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Sample records for association study analyses

  1. The Quality of Meta-Analyses of Genetic Association Studies: A Review With Recommendations

    OpenAIRE

    Minelli, Cosetta; John R. Thompson; Abrams, Keith R; Thakkinstian, Ammarin; Attia, John

    2009-01-01

    Although there has been a rapid rise in the publication of meta-analyses of genetic association studies, little is known about their methodological quality. The authors reviewed the quality of 120 randomly selected genetic meta-analyses published between 2005 and 2007. Data extracted included issues of general relevance and other issues specific to genetic epidemiology. Quality was markedly poorer in the 26% of the meta-analyses that accompanied a report on a primary study. Such meta-analyses...

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

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and it

  3. Systematic meta-analyses of gene-specific genetic association studies in prostate cancer

    Science.gov (United States)

    Hao, Qiang; Wei, Dong; Zhang, Yaoguang; Chen, Xin; Yang, Fan; Yang, Ze; Zhu, Xiaoquan; Wang, Jianye

    2016-01-01

    In the past twenty-five years, over 700 case-control association studies on the risk of prostate cancer have been published worldwide, but their results were largely inconsistent. To facilitate following and explaining these findings, we performed a systematic meta-analysis using allelic contrasts for gene-specific SNVs from at least three independent population-based case-control studies, which were published in the field of prostate cancer between August 1, 1990 and August 1, 2015. Across 66 meta-analyses, a total of 20 genetic variants involving 584,100 subjects in 19 different genes (KLK3, IGFBP3, ESR1, SOD2, CAT, CYP1B1, VDR, RFX6, HNF1B, SRD5A2, FGFR4, LEP, HOXB13, FAS, FOXP4, SLC22A3, LMTK2, EHBP1 and MSMB) exhibited significant association with prostate cancer. The average summary OR was 1.33 (ranging from: 1.016–3.788) for risk alleles and 0.838 (ranging from: 0.757–0.896) for protective alleles. Of these positive variants, FOXP4 rs1983891, LMTK2 rs6465657 and RFX6 rs339331 had not been previously meta-analyzed. Further analyses with sufficient power design and investigations of the potential biological roles of these genetic variants in prostate cancer should be conducted. PMID:26967244

  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. PMID:27209127

  5. Integrated analyses of gene expression and genetic association studies in a founder population

    Science.gov (United States)

    Cusanovich, Darren A.; Caliskan, Minal; Billstrand, Christine; Michelini, Katelyn; Chavarria, Claudia; De Leon, Sherryl; Mitrano, Amy; Lewellyn, Noah; Elias, Jack A.; Chupp, Geoffrey L.; Lang, Roberto M.; Shah, Sanjiv J.; Decara, Jeanne M.; Gilad, Yoav; Ober, Carole

    2016-01-01

    Genome-wide association studies (GWASs) have become a standard tool for dissecting genetic contributions to disease risk. However, these studies typically require extraordinarily large sample sizes to be adequately powered. Strategies that incorporate functional information alongside genetic associations have proved successful in increasing GWAS power. Following this paradigm, we present the results of 20 different genetic association studies for quantitative traits related to complex diseases, conducted in the Hutterites of South Dakota. To boost the power of these association studies, we collected RNA-sequencing data from lymphoblastoid cell lines for 431 Hutterite individuals. We then used Sherlock, a tool that integrates GWAS and expression quantitative trait locus (eQTL) data, to identify weak GWAS signals that are also supported by eQTL data. Using this approach, we found novel associations with quantitative phenotypes related to cardiovascular disease, including carotid intima-media thickness, left atrial volume index, monocyte count and serum YKL-40 levels. PMID:26931462

  6. 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 ...

  7. 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

    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 ove

  8. 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

  9. Systematic review with meta-analyses of studies on the association between cirrhosis and liver metastases

    DEFF Research Database (Denmark)

    Dahl, Emilie; Rumessen, Jüri; Gluud, Lise L

    2011-01-01

    effects models due to an expected clinical heterogeneity. Sixteen studies were included. Evidence of liver metastases was diagnosed in 22% of cases and 38% of controls based on autopsies (n = 14 studies) or laparoscopy (n = 2 studies). Random effects meta-analysis suggested that patients with cirrhosis...... (Medline, Embase, and Web of Science) and manual searches were combined (October 2010) to identify observational studies on patients with malignant disease reporting the risk of liver metastases among cases (with cirrhosis) and controls (without liver disease). Meta-analysis was performed using random...

  10. Gastric inhibitory polypeptide receptor: association analyses for obesity of several polymorphisms in large study groups

    Directory of Open Access Journals (Sweden)

    Rief Winfried

    2009-03-01

    Full Text Available Abstract Background Gastric inhibitory polypeptide (GIP is postulated to be involved in type 2 diabetes mellitus and obesity. It exerts its function through its receptor, GIPR. We genotyped three GIPR SNPs (rs8111428, rs2302382 and rs1800437 in German families with at least one obese index patient, two case-control studies and two cross-sectional population-based studies. Methods Genotyping was performed by MALDI-TOF, ARMS-PCR and RFLP. The family-study: 761 German families with at least one extremely obese child or adolescent (n = 1,041 and both parents (n = 1,522. Case-control study: (a German obese children (n = 333 and (b obese adults (n = 987 in comparison to 588 adult lean controls. The two cross-sectional population-based studies: KORA (n = 8,269 and SHIP (n = 4,310. Results We detected over-transmission of the A-allele of rs2302382 in the German families (pTDT-Test = 0.0089. In the combined case-control sample, we estimated an odd ratio of 1.54 (95%CI 1.09;2.19, pCA-Test = 0.014 for homozygotes of the rs2302382 A-allele compared to individuals with no A-allele. A similar trend was found in KORA where the rs2302382 A-allele led to an increase of 0.12 BMI units (p = 0.136. In SHIP, however, the A-allele of rs2302382 was estimated to contribute an average decrease of 0.27 BMI units (p-value = 0.031. Conclusion Our data suggest a potential relevance of GIPR variants for obesity. However, additional studies are warranted in light of the conflicting results obtained in one of the two population-based studies.

  11. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  12. Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses.

    Science.gov (United States)

    Mattis, Daiva M; Chervin, Adam S; Ranoa, Diana R; Kelley, Stacy L; Tapping, Richard I; Kranz, David M

    2015-12-01

    Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: (1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, (2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, (3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and (4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein. PMID:26320630

  13. Dynamic Associations of Change in Physical Activity and Change in Cognitive Function: Coordinated Analyses of Four Longitudinal Studies

    Directory of Open Access Journals (Sweden)

    Magnus Lindwall

    2012-01-01

    Full Text Available The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person and time-varying (within-person predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency.

  14. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

    Science.gov (United States)

    Tang, Wenbo; Kowgier, Matthew; Loth, Daan W.; Soler Artigas, María; Joubert, Bonnie R.; Hodge, Emily; Gharib, Sina A.; Smith, Albert V.; Ruczinski, Ingo; Gudnason, Vilmundur; Mathias, Rasika A.; Harris, Tamara B.; Hansel, Nadia N.; Launer, Lenore J.; Barnes, Kathleen C.; Hansen, Joyanna G.; Albrecht, Eva; Aldrich, Melinda C.; Allerhand, Michael; Barr, R. Graham; Brusselle, Guy G.; Couper, David J.; Curjuric, Ivan; Davies, Gail; Deary, Ian J.; Dupuis, Josée; Fall, Tove; Foy, Millennia; Franceschini, Nora; Gao, Wei; Gläser, Sven; Gu, Xiangjun; Hancock, Dana B.; Heinrich, Joachim; Hofman, Albert; Imboden, Medea; Ingelsson, Erik; James, Alan; Karrasch, Stefan; Koch, Beate; Kritchevsky, Stephen B.; Kumar, Ashish; Lahousse, Lies; Li, Guo; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Lohman, Kurt; Lumley, Thomas; McArdle, Wendy L.; Meibohm, Bernd; Morris, Andrew P.; Morrison, Alanna C.; Musk, Bill; North, Kari E.; Palmer, Lyle J.; Probst-Hensch, Nicole M.; Psaty, Bruce M.; Rivadeneira, Fernando; Rotter, Jerome I.; Schulz, Holger; Smith, Lewis J.; Sood, Akshay; Starr, John M.; Strachan, David P.; Teumer, Alexander; Uitterlinden, André G.; Völzke, Henry; Voorman, Arend; Wain, Louise V.; Wells, Martin T.; Wilk, Jemma B.; Williams, O. Dale; Heckbert, Susan R.; Stricker, Bruno H.; London, Stephanie J.; Fornage, Myriam; Tobin, Martin D.; O′Connor, George T.; Hall, Ian P.; Cassano, Patricia A.

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24983941

  15. 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.

  16. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    Science.gov (United States)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

    2010-10-01

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  17. 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 diagno

  18. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali;

    2016-01-01

    UNLABELLED: 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...

  19. Comprehensive Review of Genetic Association Studies and Meta-Analyses on miRNA Polymorphisms and Cancer Risk

    OpenAIRE

    Srivastava, Kshitij; Srivastava, Anvesha

    2012-01-01

    Background 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-s...

