in plant development and abiotic stress response, consistent with gene ontology annotations. Together, these results provide a useful framework for further experimental studies for the functional characterization of the target MYB genes in the context of regulation of phenylpropanoid biosynthesis and plant stress response.

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

    NARCIS (Netherlands)

    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

    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

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

    NARCIS (Netherlands)

    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.

    2016-01-01

    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

  7. Analyses of more than 60,000 exomes questions the role of numerous genes previously associated with dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Nouhravesh, Nina; Ahlberg, Gustav; Ghouse, Jonas

    2016-01-01

    BACKGROUND: Hundreds of genetic variants have been described as disease causing in dilated cardiomyopathy (DCM). Some of these associations are now being questioned. We aimed to identify the prevalence of previously DCM associated variants in the Exome Aggregation Consortium (ExAC), in order...

  8. Study Quality in SLA: An Assessment of Designs, Analyses, and Reporting Practices in Quantitative L2 Research

    Science.gov (United States)

    Plonsky, Luke

    2013-01-01

    This study assesses research and reporting practices in quantitative second language (L2) research. A sample of 606 primary studies, published from 1990 to 2010 in "Language Learning and Studies in Second Language Acquisition," was collected and coded for designs, statistical analyses, reporting practices, and outcomes (i.e., effect…

  9. Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study

    DEFF Research Database (Denmark)

    Sørensen, Louise Bergmann; Damsgaard, Camilla Trab; Dalskov, Stine-Mathilde

    2015-01-01

    analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance......' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95 % CI 0·15, 0·27) w/w % (P...... intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster...

  10. GENOME-WIDE ASSOCIATION ANALYSES BASED ON WHOLE-GENOME SEQUENCING IN SARDINIA PROVIDE INSIGHTS INTO REGULATION OF HEMOGLOBIN LEVELS

    Science.gov (United States)

    Danjou, Fabrice; Zoledziewska, Magdalena; Sidore, Carlo; Steri, Maristella; Busonero, Fabio; Maschio, Andrea; Mulas, Antonella; Perseu, Lucia; Barella, Susanna; Porcu, Eleonora; Pistis, Giorgio; Pitzalis, Maristella; Pala, Mauro; Menzel, Stephan; Metrustry, Sarah; Spector, Timothy D.; Leoni, Lidia; Angius, Andrea; Uda, Manuela; Moi, Paolo; Thein, Swee Lay; Galanello, Renzo; Abecasis, Gonçalo R.; Schlessinger, David; Sanna, Serena; Cucca, Francesco

    2015-01-01

    We report GWAS results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, FOG1, NFIX, and CCND3. Among those at known loci, 10 are new lead variants and 4 are novel independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and revealed features of coordinated hemoglobin species production. PMID:26366553

  11. Can Educational Systems Achieve Both Quality and Equity? Secondary Analyses of PISA (Programme for International Student Assessment) and TIMSS (Trends in International Mathematics and Science Study) Studies

    NARCIS (Netherlands)

    Kyriakides, Leonidas; Charalambous, Evi; Creemers, Bert; Charalambous, Charalambos Y.; Dimosthenous, Antria

    2015-01-01

    This paper argues for the importance of investigating both quality and equity dimensions of effectiveness at the country level. Secondary analyses of each PISA study, TIMSS 2007 and TIMSS 2011 were undertaken. For each study, separate multilevel analyses per country were conducted. In each study, a

  12. Biosynthesis of vitamins and cofactors in bacterium-harbouring trypanosomatids depends on the symbiotic association as revealed by genomic analyses.

    Science.gov (United States)

    Klein, Cecilia C; Alves, João M P; Serrano, Myrna G; Buck, Gregory A; Vasconcelos, Ana Tereza R; Sagot, Marie-France; Teixeira, Marta M G; Camargo, Erney P; Motta, Maria Cristina M

    2013-01-01

    Some non-pathogenic trypanosomatids maintain a mutualistic relationship with a betaproteobacterium of the Alcaligenaceae family. Intensive nutritional exchanges have been reported between the two partners, indicating that these protozoa are excellent biological models to study metabolic co-evolution. We previously sequenced and herein investigate the entire genomes of five trypanosomatids which harbor a symbiotic bacterium (SHTs for Symbiont-Haboring Trypanosomatids) and the respective bacteria (TPEs for Trypanosomatid Proteobacterial Endosymbiont), as well as two trypanosomatids without symbionts (RTs for Regular Trypanosomatids), for the presence of genes of the classical pathways for vitamin biosynthesis. Our data show that genes for the biosynthetic pathways of thiamine, biotin, and nicotinic acid are absent from all trypanosomatid genomes. This is in agreement with the absolute growth requirement for these vitamins in all protozoa of the family. Also absent from the genomes of RTs are the genes for the synthesis of pantothenic acid, folic acid, riboflavin, and vitamin B6. This is also in agreement with the available data showing that RTs are auxotrophic for these essential vitamins. On the other hand, SHTs are autotrophic for such vitamins. Indeed, all the genes of the corresponding biosynthetic pathways were identified, most of them in the symbiont genomes, while a few genes, mostly of eukaryotic origin, were found in the host genomes. The only exceptions to the latter are: the gene coding for the enzyme ketopantoate reductase (EC:1.1.1.169) which is related instead to the Firmicutes bacteria; and two other genes, one involved in the salvage pathway of pantothenic acid and the other in the synthesis of ubiquinone, that are related to Gammaproteobacteria. Their presence in trypanosomatids may result from lateral gene transfer. Taken together, our results reinforce the idea that the low nutritional requirement of SHTs is associated with the presence of the

  13. Size and concentration analyses of extracellular vesicles by nanoparticle tracking analysis: a variation study

    Science.gov (United States)

    Vestad, Beate; Llorente, Alicia; Neurauter, Axl; Phuyal, Santosh; Kierulf, Bente; Kierulf, Peter; Skotland, Tore; Sandvig, Kirsten; Haug, Kari Bente F.; Øvstebø, Reidun

    2017-01-01

    ABSTRACT Current methods for characterisation of extracellular vesicles (EVs) need further standardisation in order to obtain an acceptable level of data comparability. Size and concentration of EVs can be determined by nanoparticle tracking analysis (NTA). However, both the heterogeneity of EVs and the choice of instrument settings may cause an appreciable analytical variation. Intra-assay (within-day, n = 6) and inter-assay (day-to-day, n = 6) variations (coefficient of variation, % CV) of different preparations of EVs and artificial vesicles or beads were determined using two NanoSight NS500 instruments, located at different laboratories. All analyses were performed by the same operator. The effect of applying identical software settings or instrument-optimised settings for each sample type and instrument was also evaluated. Finally, the impact of different operators and the use of two different software versions were investigated. The intra-assay CVs were 1–12% for both EVs and artificial samples, measured on the same instrument. The overall day-to-day variation was similar for both instruments, ranging from 2% to 25%. However, significantly different results were observed between the two instruments using identical software settings. The effect of applying instrument-optimised settings reduced the mismatch between the instruments, resulting in little to no significant divergences. The impact of using different operators and software versions when analysing silica microspheres and microvesicles from monocytes using instrument-optimised settings on the same instrument did not contribute to significant variation compared to the overall day-to-day variation of one operator. Performance differences between two similar NTA instruments may display significant divergences in size and concentration measurements when analysing EVs, depending on applied instrument settings and technical conditions. The importance of developing a streamlined and standardised

  14. Study of dimensionless quantities to analyse front and rear wall of ...

    Indian Academy of Sciences (India)

    LBW) process influence the associated heat and mass transfer. In an attempt to describe these complexities for eventual optimization of LBW parameters, a dimensionless analysis using Mach (Ma), Raleigh (Ra), Reynolds (Re) and Marangoni ...

  15. Radiological analyses of France Telecom surge arresters. Study performed for the CGT FAPT Cantal; Analyses radiologiques de parasurtenseurs FRANCE TELECOM. Etude effectuee pour la CGT FAPT Cantal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-02-15

    This document reports the radiological characterization of various versions of surge arresters used in the past to protect telephone lines against over-voltages. These equipment, which use various radioactive materials, were assessed by gamma radiation flow measurements, alpha-beta-gamma count rate measurements, dose rate measurements, gamma spectrometry analyses, tritium emanation test, radon 222 emanation test, smearing. Recommendations are formulated to manage radioactive surge arresters which are still being operated

  16. Phylogenetic and functional analyses of a plant protein related to human B-cell receptor-associated proteins.

    Science.gov (United States)

    Atabekova, Anastasia K; Pankratenko, Anna V; Makarova, Svetlana S; Lazareva, Ekaterina A; Owens, Robert A; Solovyev, Andrey G; Morozov, Sergey Y

    2017-01-01

    Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed 'plant BAP-like proteins' (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem. Here, we have compared the sequences of PBL proteins and studied the biochemical properties of NtPBL. Analysis of a number of fully sequenced plant genomes revealed that PBL-encoding genes represent a small multigene family with up to six members per genome. Two conserved motifs were identified in the C-terminal region of PBL proteins. The NtPBL C-terminal hydrophilic region (NtPBL-C) was expressed in bacterial cells, purified, and used for analysis of its RNA binding properties in vitro. In gel shift experiments, NtPBL-C was found to bind several tested RNAs, showing the most efficient binding to microRNA precursors (pre-miRNA) and less efficient interaction with PSTVd. Mutational analysis suggested that NtPBL-C has a composite RNA-binding site, with two conserved lysine residues in the most C-terminal protein region being involved in binding of pre-miRNA but not PSTVd RNA. Virus-mediated transient expression of NtPBL-C in plants resulted in stunting and leaf malformation, developmental abnormalities similar to those described previously for blockage of miRNA biogenesis/function. We hypothesize that the NtPBL protein represents a previously undiscovered component of the miRNA pathway. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Perceived public transport infrastructure modifies the association between public transport use and mental health: Multilevel analyses from the United Kingdom

    Science.gov (United States)

    Feng, Xiaoqi; Feng, Zhiqiang; Astell-Burt, Thomas

    2017-01-01

    Aims Investments to promote public transport utilisation are being championed to achieve sustainable development, but the potential co-benefits for mental health are comparatively under-researched. We hypothesised that frequent users of public transport would be more likely to have better mental health (possibly due to increased levels of physical activity), but among the more frequent users, less favourable perceptions of public transport infrastructure (PPTI) could have a negative influence on mental health. Methods Multilevel linear and logistic regressions were fitted on 30,214 participants in the UK Household Longitudinal Study with lagged PPTI and confounder measures at baseline and indicators of active travel and mental health (General Health Questionnaire (GHQ), SF-12 Mental Component Scale (MCS) and the Warwick Edinburgh Mental Well Being Scale (WEMWBS)) at follow-up. Results Compared to participants expressing poor PPTI, those who felt it was excellent were 1.29 (95%CI 1.15, 1.45) times more likely to be frequent users of public transport and 1.53 (95%CI 1.33, 1.76) times more likely to choose to walk or cycle journeys of less than two to three miles. Frequent use of public transport was found to be consistently associated with better mental health for GHQ caseness (OR 0.85, 95%CI 0.79, 0.91), GHQ score (coefficient -0.28, 95%CI -0.41, -0.16), MCS (coefficient 0.45, 95%CI 0.23, 0.66), and WEMWBS (coefficient 0.30, 95%CI 0.19, 0.40). Among frequent users of public transport, participants expressing poor PPTI were 1.46 (95%CI 1.11, 1.93) times more likely to report poorer mental health according to the GHQ caseness indicator, compared to frequent users that regarded PPTI as excellent. Similar results were observed for the other indicators of mental health. Conclusions These findings indicate that while the provision of public transport infrastructure is a necessary pre-condition for stimulating population increases in physical activity, PPTI improvements

  18. Perceived public transport infrastructure modifies the association between public transport use and mental health: Multilevel analyses from the United Kingdom.

    Science.gov (United States)

    Feng, Xiaoqi; Feng, Zhiqiang; Astell-Burt, Thomas

    2017-01-01

    Investments to promote public transport utilisation are being championed to achieve sustainable development, but the potential co-benefits for mental health are comparatively under-researched. We hypothesised that frequent users of public transport would be more likely to have better mental health (possibly due to increased levels of physical activity), but among the more frequent users, less favourable perceptions of public transport infrastructure (PPTI) could have a negative influence on mental health. Multilevel linear and logistic regressions were fitted on 30,214 participants in the UK Household Longitudinal Study with lagged PPTI and confounder measures at baseline and indicators of active travel and mental health (General Health Questionnaire (GHQ), SF-12 Mental Component Scale (MCS) and the Warwick Edinburgh Mental Well Being Scale (WEMWBS)) at follow-up. Compared to participants expressing poor PPTI, those who felt it was excellent were 1.29 (95%CI 1.15, 1.45) times more likely to be frequent users of public transport and 1.53 (95%CI 1.33, 1.76) times more likely to choose to walk or cycle journeys of less than two to three miles. Frequent use of public transport was found to be consistently associated with better mental health for GHQ caseness (OR 0.85, 95%CI 0.79, 0.91), GHQ score (coefficient -0.28, 95%CI -0.41, -0.16), MCS (coefficient 0.45, 95%CI 0.23, 0.66), and WEMWBS (coefficient 0.30, 95%CI 0.19, 0.40). Among frequent users of public transport, participants expressing poor PPTI were 1.46 (95%CI 1.11, 1.93) times more likely to report poorer mental health according to the GHQ caseness indicator, compared to frequent users that regarded PPTI as excellent. Similar results were observed for the other indicators of mental health. These findings indicate that while the provision of public transport infrastructure is a necessary pre-condition for stimulating population increases in physical activity, PPTI improvements needs to be prioritised to leverage

  19. Pioglitazone and bladder cancer in human studies: Is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    2012-03-01

    Full Text Available This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069. However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%–40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between

  20. Koala retrovirus genotyping analyses reveal a low prevalence of KoRV-A in Victorian koalas and an association with clinical disease.

    Science.gov (United States)

    Legione, Alistair R; Patterson, Jade L S; Whiteley, Pam; Firestone, Simon M; Curnick, Megan; Bodley, Kate; Lynch, Michael; Gilkerson, James R; Sansom, Fiona M; Devlin, Joanne M

    2017-02-01

    Koala retrovirus (KoRV) is undergoing endogenization into the genome of koalas in Australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. The prevalence of KoRV in north-eastern Australia (Queensland and New South Wales) is 100 %, whereas previous preliminary investigations in south-eastern Australia (Victoria) suggested KoRV is present at a lower prevalence, although the values have varied widely. Here, we describe a large study of free-ranging koalas in Victoria to estimate the prevalence of KoRV and assess the clinical significance of KoRV infection in wild koalas. Blood or spleen samples from 648 koalas where tested for KoRV provirus, and subsequently genotyped, using PCRs to detect the pol and env genes respectively. Clinical data was also recorded where possible and analysed in comparison to infection status. The prevalence of KoRV was 24.7 % (160/648). KoRV-A was detected in 141/160 cases, but KoRV-B, a genotype associated with neoplasia in captive koalas, was not detected. The genotype in 19 cases could not be determined. Genomic differences between KoRV in Victoria and type strains may have impacted genotyping. Factors associated with KoRV infection, based on multivariable analysis, were low body condition score, region sampled, and 'wet bottom' (a staining of the fur around the rump associated with chronic urinary incontinence). Koalas with wet bottom were nearly twice as likely to have KoRV provirus detected than those without wet bottom (odds ratio=1.90, 95 % confidence interval 1.21, 2.98). Our findings have important implications for the conservation of this iconic species, particularly regarding translocation potential of Victorian koalas.

  1. Survey of huanglongbing associated with ‘Candidatus Liberibacter’ species in Spain: analyses of citrus plants and Trioza erytreae

    Directory of Open Access Journals (Sweden)

    Felipe SIVERIO

    2017-05-01

    Full Text Available The disease huanglongbing (HLB, caused by the phloem-limited and psyllid-vectored ‘Candidatus Liberibacter’ spp., is threatening the Mediterranean citrus industry. The African psyllid (Trioza erytreae vector of the pathogen was detected in Madeira (Portugal in 1994 and in the Canary Islands (Spain in 2002, and its arrival in 2014 in northwest Spain and Portugal along the Atlantic coast instigated a biological alert, and a contingency management plan was developed. Extensive surveys were conducted in Canary Islands from 2009 to 2015 and in the northwest mainland Spain (Galicia since the first detection of T. erytreae. Symptoms of the psyllid were observed in most sweet orange orchards of five islands in Canary Islands (93% of the inspected plots. In northwest mainland Spain, 65% of the inspected plots up to 2016 showed T. erytreae symptoms. During the surveys, ten leaves/tree from trees showing suspicious symptoms and from symptomless trees, as well as adult psyllids, were collected and analysed by real-time PCR using a universal ‘Ca. Liberibacter’ spp. kit, according to the EPPO standard. Suspected samples from other surveyed Spanish regions free of the vector were also analysed. The few samples that were positive in the screening test were tested by species-specific real-time PCR protocols, and they did not show amplification. These data confirm that the Spanish citrus industry is currently free of the ‘Ca. Liberibacter’ spp., but strict measures to prevent the introduction of this pathogen are required as the presence of T. erytreae increases the risk of its dissemination.

  2. New environmental metabarcodes for analysing soil DNA: potential for studying past and present ecosystems.

    Science.gov (United States)

    Epp, Laura S; Boessenkool, Sanne; Bellemain, Eva P; Haile, James; Esposito, Alfonso; Riaz, Tiayyba; Erséus, Christer; Gusarov, Vladimir I; Edwards, Mary E; Johnsen, Arild; Stenøien, Hans K; Hassel, Kristian; Kauserud, Håvard; Yoccoz, Nigel G; Bråthen, Kari Anne; Willerslev, Eske; Taberlet, Pierre; Coissac, Eric; Brochmann, Christian

    2012-04-01

    Metabarcoding approaches use total and typically degraded DNA from environmental samples to analyse biotic assemblages and can potentially be carried out for any kinds of organisms in an ecosystem. These analyses rely on specific markers, here called metabarcodes, which should be optimized for taxonomic resolution, minimal bias in amplification of the target organism group and short sequence length. Using bioinformatic tools, we developed metabarcodes for several groups of organisms: fungi, bryophytes, enchytraeids, beetles and birds. The ability of these metabarcodes to amplify the target groups was systematically evaluated by (i) in silico PCRs using all standard sequences in the EMBL public database as templates, (ii) in vitro PCRs of DNA extracts from surface soil samples from a site in Varanger, northern Norway and (iii) in vitro PCRs of DNA extracts from permanently frozen sediment samples of late-Pleistocene age (~16,000-50,000 years bp) from two Siberian sites, Duvanny Yar and Main River. Comparison of the results from the in silico PCR with those obtained in vitro showed that the in silico approach offered a reliable estimate of the suitability of a marker. All target groups were detected in the environmental DNA, but we found large variation in the level of detection among the groups and between modern and ancient samples. Success rates for the Pleistocene samples were highest for fungal DNA, whereas bryophyte, beetle and bird sequences could also be retrieved, but to a much lesser degree. The metabarcoding approach has considerable potential for biodiversity screening of modern samples and also as a palaeoecological tool. © 2012 Blackwell Publishing Ltd.

  3. Association and haplotype analyses of positional candidate genes in five genomic regions linked to scrotal hernia in commercial pig lines.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Du

    Full Text Available Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1, the epithelial-mesenchymal transition (ELF5 and the collagen metabolism pathway (COL23A1, which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs.

  4. Association and haplotype analyses of positional candidate genes in five genomic regions linked to scrotal hernia in commercial pig lines.

    Science.gov (United States)

    Du, Zhi-Qiang; Zhao, Xia; Vukasinovic, Natascha; Rodriguez, Fernanda; Clutter, Archie C; Rothschild, Max F

    2009-01-01

    Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1), the epithelial-mesenchymal transition (ELF5) and the collagen metabolism pathway (COL23A1), which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs.

  5. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

    NARCIS (Netherlands)

    Wain, Louise V.; Shrine, Nick R. G.; Artigas, Maria Soler; Erzurumluoglu, A Mesut; Noyvert, Boris; Bossini-Castillo, Lara; Obeidat, Ma'en; Henrys, Amanda P.; Portelli, Michael A.; Hall, Robert J; Billington, Charlotte K.; Rimington, Tracy L; Fenech, Anthony G; John, Catherine; Blake, Tineka; Jackson, Victoria E.; Allen, Richard J; Prins, Bram P.; Campbell, Archie; Porteous, David J.; Jarvelin, Marjo-Riitta; Wielscher, Matthias; Jamess, Alan L.; Hui, Jennie; Wareham, Nicholas J.; Zhao, Jing Hua; Wilson, James F.; Joshi, Peter K.; Stubbe, Beate; Rawal, Rajesh; Schulz, Holger; Imboden, Medea; Probst-Hensch, Nicole M.; Karrasch, Stefan; Gieger, Christian; Deary, Ian J.; Harris, Sarah E.; Marten, Jonathan; Rudan, Igor; Enroth, Stefan; Gyllensten, Ulf; Kerr, Shona M.; Polasek, Ozren; Kahonen, Mika; Surakka, Ida; Vitart, Veronique; Hayward, Caroline; Lehtimaki, Terho; Raitakari, Olli T.; Evans, David M.; Henderson, A. John; Pennell, Craig E.; Wang, Carol A.; Sly, Peter D.; Wan, Emily S; Busch, Robert; Hobbs, Brian D; Litonjua, Augusto; Sparrow, David W; Gulsvik, Amund; Bakke, Per S.; Crapo, James D.; Beaty, Terri H.; Hansel, Nadia N.; Mathias, Rasika A.; Ruczinski, Ingo; Barnes, Kathleen C.; Bosse, Yohan; Joubert, Philippe; van den Berge, Maarten; Brandsma, Corry-Anke; Pare, Peter D.; Sin, Don; Nickle, David C.; Hao, Ke; Gottesman, Omri; Dewey, Frederick E; Bruse, Shannon E; Carey, David J.; Kirchner, H Lester; Jonsson, Stefan; Thorleifsson, Gudmar; Jonsdottir, Ingileif; Gislason, Thorarinn; Stefansson, Kari; Schurmann, Claudia; Nadkarni, Girish N; Bottinger, Erwin P.; Loos, Ruth J. F.; Walters, Robin G.; Chen, Zhengming; Millwood, Iona Y; Vaucher, Julien; Kurmi, Om P; Li, Liming; Hansell, Anna L.; Brightling, Chris; Zeggini, Eleftheria; Cho, Michael H.; Silverman, Edwin K.; Sayers, Ian; Trynka, Gosia; Morris, Andrew P.; Strachan, David P.; Halls, Ian P.; Tobin, Martin D.

    Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375

  6. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

    NARCIS (Netherlands)

    Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A.; Low, Siew-Kee; Weeke, Peter E.; Mueller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Doerr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurmann, Claudia; Kleber, Marcus E.; Lyytikainen, Leo-Pekka; Seppala, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Theriault, Sebastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati H.; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Pare, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kahonen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge A.; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann-Heimbach, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Voelker, Uwe; Joeckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; Maerz, Winfried; Lehtimaki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kaeaeb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial

  7. RNA Expression and Post-Transcriptional Editing Analyses of Cucumber Plastids Reveals Genetic Differences Associated with Chilling Tolerance

    Science.gov (United States)

    Tolerance to chilling injury in cucumber (Cucumis sativus L.) is associated with three plastomic single nucleotide polymorphisms (ptSNPs) at bp positions 4,813, 56,561, and 126,349 that are co-inherited. An understanding of the genetic expression of these ptSNPs as a response to chilling is critical...

  8. Associations of alcohol, nicotine, cannabis, and drug use/dependence with educational attainment: evidence from cotwin-control analyses.

    Science.gov (United States)

    Grant, Julia D; Scherrer, Jeffrey F; Lynskey, Michael T; Agrawal, Arpana; Duncan, Alexis E; Haber, Jon Randolph; Heath, Andrew C; Bucholz, Kathleen K

    2012-08-01

    Although substance use is associated with reduced educational attainment, this association may be owing to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics. Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins (n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U.S. military during the Vietnam era and therefore, were eligible for educational benefits after military service. Reduced educational attainment (alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence. Three significant differences were observed between at-risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing education was significantly increased for the following: (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to 2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR = 1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30 or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence. Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment. Copyright © 2012 by the Research Society on Alcoholism.

  9. Study of dimensionless quantities to analyse front and rear wall of ...

    Indian Academy of Sciences (India)

    Abstract. Fluid flow mechanisms present in Keyhole (KH) during Laser Beam. Welding (LBW) process influence the associated heat and mass transfer. In an attempt to describe these complexities for eventual optimization of LBW parameters, a dimen- sionless analysis using Mach (Ma), Raleigh (Ra), Reynolds (Re) and ...

  10. Association study of 182 candidate genes in anorexia nervosa.

    Science.gov (United States)

    Pinheiro, Andrea Poyastro; Bulik, Cynthia M; Thornton, Laura M; Sullivan, Patrick F; Root, Tammy L; Bloss, Cinnamon S; Berrettini, Wade H; Schork, Nicholas J; Kaye, Walter H; Bergen, Andrew W; Magistretti, Pierre; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M; Goldman, David; Halmi, Katherine A; Johnson, Craig; Kaplan, Allan S; Keel, Pamela K; Klump, Kelly L; La Via, Maria; Mitchell, James E; Strober, Michael; Rotondo, Alessandro; Treasure, Janet; Woodside, D Blake

    2010-07-01

    We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN. (c) 2010 Wiley-Liss, Inc.

  11. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses

    Science.gov (United States)

    2011-01-01

    Introduction Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA. Methods A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy. Results In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen. Conclusions Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy. PMID:21884589

  12. 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...

  13. Association and Haplotype Analyses of Positional Candidate Genes in Five Genomic Regions Linked to Scrotal Hernia in Commercial Pig Lines

    OpenAIRE

    Zhi-Qiang Du; Xia Zhao; Natascha Vukasinovic; Fernanda Rodriguez; Clutter, Archie C.; Rothschild, Max F.

    2009-01-01

    Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four re...

  14. [Prevalence and factors associated with intimate partner abuse in female users of public health services in Mexico: a comparative analyses].

    Science.gov (United States)

    Ávila-Burgos, Leticia; Valdez-Santiagob, Rosario; Barroso-Quiab, Abigail; Híjar, Martha; Rojas, Rosalba; Del Río-Zolezzi, Aurora

    2014-01-01

    To analyze the evolution of the prevalence in intimate partner violence during the years 2003 and 2006 in Mexico, identifying factors associated with its severity, comparing our results with findings from 2003. Data from the Encuesta Nacional de Violencia contra las Mujeres (ENVIM 2006) was used; it has urban-rural national representation of female users of Mexican public health services. A total of 22,318 women above 14 years of age were interviewed. A multinomial logistic regression model was adjusted. The dependent variable was the Index of Intimate Partner Abuse. Intimate partner abuse increased 17% in comparison to the year 2003. Women's personal history of childhood abuse (ORA= 5.12, 95% CI4.15-6.30) and rape (ORA = 3.5, 95% CI = 2.66-4.62) were the most important women's factors that were found associated with severe violence. Male partner's daily alcohol consumption increased eleven fold the possibility of severe violence; higher disagreement with traditional female gender roles and higher education of both partners were protective factors. Factors associated with violence and their severities were consistent with findings reported in 2003. Intimate partner violence is a highly prevalent social problem which requires comprehensive strategies supporting empowerment of women through higher education, early detection and care of those battered, as well as structured interventions to prevent violence in future generations.

  15. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

    Science.gov (United States)

    Kapeli, Katannya; Pratt, Gabriel A; Vu, Anthony Q; Hutt, Kasey R; Martinez, Fernando J; Sundararaman, Balaji; Batra, Ranjan; Freese, Peter; Lambert, Nicole J; Huelga, Stephanie C; Chun, Seung J; Liang, Tiffany Y; Chang, Jeremy; Donohue, John P; Shiue, Lily; Zhang, Jiayu; Zhu, Haining; Cambi, Franca; Kasarskis, Edward; Hoon, Shawn; Ares, Manuel; Burge, Christopher B; Ravits, John; Rigo, Frank; Yeo, Gene W

    2016-07-05

    The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3' untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

  16. Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

    Science.gov (United States)

    Cichon, Sven; Craddock, Nick; Daly, Mark; Faraone, Stephen V; Gejman, Pablo V; Kelsoe, John; Lehner, Thomas; Levinson, Douglas F; Moran, Audra; Sklar, Pamela; Sullivan, Patrick F

    2009-05-01

    The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. A literature review was carried out, power and other issues discussed, and planned studies assessed. Most of the genomic DNA sequence differences between any two people are common (frequency >5%) single nucleotide polymorphisms (SNPs). Because of localized patterns of correlation (linkage disequilibrium), 500,000 to 1,000,000 of these SNPs can test the hypothesis that one or more common variants explain part of the genetic risk for a disease. GWAS technologies can also detect some of the copy number variants (deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing analyses. GWAS methods have detected a remarkable number of robust genetic associations for dozens of common diseases and traits, leading to new pathophysiological hypotheses, although only small proportions of genetic variance have been explained thus far and therapeutic applications will require substantial further effort. Study design issues, power, and limitations are discussed. For psychiatric disorders, there are initial significant findings for common SNPs and for rare copy number variants, and many other studies are in progress. GWAS of large samples have detected associations of common SNPs and of rare copy number variants with psychiatric disorders. More findings are likely, since larger GWAS samples detect larger numbers of common susceptibility variants, with smaller effects. The Psychiatric GWAS Consortium is conducting GWAS meta-analyses for schizophrenia, bipolar disorder, major depressive disorder, autism, and attention deficit hyperactivity disorder. Based on results for other diseases, larger samples will be required. The contribution of GWAS will depend on the true genetic architecture of each disorder.