  20. Analysing uncertainties associated with flood hazard assessment

    Science.gov (United States)

    Neuhold, Clemens; Stanzel, Philipp; Nachtnebel, Hans-Peter

    2010-05-01

    Risk zonation maps are mostly derived from design floods which propagate through the study area. The respective delineation of inundated flood plains is a fundamental input for the flood risk assessment of exposed objects. It is implicitly assumed that the river morphology will not vary, even though it is obvious that the river bed elevation can quickly and drastically change during flood events. The objectives of this study were (1) to integrate river bed dynamics into flood risk assessment and (2) to quantify uncertainties associated to flood hazard modelling by means of (i) hydrology (input hydrographs) (ii) sediment transport (torrential input, river bed elevation) (iii) hydrodynamics (water surface levels) The proposed concept was applied to the River Ill in the Western Austrian Alps. In total, 138 flood and associated sediment transport scenarios were considered, simulated and illustrated for the main river stem. The calculated morphological changes of the river bed during peak flow provided a basis to estimate the variability of possible water surface levels and inundated areas, necessary for flood hazard assessment. The applied multi-scenario approach was compared to the normatively defined design flood event to account for the uncertainty of flood risk management decisions based on a few scenarios. Due to the incorporation of river morphological changes and variations in rainfall characteristics into flood hazard assessment, for 12 % of considered cross sections inundations were calculated where safety was expected.

  1. 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

  2. Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease.

    Science.gov (United States)

    Wüst, Richard; Maurer, Brigitte; Hauser, Kathrin; Woitalla, Dirk; Sharma, Manu; Krüger, Rejko

    2016-03-01

    Presenilin-associated rhomboid-like (PARL), a serine protease located in the inner mitochondrial membrane, has been shown to genetically interact and process PTEN-induced putative kinase a protein known for its critical role in mitochondrial homeostasis and early-onset forms of Parkinson's disease (PD). The identification of a PD-associated variant in the PARL gene (p.Ser77Asn) led us to assess the relevance of PARL for PD pathogenesis using a mutation screening of the coding sequences and adjacent intronic sequences. We investigated 3 single nucleotide polymorphisms (rs3792589, rs13091, and rs3732581), a synonymous base substitution (Leu79Leu) and the previously described p.Ser77Asn mutation, which were subsequently screened in more than 2000 patients and controls. Not detecting the p.Ser77Asn mutation in our cohort, nor a robust association between variations in the PARL gene and PD, the role of disease causing genetic variants in the PARL gene could not be further substantiated in our samples. Our findings indicate that PARL mutations are a rare cause of PD and genetic variants are neither strong nor common risk factors in PD. PMID:26778534

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

    Directory of Open Access Journals (Sweden)

    Stirbu Irina

    2009-03-01

    Full Text Available Abstract 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

  4. 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).

  5. 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

  6. On study design in neuroimaging heritability analyses

    Science.gov (United States)

    Koran, Mary Ellen; Li, Bo; Jahanshad, Neda; Thornton-Wells, Tricia A.; Glahn, David C.; Thompson, Paul M.; Blangero, John; Nichols, Thomas E.; Kochunov, Peter; Landman, Bennett A.

    2014-03-01

    Imaging genetics is an emerging methodology that combines genetic information with imaging-derived metrics to understand how genetic factors impact observable structural, functional, and quantitative phenotypes. Many of the most well-known genetic studies are based on Genome-Wide Association Studies (GWAS), which use large populations of related or unrelated individuals to associate traits and disorders with individual genetic factors. Merging imaging and genetics may potentially lead to improved power of association in GWAS because imaging traits may be more sensitive phenotypes, being closer to underlying genetic mechanisms, and their quantitative nature inherently increases power. We are developing SOLAR-ECLIPSE (SE) imaging genetics software which is capable of performing genetic analyses with both large-scale quantitative trait data and family structures of variable complexity. This program can estimate the contribution of genetic commonality among related subjects to a given phenotype, and essentially answer the question of whether or not the phenotype is heritable. This central factor of interest, heritability, offers bounds on the direct genetic influence over observed phenotypes. In order for a trait to be a good phenotype for GWAS, it must be heritable: at least some proportion of its variance must be due to genetic influences. A variety of family structures are commonly used for estimating heritability, yet the variability and biases for each as a function of the sample size are unknown. Herein, we investigate the ability of SOLAR to accurately estimate heritability models based on imaging data simulated using Monte Carlo methods implemented in R. We characterize the bias and the variability of heritability estimates from SOLAR as a function of sample size and pedigree structure (including twins, nuclear families, and nuclear families with grandparents).

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

    Directory of Open Access Journals (Sweden)

    David A Hanauer

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  8. Clinical analyses of perinuclear antineutrophil cytoplasmic antibody associated hypertrophic pachymeningitis

    Institute of Scientific and Technical Information of China (English)

    赵鹏

    2013-01-01

    Objective To explore the clinical characteristics,diagnosis,treatment and prognosis of perinuclear antineutrophil cytoplasmic antibody(p-ANCA)associated hypertrophic pachymeningitis.Methods A retrospective study

  9. Genome wide association and linkage analyses identified three loci -- 4q25, 17q23.2 and 10q11.21 -- associated with variation in leukocyte telomere length: The Long Life Family Study

    Directory of Open Access Journals (Sweden)

    Joseph H Lee

    2014-01-01

    Full Text Available Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near PAPSS1 and DKK2 on 4q25 (p=4.7E-8. From our linkage analysis, we identified two additional loci with HLOD scores exceeding three, including 4.77 for 17q23.2 and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including DCAF7, POLG2, CEP95, and SMURF2 at 17q23.2; and RASGEF1A, HNRNPF, ANF487, CSTF2T, and PRKG1 at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in CEP95 and SMURF2. We also show that three previously reported genes – TERC, MYNN, and OBFC1 – were significantly associated with leukocyte telomere length at pempirical smaller than 0.05.

  10. Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study

    DEFF Research Database (Denmark)

    Lee, J. H.; Cheng, R.; Honig, L. S.;

    2014-01-01

    Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait......, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may...... contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near PAPSS1 and DKK2 on 4q25 (p = 4.7E-8). From our linkage analysis, we identified two...

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

    NARCIS (Netherlands)

    Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth J F; Wolffenbuttel, Bruce

    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

  12. 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) Q...

  13. Associations Between Funding Source and Results of Cost Effectiveness Analyses of Drugs Used in Breast Cancer

    OpenAIRE

    Lane, Jordan D.

    2015-01-01

    Background: Cost effectiveness studies are increasingly included in the regulatory decisions of many countries and in formulary decisions in the United States. Pharmaceutical company sponsorship of economic analyses of oncology drugs previously has been associated with reduced likelihood of reporting unfavorable results. Demonstrating persistence of this relationship may help enable better interpretation of study results and development of strategies to address potential bias. Methods: ...

  14. 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

  15. 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 publ

  16. Therapy-associated late effects after irradiation of malignant diseases in childhood and adolescence. Feasibility analyses of a prospective multicenter register study; Behandlungsassoziierte Spaetfolgen nach Strahlentherapie maligner Erkrankungen im Kindes- und Jugendalter. Machbarkeitsanalyse einer prospektiven multizentrischen Registerstudie

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, T.; Schuck, A.; Hesselmann, S.; Willich, N. [Klinik fuer Strahlentherapie, Universitaetsklinikum Muenster (Germany); Ruebe, C.; Speiser-Held, I. [Klinik fuer Strahlentherapie, Universitaetsklinikum Homburg/Saar (Germany); Pape, H. [Klinik fuer Strahlentherapie, Universitaetsklinikum Duesseldorf (Germany); Dieckmann, K. [Klinik fuer Strahlentherapie, Universitaetsklinikum Wien (Austria); Poellinger, B. [Klinik fuer Strahlentherapie, Universitaetsklinikum Muenchen (Germany); Kortmann, R.D. [Klinik fuer Strahlentherapie, Universitaetsklinikum Leipzig (Germany); Meyer, F.M. [Klinik fuer Strahlentherapie, Klinikum Augsburg (Germany); Martini, C. [Klinik fuer Strahlentherapie, Universitaetsklinikum Freiburg (Germany); Asadpour, B. [Klinik fuer Strahlentherapie, Universitaetsklinikum Aachen (Germany); Timmermann, B. [Paul-Scherrer-Inst. Villigen (Switzerland); Beck, J.D.; Langer, T.; Paulides, M. [Abt. fuer Paediatrische Onkologie, LESS-Zentrum, Universitaetskinderklinik Erlangen (Germany); Schmidt, B. [Klinik fuer Strahlentherapie, Katharinenhospital Stuttgart (Germany)

    2006-08-15

    Background and purpose: Radiogenic late effects in children and adolescents have been evaluated retrospectively in most analyses, with small patient numbers. The German Group of Pediatric Radiation Oncology (APRO) has generated a concept for a prospective evaluation of radiation-associated late effects in childhood. The aim of this study was to evaluate the feasibility of a nationwide central database for the documentation of radiation parameters and side effects of all children treated within therapy protocols of the German Society of Pediatric Oncology and Hematology (GPOH). Material and methods: A study center has been implemented in Muenster, the documentation has started in July 2001 in few centers in a pilot phase. Since February 2004 the documentation is done countrywide. Detailed documentation forms have been designed for treatment parameters and for doses applied at organs at risk. Furthermore, a uniform toxicity documentation, according to the RTOG/EORTC criteria, was chosen. Patients were reported from the study centers of the GPOH to the study center. All information was collected and analyzed in the study center. Results: Till July 31, 2205, 438 documentations of radiation and 579 toxicity documentations of side effects have been collected in the study center. 46 centers for radiotherapy in Germany and one center each in Austria and in Switzerland took part in the documentation. The quality of documentation regarding completeness and plausibility fulfilled the expected criteria in most cases. This feasibility analysis showed that important information about organ dose levels and side effects was documented in a large number of patients (Figures 1 and 2). Conclusion: This prospective evaluation of radiotherapy and radiogenic side effects in children and adolescents will allow correlating doses at organs at risk and the incidence of acute and late sequelae in Germany. Further documentations and a longer follow-up are necessary to obtain powerful results

  17. Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.

    Science.gov (United States)

    Agrawal, Arpana; Edenberg, Howard J; Gelernter, Joel

    2016-09-01

    Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium. PMID:27588522

  18. Haematuria analysed--a prospective study.

    OpenAIRE

    Gillatt, D A; O'Reilly, P H

    1987-01-01

    One hundred consecutive cases of haematuria were studied prospectively. The results showed a high proportion (52%) of serious urological disease. The need for thorough investigation of even minor degrees of haematuria is again emphasized.

  19. GEMBASSY: an EMBOSS associated software package for comprehensive genome analyses

    OpenAIRE

    Itaya, Hidetoshi; Oshita, Kazuki; Arakawa, Kazuharu; Tomita, Masaru

    2013-01-01

    The popular European Molecular Biology Open Software Suite (EMBOSS) currently contains over 400 tools used in various bioinformatics researches, equipped with sophisticated development frameworks for interoperability and tool discoverability as well as rich documentations and various user interfaces. In order to further strengthen EMBOSS in the fields of genomics, we here present a novel EMBOSS associated software (EMBASSY) package named GEMBASSY, which adds more than 50 analysis tools from t...

  20. 遗传关联研究Meta分析中文文献方法学质量评价%Methodological quality of Meta-analyses regarding studies related to genetic association on papers published in Chinese journals

    Institute of Scientific and Technical Information of China (English)

    李帅; 方凯; 孙傲伊; 孙可欣; 胡永华

    2013-01-01

    目的 评价遗传关联研究Meta分析中文文献的方法学质量.方法 检索中国生物医学数据库、中国期刊全文数据库(CNKI)、万方数据资源系统和维普中国科技期刊全文数据库2012年12月前的遗传关联研究Meta分析文章.2名研究者独立按纳入排除标准进行文献筛选,意见不一致时咨询第三位研究者.运用系统综述评价工具(AMSTAR)量表对入选文献的方法学质量进行评价.结果 共纳入440篇文献.方法学质量得分平均为5.77分(满分11分).没有文章符合AMSTAR量表全部11项条目的要求.人选文章中,89.5%有前期设计方案,38.6%在纳入文献和信息提取方面有可重复性,72.7%实施了广泛文献检索,14.8%考虑了文献发表状态,10.9%提供了纳入和排除文献清单,92.5%描述了纳入文献特征,32.0%评估了文献质量,50.0%将文献质量用于结论推导,93.2%合并文献结果方法恰当,82.3%评估了发表偏倚,0.5%声明利益冲突.结论 遗传关联研究Meta分析中文文章方法学质量中等,在文献的筛选和信息提取、考虑文献的发表情况、提供纳入和排除文献清单、对文献进行质量评估、声明利益冲突等方面需要提高.%Objective To assess the methodological quality of Meta-analyses on papers published in Chinese journals regarding studies on genetic association.Methods Meta-analyses of genetic association study published in Chinese journals up to December 2012 had been searched through on 4 Chinese electronic databases (China biomedicine database,CNKI,Wanfang database and VIP Information).Articles independently selected by both two researchers under definite inclusion and exclusion criteria were included in this study (with consultation on a third researcher if inconsistent opinions existed).A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR) checklist was used to evaluate the methodological quality together with the

  1. Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer's Disease: Insights from Meta-Analyses.

    Science.gov (United States)

    Shen, Liang; Ji, Hong-Fang

    2015-01-01

    The associations between homocysteine (Hcy), folic acid, and vitamin B12 and Alzheimer's disease (AD) have gained much interest, while remaining controversial. We aim to perform meta-analyses to evaluate comprehensively: i) Hcy, folic acid, and vitamin B12 levels in AD patients in comparison with controls; and ii) the association between Hcy, folic acid, and vitamin B12 levels and risk of AD. A literature search was performed using Medline and Scopus databases. A total of 68 studies were identified and included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analyses. First, AD patients may have higher level of Hcy, and lower levels of folate and vitamin B12 in plasma than controls. Further age-subgroup analysis showed no age effect for Hcy levels in plasma between AD patients and matched controls, while the differences in folate and vitamin B12 levels further enlarged with increased age. Second, data suggests that high Hcy and low folate levels may correlate with increased risk of AD occurrence. The comprehensive meta-analyses not only confirmed higher Hcy, lower folic acid, and vitamin B12 levels in AD patients than controls, but also implicated that high Hcy and low folic acid levels may be risk factors of AD. Further studies are encouraged to elucidate mechanisms linking these conditions. PMID:25854931

  2. 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...... 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...

  3. 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.

  4. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  5. 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...

  6. 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......, IRX5, IRX6 and EYA1). Subsequent pathway analysis with GRAIL and DEPICT provided additional insight into possible genetic mechanisms causing hypospadias....

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

    Science.gov (United States)

    Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth J F

    2014-05-01

    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 at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide 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 size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete. PMID:24762786

  8. 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...

  9. Association analyses of the INSIG2 polymorphism in the obesity and cholesterol levels of Korean populations

    Directory of Open Access Journals (Sweden)

    Shin Hyoung

    2009-09-01

    Full Text Available Abstract Background While INSIG2 has been reported to be associated with BMI in many populations, conflicting results have prevented consensus over its role. In analyses of mice and cell cultures the gene has been found to be involved in the regulation of cholesterol synthesis; however, no relationship has been found with cholesterol metabolism in human epidemiological research. Therefore, this study attempts to assess the effect of rs7566605 near INSIG2 on both obesity- and cholesterol-related traits in Koreans. Methods The rs7566605 polymorphism was genotyped with 2,364 Koreans, and associations with obesity- and cholesterol-related traits were analyzed statistically via an ANOVA or T-test. Results Replication of an association with BMI, WHR, fat mass, fat percent, and abdominal fat area failed, and the C allele of rs7566605 was not associated significantly with total cholesterol, HDL cholesterol, or triglyceride. However, it was found in a meta-analysis of a dominant model that the C allele of rs7566605 appeared to affect the level of the total cholesterol, especially in female subjects. Conclusion We failed to show associations of rs7566605 with cholesterol- and obesity-related phenotypes, although we newly suggest the possible involvement of INSIG2 with the plasma level of the total cholesterol in women.

  10. 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

  11. 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

    2012-01-01

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:23118445

  12. Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

    Directory of Open Access Journals (Sweden)

    Camille Jung

    Full Text Available BACKGROUND & AIMS: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD. However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. METHOD: A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. RESULTS: The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001 and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively. Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51] and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74] and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]. The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively. However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03. CONCLUSIONS: It is not recommended to genotype the studied polymorphisms in routine practice.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    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. Association analyses of 249,796 individuals reveal 18 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; Lango Allen, Hana; 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; Segrè, 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, 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-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

    2010-11-01

    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 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

  17. Comparative study of bridge plate associated to the intramedullary pin and the dynamic compression plate on the experimental osteotomy fixation of femoral in rabbits (Oryctolagus cuniculus). Clinical, radiographic, histological and scintigraphy analyses

    International Nuclear Information System (INIS)

    The objectives were to benchmark and monitor the fracture healing of femoral osteotomy in rabbits after fixation with dynamic compression plate and bridge plate associated with intramedullary pin. Were used 14 New Zealand rabbits, four months old with mean weight of 3.5 pounds, from the Experimental Farm Professor Helio Barbosa of the Veterinary School of Minas Gerais Federal Univ. (UFMG). The animals were randomly divided into two groups (I and II). All rabbits underwent osteotomy across the middle third of right femur. In the group I was made to fix the osteotomy with the bridge plate (BP) associated with intramedullary pin, introduced the technique of minimal invasion. In group II, we used dynamic compression plate (DCP) via the conventional approach. Both groups were evaluated clinical, radiographic, histologic and scintigraphic findings. Clinical assessments were performed weekly until the 12th postoperative week and radiographic examinations were performed before, immediately after, at 15, 30, 45, 60 and 90 days. The bone scintigraphy were performed before and at 20, 50 and 90 days after surgery to monitor the bone metabolism qualitatively and quantitatively. Observed perfusion and bone healing process. After 90 days of study, there was histopathologic evaluation of the osteotomized area and the insertion of screws. In the region of the osteotomy was observed predominance of trabecular bone in group I and group II, the predominance of bone osteons, compatible with the original bone. On insertion of the screws did not differ between groups and there was cortical discontinuity, little necrosis and local hemorrhage. The two types of fixation have led to consolidation within the scheduled period, maturing in early fixation with DCP fixation compared with BP. Scintigraphy demonstrated by the indices of activity and image characteristics, the process of bone healing was significantly greater in animals undergoing early fixation with DCP. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  1. 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...