  17. Chromosome analyses in dogs.

    Science.gov (United States)

    Reimann-Berg, N; Bullerdiek, J; Murua Escobar, H; Nolte, I

    2012-01-01

    Cytogenetics is the study of normal and abnormal chromosomes. Every species is characterized by a given number of chromosomes that can be recognized by their specific shape. The chromosomes are arranged according to standard classification schemes for the respective species. While pre- and postnatal chromosome analyses investigate the constitutional karyotype, tumor cytogenetics is focused on the detection of clonal acquired, tumor-associated chromosome aberrations. Cytogenetic investigations in dogs are of great value especially for breeders dealing with fertility problems within their pedigrees, for veterinarians and last but not least for the dog owners. Dogs and humans share a variety of genetic diseases, including cancer. Thus, the dog has become an increasingly important model for genetic diseases. However, cytogenetic analyses of canine cells are complicated by the complex karyotype of the dog. Only just 15 years ago, a standard classification scheme for the complete canine karyotype was established. For chromosome analyses of canine cells the same steps of chromosome preparation are used as in human cytogenetics. There are few reports about cytogenetic changes in non-neoplastic cells, involving predominantly the sex chromosomes. Cytogenetic analyses of different entities of canine tumors revealed that, comparable to human tumors, tumors of the dog are often characterized by clonal chromosome aberrations, which might be used as diagnostic and prognostic markers. The integration of modern techniques (molecular genetic approaches, adaptive computer programs) will facilitate and complete conventional cytogenetic studies. However, conventional cytogenetics is still non-replaceable.

  18. Applicability study of deuterium excess in bottled water life cycle analyses

    Directory of Open Access Journals (Sweden)

    Mihael Brenčič

    2014-12-01

    Full Text Available Paper explores the possible use of d‑excess in the investigation of bottled water. Based on the data set from Brencic and Vreca’s paper (2006. Identification of sources and production processes of bottled waters by stable hydrogen and oxygen isotope ratios, d‑excess values were statistically analysed and compared among different bottled water groups and different bottlers. The bottled water life cycle in relation to d‑excess values was also theoretically identified. Descriptive statistics and one-way ANOVA showed no significant differences among the groups. Differences were detected in the shape of empirical distributions. Groups of still and flavoured waters have similar shapes, but sparkling waters differed to the others. Two distinctive groups of bottlers could be discerned. The first group is represented by bottlers with a high range of d‑excess (from 7.7 ‰ to 18.6 ‰ with average of 12.0 ‰ exploring waters originating from the aquifers rich in highly mineralised groundwater and relatively high concentrations of CO2 gas. The second group is represented by bottlers using groundwater from relatively shallow aquifers. Their d‑excess values have characteristics similar to the local precipitation (from 7.8 ‰ to 14.3 ‰ with average of 10.3 ‰. More frequent sampling and better knowledge of production phases are needed to improve usage of isotope fingerprint for authentication of bottled waters.

  19. A Study of Two Multi-Element Resonant DC-DC Topologies with Loss Distribution Analyses

    Directory of Open Access Journals (Sweden)

    Yifeng Wang

    2017-09-01

    Full Text Available In this paper, two multi-element resonant DC-DC converters are analyzed in detail. Since their resonant tanks have multiple resonant components, the converters display different resonant characteristics within different operating frequency ranges. Through appropriate design, both of the two proposed converters successfully lower the conversion losses and, meanwhile, broaden the voltage gain ranges as well: one converter is able to take full usage of the third order harmonic to deliver the active power, and thus the effective utilization rate of the resonant current is elevated; while the another minimizes the entire switching losses for power switching devices by restricting the input impedance angle of the resonant tank. Besides, the loss distribution is analyzed for the purpose of guiding the component design. In the end, two 500 W prototypes are fabricated to test the theoretical analyses. The results demonstrate that the two proposed converters can achieve wide voltage gain with the small frequency deviation, which noticeably contributes to highly efficient conversion. Their peak efficiencies are measured as 95.4% and 95.3%, respectively.

  20. Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

    Science.gov (United States)

    Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

    2017-01-10

    Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

  1. Genome-wide Association and Longitudinal Analyses Reveal Genetic Loci Linking Pubertal Height Growth, Pubertal Timing, and Childhood Adiposity

    DEFF Research Database (Denmark)

    Cousminer, Diana L; Berry, Diane J; Timpson, Nicholas J

    2013-01-01

    The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. While little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer...... and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty, and cancer progression, pointing to shared underlying mechanisms.To discover genetic loci influencing pubertal height and growth and place them...

  2. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer

    NARCIS (Netherlands)

    Kim, D.-H.; Smith-Warner, S.A.; Spiegelman, D.; Yaun, S.-S.; Colditz, G.A.; Freudenheim, J.L.; Giovannucci, E.; Goldbohm, R.A.; Graham, S.; Harnack, L.; Jacobs, E.J.; Leitzmann, M.; Mannisto, S.; Miller, A.B.; Potter, J.D.; Rohan, T.E.; Schatzkin, A.; Speizer, F.E.; Stevens, V.L.; Stolzenberg-Solomon, R.; Terry, P.; Toniolo, P.; Weijenberg, M.P.; Willett, W.C.; Wolk, A.; Zeleniuch-Jacquotte, A.; Hunter, D.J.

    2010-01-01

    Objective: Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies. Methods: Study-and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards

  3. CIRFT Data Update and Data Analyses for Spent Nuclear Fuel Vibration Reliability Study

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jy-An John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Hong [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2018-01-01

    The objective of this research is to collect experimental data on spent nuclear fuel (SNF) from pressurized water reactors (PWRs), including the H. B. Robinson Nuclear Power Station (HBR), Catawba Nuclear Station, North Anna Nuclear Power Station (NA), and the Limerick Nuclear Power Station (LMK) boiling water reactor (BWR). Data will be collected under simulated transportation environments using the cyclic integrated reversible-bending fatigue tester (CIRFT), an enabling hot-cell testing technology developed at Oak Ridge National Laboratory (ORNL). These data will be used to support ongoing SNF modeling activities and to address regulatory issues associated with SNF transport.

  4. Phylogenetic analyses of Podaxis specimens from Southern Africa reveal hidden diversity and new insights into associations with termites.

    Science.gov (United States)

    Conlon, Benjamin H; de Beer, Z Wilhelm; De Fine Licht, Henrik H; Aanen, Duur K; Poulsen, Michael

    2016-09-01

    Although frequently found on mounds of the grass-cutting termite genus Trinervitermes, virtually nothing is known about the natural history of the fungal genus Podaxis (Agaricaceae) nor why it associates with termite mounds. More than 40 species of this secotioid genus have been described since Linnaeus characterised the first species in 1771. However, taxonomic confusion arose when most of these species were reduced to synonymy with Podaxis pistillaris in 1933. Although a few more species have since been described, the vast majority of specimens worldwide are still treated as P. pistillaris. Using 45 fresh and herbarium specimens from Southern Africa, four from North America and one each from Ethiopia, and Kenya, we constructed the first comprehensive phylogeny of the genus. Four of the genotyped specimens were more than 100 y old. With the exception of the type specimen of Podaxis rugospora, all herbarium specimens were labelled as P. pistillaris or Podaxis sp. However, our data shows that the genus contains at least five well-supported clades with significant inter-clade differences in spore length, width and wall thickness, and fruiting body length, supporting that clades likely represent distinct Podaxis species. Certain clades consistently associate with termites while others appear entirely free-living. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study

    NARCIS (Netherlands)

    Vale, C.L.; Rydzewska, L.H.; Rovers, M.M.; Emberson, J.R.; Gueyffier, F.; Stewart, L.A.

    2015-01-01

    OBJECTIVE: To establish the extent to which systematic reviews and meta-analyses of individual participant data (IPD) are being used to inform the recommendations included in published clinical guidelines. DESIGN: Descriptive study. SETTING: Database maintained by the Cochrane IPD Meta-analysis

  6. Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study

    NARCIS (Netherlands)

    Vale, Claire L.; Rydzewska, Larysa H. M.; Rovers, Maroeska M.; Emberson, Jonathan R.; Gueyffier, François; Stewart, Lesley A.; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B. W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J. P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

    2015-01-01

    OBJECTIVE To establish the extent to which systematic reviews and meta-analyses of individual participant data (IPD) are being used to inform the recommendations included in published clinical guidelines. DESIGN Descriptive study. SETTING Database maintained by the Cochrane IPD Meta-analysis Methods

  7. Nanoscale “Quantum” Islands on Metal Substrates: Microscopy Studies and Electronic Structure Analyses

    Directory of Open Access Journals (Sweden)

    Da-Jiang Liu

    2010-07-01

    Full Text Available Confinement of electrons can occur in metal islands or in continuous films grown heteroepitaxially upon a substrate of a different metal or on a metallic alloy. Associated quantum size effects (QSE can produce a significant height-dependence of the surface free energy for nanoscale thicknesses of up to 10–20 layers. This may suffice to induce height selection during film growth. Scanning STM analysis has revealed remarkable flat-topped or mesa-like island and film morphologies in various systems. We discuss in detail observations of QSE and associated film growth behavior for Pb/Cu(111, Ag/Fe(100, and Cu/fcc-Fe/Cu(100 [A/B or A/B/A], and for Ag/NiAl(110 with brief comments offered for Fe/Cu3Au(001 [A/BC binary alloys]. We also describe these issues for Ag/5-fold i-Al-Pd-Mn and Bi/5-fold i-Al-Cu-Fe [A/BCD ternary icosohedral quasicrystals]. Electronic structure theory analysis, either at the level of simple free electron gas models or more sophisticated Density Functional Theory calculations, can provide insight into the QSE-mediated thermodynamic driving force underlying height selection.

  8. The interplay between QSAR/QSPR studies and partial order ranking and formal concept analyses.

    Science.gov (United States)

    Carlsen, Lars

    2009-04-17

    The often observed scarcity of physical-chemical and well as toxicological data hampers the assessment of potentially hazardous chemicals released to the environment. In such cases Quantitative Structure-Activity Relationships/Quantitative Structure-Property Relationships (QSAR/QSPR) constitute an obvious alternative for rapidly, effectively and inexpensively generatng missing experimental values. However, typically further treatment of the data appears necessary, e.g., to elucidate the possible relations between the single compounds as well as implications and associations between the various parameters used for the combined characterization of the compounds under investigation. In the present paper the application of QSAR/QSPR in combination with Partial Order Ranking (POR) methodologies will be reviewed and new aspects using Formal Concept Analysis (FCA) will be introduced. Where POR constitutes an attractive method for, e.g., prioritizing a series of chemical substances based on a simultaneous inclusion of a range of parameters, FCA gives important information on the implications associations between the parameters. The combined approach thus constitutes an attractive method to a preliminary assessment of the impact on environmental and human health by primary pollutants or possibly by a primary pollutant well as a possible suite of transformation subsequent products that may be both persistent in and bioaccumulating and toxic. The present review focus on the environmental - and human health impact by residuals of the rocket fuel 1,1-dimethylhydrazine (heptyl) and its transformation products as an illustrative example.

  9. Wind energy applications for municipal water services: Opportunities, situational analyses, and case studies

    Energy Technology Data Exchange (ETDEWEB)

    Flowers, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Miner-Nordstrom, L. [U.S. Dept. of Energy, Washington, D.C. (United States)

    2006-01-01

    As communities grow, greater demands are placed on water supplies, wastewater services, and the electricity needed to power the growing water services infrastructure. Water is also a critical resource for thermoelectric power plants. Future population growth in the United States is therefore expected to heighten competition for water resources. Especially in arid U.S. regions, communities may soon face hard choices with respect to water and electric power. Many parts of the United States with increasing water stresses also have significant wind energy resources. Wind power is the fastest-growing electric generation source in the United States and is decreasing in cost to be competitive with thermoelectric generation. Wind energy can potentially offer communities in water-stressed areas the option of economically meeting increasing energy needs without increasing demands on valuable water resources. Wind energy can also provide targeted energy production to serve critical local water-system needs. The U.S. Department of Energy (DOE) Wind Energy Technologies Program has been exploring the potential for wind power to meet growing challenges for water supply and treatment. The DOE is currently characterizing the U.S. regions that are most likely to benefit from wind-water applications and is also exploring the associated technical and policy issues associated with bringing wind energy to bear on water resource challenges.

  10. Associative Visual Agnosia: A Case Study

    OpenAIRE

    A. Charnallet; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  11. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  12. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Farida El-Baz Mohamed

    2016-03-10

    Mar 10, 2016 ... Study of obesity associated proopiomelanocortin ... Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth ... Cases were compared to fifty age-, sex- and pubertal stage-matched healthy non obese children and adolescents as a control group. The work was carried ...

  13. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of

  14. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    Jane

    2011-09-28

    Sep 28, 2011 ... We wanted to determine the association between alcohol addiction and ethanol metabolizing genes and neurotransmitter related genes. MATERIALS AND METHODS. Study population. A total of 332 DNA samples from unrelated Chinese Han population in Yunnan region were obtained (214 controls and ...

  15. A graphical method for practical and informative identifiability analyses of physiological models: A case study of insulin kinetics and sensitivity

    Directory of Open Access Journals (Sweden)

    Lotz Thomas F

    2011-05-01

    Full Text Available Abstract Background Derivative based a-priori structural identifiability analyses of mathematical models can offer valuable insight into the identifiability of model parameters. However, these analyses are only capable of a binary confirmation of the mathematical distinction of parameters and a positive outcome can begin to lose relevance when measurement error is introduced. This article presents an integral based method that allows the observation of the identifiability of models with two-parameters in the presence of assay error. Methods The method measures the distinction of the integral formulations of the parameter coefficients at the proposed sampling times. It can thus predict the susceptibility of the parameters to the effects of measurement error. The method is tested in-silico with Monte Carlo analyses of a number of insulin sensitivity test applications. Results The method successfully captured the analogous nature of identifiability observed in Monte Carlo analyses of a number of cases including protocol alterations, parameter changes and differences in participant behaviour. However, due to the numerical nature of the analyses, prediction was not perfect in all cases. Conclusions Thus although the current method has valuable and significant capabilities in terms of study or test protocol design, additional developments would further strengthen the predictive capability of the method. Finally, the method captures the experimental reality that sampling error and timing can negate assumed parameter identifiability and that identifiability is a continuous rather than discrete phenomenon.