  2. 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

  3. Budget-Impact Analyses: A Critical Review of Published Studies

    OpenAIRE

    Ewa Orlewska; Laszlo Gulcsi

    2009-01-01

    This article reviews budget-impact analyses (BIAs) published to date in peer-reviewed bio-medical journals with reference to current best practice, and discusses where future research needs to be directed. Published BIAs were identified by conducting a computerized search on PubMed using the search term 'budget impact analysis'. The years covered by the search included January 2000 through November 2008. Only studies (i) named by authors as BIAs and (ii) predicting financial consequences of a...

  4. Monte Carlo parameter studies and uncertainty analyses with MCNP5

    International Nuclear Information System (INIS)

    A software tool called mcnppstudy has been developed to automate the setup, execution, and collection of results from a series of MCNP5 Monte Carlo calculations. This tool provides a convenient means of performing parameter studies, total uncertainty analyses, parallel job execution on clusters, stochastic geometry modeling, and other types of calculations where a series of MCNP5 jobs must be performed with varying problem input specifications. (authors)

  5. 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

    2016-01-01

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:25861698

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

    Science.gov (United States)

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

    2015-01-21

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

  7. 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

  8. Defining best practice for microarray analyses in nutrigenomic studies

    NARCIS (Netherlands)

    Garosi, P.; Filippo, C. de; Erk, M. van; Rocca-Serra, P.; Sansone, S.A.; Elliott, R.

    2005-01-01

    Microarrays represent a powerful tool for studies of diet-gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues ass

  9. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci

    Institute of Scientific and Technical Information of China (English)

    Yong Yong SHI; Lin HE

    2005-01-01

    In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses of linkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large number of samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study with high efficiency. The platform has been well evaluated by several sets of real data.

  10. 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.

  11. Analyses of the role of the glucocorticoid receptor gene polymorphism (rs41423247) as a potential moderator in the association between childhood overweight, psychopathology, and clinical outcomes in Eating Disorders patients: A 6 years follow up study.

    Science.gov (United States)

    Castellini, Giovanni; Lelli, Lorenzo; Tedde, Andrea; Piaceri, Irene; Bagnoli, Silvia; Lucenteforte, Ersilia; Sorbi, Sandro; Monteleone, Alessio Maria; Hudziak, James J; Nacmias, Benedetta; Ricca, Valdo

    2016-09-30

    Childhood overweight and the SNP rs41423247 of the glucocorticoid receptor gene (GR) were reported to represent predisposing factors for Eating Disorders (EDs). The distribution of the polymorphism was evaluated in 202 EDs patients, and in 116 healthy subjects. The Structured Clinical Interview for the DSM-IV and self-reported questionnaires were administered at the admission to the clinic and at 3 time points (end of a cognitive behavioral therapy, 3 and 6 years follow up). G-allele was associated with childhood overweight, depressive disorder comorbidity, and diagnostic instability. G-allele carriers reporting childhood overweight showed greater frequency of subjective binge eating and emotional eating.

  12. Cultural Studies og kritisk diskurs analyse i 8. klasse

    DEFF Research Database (Denmark)

    Svarstad, Lone Krogsgaard

    2015-01-01

    to be multiplicative and dynamic and power is foregrounded. Critical discourse analysis is used as a tool in class to analyse a dispute on Facebook between Miley Cyrus and Sinead O’Connor. Students work with active construction, making connections, social interaction, reflection, responsibility and they do so......The article presents an exploration of a Cultural Studies and Critical Cultural Pedagogy approach to intercultural competence in lower secondary English classes in Denmark. The presentation is based on the second intervention in a participatory action research project in connection with my doctoral...... thesis in the school year 2013-2014.The approach is based on Cultural Studies and knowledge of social categories and representation, and how these can be taught and discussed in class through an intersectional lens. An intersectional lens allows for the conceptualization of categories...

  13. 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 dia...

  14. 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.

  15. Trajectory data analyses for pedestrian space-time activity study.

    Science.gov (United States)

    Qi, Feng; Du, Fei

    2013-01-01

    It is well recognized that human movement in the spatial and temporal dimensions has direct influence on disease transmission(1-3). An infectious disease typically spreads via contact between infected and susceptible individuals in their overlapped activity spaces. Therefore, daily mobility-activity information can be used as an indicator to measure exposures to risk factors of infection. However, a major difficulty and thus the reason for paucity of studies of infectious disease transmission at the micro scale arise from the lack of detailed individual mobility data. Previously in transportation and tourism research detailed space-time activity data often relied on the time-space diary technique, which requires subjects to actively record their activities in time and space. This is highly demanding for the participants and collaboration from the participants greatly affects the quality of data(4). Modern technologies such as GPS and mobile communications have made possible the automatic collection of trajectory data. The data collected, however, is not ideal for modeling human space-time activities, limited by the accuracies of existing devices. There is also no readily available tool for efficient processing of the data for human behavior study. We present here a suite of methods and an integrated ArcGIS desktop-based visual interface for the pre-processing and spatiotemporal analyses of trajectory data. We provide examples of how such processing may be used to model human space-time activities, especially with error-rich pedestrian trajectory data, that could be useful in public health studies such as infectious disease transmission modeling. The procedure presented includes pre-processing, trajectory segmentation, activity space characterization, density estimation and visualization, and a few other exploratory analysis methods. Pre-processing is the cleaning of noisy raw trajectory data. We introduce an interactive visual pre-processing interface as well as an

  16. Trajectory data analyses for pedestrian space-time activity study.

    Science.gov (United States)

    Qi, Feng; Du, Fei

    2013-01-01

    It is well recognized that human movement in the spatial and temporal dimensions has direct influence on disease transmission(1-3). An infectious disease typically spreads via contact between infected and susceptible individuals in their overlapped activity spaces. Therefore, daily mobility-activity information can be used as an indicator to measure exposures to risk factors of infection. However, a major difficulty and thus the reason for paucity of studies of infectious disease transmission at the micro scale arise from the lack of detailed individual mobility data. Previously in transportation and tourism research detailed space-time activity data often relied on the time-space diary technique, which requires subjects to actively record their activities in time and space. This is highly demanding for the participants and collaboration from the participants greatly affects the quality of data(4). Modern technologies such as GPS and mobile communications have made possible the automatic collection of trajectory data. The data collected, however, is not ideal for modeling human space-time activities, limited by the accuracies of existing devices. There is also no readily available tool for efficient processing of the data for human behavior study. We present here a suite of methods and an integrated ArcGIS desktop-based visual interface for the pre-processing and spatiotemporal analyses of trajectory data. We provide examples of how such processing may be used to model human space-time activities, especially with error-rich pedestrian trajectory data, that could be useful in public health studies such as infectious disease transmission modeling. The procedure presented includes pre-processing, trajectory segmentation, activity space characterization, density estimation and visualization, and a few other exploratory analysis methods. Pre-processing is the cleaning of noisy raw trajectory data. We introduce an interactive visual pre-processing interface as well as an

  17. Association of HLA-DQA1 and -DQB1 alleles with type I diabetes in Arabs: a meta-analyses.

    Science.gov (United States)

    Hamzeh, A R; Nair, P; Al-Khaja, N; Al Ali, M T

    2015-07-01

    This study aimed at assessing the nature and significance of associations between various alleles of HLA-DQA1, HLA-DQB1, and type I diabetes (T1D) in Arab populations. Evidence from literature (published before 20 April 2015) was amassed and analysed through multiple meta-analyses, which yielded effect summary odds ratios and 95% confidence intervals for 24 alleles and 4 haplotypes. A total of 1273 cases and 1747 controls from 16 studies were analysed. High levels of significance were obtained to support higher T1D risk when harbouring DQA1*03:01. The alleles DQB1*02:01 and *03:02 and the haplotypes DR3 and DR4 were significant risk factors, albeit with high publication heterogeneity. The protective effects of DQA1*01:01, DQB1*05:03, *06:02, *06:03, and *06:04 were robustly suggested by all indicators of meta-analyses. The haplotypes DR7 and DR11 were strongly suggested to be protective in Arabs. A relatively small number of studies have emerged from Arab countries, mostly with inadequate power on an individual basis. This study fills the gap by providing significant size effect of human leukocyte antigen (HLA) alleles and completes the continuum of global ethnic differences in this context.

  18. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    Directory of Open Access Journals (Sweden)

    Lisette J. A. Kogelman

    2014-07-01

    Full Text Available 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 of haplotype blocks. We built Weighted Interaction SNP Hub (WISH and differentially wired (DW networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g. NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways

  19. The Current Situation and Financial Performance Analyses of Rice Farmers Associations

    Directory of Open Access Journals (Sweden)

    Faruk Adıgüzel

    2015-09-01

    Full Text Available The aim of this study is to determine the current situation and to analyze financial performance of rice farmers associations. The data obtained with the questionnaire method from a single rice farmers association selected as purposeful constitute material of the research. First, a general assessment of the association was conducted, and then, the financial performance of the association was analyzed using Financial Statement Analysis, Percentage Method, Trend Analysis and Ratio Analysis techniques with the aid of financial statement and income chart for the period of 2011-2013. As a result, it is determined association was founded in 2006, have a total of 220 active members and 10 women members in district and 18 villages and two university graduate staff. In addition, management and audit committee members are men, middle-aged, and primary or secondary graduated. The participation rate of members in general assembly is high. The important problems of the association are lack of solidarity among members and irregular payment of membership’s fee. In the period under investigation, decreased use of external resource, strengthening equity and increased profitability in the association were determined. It is possible to develop association as financial statue with positive relationships between association and members and activation of association in terms of marketing.

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

    Science.gov (United States)

    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

    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 (|ρ̂| ≈ 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

  1. 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.

  2. Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse.

    Science.gov (United States)

    Peña-Oliver, Yolanda; Carvalho, Fabiana M; Sanchez-Roige, Sandra; Quinlan, Erin B; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L; Pearl, Frances M G; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia J; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Schumann, Gunter; Stephens, David N

    2016-01-01

    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 behavior 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. Behavioral 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 homologs 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 homologs 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. PMID:27092175

  3. 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.

  4. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers.

    Science.gov (United States)

    Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Naitza, Silvia; Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega Del Vecchyo, Vicente Diego; Chiang, Charleston W K; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-11-01

    We report ∼17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ∼76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  5. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  7. 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.

  8. Whole brain expression of bipolar disorder associated genes: structural and genetic analyses.

    Directory of Open Access Journals (Sweden)

    Michael J McCarthy

    Full Text Available Studies of bipolar disorder (BD suggest a genetic basis of the illness that alters brain function and morphology. In recent years, a number of genetic variants associated with BD have been identified. However, little is known about the associated genes, or brain circuits that rely upon their function. Using an anatomically comprehensive survey of the human transcriptome (The Allen Brain Atlas, we mapped the expression of 58 genes with suspected involvement in BD based upon their relationship to SNPs identified in genome wide association studies (GWAS. We then conducted a meta-analysis of structural MRI studies to identify brain regions that are abnormal in BD. Of 58 BD associated genes, 22 had anatomically distinct expression patterns that could be categorized into one of three clusters (C1-C3. Brain regions with the highest and lowest expression of these genes did not overlap strongly with anatomical sites identified as abnormal by structural MRI except in the parahippocampal gyrus, the inferior/superior temporal gyrus and the cerebellar vermis, regions where overlap was significant. Using the 22 genes in C1-C3 as reference points, additional genes with correlated expression patterns were identified and organized into sets based on similarity. Further analysis revealed that five of these gene sets were significantly associated with BD, suggesting that anatomical expression profile is correlated with genetic susceptibility to BD, particularly for genes in C2. Our data suggest that expression profiles of BD-associated genes do not explain the majority of structural abnormalities observed in BD, but may be useful in identifying new candidate genes. Our results highlight the complex neuroanatomical basis of BD, and reinforce illness models that emphasize impaired brain connectivity.

  9. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

  10. Usage of cathodoluminescence and Raman analyses in shock metamorphic studies

    International Nuclear Information System (INIS)

    The studies of in this dissertation have focused on shock metamorphic and cathodoluminescence (combination with Raman spectroscopy) properties of experimentally and naturally shock-metamorphosed minerals, such as zircon, quartzite, a tektite, and impact glasses. The purpose of these investigations is to further investigate the capability of the Scanning Electron Microscope-Cathodoluminescence (SEM-CL) technique including BSE/CL images and cathodoluminescence spectroscopy and Raman spectroscopy to document shock deformations and to determine whether specific CL or Raman effects in zircon/scheelite-structure, quartz, tektite and impact glasses can be utilised to determine particular shock pressure stages. The CL spectra of unshocked and shocked (20, 38, 40, 60 and 80 GPa) zircon samples are dominated by narrow emission lines and broad bands in the region of visible light and in the near-ultraviolet range. The emission lines result from rare earth element activators and the broad bands might be associated with lattice defects. Raman spectra revealed that the unshocked and 20 GPa samples represent zircon-structure material, whereas the 38, 40, 60, 80 GPa samples yielded additional peaks with relatively high peak intensities, which are indicative of the presence of the scheelite-type high-pressure phase. According to the Raman measurements, the naturally shock-deformed zircons from the Ries impact structure might be related to the low-shock regime (4 groups. According to the Raman spectra, the stretching (symmetric and antisymmetric) vibrational modes are characteristic for quartz in the unshocked and 12 GPa samples. In the 25 and 28 GPa samples, the background fluorescence is higher compared to the other samples. The energy diagrams of the cathodoluminescence emission centers confirm that recombination centers or traps are closely-spaced in the band gap between conduction and valance bands of quartz as a function of the increasing shock pressure causing non

  11. 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.

  12. 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.

  13. 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 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. PMID:27306435

  14. Association analyses identify six new psoriasis susceptibility loci in the Chinese population

    OpenAIRE

    Sun, Liang-Dan; Cheng, Hui; Wang, Zai-Xing; Zhang, An-Ping; Wang, Pei-Guang; Xu, Jin-Hua; Zhu, Qi-Xing; Zhou, Hai-Sheng; Buchert, Eva; Zhang, Fu-Ren; Pu, Xiong-Ming; Yang, Xue-Qin; Zhang, Jian-Zhong; Xu, Ai-E; Wu, Ri-Na

    2010-01-01

    We extended our previous GWAS for psoriasis with a a multistage replication study including 8,312 cases and 12,919 controls from China as well as 3,293 cases, 4,188 controls from Germany and the USA, and 254 nuclear families from the USA. We identified 6 new susceptibility loci associated to psoriasis in Chinese, containing candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8, ZNF816A (PCombined

  15. Association and mutation analyses of 16p11.2 autism candidate genes.

    Directory of Open Access Journals (Sweden)

    Ravinesh A Kumar

    Full Text Available BACKGROUND: Autism is a complex childhood neurodevelopmental disorder with a strong genetic basis. Microdeletion or duplication of a approximately 500-700-kb genomic rearrangement on 16p11.2 that contains 24 genes represents the second most frequent chromosomal disorder associated with autism. The role of common and rare 16p11.2 sequence variants in autism etiology is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To identify common 16p11.2 variants with a potential role in autism, we performed association studies using existing data generated from three microarray platforms: Affymetrix 5.0 (777 families, Illumina 550 K (943 families, and Affymetrix 500 K (60 families. No common variants were identified that were significantly associated with autism. To look for rare variants, we performed resequencing of coding and promoter regions for eight candidate genes selected based on their known expression patterns and functions. In total, we identified 26 novel variants in autism: 13 exonic (nine non-synonymous, three synonymous, and one untranslated region and 13 promoter variants. We found a significant association between autism and a coding variant in the seizure-related gene SEZ6L2 (12/1106 autism vs. 3/1161 controls; p = 0.018. Sez6l2 expression in mouse embryos was restricted to the spinal cord and brain. SEZ6L2 expression in human fetal brain was highest in post-mitotic cortical layers, hippocampus, amygdala, and thalamus. Association analysis of SEZ6L2 in an independent sample set failed to replicate our initial findings. CONCLUSIONS/SIGNIFICANCE: We have identified sequence variation in at least one candidate gene in 16p11.2 that may represent a novel genetic risk factor for autism. However, further studies are required to substantiate these preliminary findings.

  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; Tuke, Marcus A.; Yaghootkar, Hanieh; Hu, Youna; Teder-Laving, Maris; Hayward, Caroline; Roenneberg, Till; Del Greco, Fabiola; Hicks, Andrew A.; Shin, Chol; Metspalu, Andres; Byrne, Enda M.; Gehrman, Philip R.; Tiemeier, Henning; Allebrandt, Karla V.; Murray, Anna; Hinds, David A.

    2016-01-01

    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 (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 circadian

  17. 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. PMID:26428711

  18. 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...

  19. 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

    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...... 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...

  20. Analysing interview data of case study in educational research

    Institute of Scientific and Technical Information of China (English)

    赵艳敏

    2014-01-01

    interviews are an essential source in collecting case study data, because most of case studies are about human affairs. Yin (2003) reported that human affairs should be interpreted through the eyes and body languages of interviewees, and they can provide very important insights into a situation. However, it is also necessary to pay attention to the common biases caused by interview, such as poor recall, inaccurate articulation and time-consuming.