  16. Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population.

    Science.gov (United States)

    Nishimura, Y; Ito, H; Fujii, S; Tabata, H; Tokano, Y; Chen, Y Z; Matsuda, I; Mitsuya, H; Kira, J; Hashimoto, H; Senju, S; Matsushita, S

    2001-06-01

    Abstract It is well known that individuals who are positive for particular HLA class II alleles show a high risk of developing autoimmune diseases. HLA class II molecules expressed on antigen-presenting cells present antigenic peptides to CD4(+) T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. In order to gain a better understanding of mechanisms of the association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many of the autoimmune diseases are observed in all ethnic groups, whereas the incidence of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoantigenic peptides, and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in elucidating the pathogenesis of the diseases. In this review, we describe our recent findings on (1) the uniqueness of both clinical manifestations and the HLA-linked genetic background of Asian-type (opticospinal form) multiple sclerosis, (2) the characteristics of glutamic acid decarboxylase 65 (GAD65) or β2-glycoprotein I (β2-GPI) autoreactive T cells in Japanese patients with insulin-dependent diabetes mellitus (IDDM) or anti-β2-GPI antibody-associated autoimmunity, respectively, and (3) the generation of an efficient delivery system of peptides to the HLA class II-restricted antigen presentation path-way by utilizing a class II-associated invariant chain peptide (CLIP

  17. STUDY OF THE MICROBIOLOGICAL ANALYSES CARRIED OUT AT THE LABORATORY OF A PUBLIC HOSPITAL (CHR AL IDRISSI OF KENITRA

    Directory of Open Access Journals (Sweden)

    A. Aziane

    2015-07-01

    Full Text Available The present work attempts to make a study on the microbiological analyses of pathogens (bacteria or viruses that are at the origin of the human disease, carried out in the laboratory of microbiological analyses of hospital regional CHR al IDRISSI of Kenitra for a period that extends from the year 2007 to 2009 in order to clarify the methodology of work and the problem of infections in developing countries. Our work is based on the monthly inventory of pathogens (E. Coli, Staphylococcus, Streptococcus, Klebsiella, Enterobacter, Candida albicans, Pseudomonas, Syphilis, hepatitis viruses and HIV in deferens samples (Urine, Pus, saddle, like and Serum in patients in relation with total analyses carried out for 3 years. Then we follow their development during this period with the analysis of the results.

  18. Chapter 11: Genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    William S Bush

    Full Text Available Genome-wide association studies (GWAS have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

  19. Electronic media exposure and its association with activity-related outcomes in female adolescents: cross-sectional and longitudinal analyses.

    Science.gov (United States)

    Lobelo, Felipe; Dowda, Marsha; Pfeiffer, Karin A; Pate, Russell R

    2009-03-01

    Few investigations have assessed in adolescent girls the cross-sectional and longitudinal associations between elevated exposure to electronic media (EM) and activity-related outcomes such as compliance with physical activity (PA) standards or cardiorespiratory fitness (CRF). Four-hundred thirty-seven white and African American girls were assessed at the 8th, 9th, and 12th grades. PA and EM (TV/video watching, electronic games, Internet use) were self-reported, and CRF was estimated using a cycle-ergometer test. Hi EM exposure was defined as >or=four 30-minute blocks/d. 8th-, 9th-, and 12th-grade girls in the Hi EM group showed lower compliance with PA standards and had lower CRF than the Low EM group (Pgrades had lower vigorous PA and CRF levels at 12th grade than girls reporting less EM exposure (PInternet use to a combined maximum of 2 hours.

  20. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

  1. Whole Genome and Core Genome Multilocus Sequence Typing and Single Nucleotide Polymorphism Analyses of Listeria monocytogenes Isolates Associated with an Outbreak Linked to Cheese, United States, 2013

    Science.gov (United States)

    Luo, Yan; Carleton, Heather; Timme, Ruth; Melka, David; Muruvanda, Tim; Wang, Charles; Kastanis, George; Katz, Lee S.; Turner, Lauren; Fritzinger, Angela; Moore, Terence; Stones, Robert; Blankenship, Joseph; Salter, Monique; Parish, Mickey; Hammack, Thomas S.; Evans, Peter S.; Tarr, Cheryl L.; Allard, Marc W.; Strain, Errol A.; Brown, Eric W.

    2017-01-01

    ABSTRACT Epidemiological findings of a listeriosis outbreak in 2013 implicated Hispanic-style cheese produced by company A, and pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) were performed on clinical isolates and representative isolates collected from company A cheese and environmental samples during the investigation. The results strengthened the evidence for cheese as the vehicle. Surveillance sampling and WGS 3 months later revealed that the equipment purchased by company B from company A yielded an environmental isolate highly similar to all outbreak isolates. The whole genome and core genome multilocus sequence typing and single nucleotide polymorphism (SNP) analyses results were compared to demonstrate the maximum discriminatory power obtained by using multiple analyses, which were needed to differentiate outbreak-associated isolates from a PFGE-indistinguishable isolate collected in a nonimplicated food source in 2012. This unrelated isolate differed from the outbreak isolates by only 7 to 14 SNPs, and as a result, the minimum spanning tree from the whole genome analyses and certain variant calling approach and phylogenetic algorithm for core genome-based analyses could not provide differentiation between unrelated isolates. Our data also suggest that SNP/allele counts should always be combined with WGS clustering analysis generated by phylogenetically meaningful algorithms on a sufficient number of isolates, and the SNP/allele threshold alone does not provide sufficient evidence to delineate an outbreak. The putative prophages were conserved across all the outbreak isolates. All outbreak isolates belonged to clonal complex 5 and serotype 1/2b and had an identical inlA sequence which did not have premature stop codons. IMPORTANCE In this outbreak, multiple analytical approaches were used for maximum discriminatory power. A PFGE-matched, epidemiologically unrelated isolate had high genetic similarity to the outbreak-associated

  2. Factors associated with phantom limb pain : a 31/2-year prospective study

    NARCIS (Netherlands)

    Bosmans, J.C.; Geertzen, J.H.B.; Post, W.J.; van der Schans, C.P.; Dijkstra, P.U.

    Objective: To analyse the prevalence of phantom (limb) pain over time and to analyse factors associated with phantom (limb) pain in a prospective cohort of amputees. Design: A multicentre longitudinal study. Patients: One hundred and thirty-four patients scheduled for amputation were included.

  3. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.

    NARCIS (Netherlands)

    Whitlock, G.; Lewington, S.; Sherliker, P.; Clarke, R.; Kromhout, D.

    2009-01-01

    Background - The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies.

  4. PCR-RFLP analyses for studying the diversity of GH and Pit-1 genes in Slovak Simmental cattle

    Directory of Open Access Journals (Sweden)

    Anna Trakovická

    2013-10-01

    Full Text Available The aim of this study was evaluation of growth hormone (GH and specific pituitary transcription factor (Pit-1 genes diversity in population of 353 Slovak Simmental cows. The analyses were based on single nucleotide polymorphisms GH/AluI and Pit-1/HinfI detections. A polymorphic site of GH gene (AluI has been linked to differences in circulating metabolites, metabolic hormones and milk yield. Bovine Pit-1 is responsible for pituitary development and hormone secreting gene expression, including GH gene. The Pit-1/HinfI locus was associated with growth, milk production and reproduction performance in cattle. Samples of genomic DNA were analyzed by PCR-RFLP method. Digestion of GH gene PCR products with restriction enzyme AluI revealed allele L and V with frequency 0.695 and 0.305, respectively. The digested Pit-1 gene PCR products with enzyme HinfI revealed alleles A (0.249 and B (0.751. Dominant genotypes were for GH gene heterozygous LV (0.47 and for Pit-1 gene homozygous BB (0.56 animals. The observed heterozygosity, effective allele numbers and polymorphism information content of GH/AluI and Pit-1/HinfI bovine loci population were 0.42/0.37, 1.73/1.59 and 0.33/0.30, respectively. The median polymorphic information content of loci was also transferred to the higher observed homozygosity in population (0.58/0.63. Keywords: cattle, growth hormone, leptin, PCR, Pit-1, polymorphism.

  5. Perceived Social Isolation Makes Me Sad: Five Year Cross-Lagged Analyses of Loneliness and Depressive Symptomatology in the Chicago Health, Aging, and Social Relations Study

    Science.gov (United States)

    Cacioppo, John T.; Hawkley, Louise C.; Thisted, Ronald A.

    2009-01-01

    We present evidence from a five year longitudinal study for the prospective associations between loneliness and depressive symptoms in a population-based, ethnically diverse sample of 229 men and women who were 50-68 years old at study onset. Cross-lagged panel models were used in which the criterion variables were loneliness and depressive symptoms considered simultaneously. Variations on this model evaluated the possible effects of gender, ethnicity, education, physical functioning, medications, social network size, neuroticism, stressful life events, perceived stress, and social support on the observed associations between loneliness and depressive symptoms. Cross-lag analyses indicated that loneliness predicted subsequent changes in depressive symptomatology but not vice versa, and that this temporal association was not attributable to demographic variables, objective social isolation, dispositional negativity, stress, or social support. The importance of distinguishing between loneliness and depressive symptoms and the implications for loneliness and depressive symptomatology in older adults are discussed. PMID:20545429

  6. Multi-core computation in chemometrics: case studies of voltammetric and NIR spectrometric analyses

    National Research Council Canada - National Science Library

    Anderson da Silva Soares; Roberto K. H Galvão; Mário César U Araújo; Sófacles F. C Soares; Luiz Alberto Pinto

    2010-01-01

    .... In particular, the present study considers the problem of variable selection employing the successive projections algorithm and the genetic algorithm, as well as the use of cross-validation in partial least squares...

  7. Diffraction Studies from Minerals to Organics - Lessons Learned from Materials Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Whitfield, Pamela S [ORNL

    2014-01-01

    In many regards the study of materials and minerals by powder diffraction techniques are complimentary, with techniques honed in one field equally applicable to the other. As a long-time materials researcher many of the examples are of techniques developed for materials analysis applied to minerals. However in a couple of cases the study of new minerals was the initiation into techniques later used in materials-based studies. Hopefully they will show that the study of new minerals structures can provide opportunities to add new methodologies and approaches to future problems. In keeping with the AXAA many of the examples have an Australian connection, the materials ranging from organics to battery materials.

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

    National Research Council Canada - National Science Library

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

    2012-01-01

    .... 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...

  9. Temporal analyses of coral snakebite severity published in the American Association of Poison Control Centers' Annual Reports from 1983 through 2007.

    Science.gov (United States)

    Walter, Frank G; Stolz, Uwe; Shirazi, Farshad; McNally, Jude

    2010-01-01

    The only U.S. Food and Drug Administration-approved coral snake antivenom was officially discontinued in 2007, causing ever-diminishing supplies. This study describes the severity of U.S. coral snakebites during the last 25 years to determine trends in annual rates of these bites' medical outcomes. This study retrospectively analyzed all human coral snakebites voluntarily reported by the public and/or health care professionals to poison centers that were subsequently published in the Annual Reports of the American Association of Poison Control Centers (AAPCC) from 1983 through 2007. Annual rates of medical outcomes from coral snakebites were calculated by dividing the annual number of people bitten by coral snakes who developed fatal, major, moderate, minor, or no effect outcomes by the total annual number of people bitten by coral snakes. Negative binomial regression was used to examine trends in annual rates. From 1983 through 2007, the incidence rate of coral snakebites producing no effects significantly decreased by 4.7% per year [incidence rate ratio (IRR) = 0.953; 95% confidence interval (CI) = 0.920-0.987]. From 1985 through 2007, the incidence rates of minor and major outcomes did not significantly change; however, moderate outcomes significantly increased by 3.4% per year (IRR = 1.034; 95% CI = 1.004-1.064). No fatalities were reported from 1983 through 2007. Annual rates of coral snakebites producing no effects significantly decreased and those producing moderate outcomes significantly increased in our analyses of data from the last 25 years of published AAPCC Annual Reports. This study has important limitations that must be considered when interpreting these conclusions.

  10. Low-rank coal study. Volume 4. Regulatory, environmental, and market analyses

    Energy Technology Data Exchange (ETDEWEB)

    1980-11-01

    The regulatory, environmental, and market constraints to development of US low-rank coal resources are analyzed. Government-imposed environmental and regulatory requirements are among the most important factors that determine the markets for low-rank coal and the technology used in the extraction, delivery, and utilization systems. Both state and federal controls are examined, in light of available data on impacts and effluents associated with major low-rank coal development efforts. The market analysis examines both the penetration of existing markets by low-rank coal and the evolution of potential markets in the future. The electric utility industry consumes about 99 percent of the total low-rank coal production. This use in utility boilers rose dramatically in the 1970's and is expected to continue to grow rapidly. In the late 1980's and 1990's, industrial direct use of low-rank coal and the production of synthetic fuels are expected to start growing as major new markets.

  11. Poor replication validity of biomedical association studies reported by newspapers.

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

    Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings

  12. Poor replication validity of biomedical association studies reported by newspapers.

    Science.gov (United States)

    Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings

  13. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  14. Database of somatic mutations in EGFR with analyses revealing indel hotspots but no smoking-associated signature.

    Science.gov (United States)

    Gu, Dongqing; Scaringe, William A; Li, Kai; Saldivar, Juan-Sebastian; Hill, Kathleen A; Chen, Zhenbin; Gonzalez, Kelly D; Sommer, Steve S

    2007-08-01

    We created an Epidermal Growth Factor Receptor (EGFR) Mutation Database (http://www.cityofhope.org/cmdl/egfr_db) that curates a convenient compilation of somatic EGFR mutations in non-small-cell lung cancer (NSCLC) and associated epidemiological and methodological data, including response to the tyrosine kinase inhibitors Gefitinib and Erlotinib. Herein, we analyze 809 mutations collected from 26 publications. Four super hotspots account for 70% of reported mutations while two-thirds of 131 unique mutations have been reported only once and account for only 11% of reported mutations. Consistent with strong biological selection for gain of function, the reported mutations are virtually all missense substitutions or in-frame microdeletions, microinsertions, or microindels (colocalized insertion and deletion with a net gain or loss of 1-50 nucleotides). Microdeletions and microindels are common in a region of exon 19. Microindels, which account for 8% of mutations, have smaller inserted sequences (95% are 1 to 5 bp) and are elevated 16-fold relative to mouse somatic microindels and to human germline microindels. Microdeletions/microindels are significantly more frequent in responders to Gefitinib or Erlotinib (P = 0.003). In addition, EGFR mutations in smokers do not carry signatures of mutagens in cigarette smoke. Otherwise, the mutation pattern does not differ significantly with respect to gender, age, or tumor histology. The EGFR Mutation Database is a central resource of EGFR sequence variant data for clinicians, geneticists, and other researchers. Authors are encouraged to submit new publications with EGFR sequence variants to be included in the database or to provide direct submissions via The WayStation submission and publication process (http://www.centralmutations.org). (c) 2007 Wiley-Liss, Inc.