  1. 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

  2. In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations.

    Directory of Open Access Journals (Sweden)

    Anna Gaertner

    Full Text Available BACKGROUND: Although numerous sequence variants in desmoglein-2 (DSG2 have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC, the functional impact of new sequence variations is difficult to estimate. METHODOLOGY/PRINCIPAL FINDINGS: To test the functional consequences of DSG2-variants, we established an expression system for the extracellular domain and the full-length DSG2 using the human cell line HT1080. We established new tools to investigate ARVC-associated DSG2 variations and compared wild-type proteins and proteins with one of the five selected variations (DSG2-p.R46Q, -p.D154E, -p.D187G, -p.K294E, -p.V392I with respect to prodomain cleavage, adhesion properties and cellular localisation. CONCLUSIONS/SIGNIFICANCE: The ARVC-associated DSG2-p.R46Q variation was predicted to be probably damaging by bioinformatics tools and to concern a conserved proprotein convertase cleavage site. In this study an impaired prodomain cleavage and an influence on the DSG2-properties could be demonstrated for the R46Q-variant leading to the classification of the variant as a potential gain-of-function mutant. In contrast, the variants DSG2-p.K294E and -p.V392I, which have an arguable impact on ARVC pathogenesis and are predicted to be benign, did not show functional differences to the wild-type protein in our study. Notably, the variants DSG2-p.D154E and -p.D187G, which were predicted to be damaging by bioinformatics tools, had no detectable effects on the DSG2 protein properties in our study.

  3. In Vitro Functional Analyses of Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmoglein-2-Missense Variations

    Science.gov (United States)

    Gaertner, Anna; Klauke, Baerbel; Stork, Ines; Niehaus, Karsten; Niemann, Gesa; Gummert, Jan; Milting, Hendrik

    2012-01-01

    Background Although numerous sequence variants in desmoglein-2 (DSG2) have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the functional impact of new sequence variations is difficult to estimate. Methodology/Principal Findings To test the functional consequences of DSG2-variants, we established an expression system for the extracellular domain and the full-length DSG2 using the human cell line HT1080. We established new tools to investigate ARVC-associated DSG2 variations and compared wild-type proteins and proteins with one of the five selected variations (DSG2-p.R46Q, -p.D154E, -p.D187G, -p.K294E, -p.V392I) with respect to prodomain cleavage, adhesion properties and cellular localisation. Conclusions/Significance The ARVC-associated DSG2-p.R46Q variation was predicted to be probably damaging by bioinformatics tools and to concern a conserved proprotein convertase cleavage site. In this study an impaired prodomain cleavage and an influence on the DSG2-properties could be demonstrated for the R46Q-variant leading to the classification of the variant as a potential gain-of-function mutant. In contrast, the variants DSG2-p.K294E and -p.V392I, which have an arguable impact on ARVC pathogenesis and are predicted to be benign, did not show functional differences to the wild-type protein in our study. Notably, the variants DSG2-p.D154E and -p.D187G, which were predicted to be damaging by bioinformatics tools, had no detectable effects on the DSG2 protein properties in our study. PMID:23071725

  4. 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. PMID:27166759

  5. Genome-wide association analyses for fatty acid composition in porcine muscle and abdominal fat tissues.

    Directory of Open Access Journals (Sweden)

    Bin Yang

    Full Text Available Fatty acid composition is an important phenotypic trait in pigs as it affects nutritional, technical and sensory quality of pork. Here, we reported a genome-wide association study (GWAS for fatty acid composition in the longissimus muscle and abdominal fat tissues of 591 White Duroc×Erhualian F2 animals and in muscle samples of 282 Chinese Sutai pigs. A total of 46 loci surpassing the suggestive significance level were identified on 15 pig chromosomes (SSC for 12 fatty acids, revealing the complex genetic architecture of fatty acid composition in pigs. Of the 46 loci, 15 on SSC5, 7, 14 and 16 reached the genome-wide significance level. The two most significant SNPs were ss131535508 (P = 2.48×10(-25 at 41.39 Mb on SSC16 for C20∶0 in abdominal fat and ss478935891 (P = 3.29×10(-13 at 121.31 Mb on SSC14 for muscle C18∶0. A meta-analysis of GWAS identified 4 novel loci and enhanced the association strength at 6 loci compared to those evidenced in a single population, suggesting the presence of common underlying variants. The longissimus muscle and abdominal fat showed consistent association profiles at most of the identified loci and distinct association signals at several loci. All loci have specific effects on fatty acid composition, except for two loci on SSC4 and SSC7 affecting multiple fatness traits. Several promising candidate genes were found in the neighboring regions of the lead SNPs at the genome-wide significant loci, such as SCD for C18∶0 and C16∶1 on SSC14 and ELOVL7 for C20∶0 on SSC16. The findings provide insights into the molecular basis of fatty acid composition in pigs, and would benefit the final identification of the underlying mutations.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication - A Systematic Review with Meta-Analyses of Randomised Trials

    DEFF Research Database (Denmark)

    Penninga, Elisabeth I; Graudal, Niels; Ladekarl, Morten Baekbo;

    2016-01-01

    the risk of (S)AEs associated with the use of flumazenil in patients with impaired consciousness due to known or suspected benzodiazepine overdose. Studies included in the meta-analyses were identified by literature search in Medline, Cochrane Library and Embase using combinations of the words flumazenil...

  11. Surface Analyses and Immune Reactivities of Major Cell Wall-Associated Proteins of Group A Streptococcus

    OpenAIRE

    Cole, Jason N; Ramirez, Ruben D.; Currie, Bart J.; Cordwell, Stuart J.; Djordjevic, Steven P.; Mark J Walker

    2005-01-01

    A proteomic analysis was undertaken to identify cell wall-associated proteins of Streptococcus pyogenes. Seventy-four distinct cell wall-associated proteins were identified, 66 of which were novel. Thirty-three proteins were immunoreactive with pooled S. pyogenes-reactive human antisera. Biotinylation of the GAS cell surface identified 23 cell wall-associated proteins that are surface exposed.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  13. 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...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  15. 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.

  16. Neuroinformatic Analyses of Common and Distinct Genetic Components Associated with Major Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Amit eLotan

    2014-11-01

    Full Text Available Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders—attention deficit hyperactivity disorder, anxiety disorders, autistic spectrum disorders, bipolar disorder, major depressive disorder and schizophrenia. We curated a well-vetted list of genes based on large-scale human genetic studies and verified their appearance on the NHGRI catalog of published genome-wide association studies. A total of 180 genes were accepted into the analysis on the basis of low but liberal GWAS p-values (<10-5. 22% of genes overlapped two or more disorders. The most widely shared subset of genes—common to five of six disorders–included ANK3, AS3MT, CACNA1C, CACNB2, CNNM2, CSMD1, DPCR1, ITIH3, NT5C2, PPP1R11, SYNE1, TCF4, TENM4, TRIM26, and ZNRD1. Using a suite of neuroinformatic resources, we showed that many of the shared genes are implicated in the postsynaptic density, expressed in immune tissues and co-expressed in developing human brain.. Using a translational cross-species approach, we detected two distinct genetic components that were both shared by each of the six disorders; the 1st component is involved in CNS development, neural projections and synaptic transmission, while the 2nd is implicated in various cytoplasmic organelles and cellular processes. Combined, these genetic components account for 20–30% of the genetic load. The remaining risk is conferred by distinct, disorder-specific variants. Nevertheless, the convergence of different analytical approaches on similar targets may bear important implications. Thus, although adding mostly confirmatory findings, higher resolution of shared and unique genetic factors provided in this manuscript could ultimately translate into improved diagnosis and treatment of

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

    Science.gov (United States)

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

    2011-01-01

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

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

    OpenAIRE

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue,; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Chun XU; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana

    2010-01-01

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

  19. Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Bansal, Sandeep Kumar; Gupta, Gopal; Rajender, Singh

    2016-01-01

    Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19-2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65-1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28-3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43-4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21-1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95-1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral. PMID:27246180

  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. Differential Expression of Proteins Associated with the Hair Follicle Cycle - Proteomics and Bioinformatics Analyses.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Hair follicle cycling can be divided into the following three stages: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still unknown. To better understand the detailed protein networks controlling this process, proteomics and bioinformatics analyses were performed to construct comparative protein profiles of mouse skin at specific time points (0, 8, and 20 days. Ninety-five differentially expressed protein spots were identified by MALDI-TOF/TOF as 44 proteins, which were found to change during hair follicle cycle transition. Proteomics analysis revealed that these changes in protein expression are involved in Ca2+-regulated biological processes, migration, and regulation of signal transduction, among other processes. Subsequently, three proteins were selected to validate the reliability of expression patterns using western blotting. Cluster analysis revealed three expression patterns, and each pattern correlated with specific cell processes that occur during the hair cycle. Furthermore, bioinformatics analysis indicated that the differentially expressed proteins impacted multiple biological networks, after which detailed functional analyses were performed. Taken together, the above data may provide insight into the three stages of mouse hair follicle morphogenesis and provide a solid basis for potential therapeutic molecular targets for this hair disease.

  2. 3-dimensional slope stability analyses using non-associative stress-strain relationships

    Institute of Scientific and Technical Information of China (English)

    CHEN ZuYu; SUN Ping; WANG YuJie; ZHANG HongTao

    2009-01-01

    The research work presented in this paper refers to a new slope stability analysis method used for landslide risk evaluations. It is an extension of the 3-dimensional upper-bound slope stability analysis method proposed by Chen et sl. in 2001, which employs the Mohr-Coulomb's associative flow rule. It has been found that in a 3-dimensional area, a prism may not be able to move at friction angles to all its surrounding interfaces, as required by this associative rule, and convergence problems may occa-sionally arise. The new method establishes two velocity fields: (i) The plastic one that represents a non-associative and the best representative dilation behavior, and (ii) the virtual one that permits the solution for factor of safety in the work and energy balance equation. The new method can then allow any input value of dilation angle and thus solve the convergence problem. A practical application to a concrete dam foundation is illustrated.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  4. Validation of the automatic image analyser to assess retinal vessel calibre (ALTAIR): a prospective study protocol

    OpenAIRE

    Garcia-Ortiz, Luis; Gómez-Marcos, Manuel A.; Recio-Rodríguez, Jose I; Maderuelo-Fernández, Jose A; Chamoso-Santos, Pablo; Rodríguez-González, Sara; de Paz-Santana, Juan F; Merchan-Cifuentes, Miguel A; Corchado-Rodríguez, Juan M

    2014-01-01

    Introduction The fundus examination is a non-invasive evaluation of the microcirculation of the retina. The aim of the present study is to develop and validate (reliability and validity) the ALTAIR software platform (Automatic image analyser to assess retinal vessel calibre) in order to analyse its utility in different clinical environments. Methods and analysis A cross-sectional study in the first phase and a prospective observational study in the second with 4 years of follow-up. The study ...

  5. Optimised procedure to analyse maillard reaction-associated fluorescence in cereal-based products

    OpenAIRE

    Delgado Andrade, Cristina; Rufián Henares, J. A.; Morales, F. J.

    2008-01-01

    Fluorescent Maillard compounds measurement provides more specific information on the extent of the Maillard reaction than other unspecific tools to monitor the reaction, and is suitable, as the first approach, to assess the nutritional quality of foods as related to protein damage. This work presents an optimised laboratory procedure for the measurement of total fluorescent intermediate compounds (FIC) associated with Maillard reaction, described and evaluated in a cereal-based product. Total...

  6. 3-dimensional slope stability analyses using non-associative stress-strain relationships

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The research work presented in this paper refers to a new slope stability analysis method used for landslide risk evaluations. It is an extension of the 3-dimensional upper-bound slope stability analysis method proposed by Chen et al. in 2001,which employs the Mohr-Coulomb’s associative flow rule. It has been found that in a 3-dimensional area,a prism may not be able to move at friction angles to all its surrounding interfaces,as required by this associative rule,and convergence problems may occasionally arise. The new method establishes two velocity fields:(i) The plastic one that represents a non-associative and the best representative dilation behavior,and (ii) the virtual one that permits the solution for factor of safety in the work and energy balance equation. The new method can then allow any input value of dilation angle and thus solve the convergence problem. A practical application to a concrete dam foundation is illustrated.

  7. Refining analyses of copy number variation identifies specific genes associated with developmental delay.

    Science.gov (United States)

    Coe, Bradley P; Witherspoon, Kali; Rosenfeld, Jill A; van Bon, Bregje W M; Vulto-van Silfhout, Anneke T; Bosco, Paolo; Friend, Kathryn L; Baker, Carl; Buono, Serafino; Vissers, Lisenka E L M; Schuurs-Hoeijmakers, Janneke H; Hoischen, Alex; Pfundt, Rolph; Krumm, Nik; Carvill, Gemma L; Li, Deana; Amaral, David; Brown, Natasha; Lockhart, Paul J; Scheffer, Ingrid E; Alberti, Antonino; Shaw, Marie; Pettinato, Rosa; Tervo, Raymond; de Leeuw, Nicole; Reijnders, Margot R F; Torchia, Beth S; Peeters, Hilde; O'Roak, Brian J; Fichera, Marco; Hehir-Kwa, Jayne Y; Shendure, Jay; Mefford, Heather C; Haan, Eric; Gécz, Jozef; de Vries, Bert B A; Romano, Corrado; Eichler, Evan E

    2014-10-01

    Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Follow-up of a subset of affected individuals identified new clinical subtypes of pediatric disease and the genes responsible for disease-associated CNVs. These genetic changes include haploinsufficiency of SETBP1 associated with intellectual disability and loss of expressive language and truncations of ZMYND11 in individuals with autism, aggression and complex neuropsychiatric features. This combined CNV and SNV approach facilitates the rapid discovery of new syndromes and genes involved in neuropsychiatric disease despite extensive genetic heterogeneity. PMID:25217958

  8. A Genomewide Association Study of DSM-IV Cannabis Dependence

    OpenAIRE

    Agrawal, Arpana; Lynskey, Michael T.; Hinrichs, Anthony; Grucza, Richard; Saccone, Scott F; Krueger, Robert; Neuman, Rosalind; Howells, William; Fisher, Sherri; Fox, Louis; Cloninger, Robert,; Dick, Danielle M; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.

    2010-01-01

    Despite twin studies showing that 50–70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genomewide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis dependent cases with 2,346 cannabis exposed nondependent controls was conducted using logistic regression in PLINK. None of the 948,142 SNPs met genomewide signif...

  9. 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.

  10. ASSOCIATION ANALYSES OF ADRENERGIC RECEPTOR POLYMORPHISMS WITH OBESITY AND METABOLIC ALTERATIONS

    OpenAIRE

    Lima, John J.; Feng, Hua; Duckworth, Laurie; Wang, Jianwei; Sylvester, James E.; Kissoon, Niranjan; Garg, Hardesh

    2007-01-01

    Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in β1 (ADRB1), β2 (ADRB2), β3 (ADRB3) and α2a adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 Caucasian males and females (age: 18–49y) to participate in this case-control genetic assoc...

  11. Genome-wide association and systems genetic analyses of residual feed intake, daily feed consumption, backfat and weight gain in pigs

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Ostersen, Tage; Strathe, Anders Bjerring;

    2014-01-01

    Feed efficiency is one of the major components determining costs of animal production. Residual feed intake (RFI) is defined as the difference between the observed and the expected feed intake given a certain production. Residual feed intake 1 (RFI1) was calculated based on regression of individu...... and mechanisms affecting RFI in pigs is lacking. The study aimed to identify genetic markers and candidate genes for RFI and its component traits as well as pathways associated with RFI in Danish Duroc boars by genome-wide associations and systems genetic analyses....

  12. Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality.

    Science.gov (United States)

    McCaddon, Andrew; Miller, Joshua W

    2015-10-01

    Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed. PMID:26293664

  13. X-ray CT analyses, models and numerical simulations: a comparison with petrophysical analyses in an experimental CO2 study

    Science.gov (United States)

    Henkel, Steven; Pudlo, Dieter; Enzmann, Frieder; Reitenbach, Viktor; Albrecht, Daniel; Ganzer, Leonhard; Gaupp, Reinhard

    2016-06-01

    An essential part of the collaborative research project H2STORE (hydrogen to store), which is funded by the German government, was a comparison of various analytical methods for characterizing reservoir sandstones from different stratigraphic units. In this context Permian, Triassic and Tertiary reservoir sandstones were analysed. Rock core materials, provided by RWE Gasspeicher GmbH (Dortmund, Germany), GDF Suez E&P Deutschland GmbH (Lingen, Germany), E.ON Gas Storage GmbH (Essen, Germany) and RAG Rohöl-Aufsuchungs Aktiengesellschaft (Vienna, Austria), were processed by different laboratory techniques; thin sections were prepared, rock fragments were crushed and cubes of 1 cm edge length and plugs 3 to 5 cm in length with a diameter of about 2.5 cm were sawn from macroscopic homogeneous cores. With this prepared sample material, polarized light microscopy and scanning electron microscopy, coupled with image analyses, specific surface area measurements (after Brunauer, Emmet and Teller, 1938; BET), He-porosity and N2-permeability measurements and high-resolution microcomputer tomography (μ-CT), which were used for numerical simulations, were applied. All these methods were practised on most of the same sample material, before and on selected Permian sandstones also after static CO2 experiments under reservoir conditions. A major concern in comparing the results of these methods is an appraisal of the reliability of the given porosity, permeability and mineral-specific reactive (inner) surface area data. The CO2 experiments modified the petrophysical as well as the mineralogical/geochemical rock properties. These changes are detectable by all applied analytical methods. Nevertheless, a major outcome of the high-resolution μ-CT analyses and following numerical data simulations was that quite similar data sets and data interpretations were maintained by the different petrophysical standard methods. Moreover, the μ-CT analyses are not only time saving, but also non

  14. Improved method of plasma 8-Isoprostane measurement and association analyses with habitual drinking and smoking

    Institute of Scientific and Technical Information of China (English)

    Soichi Kitano; Hisashi Hisatomi; Nozomu Hibi; Katsumi Kawano; Shoji Harada

    2006-01-01

    was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.

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

    OpenAIRE

    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 st...

  16. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  18. RooStatsCms: a tool for analyses modelling, combination and statistical studies

    CERN Document Server

    Piparo, D; Quast, Prof G

    2008-01-01

    The RooStatsCms (RSC) software framework allows analysis modelling and combination, statistical studies together with the access to sophisticated graphics routines for results visualisation. The goal of the project is to complement the existing analyses by means of their combination and accurate statistical studies.

  19. RooStatsCms: a tool for analyses modelling, combination and statistical studies

    Science.gov (United States)

    Piparo, D.; Schott, G.; Quast, G.

    2009-12-01

    The RooStatsCms (RSC) software framework allows analysis modelling and combination, statistical studies together with the access to sophisticated graphics routines for results visualisation. The goal of the project is to complement the existing analyses by means of their combination and accurate statistical studies.