  15. Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Longjuan Qin

    Full Text Available Genome-wide association studies (GWASs have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and "hub" genes of osteoporosis GWAS-associated genes.We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding, gene ontology analysis, pathway analysis and protein-protein interaction analysis.Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3 and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected "hub" genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST.Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.

  16. Solar power satellite system definition study. Volume 7, phase 1: SPS and rectenna systems analyses

    Science.gov (United States)

    1979-01-01

    A systems definition study of the solar power satellite systems is presented. The design and power distribution of the rectenna system is discussed. The communication subsystem and thermal control characteristics are described and a failure analysis performed on the systems is reported.

  17. Pressure-flow study analyses in patients treated with high energy thermotherapy

    NARCIS (Netherlands)

    de la Rosette, J. J.; de Wildt, M. J.; Höfner, K.; Carter, S. S.; Debruyne, F. M.; Tubaro, A.

    1996-01-01

    We evaluated the urodynamic changes after high energy microwave thermotherapy in patients with lower urinary tract symptoms and benign prostatic enlargement. A total of 120 patients was available for analysis with urodynamic investigation and pressure-flow studies before and 6 months after

  18. Higher Education Business Management Staff and the MBA: A Small Study Analysing Intrinsic and Extrinsic Benefits

    Science.gov (United States)

    Gander, Michelle

    2015-01-01

    Higher education is a key sector for the United Kingdom contributing over £70 billion of output. It functions in an increasingly complex operating, regulatory, and legislative environment that has led to an increased need for effective nonacademic business managers. This study evaluates the benefits of a specialist master of business…

  19. RESULTS OF A METHOD VERIFICATION STUDY FOR ANALYSES OF PCP IN SOIL

    Science.gov (United States)

    As a prelude to a field demonstration of the fungal treatment technology by the SITE Program, a field treatability study was performed to select optimal fungal species and loading rates.using the site-specific soil matrix contaminated with Wood preserving wastes: PCP and PAHS. ur...

  20. Epigenome-Wide Association Study of Wellbeing.

    Science.gov (United States)

    Baselmans, Bart M L; van Dongen, Jenny; Nivard, Michel G; Lin, Bochao D; Zilhão, Nuno R; Boomsma, Dorret I; Bartels, Meike

    2015-12-01

    Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10(-8) and cg01940273, p = 2.34 * 10(-8)) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10(-7); cg09716613, p = 3.23 * 10(-7); cg04387347, p = 3.95 * 10(-7); and cg02290168, p = 5.23 * 10(-7)) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

  1. Applying cost analyses to drive policy that protects children. Mercury as a case study

    Energy Technology Data Exchange (ETDEWEB)

    Leonardo Trasande; Clyde Schechter; Karla A. Haynes; Philip J. Landrigan [Mount Sinai School of Medicine, New York, NY (United States). Department of Community and Preventive Medicine

    2006-09-15

    Exposure in prenatal life to methylmercury (MeHg) has become the topic of intense debate in the United States after the Environmental Protection Agency (EPA) announced a proposal in 2004 to reverse strict controls on emissions of mercury from coal-fired power plants that had been in effect for the preceding 15 years. This proposal failed to incorporate any consideration of the health impacts on children that would result from increased mercury emissions. We assessed the impact on children's health of industrial mercury emissions and found that between 316,588 and 637,233 babies are born with mercury-related losses of cognitive function ranging from 0.2 to 5.13 points. We calculated that decreased economic productivity resulting from diminished intelligence over a lifetime results in an aggregate economic cost in each annual birth cohort of $8.7 billion annually. $1.3 billion of this cost is attributable to mercury emitted from American coal-fired power plants. Downward shifts in intellectual quotient (IQ) are also associated with 1566 excess cases of mental retardation annually. This number accounts for 3.2% of MR cases in the United States. If the lifetime excess cost of a case of MR is $1,248,648 in 2000 dollars, then the cost of these excess cases of MR is $2.0 billion annually. Preliminary data suggest that more stringent mercury policy options would prevent thousands of cases of MR and billions of dollars over the next 25 years.

  2. Use of diplotypes – matched haplotype pairs from homologous chromosomes – in gene-disease association studies

    Science.gov (United States)

    ZUO, Lingjun; WANG, Kesheng; LUO, Xingguang

    2014-01-01

    Summary Alleles, genotypes and haplotypes (combinations of alleles) have been widely used in gene-disease association studies. More recently, association studies using diplotypes (haplotype pairs on homologous chromosomes) have become increasingly common. This article reviews the rationale of the four types of association analyses and discusses the situations in which diplotype-based analyses are more powerful than the other types of association analyses. Haplotype-based association analyses are more powerful than allele-based association analyses, and diplotype-based association analyses are more powerful than genotype-based analyses. In circumstances where there are no interaction effects between markers and where the criteria for Hardy-Weinberg Equilibrium (HWE) are met, the larger sample size and smaller degrees of freedom of allele-based and haplotype-based association analyses make them more powerful than genotype-based and diplotype-based association analyses, respectively. However, under certain circumstances diplotype-based analyses are more powerful than haplotype-based analysis. PMID:25114493

  3. Case Study Analyses of the Impact of Flipped Learning in Teaching Programming Robots

    Directory of Open Access Journals (Sweden)

    Majlinda Fetaji

    2016-11-01

    Full Text Available The focus of the research study was to investigate and find out the benefits of the flipped learning pedagogy on the student learning in teaching programming Robotics classes. Also, the assessment of whether it has any advantages over the traditional teaching methods in computer sciences. Assessment of learners on their attitudes, motivation, and effectiveness when using flipped classroom compared with traditional classroom has been realized. The research questions investigated are: “What kind of problems can we face when we have robotics classes in the traditional methods?”, “If we applied flipped learning method, can we solve these problems?”. In order to analyze all this, a case study experiment was realized and insights as well as recommendations are presented.

  4. Phenomenological study of decline of personal health records: Empirical evidence from thematic analyses of blogs’ content

    Directory of Open Access Journals (Sweden)

    Ravi Chinta

    2015-12-01

    Full Text Available This study examines the current state of personal health records (PHRs in electronic health care. Surveys report that the PHR usage is generally increasing, and yet, even an influential organization such as the Google decided to end its “Google Health” venture. If the potential for use and future growth is high, why are there so many obstacles to the adoption of PHRs? We analyze comments to articles and blogs related to PHRs in order to identify the current status, barriers to adoption, and future potential of PHRs. This study identifies issues of PHRs clustering mainly around certain key ideas: trust, communication, markets, standards, usability, politics, usefulness, and data ownership. It appears that disparity among the multiple stakeholders as to the expected benefits is the main barrier to its adoption.

  5. Neuroimaging Study Designs, Computational Analyses and Data Provenance Using the LONI Pipeline

    Science.gov (United States)

    Dinov, Ivo; Lozev, Kamen; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Pierce, Jonathan; Zamanyan, Alen; Chakrapani, Shruthi; Van Horn, John; Parker, D. Stott; Magsipoc, Rico; Leung, Kelvin; Gutman, Boris; Woods, Roger; Toga, Arthur

    2010-01-01

    Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu. PMID:20927408

  6. Rainfall Analyses of Coonoor Hill Station of Nilgiris District for Landslide Studies

    Science.gov (United States)

    Ramani Sujatha, Evangelin; Suribabu, C. R.

    2017-07-01

    The most common triggering factor of landslides in a hill terrain is rainfall. Assessment of the extreme and antecedent rainfall events and its quantum is imperative to evaluate the temporal occurrence of landslides. It also plays a vital role in the choice of the preventive measures to be adopted. This study focuses on an in-depth rainfall analysis of Coonoor hill station. The analysis includes the study of monthly, seasonal and annual rainfall patterns for a period of 80 years, between 1935 and 2013. Further, one day maximum, 5 day and more antecedent rainfall and its amount is calculated for the years between 2007-2012, 2014 and 2015.The result of the study indicates an increase in the normal rainfall based on the mean of 30 years of data (for the recent decades) and erratic pattern of rainfall during pre-monsoon, post-monsoon south-west monsoon periods. A detailed analysis of daily rainfall for the selected period indicates that extreme highest daily rainfall of more than 300 mm above occurred after consecutive rainfall trigged massive landslides comparing highest rainfall amount around 100 to 180 mm rainfall events.

  7. Neuroimaging study designs, computational analyses and data provenance using the LONI pipeline.

    Directory of Open Access Journals (Sweden)

    Ivo Dinov

    2010-09-01

    Full Text Available Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges--management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu.

  8. Assessment of stakeholder perceptions in water infrastructure projects using system-of-systems and binary probit analyses: a case study.

    Science.gov (United States)

    Faust, Kasey; Abraham, Dulcy M; DeLaurentis, Dan

    2013-10-15

    Globally, water management is evolving toward integrating participatory processes for decision-making to increase the sustainability of the decision outcome. Information about the perceptions and concerns of stakeholders needs to be readily available to those involved in the decision-making process early in the planning stage to assist in developing viable alternatives that may be implementable with limited public opposition and engender general consensus among stakeholders. The current literature does not identify an appropriate means to incorporate stakeholder views early in the preliminary planning stages without requiring relatively large time commitments or the physical presence of the key stakeholders for meetings and discussions. This study develops and demonstrates a decision-support framework that incorporates the system-of-systems school of thought with binary probit analysis to aid in efficient participatory processes by providing insight regarding the stakeholders' demographics and select behavioral characteristics in a decision-making process. The methodology first frames the water system as a system-of-systems, an approach that inherently pinpoints the necessity for diverse stakeholder involvement and maps the stakeholders in the system's hierarchy. Then, binary probit analyses are used to quantify the effect of stakeholder characteristics on the likelihood that (1) they perceive or do not perceive a need for new capital-intensive water infrastructure, and (2) they support or oppose new capital-intensive water infrastructure. A water system decision in the Sacramento-San Joaquin Delta serves as a case study to demonstrate the methodology. Data regarding stakeholder beliefs and perceptions were collected via a web-based survey deployed throughout Southern and Central California The study results indicate that individuals between 18 and 25 years, persons living solely with their spouse, persons associated with environmental stakeholder groups, and

  9. Genome-Wide Association Studies of Cancer

    Science.gov (United States)

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  10. A prospective study of the association between weight changes and self-rated health

    DEFF Research Database (Denmark)

    Simonsen, Mette K; Hundrup, Yrsa A; Grønbaek, Morten

    2008-01-01

    Obesity and self-rated health (SRH) are strong predictors of morbidity and mortality but their interrelation is sparsely studied. The aim of this study was to analyse the association between weight changes and changes in SRH among women. We also examined if poor SRH at baseline was associated...... with later weight gain....

  11. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  12. Clinical Presentation and Microbial Analyses of Contact Lens Keratitis; an Epidemiologic Study

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Rasoulinejad

    2014-09-01

    Full Text Available Introduction: Microbial keratitis is an infective process of the cornea with a potentially and serious visual impairments. Contact lenses are a major cause of microbial keratitis in the developed countries especially among young people. Therefore, the purpose of the present study was to evaluate the frequency and microbiological characteristic of CLK in patients referred to the emergency department (ED of teaching hospitals, Babol, Iran. Methods: This is a cross-sectional study of all patients with contact lens induced corneal ulcers admitted to the teaching hospitals of Babol, Iran, from 2011- 2013. An ophthalmologist examined patients with the slit-lamp and clinical features of them were noted (including pain, redness, foreign body sensation, chemosis, epiphora, blurred vision, discomfort, photophobia, discharge, ocular redness and swelling. All suspected infectious corneal ulcers were scraped for microbial culture and two slides were prepared. Data were analyzed using SPSS software, version 18.0. Results: A total of 14 patients (17 eyes were recruited into the study (100% female. The patients’ age ranged from 16-37 years old (mean age 21.58±7.23 years. The most prevalent observed clinical signs were pain and redness. Three samples reported as sterile. The most common isolated causative organism was pseudomonas aeroginosa (78.6%, Staphylococcus aureus 14.3%, and enterobacter 7.1%, respectively. Treatment outcome was excellent in 23.5%, good in 47.1%, and poor in 29.4% of cases. Conclusion: Improper lens wear and care as well as the lack of awareness about the importance of aftercare visits have been identified as potential risk factors for the corneal ulcer among contact lens wearers. Training and increasing the awareness of adequate lens care and disinfection practices, consulting with an ophthalmologist, and frequent replacement of contact lens storage cases would greatly help reducing the risk of microbial keratitis.

  13. Anatomical study and morphometric analyses on the femoral insertions of the posterior cruciate ligament

    Directory of Open Access Journals (Sweden)

    Julio Cesar Gali

    2013-04-01

    Full Text Available PURPOSE: To provide an anatomical and morphometric basis for the femoral insertions of the posterior cruciate ligament (PCL in order to aid in the creation of anatomical femoral tunnels in ligament surgical reconstruction. Study design: laboratory controlled study. MATERIAL AND METHODS: The macroscopic details of the femoral insertions of the PCL's anterolateral (AL and posteromedial (PM bundles were analyzed in 24 cadaver knees. The specimens were photographed with a digital camera and the images obtained were studied using the software ImageJ. The bundles' insertion areas were measured in square millimeters, and the length of the structures and the distances between significant points were measured in millimeters. RESULTS: The PCL's femoral insertion average total area was 87.29 ± 31.42 mm².The mean insertion's areas of the AL and PM bundles were, respectively, 47.13 ± 19.14 and 40.67 ± 16.19 mm². In 95.8% of the examined knees was verified the presence of the medial intercondylar ridge and in 83.3% of the knees was noted the medial bifurcated ridge. The average length of the medial intercondylar ridge was 20.54 ± 2.26 mm and the medial bifurcated ridge's average length was 7.62 ± 2.35 mm. CONCLUSIONS: The AL had a femoral insertion area larger than the PM bundle; these bundles' insertion areas were lower than those previously described in the literature. There were important individual variations related to the area of the bundles in the samples, suggesting that there should be an individual recommendation for anatomical reconstructions of the PCL with single or double femoral tunnels.

  14. Studies with group treatments required special power calculations, allocation methods, and statistical analyses.

    Science.gov (United States)

    Faes, Miriam C; Reelick, Miriam F; Perry, Marieke; Olde Rikkert, Marcel G M; Borm, George F

    2012-02-01

    In some trials, the intervention is delivered to individuals in groups, for example, groups that exercise together. The group structure of such trials has to be taken into consideration in the analysis and has an impact on the power of the trial. Our aim was to provide optimal methods for the design and analysis of such trials. We described various treatment allocation methods and presented a new allocation algorithm: optimal batchwise minimization (OBM). We carried out a simulation study to evaluate the performance of unrestricted randomization, stratification, permuted block randomization, deterministic minimization, and OBM. Furthermore, we described appropriate analysis methods and derived a formula to calculate the study size. Stratification, deterministic minimization, and OBM had considerably less risk of imbalance than unrestricted randomization and permuted block randomization. Furthermore, OBM led to unpredictable treatment allocation. The sample size calculation and the analysis of the study must be based on a multilevel model that takes the group structure of the trial into account. Trials evaluating interventions that are carried out in subsequent groups require adapted treatment allocation, power calculation, and analysis methods. From the perspective of obtaining overall balance, we conclude that minimization is the method of choice. When the number of prognostic factors is low, stratification is an excellent alternative. OBM leads to better balance within the batches, but it is more complicated. It is probably most worthwhile in trials with many prognostic factors. From the perspective of predictability, a treatment allocation method, such as OBM, that allocates several subjects at the same time, is superior to other methods because it leads to the lowest possible predictability. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. 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

  16. 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

  17. Wind Energy Applications for Municipal Water Services: Opportunities, Situation Analyses, and Case Studies; Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Flowers, L.; Miner-Nordstrom, L.

    2006-01-01

    As communities grow, greater demands are placed on water supplies, wastewater services, and the electricity needed to power the growing water services infrastructure. Water is also a critical resource for thermoelectric power plants. Future population growth in the United States is therefore expected to heighten competition for water resources. Many parts of the United States with increasing water stresses also have significant wind energy resources. Wind power is the fastest-growing electric generation source in the United States and is decreasing in cost to be competitive with thermoelectric generation. Wind energy can offer communities in water-stressed areas the option of economically meeting increasing energy needs without increasing demands on valuable water resources. Wind energy can also provide targeted energy production to serve critical local water-system needs. The research presented in this report describes a systematic assessment of the potential for wind power to support water utility operation, with the objective to identify promising technical applications and water utility case study opportunities. The first section describes the current situation that municipal providers face with respect to energy and water. The second section describes the progress that wind technologies have made in recent years to become a cost-effective electricity source. The third section describes the analysis employed to assess potential for wind power in support of water service providers, as well as two case studies. The report concludes with results and recommendations.

  18. Extreme temperature indices analyses: A case study of five meteorological stations in Peninsular Malaysia

    Science.gov (United States)

    Hasan, Husna; Salleh, Nur Hanim Mohd

    2015-10-01

    Extreme temperature events affect many human and natural systems. Changes in extreme temperature events can be detected and monitored by developing the indices based on the extreme temperature data. As an effort to provide the understanding of these changes to the public, a study of extreme temperature indices is conducted at five meteorological stations in Peninsular Malaysia. In this study, changes in the means and extreme events of temperature are assessed and compared using the daily maximum and minimum temperature data for the period of 2004 to 2013. The absolute extreme temperature indices; TXx, TXn, TXn and TNn provided by Expert Team on Climate Change Detection and Indices (ETCCDI) are utilized and linear trends of each index are extracted using least square likelihood method. The results indicate that there exist significant decreasing trend in the TXx index for Kota Bharu station and increasing trend in TNn index for Chuping and Kota Kinabalu stations. The comparison between the trend in mean and extreme temperatures show the same significant tendency for Kota Bharu and Kuala Terengganu stations.

  19. Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.

    Science.gov (United States)

    Faraone, S V; Blehar, M; Pepple, J; Moldin, S O; Norton, J; Nurnberger, J I; Malaspina, D; Kaufmann, C A; Reich, T; Cloninger, C R; DePaulo, J R; Berg, K; Gershon, E S; Kirch, D G; Tsuang, M T

    1996-03-01

    The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other.

  20. Quantifying the relative importance of predictors in multiple linear regression analyses for public health studies.

    Science.gov (United States)

    Chao, Yi-Chun E; Zhao, Yue; Kupper, Lawrence L; Nylander-French, Leena A

    2008-08-01

    Multiple linear regression analysis is widely used in many scientific fields, including public health, to evaluate how an outcome or response variable is related to a set of predictors. As a result, researchers often need to assess "relative importance" of a predictor by comparing the contributions made by other individual predictors in a particular regression model. Hence, development of valid statistical methods to estimate the relative importance of a set of predictors is of great interest. In this research, the authors considered the relative importance of a predictor when defined by that portion of the squared multiple correlation explained by the contribution of each predictor in the final model of interest. Here, a number of suggested relative importance indices motivated by this definition are reviewed, including the squared zero-order correlation, squared semipartial correlation, Product Measure (i.e., Pratt's Index), General Dominance Index, and Johnson's Relative Weight. The authors compared these indices using data sets from an occupational health study in which human inhalation exposure to styrene was measured and from a laboratory animal study on risk factors for atherosclerosis, and statistical properties using bootstrap methods were examined. The analysis suggests that the General Dominance Index and Johnson's Relative Weight are preferred methods for quantifying the relative importance of predictors in a multiple linear regression model. Johnson's Relative Weight involves significantly less computational burden than the General Dominance Index when the number of predictors in the final model is large.

  1. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia

    NARCIS (Netherlands)

    Chen, X.; Lee, G.; Maher, B. S.; Fanous, A. H.; Chen, J.; Zhao, Z.; Guo, A.; van den Oord, E.; Sullivan, P. F.; Shi, J.; Levinson, D. F.; Gejman, P. V.; Sanders, A.; Duan, J.; Owen, M. J.; Craddock, N. J.; O'Donovan, M. C.; Blackman, J.; Lewis, D.; Kirov, G. K.; Qin, W.; Schwab, S.; Wildenauer, D.; Chowdari, K.; Nimgaonkar, V.; Straub, R. E.; Weinberger, D. R.; O'Neill, F. A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A. K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M. M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O. A.; Cantor, R. M.; Ophoff, R.; Corvin, A.; Morris, D. W.; Gill, M.; Pato, C. N.; Pato, M. T.; Macedo, A.; Gurling, H. M. D.; McQuillin, A.; Pimm, J.; Hultman, C.; Lichtenstein, P.; Sklar, P.; Purcell, S. M.; Scolnick, E.; St Clair, D.; Blackwood, D. H. R.; Kendler, K. S.; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez; O'Donovan, Michael C.; Kirov, George K.; Craddock, Nick J.; Holmans, Peter A.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.; Toncheva, Draga; Milanova, Vihra; Owen, Michael J.; Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.; Sullivan, Patrick; Morris, Derek W.; O'Dushlaine, Colm T.; Kenny, Elaine; Quinn, Emma M.; Gill, Michael; Corvin, Aiden; McQuillin, Andrew; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Thirumalai, Srinivasa; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Quested, Digby; Bass, Nicholas; Gurling, Hugh; Crombie, Caroline; Fraser, Gillian; Kuan, Soh Leh; Walker, Nicholas; St Clair, David; Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; van Beck, Margaret; Wray, Naomi R.; Macgregor, Stuart; Visscher, Peter M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank; Carvalho, Celia; Morley, Christopher; Fanous, Ayman; Conti, David; Knowles, James A.; Ferreira, Carlos Paz; Macedo, Antonio; Azevedo, M. Helena; Pato, Carlos N.; Stone, Jennifer L.; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Purcell, Shaun M.; Sklar, Pamela; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.; Scolnick, Edward M.

    2011-01-01

    We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed

  2. Experimental studies and performance analyses on polyurethane and nitrile rubber rod seals

    Science.gov (United States)

    Mirza, M.; Temiz, V.; Kamburoǧlu, E.

    2012-09-01

    The aim of this study is to determine the friction and leakage properties of rod seals made of polyethylene and nitrile rubber with different design geometries, under various pressure and lubricating oil viscosity conditions, in order to make assumptions about their general sealing characteristics and their pros and cons under certain working conditions that involve a range of fluid pressures. The test specimens consist of commercial rod seals of various designs and materials and were mounted on a hard chrome coated shaft subject to reciprocating motion. The test rig is capable of measuring friction force by means of strain measurements on a load cell transmitting the linear motion of a screw shaft to the test shaft. The test results of the reciprocating rod seal samples were evaluated according to leakage amount and friction resistance as a function of materials, design geometries and fluid pressures as well as the lubricating oil viscosity.

  3. Multi-path transportation futures study : vehicle characterization and scenario analyses.

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, S. E.; Singh, M. K.; Energy Systems; TA Engineering; ORNL

    2009-12-03

    Projecting the future role of advanced drivetrains and fuels in the light vehicle market is inherently difficult, given the uncertainty (and likely volatility) of future oil prices, inadequate understanding of likely consumer response to new technologies, the relative infancy of several important new technologies with inevitable future changes in their performance and costs, and the importance - and uncertainty - of future government marketplace interventions (e.g., new regulatory standards or vehicle purchase incentives). This Multi-Path Transportation Futures (MP) Study has attempted to improve our understanding of this future role by examining several scenarios of vehicle costs, fuel prices, government subsidies, and other key factors. These are projections, not forecasts, in that they try to answer a series of 'what if' questions without assigning probabilities to most of the basic assumptions.

  4. Back-Analyses of Landfill Instability Induced by High Water Level: Case Study of Shenzhen Landfill

    Directory of Open Access Journals (Sweden)

    Ren Peng

    2016-01-01

    Full Text Available In June 2008, the Shenzhen landfill slope failed. This case is used as an example to study the deformation characteristics and failure mode of a slope induced by high water levels. An integrated monitoring system, including water level gauges, electronic total stations, and inclinometers, was used to monitor the slope failure process. The field measurements suggest that the landfill landslide was caused by a deep slip along the weak interface of the composite liner system at the base of the landfill. The high water level is considered to be the main factor that caused this failure. To calculate the relative interface shear displacements in the geosynthetic multilayer liner system, a series of numerical direct shear tests were carried out. Based on the numerical results, the composite lining system simplified and the centrifuge modeling technique was used to quantitatively evaluate the effect of water levels on landfill instability.

  5. Municipal solid waste composition: Sampling methodology, statistical analyses, and case study evaluation

    DEFF Research Database (Denmark)

    Edjabou, Vincent Maklawe Essonanawe; Jensen, Morten Bang; Götze, Ramona

    2015-01-01

    stratification parameter. Separating food leftovers from food packaging during manual sorting of the sampled waste did not have significant influence on the proportions of food waste and packaging materials, indicating that this step may not be required. (C) 2014 Elsevier Ltd. All rights reserved.......Sound waste management and optimisation of resource recovery require reliable data on solid waste generation and composition. In the absence of standardised and commonly accepted waste characterisation methodologies, various approaches have been reported in literature. This limits both...... comparability and applicability of the results. In this study, a waste sampling and sorting methodology for efficient and statistically robust characterisation of solid waste was introduced. The methodology was applied to residual waste collected from 1442 households distributed among 10 individual sub...

  6. Phylogeographic lineages and species comparisons in conservation analyses: a case study of california herpetofauna.

    Science.gov (United States)

    Rissler, Leslie J; Hijmans, Robert J; Graham, Catherine H; Moritz, Craig; Wake, David B

    2006-05-01

    Many phylogeographic studies have revealed strongly diverged lineages within species that are masked by a lack of congruent morphological differentiation. To assess the extent to which the genetic component of diversity affects conservation assessments, we compared spatial patterns of endemism and conservation value for 22 species of Californian amphibians and reptiles with the 75 phylogeographic lineages that they contain. We used bioclimatic distribution modeling with environmental layers to generate 5-km spatial-resolution maps of predicted distribution for each species and lineage. We found concentrations of lineage breaks across the Central Valley, San Francisco Bay, the Sierra Nevada, and the Tehachapi and Trinity ranges. Subdivision of the ranges of species into phylogeographic units revealed novel areas of endemism. Several areas of very high conservation value for lineages were not evident in the species-level analysis. These observations illustrate the importance of considering multiple levels of biodiversity in conservation assessments.

  7. A Study of Thermal Analyses and Fundamental Combustion Characteristics for Thermal Utility with Biomass Volatile Matter

    Science.gov (United States)

    Ida, Tamio; Namba, Kunihiko; Sano, Hiroshi

    Based on un-use biomass utilities, Carbonized technology is noticed as material utilities and solid fuel. Therefore, this technology is tackling by national project as large-scale utilities. But, this technology is dehydrated volatiles matter during carbonized from biomass. Especially, Woody tar into one of volatile matter has vicious handling to get into trouble in carbonized equipment. In this study, we propose to get fundamental knowledge for effective thermal utility through thermal decompositions and fundamental combustion properties on experimental results. Woody tar has high caloric value (approximately 30MJ/kg) and high carbon ration. On the other hand, a woody vinegar liquid has thermal decomposition property close to water property with heat absorption as evaporation latent heat of water. In fundamental combustion experimental result, a woody tar has fl ammable combustion and surface combustion. Especially, a total combustion and ignition time properties has hyperbola relation to environment temperatures in furnace.

  8. Government-promoted collective research and development in Japan: Analyses of the organization through case studies

    Energy Technology Data Exchange (ETDEWEB)

    Hane, G.J.

    1990-06-01

    A study was commissioned by the Energy Conservation and Utilization Technologies (ECUT) Program of the US Department of Energy (DOE) to better understand the strategies used for cooperative and joint-venture research and development (R D) overseas. The study evaluates the organization and management of several different types of cooperative R D programs in Japan that are sponsored under the Ministry of International Trade and Industry (MITI) Program, Exploratory Research for Advanced Technology (ERATO) Program, and the Key Technology Center (KTC) Program. The ERATO Program grew out of a concern over revising the government's approach to supporting research and technology development. The program was initiated to address what was regarded as a lack of creativity in areas at the forefront of science. The program recruits young researchers and allows them flexibility to explore multi-disciplinary areas at the forefront of science. It has been organized to allow for individual creativity but at the same time to benefit from the combined knowledge of an assembly of researchers. Because the plan is such a radical departure from conventional Japanese philosophy, it has met with certain bureaucratic obstacles. Visits to four ERATO projects are described. The third program, the KTC Program, focuses on getting private firms to venture into risky areas of advanced technology to pave the way for future industries. Its goal is to encourage a shift of resources in the private sector toward areas that are considered essential for the competitive development of future industries. The principal philosophy behind the KTC is that the private sector is in the best position to identify promising technical challenges and to weigh their commercial potential against research uncertainties. Three KTC research joint ventures are briefly described. 13 refs., 9 figs., 35 tabs.

  9. Comparative study analysing women's childbirth satisfaction and obstetric outcomes across two different models of maternity care.

    Science.gov (United States)

    Conesa Ferrer, Ma Belén; Canteras Jordana, Manuel; Ballesteros Meseguer, Carmen; Carrillo García, César; Martínez Roche, M Emilia

    2016-08-26

    To describe the differences in obstetrical results and women's childbirth satisfaction across 2 different models of maternity care (biomedical model and humanised birth). 2 university hospitals in south-eastern Spain from April to October 2013. A correlational descriptive study. A convenience sample of 406 women participated in the study, 204 of the biomedical model and 202 of the humanised model. The differences in obstetrical results were (biomedical model/humanised model): onset of labour (spontaneous 66/137, augmentation 70/1, p=0.0005), pain relief (epidural 172/132, no pain relief 9/40, p=0.0005), mode of delivery (normal vaginal 140/165, instrumental 48/23, p=0.004), length of labour (0-4 hours 69/93, >4 hours 133/108, p=0.011), condition of perineum (intact perineum or tear 94/178, episiotomy 100/24, p=0.0005). The total questionnaire score (100) gave a mean (M) of 78.33 and SD of 8.46 in the biomedical model of care and an M of 82.01 and SD of 7.97 in the humanised model of care (p=0.0005). In the analysis of the results per items, statistical differences were found in 8 of the 9 subscales. The highest scores were reached in the humanised model of maternity care. The humanised model of maternity care offers better obstetrical outcomes and women's satisfaction scores during the labour, birth and immediate postnatal period than does the biomedical model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Delayed-Start Analyses in the Phase 3 Solanezumab EXPEDITION3 Study in Mild Alzheimer's Disease.

    Science.gov (United States)

    Liu-Seifert, H; Case, M G; Andersen, S W; Holdridge, K C; Aisen, P S; Kollack-Walker, S; Siemers, E

    2018-01-01

    A delayed-start design has been proposed to assess a potential disease-modifying effect in investigational drugs for Alzheimer's disease that target the underlying disease process. We extended this methodology to recently obtained data from the EXPEDITION3. EXPEDITION3 was a Phase 3, double-blind study with participants randomized to solanezumab (400 mg) or placebo every 4 weeks for 80 weeks, with an optional extension of active treatment. The delayed-start analysis was designed to determine if a statistically significant treatment difference established during the placebo-controlled period is maintained (at predefined level) during the delayed-start period, which would suggest the active drug has a disease-modifying effect. The delayed-start analysis was assessed across multiple efficacy measures, and includes data from baseline in the placebo-controlled period and up to 9 months in the delayed-start period. No significant difference was observed between the placebo and solanezumab treatment groups at the end of the placebo-controlled period for the Alzheimer's Disease Assessment Scale-Cognitive 14-item subscale. A significant treatment difference was observed at the end of the placebo-controlled period for the Alzheimer's Disease Cooperative Study-Activities of Daily Living instrumental items, an effect also seen at 6 months in the delayed-start period, and the noninferiority criterion was met. No other efficacy measures met these criteria. Delayed-start statistical methodology was used to understand the longitudinal outcomes in EXPEDITION3 and its extension. The small treatment differences observed at the end of the placebo-controlled phase prevented adequate assessment of any putative disease modifying effect.

  11. Association between urbanisation and type 2 diabetes: an ecological study.

    Science.gov (United States)

    Gassasse, Zakariah; Smith, Dianna; Finer, Sarah; Gallo, Valentina

    2017-01-01

    Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide.

  12. Deformation Monitoring and Bathymetry Analyses in Rock-Fill Dams, a Case Study at Ataturk Dam

    Science.gov (United States)

    Kalkan, Y.; Bilgi, S.

    2014-12-01

    Turkey has 595 dams constructed between 1936 and 2013 for the purposes of irrigation, flood control, hydroelectric energy and drinking water. A major portion of the dam basins in Turkey are deprived of vegetation and have slope topography on near surrounding area. However, landscaping covered with forest around the dam basin is desirable for erosion control. In fact; the dams, have basins deprived of vegetation, fill up quickly due to sediment transport. Erosion control and forestation are important factors, reducing the sediment, to protect the water basins of the dams and increase the functioning life of the dams. The functioning life of dams is as important as the investment and construction. Nevertheless, in order to provide safety of human life living around, well planned monitoring is essential for dams. Dams are very large and critical structures and they demand the use or application of precise measuring systems. Some basic physical data are very important for assessing the safety and performance of dams. These are movement, water pressure, seepage, reservoir and tail-water elevations, local seismic activities, total pressure, stress and strain, internal concrete temperature, ambient temperature and precipitation. Monitoring is an essential component of the dam after construction and during operation and must en­able the timely detection of any behavior that could deteriorate the dam, potentially result in its shutdown or failure. Considering the time and labor consumed by long-term measurements, processing and analysis of measured data, importance of the small structural motions at regular intervals could be comprehended. This study provides some information, safety and the techniques about the deformation monitoring of the dams, dam safety and related analysis. The case study is the deformation measurements of Atatürk Dam in Turkey which is the 6th largest dam of world considering the filling volume of embankment. Brief information is given about the

  13. Ab initio computational study of vincristine as a biological active compound: NMR and NBO analyses

    Directory of Open Access Journals (Sweden)

    Shiva Joohari

    2015-06-01

    Full Text Available Vincristine is a biological active alkaloid that has been used clinically against a variety of neoplasms. In the current study we have theoretically investigated the magnetic properties of titled compound to predict physical and chemical properties of vincristine as a biological inhibitor. Ab initio computation using HF and B3LYP with 3-21G(d and 6-31G(d level of theory have been performed and then magnetic shielding tensor (, ppm, shielding asymmetry (, magnetic shielding anisotropy (aniso, ppm, the skew of a tensor (K, chemical shift anisotropy ( and chemical shift ( were calculated to indicate the details of the interaction mechanism between microtubules and vincristine. Moreover, EHOMO, ELUMO and Ebg were evaluated. The maximum and minimum values of Ebg were found in HF/3-21g and B3LYP/3-21g respectively. It was also uggested that O24, O37, O49 and O55 with minimum values of iso, are active sites of titled compound. Furthermore the calculated chemical shifts were compared with experimental data in DMSO and CDCl3 solvents.

  14. A study of butyl acetate synthesis 3. Analysing adsorption on catalyst

    Directory of Open Access Journals (Sweden)

    Álvaro Orjuela Londoño

    2006-01-01

    Full Text Available Reactive system (acetic acid-n-butanol-butyl acetate-water, in liquid phase, 0.76 Bar pressure adsorption on a cationic exchange resin (Bayer Lewatit K-2431 was studied in this work. Solid particle size distribution was verified and low dispersion was noticed with 86% of total mass between 20 and 30 mesh. The dried solid showed a bi- nodal distribution with 40% above 25 mesh and 45% between 25 and 45 mesh. Resin swelling assays were carried out on pure components and non-reactive binary mixtures and increased matrix volume was observed (2.2 to 3 times higher. Selective adsorption on the reactive system was observed in the sequence: water > n-butanol acid> acetate. Both ideal and non-ideal models were tested for calculating adsorption using a composite isotherm, demonstrating these models’ weakness in representing adsorption on ionic polymer matrices. Calorimetric characterisation assays were carried out on swelled catalyst and a change in solid structure caused by thermal treatment was recognised using infrared scanning.

  15. Analysing Cytochrome c Aggregation and Fibrillation upon Interaction with Acetonitrile: an in Vitro Study.

    Science.gov (United States)

    Furkan, Mohammad; Fazili, Naveed Ahmad; Afsar, Mohammad; Naeem, Aabgeena

    2016-11-01

    The propensity of native state to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. Our study was focused at analyzing the aggregation and fibrillation tendency of cytochrome c in presence of an organic solvent i.e. acetonitrile. In vitro analysis revealed that the interaction of cytochrome c with acetonitrile facilitated the oligomerization of cytochrome c via the passage through an intermediate state which was obtained at 20 % v/v concentration of acetonitrile featured by a sharp hike in the ANS fluorescence intensity with a blue shift of 20 nm compared to the native state. Oligomers and fibrils were formed at 40 and 50 % v/v concentration respectively as indicated by a significant hike in the ThT fluorescence intensity, red shift of 55 nm in congo red binding assay and an increase in absorbance at 350 nm. They possess β-sheet structure as evident from appearance of peak at 217 nm. Finally, authenticity of oligomeric and fibrillar species was confirmed by TEM imaging which revealed bead like aggregates and a meshwork of thread like fibrils respectively. It could be suggested that the fibrillation of bovine cytchrome c could serve as a model protein to unravel the general aggregation and fibrillation pattern of heme proteins. Graphical abstract ᅟ.

  16. Spectroscopic, thermal analyses, structural and antibacterial studies on the interaction of some metals with ofloxacin

    Science.gov (United States)

    Zordok, W. A.; El-Shwiniy, W. H.; El-Attar, M. S.; Sadeek, S. A.

    2013-09-01

    Reaction between the fluoroquinolone antibacterial agent ofloxacin and V(IV), Zr(IV) and U(VI) in methanol and acetone was studied. The ability of ofloxacin to form metal complexes is high. The isolated solid complexes were characterized by elemental analysis, magnetic moment, conductance measurements, infrared, electronic, 1H NMR spectra and thermal investigation. In all complexes the ofloxacin ligand is coordinated through the pyridone and carboxylate oxygen forming 1:2 M:HOfl complexes. The calculated bond length and force constant, F(Udbnd O), in the uranyl complex are 1.73 Å and 640.83 N m-1, respectively. The metal-ligand binding of the V(IV) and Zr(IV) complexes was predicted by using the density functional theory (DFT) at the B3LYP-CEP-31G level of theory and total energy, dipole moment estimation of different V(IV) and Zr(IV) ofloxacin structures. All the synthesized complexes exhibited higher biocidal activity against S. aureus K1, Bacillus subtilis K22, Br. otitidis K76, Escherichia coli K32, Pseudomonas aeruginosa SW1 and Klebsiella oxytoca K42. compared to parent compounds and standard drugs.

  17. Detecting Molecular Features of Spectra Mainly Associated with Structural and Non-Structural Carbohydrates in Co-Products from BioEthanol Production Using DRIFT with Uni- and Multivariate Molecular Spectral Analyses

    OpenAIRE

    Zhiyuan Niu; Daalkhaijav Damiran; Arash Azarfar; Peiqiang Yu

    2011-01-01

    The objective of this study was to use DRIFT spectroscopy with uni- and multivariate molecular spectral analyses as a novel approach to detect molecular features of spectra mainly associated with carbohydrate in the co-products (wheat DDGS, corn DDGS, blend DDGS) from bioethanol processing in comparison with original feedstock (wheat (Triticum), corn (Zea mays)). The carbohydrates related molecular spectral bands included: A_Cell (structural carbohydrates, peaks area region and baseline: ca. ...

  18. Functional Studies and In Silico Analyses to Evaluate Non-Coding Variants in Inherited Cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Giulia Frisso

    2016-11-01

    Full Text Available Point mutations are the most common cause of inherited diseases. Bioinformatics tools can help to predict the pathogenicity of mutations found during genetic screening, but they may work less well in determining the effect of point mutations in non-coding regions. In silico analysis of intronic variants can reveal their impact on the splicing process, but the consequence of a given substitution is generally not predictable. The aim of this study was to functionally test five intronic variants (MYBPC3-c.506-2A>C, MYBPC3-c.906-7G>T, MYBPC3-c.2308+3G>C, SCN5A-c.393-5C>A, and ACTC1-c.617-7T>C found in five patients affected by inherited cardiomyopathies in the attempt to verify their pathogenic role. Analysis of the MYBPC3-c.506-2A>C mutation in mRNA from the peripheral blood of one of the patients affected by hypertrophic cardiac myopathy revealed the loss of the canonical splice site and the use of an alternative splicing site, which caused the loss of the first seven nucleotides of exon 5 (MYBPC3-G169AfsX14. In the other four patients, we generated minigene constructs and transfected them in HEK-293 cells. This minigene approach showed that MYBPC3-c.2308+3G>C and SCN5A-c.393-5C>A altered pre-mRNA processing, thus resulting in the skipping of one exon. No alterations were found in either MYBPC3-c.906-7G>T or ACTC1-c.617-7T>C. In conclusion, functional in vitro analysis of the effects of potential splicing mutations can confirm or otherwise the putative pathogenicity of non-coding mutations, and thus help to guide the patient's clinical management and improve genetic counseling in affected families.

  19. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Multiple comparison procedures for neuroimaging genomewide association studies.

    Science.gov (United States)

    Hua, Wen-Yu; Nichols, Thomas E; Ghosh, Debashis

    2015-01-01

    Recent research in neuroimaging has focused on assessing associations between genetic variants that are measured on a genomewide scale and brain imaging phenotypes. A large number of works in the area apply massively univariate analyses on a genomewide basis to find single nucleotide polymorphisms that influence brain structure. In this paper, we propose using various dimensionality reduction methods on both brain structural MRI scans and genomic data, motivated by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We also consider a new multiple testing adjustment method and compare it with two existing false discovery rate (FDR) adjustment methods. The simulation results suggest an increase in power for the proposed method. The real-data analysis suggests that the proposed procedure is able to find associations between genetic variants and brain volume differences that offer potentially new biological insights. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Age at Menarche, Level of Education, Parity and the Risk of Hysterectomy: A Systematic Review and Meta-Analyses of Population-Based Observational Studies.

    Directory of Open Access Journals (Sweden)

    Louise F Wilson

    Full Text Available Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy.Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression.Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy-summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I2 = 0%; summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I2 = 61%. Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I2 = 86%, summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I2 = 90% and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I2 = 85% per each level lower of education. Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant.The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance

  2. Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk : results from analyses in the Netherlands : cohort study

    NARCIS (Netherlands)

    Botterweck, A.A.M.; Verhagen, H.; Goldbohm, R.A.; Kleinjans, J.; Brandt, P.A. van den

    2000-01-01

    Both carcinogenic and anticarcinogenic properties have been reported for the synthetic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS)

  3. Proteomic studies associated with Parkinson's disease.

    Science.gov (United States)

    Kasap, Murat; Akpinar, Gurler; Kanli, Aylin

    2017-03-01

    Parkinson's disease (PD) is an insidious disorder affecting more than 1-2% of the population over the age of 65. Understanding the etiology of PD may create opportunities for developing new treatments. Genomic and transcriptomic studies are useful, but do not provide evidence for the actual status of the disease. Conversely, proteomic studies deal with proteins, which are real time players, and can hence provide information on the dynamic nature of the affected cells. The number of publications relating to the proteomics of PD is vast. Therefore, there is a need to evaluate the current proteomics literature and establish the connections between the past and the present to foresee the future. Areas covered: PubMed and Web of Science were used to retrieve the literature associated with PD proteomics. Studies using human samples, model organisms and cell lines were selected and reviewed to highlight their contributions to PD. Expert commentary: The proteomic studies associated with PD achieved only limited success in facilitating disease diagnosis, monitoring and progression. A global system biology approach using new models is needed. Future research should integrate the findings of proteomics with other omics data to facilitate both early diagnosis and the treatment of PD.

  4. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  5. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

    2009-01-01

    cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially......Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive...

  6. Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer's Disease: A Replication Study and Meta-Analyses.

    Science.gov (United States)

    Wang, Zi-Xuan; Tan, Lan; Wang, Hui-Fu; Ma, Jing; Liu, Jinyuan; Tan, Meng-Shan; Sun, Jia-Hao; Zhu, Xi-Chen; Jiang, Teng; Yu, Jin-Tai

    2015-01-01

    To evaluate whether iron, zinc, and copper levels in serum are disarranged in Alzheimer's disease (AD), we performed meta-analyses of all studies on the topic published from 1984 to 2014 and contextually carried out a replication study in serum as well. Our meta-analysis results showed that serum zinc was significantly lower in AD patients. Our replication and meta-analysis results showed that serum copper was significantly higher in AD patients than in healthy controls, so our findings were consistent with the conclusions of four previously published copper meta-analyses. Even if a possible role of iron in the pathophysiology of the disease could not be ruled out, the results of our meta-analysis showed no change of serum iron levels in AD patients, but this conclusion was not robust and requires further investigation. The meta-regression analyses revealed that in some studies, differences in serum iron levels could be due to the different mean ages, while differences in zinc levels appeared to be due to the different sex ratios. However, the effect of sex ratio on serum zinc levels in our meta-analysis is subtle and needs further confirmation. Also, diverse demographic terms and methodological approaches appeared not to explain the high heterogeneity of our copper meta-analysis. Therefore, when investigating trace elements, covariants such as age and sex have to be taken into account in the analyses. In the light of these findings, we suggest that the possible alteration of serum zinc and copper levels are involved in the pathogenesis of AD.

  7. In silico genomic analyses reveal three distinct lineages of Escherichia coli O157:H7, one of which is associated with hyper-virulence

    Directory of Open Access Journals (Sweden)

    Karmali Mohamed A

    2009-06-01

    Full Text Available Abstract Background Many approaches have been used to study the evolution, population structure and genetic diversity of Escherichia coli O157:H7; however, observations made with different genotyping systems are not easily relatable to each other. Three genetic lineages of E. coli O157:H7 designated I, II and I/II have been identified using octamer-based genome scanning and microarray comparative genomic hybridization (mCGH. Each lineage contains significant phenotypic differences, with lineage I strains being the most commonly associated with human infections. Similarly, a clade of hyper-virulent O157:H7 strains implicated in the 2006 spinach and lettuce outbreaks has been defined using single-nucleotide polymorphism (SNP typing. In this study an in silico comparison of six different genotyping approaches was performed on 19 E. coli genome sequences from 17 O157:H7 strains and single O145:NM and K12 MG1655 strains to provide an overall picture of diversity of the E. coli O157:H7 population, and to compare genotyping methods for O157:H7 strains. Results In silico determination of lineage, Shiga-toxin bacteriophage integration site, comparative genomic fingerprint, mCGH profile, novel region distribution profile, SNP type and multi-locus variable number tandem repeat analysis type was performed and a supernetwork based on the combination of these methods was produced. This supernetwork showed three distinct clusters of strains that were O157:H7 lineage-specific, with the SNP-based hyper-virulent clade 8 synonymous with O157:H7 lineage I/II. Lineage I/II/clade 8 strains clustered closest on the supernetwork to E. coli K12 and E. coli O55:H7, O145:NM and sorbitol-fermenting O157 strains. Conclusion The results of this study highlight the similarities in relationships derived from multi-locus genome sampling methods and suggest a "common genotyping language" may be devised for population genetics and epidemiological studies. Future genotyping

  8. Genome-wide association analyses for meat quality traits in Chinese Erhualian pigs and a Western Duroc × (Landrace × Yorkshire) commercial population.

    Science.gov (United States)

    Liu, Xianxian; Xiong, Xinwei; Yang, Jie; Zhou, Lisheng; Yang, Bin; Ai, Huashui; Ma, Huanban; Xie, Xianhua; Huang, Yixuan; Fang, Shaoming; Xiao, Shijun; Ren, Jun; Ma, Junwu; Huang, Lusheng

    2015-05-12

    Understanding the genetic mechanisms that underlie meat quality traits is essential to improve pork quality. To date, most quantitative trait loci (QTL) analyses have been performed on F2 crosses between outbred pig strains and have led to the identification of numerous QTL. However, because linkage disequilibrium is high in such crosses, QTL mapping precision is unsatisfactory and only a few QTL have been found to segregate within outbred strains, which limits their use to improve animal performance. To detect QTL in outbred pig populations of Chinese and Western origins, we performed genome-wide association studies (GWAS) for meat quality traits in Chinese purebred Erhualian pigs and a Western Duroc × (Landrace × Yorkshire) (DLY) commercial population. Three hundred and thirty six Chinese Erhualian and 610 DLY pigs were genotyped using the Illumina PorcineSNP60K Beadchip and evaluated for 20 meat quality traits. After quality control, 35 985 and 56 216 single nucleotide polymorphisms (SNPs) were available for the Chinese Erhualian and DLY datasets, respectively, and were used to perform two separate GWAS. We also performed a meta-analysis that combined P-values and effects of 29 516 SNPs that were common to Erhualian, DLY, F2 and Sutai pig populations. We detected 28 and nine suggestive SNPs that surpassed the significance level for meat quality in Erhualian and DLY pigs, respectively. Among these SNPs, ss131261254 on pig chromosome 4 (SSC4) was the most significant (P = 7.97E-09) and was associated with drip loss in Erhualian pigs. Our results suggested that at least two QTL on SSC12 and on SSC15 may have pleiotropic effects on several related traits. All the QTL that were detected by GWAS were population-specific, including 12 novel regions. However, the meta-analysis revealed seven novel QTL for meat characteristics, which suggests the existence of common underlying variants that may differ in frequency across populations. These QTL regions contain several

  9. Genome-wide association study of sporadic brain arteriovenous malformations.

    Science.gov (United States)

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

    2016-09-01

    The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with pJAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

    Science.gov (United States)

    Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

    2016-01-01

    Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

  11. Not all risks are created equal: A twin study and meta-analyses of risk taking across seven domains.

    Science.gov (United States)

    Wang, X T Xiao-Tian; Zheng, Rui; Xuan, Yan-Hua; Chen, Jie; Li, Shu

    2016-11-01

    Humans routinely deal with both traditional and novel risks. Different kinds of risks have been a driving force for both evolutionary adaptations and personal development. This study explored the genetic and environmental influences on human risk taking in different task domains. Our approach was threefold. First, we integrated several scales of domain-specific risk-taking propensity and developed a synthetic scale, including both evolutionarily typical and modern risks in the following 7 domains: cooperation/competition, safety, reproduction, natural/physical risk, moral risk, financial risk, and gambling. Second, we conducted a twin study using the scale to estimate the contributions of genes and environment to risk taking in each of these 7 domains. Third, we conducted a series of meta-analyses of extant twin studies across the 7 risk domains. The results showed that individual differences in risk-taking propensity and its consistency across domains were mainly regulated by additive genetic influences and individually unique environmental experiences. The heritability estimates from the meta-analyses ranged from 29% in financial risk taking to 55% in safety. Supporting the notion of risk-domain specificity, both the behavioral and genetic correlations among the 7 domains were generally low. Among the relatively few correlations between pairs of risk domains, our analysis revealed a common genetic factor that regulates moral, financial, and natural/physical risk taking. This is the first effort to separate genetic and environmental influences on risk taking across multiple domains in a single study and integrate the findings of extant twin studies via a series of meta-analyses conducted in different task domains. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study.

    Science.gov (United States)

    Montano, Carolina; Taub, Margaret A; Jaffe, Andrew; Briem, Eirikur; Feinberg, Jason I; Trygvadottir, Rakel; Idrizi, Adrian; Runarsson, Arni; Berndsen, Birna; Gur, Ruben C; Moore, Tyler M; Perry, Rodney T; Fugman, Doug; Sabunciyan, Sarven; Yolken, Robert H; Hyde, Thomas M; Kleinman, Joel E; Sobell, Janet L; Pato, Carlos N; Pato, Michele T; Go, Rodney C; Nimgaonkar, Vishwajit; Weinberger, Daniel R; Braff, David; Gur, Raquel E; Fallin, Margaret Daniele; Feinberg, Andrew P

    2016-05-01

    DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. To scan genome-wide DNA methylation data to identify differentially methylated CpGs between SZ cases and controls. Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort. Identification of differentially methylated positions across the genome in SZ cases compared with controls. Of the 689 case participants in the discovery set, 477 (69%) were men and 258 (37%) were non-African American; of the 645 controls, 273 (42%) were men and 419 (65%) were non-African American. In our replication set, cases/controls were 76% male and 100% non-African American. We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate, <0.2). Of these, 625 showed changes in the same direction including 172 with P < .05 in the replication set. Some replicated differentially methylated positions are located in a top-ranked SZ region from genome-wide association study analyses. This analysis identified 172 replicated new associations with SZ after careful correction for cell type heterogeneity and other potential confounders. The overlap with previous genome

  13. Molecular analyses reveal an abundant diversity of ticks and rickettsial agents associated with wild birds in two regions of primary Brazilian Atlantic Rainforest.

    Science.gov (United States)

    Luz, Hermes Ribeiro; Faccini, João Luiz Horacio; McIntosh, Douglas

    2017-06-01

    Brazilian wild birds are recognized as frequent and important hosts for immature stages of more than half of the 32 recognized species of Amblyomma ticks recorded in that country. Several species of Amblyomma harbor rickettsial agents, including members of the spotted fever group (SFG). Most studies on this topic relied primarily on morphological characterization and reported large portions of the collected ticks at the genus rather than species level. Clearly, this factor may have contributed to an underestimation of tick diversity and distribution and makes comparisons between studies difficult. The current investigation combined morphological and molecular analyses to assess the diversity of ticks and rickettsial agents associated with wild birds, captured in two regions of native Atlantic rainforest, in the state of Rio de Janeiro, Brazil. A total of 910 birds were captured, representing two orders, 34 families and 106 species, among which 93 specimens (10.2%), were parasitized by 138 immature ticks (60 larvae and 78 nymphs), representing 10 recognized species of the genus Amblyomma; together with two reasonably well classified haplotypes (Amblyomma sp. haplotype Nazaré and Amblyomma sp. strain USNTC 6792). Amplification by PCR and sequencing of rickettsial genes (htrA, gltA, ompA and ompB), demonstrated the presence of Rickettsia DNA in 48 (34%) of the ticks. Specifically, Rickettsia bellii was detected in a single larva and a single nymph of A. aureolatum; R. amblyomatis was found in 16 of 37 A. longirostre and was recorded for the first time in three nymphs of A. calcaratum; R. rhipicephali was detected in 9 (47%) of 19 Amblyomma sp. haplotype Nazaré ticks. The remaining ticks were infected with genetic variants of R. parkeri, namely strain ApPR in 12 A. parkeri and seven Amblyomma sp. haplotype Nazaré ticks, with the strain NOD found in two specimens of A. nodosum. Interestingly, a single larvae of A. ovale was shown to be infected with the emerging

  14. MEDLINE, EMBASE, and Cochrane index most primary studies but not abstracts included in orthopedic meta-analyses.

    Science.gov (United States)

    Slobogean, Gerard P; Verma, Ashim; Giustini, Dean; Slobogean, Bronwyn L; Mulpuri, Kishore

    2009-12-01

    To test the hypothesis that all primary studies used in orthopedic meta-analyses are indexed in MEDLINE or EMBASE. Using MEDLINE from 1995 to 2005, we retrieved all published meta-analyses of orthopedic surgical interventions. The primary studies in each meta-analysis were defined as the "gold standard" set. MEDLINE and EMBASE were searched for each primary study, and a recall rate was calculated. Secondary searches were performed using Web of Science (WoS), the Cochrane databases, and CINAHL. High recall rates were achieved searching MEDLINE (90%) and EMBASE (81%) for the gold standard set, and the combined search retrieved 91%. Titles not indexed by MEDLINE or EMBASE included 45 abstracts, eight journal articles, and three unpublished studies. Searching the Cochrane databases yielded 36 titles not in MEDLINE or EMBASE. Using all three databases produced 97% recall of the primary studies; WoS and CINAHL did not increase the recall rate. These results suggest that a very high percentage of primary research in orthopedics can be found using the major databases. Additional database searches are unlikely to increase the yield of published manuscripts; however, conference proceedings and journal supplements should still be searched to ensure that relevant remaining reports are identified.

  15. Reduction and technical simplification of testing protocol for walking based on repeatability analyses: An Interreg IVa pilot study

    Directory of Open Access Journals (Sweden)

    Nejc Sarabon

    2010-12-01

    Full Text Available The aim of this study was to define the most appropriate gait measurement protocols to be used in our future studies in the Mobility in Ageing project. A group of young healthy volunteers took part in the study. Each subject carried out a 10-metre walking test at five different speeds (preferred, very slow, very fast, slow, and fast. Each walking speed was repeated three times, making a total of 15 trials which were carried out in a random order. Each trial was simultaneously analysed by three observers using three different technical approaches: a stop watch, photo cells and electronic kinematic dress. In analysing the repeatability of the trials, the results showed that of the five self-selected walking speeds, three of them (preferred, very fast, and very slow had a significantly higher repeatability of the average walking velocity, step length and cadence than the other two speeds. Additionally, the data showed that one of the three technical methods for gait assessment has better metric characteristics than the other two. In conclusion, based on repeatability, technical and organizational simplification, this study helped us to successfully define a simple and reliable walking test to be used in the main study of the project.

  16. Data on gender and subgroup specific analyses of omega-3 fatty acids in the Ludwigshafen Risk and Cardiovascular Health Study.

    Science.gov (United States)

    Kleber, Marcus E; Delgado, Graciela E; Lorkowski, Stefan; März, Winfried; von Schacky, Clemens

    2016-09-01

    This paper contains additional data related to the research article "Omega-3 fatty acids and mortality in patients referred for coronary angiography - The Ludwigshafen Risk and Cardiovascular Health Study" (Kleber et al., in press) [1]. The data shows characteristics of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study according to tertiles of omega-3 fatty acids as well as stratified by gender. The association of proportions of omega-3 fatty acids measured in erythrocyte membranes with different causes of death is investigated with a special focus on modeling the association of EPA with mortality in a nonlinear way. Further, the association of omega-3 fatty acids with all-cause mortality adjusted for high-sensitive C-reactive protein as a marker of systemic inflammation is examined as well as the association of EPA with cause-specific dea