  20. 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

    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...

  1. Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease

    Science.gov (United States)

    Li, Xue; Song, Peige; Timofeeva, Maria; Meng, Xiangrui; Rudan, Igor; Little, Julian; Satsangi, Jack; Campbell, Harry; Theodoratou, Evropi

    2016-01-01

    We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn’s disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols. PMID:27670835

  2. Disagreements in meta-analyses using outcomes measured on continuous or rating scales: observer agreement study

    DEFF Research Database (Denmark)

    Tendal, Britta; Higgins, Julian P T; Jüni, Peter;

    2009-01-01

    OBJECTIVE: To study the inter-observer variation related to extraction of continuous and numerical rating scale data from trial reports for use in meta-analyses. DESIGN: Observer agreement study. DATA SOURCES: A random sample of 10 Cochrane reviews that presented a result as a standardised mean...... to the reviews but to the protocols, where the relevant outcome was highlighted. The agreement was analysed at both trial and meta-analysis level, pairing the observers in all possible ways (45 pairs, yielding 2025 pairs of trials and 450 pairs of meta-analyses). Agreement was defined as SMDs that differed less......% v 46%), but not at meta-analysis level. Important reasons for disagreement were differences in selection of time points, scales, control groups, and type of calculations; whether to include a trial in the meta-analysis; and data extraction errors made by the observers. In 14 out of the 100 SMDs...

  3. 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

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  4. 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...

  5. Evaluation of mixed dentition analyses in north Indian population: A comparative study

    OpenAIRE

    Ravi Kumar Goyal; Vijay P Sharma; Pradeep Tandon; Amit Nagar; Gyan P Singh

    2014-01-01

    Introduction: Mixed dentition regression equations analyses (Moyers, Tanaka-Johnston) are based on European population , reliability of these methods is questionable over other population. Materials and Methods: The present study was conducted on total 260 study models. This study was done in two phases. In the first phase, linear regression equations were made. In the second phase, comparison of actual values of sum of mesiodistal width of canine, first and second premolars with the predicte...

  6. Allelic association studies of genome wide association data can reveal errors in marker position assignments

    Directory of Open Access Journals (Sweden)

    Curtis David

    2007-06-01

    Full Text Available Abstract Background Genome wide association (GWA studies provide the opportunity to develop new kinds of analysis. Analysing pairs of markers from separate regions might lead to the detection of allelic association which might indicate an interaction between nearby genes. Methods 396,591 markers typed in 541 subjects were studied. 7.8*1010 pairs of markers were screened and those showing initial evidence for allelic association were subjected to more thorough investigation along with 10 flanking markers on either side. Results No evidence was detected for interaction. However 6 markers appeared to have an incorrect map position according to NCBI Build 35. One of these was corrected in Build 36 and 2 were dropped. The remaining 3 were left with map positions inconsistent with their allelic association relationships. Discussion Although no interaction effects were detected the method was successful in identifying markers with probably incorrect map positions. Conclusion The study of allelic association can supplement other methods for assigning markers to particular map positions. Analyses of this type may usefully be applied to data from future GWA studies.

  7. 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

    2015-11-01

    We report genome-wide association study 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 signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production. PMID:26366553

  8. 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....

  9. 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

  10. Analyses of expressed sequence tags in Neurospora reveal rapid evolution of genes associated with the early stages of sexual reproduction in fungi

    Directory of Open Access Journals (Sweden)

    Nygren Kristiina

    2012-11-01

    Full Text Available Abstract Background The broadly accepted pattern of rapid evolution of reproductive genes is primarily based on studies of animal systems, although several examples of rapidly evolving genes involved in reproduction are found in diverse additional taxa. In fungi, genes involved in mate recognition have been found to evolve rapidly. However, the examples are too few to draw conclusions on a genome scale. Results In this study, we performed microarray hybridizations between RNA from sexual and vegetative tissues of two strains of the heterothallic (self-sterile filamentous ascomycete Neurospora intermedia, to identify a set of sex-associated genes in this species. We aligned Expressed Sequence Tags (ESTs from sexual and vegetative tissue of N. intermedia to orthologs from three closely related species: N. crassa, N. discreta and N. tetrasperma. The resulting four-species alignments provided a dataset for molecular evolutionary analyses. Our results confirm a general pattern of rapid evolution of fungal sex-associated genes, compared to control genes with constitutive expression or a high relative expression during vegetative growth. Among the rapidly evolving sex-associated genes, we identified candidates that could be of importance for mating or fruiting-body development. Analyses of five of these candidate genes from additional species of heterothallic Neurospora revealed that three of them evolve under positive selection. Conclusions Taken together, our study represents a novel finding of a genome-wide pattern of rapid evolution of sex-associated genes in the fungal kingdom, and provides a list of candidate genes important for reproductive isolation in Neurospora.

  11. 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.

  12. Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients

    NARCIS (Netherlands)

    Said, M. Yusof; Deetman, Petronella E.; de Vries, Aiko P. J.; Zelle, Dorien M.; Gans, Rijk O. B.; Navis, Gerjan; Joosten, Michel M.; Bakker, Stephan J. L.

    2015-01-01

    The effect of a low protein intake on survival in renal transplant recipients (RTR) is unknown. A low protein intake may increase risks of malnutrition, low muscle mass, and death. We aimed to study associations of protein intake with mortality and graft failure and to identify potential intermediat

  13. Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets

    Science.gov (United States)

    Bacolod, Manny D.; Das, Swadesh K.; Sokhi, Upneet K.; Bradley, Steven; Fenstermacher, David A.; Pellecchia, Maurizio; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.

    2016-01-01

    mda-9/Syntenin (melanoma differentiation-associated gene 9) is a PDZ domain-containing, cancer invasion-related protein. In this study, we employed multiple integrated bioinformatic approaches to identify the probable epigenetic factors, molecular pathways, and functionalities associated with mda-9 dysregulation during cancer progression. Analyses of publicly available genomic data (e.g., expression, copy number, methylation) from TCGA, GEO, ENCODE, and Human Protein Atlas projects led to the following observations: a) mda-9 expression correlates with both copy number and methylation level of an intronic CpG site (cg17197774) located downstream of the CpG island, b) cg17197774 methylation is a likely prognostic marker in glioma, c) Among 22 cancer types, melanoma exhibits the highest mda-9 level, and lowest level of methylation at cg17197774, d) cg17197774 hypomehtylation is also associated with histone modifications (at the mda-9 locus) indicative of more active transcription, e) Using Gene Set Enrichment Analysis (GSEA), and the VIGOR (Virtual Gene Over-expression or Repression ) analytical scheme, we were able to predict mda-9’s association with extracellular matrix organization (e.g., MMPs, collagen, integrins), IGFBP2 and NF-κB signaling pathways, phospholipid metabolism, cytokines (e.g., interleukins), CTLA-4, and components of complement cascade pathways. Indeed, previous publications have shown that many of the aforementioned genes and pathways are associated with mda-9’s functionality. PMID:26093898

  14. 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.

  15. 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.

  16. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2

    Science.gov (United States)

    Wong, Sunny H.; Owusu-Dabo, Ellis; Osei, Ivy; Gyapong, John; Sirugo, Giorgio; Sisay-Joof, Fatou; Enimil, Anthony; Chinbuah, Margaret A.; Floyd, Sian; Warndorff, David K.; Sichali, Lifted; Malema, Simon; Crampin, Amelia C.; Ngwira, Bagrey; Teo, Yik Y.; Small, Kerrin; Rockett, Kirk; Kwiatkowski, Dominic; Fine, Paul E.; Hill, Philip C.; Newport, Melanie; Lienhardt, Christian; Adegbola, Richard A.; Corrah, Tumani; Ziegler, Andreas; Morris, Andrew P.; Meyer, Christian G.

    2013-01-01

    We combined two tuberculosis (TB) genome-wide association studies (GWAS) from Ghana and The Gambia with subsequent replication totalling 11,425 participants. A significant association with disease was observed at SNP rs4331426 located in a gene-poor region on chromosome 18q11.2 (P=6.8×10−9, OR=1.19, 95%CI=1.13-1.27). Our finding shows that GWAS can identify novel loci for infectious causes of mortality even in Africa where levels of linkage disequilibrium are particularly low. PMID:20694014

  17. Quantification of rock heterogeneities by structural geological field studies combined with laboratory analyses

    Science.gov (United States)

    Reyer, Dorothea; Afsar, Filiz; Philipp, Sonja

    2013-04-01

    Heterogeneous rock properties in terms of layering and complex infrastructure of fault zones are typical in sedimentary successions. The knowledge of in-situ mechanical rock properties is crucial for a better understanding of processes such as fracturing and fluid transport in fractured reservoirs. To estimate in situ rock properties at different depths it is important to understand how rocks from outcrops differ from rocks at depth, for example due to alteration and removal of the overburden load. We aim at quantifying these properties by performing structural geological field studies in outcrop analogues combined with laboratory analyses of outcrop samples and drill-cores. The field studies focus on 1) fault zone infrastructure and 2) host rock fracture systems in two different study areas with different lithologies, the North German and the Bristol Channel Basin. We analyse quantitatively the dimension, geometry, persistence and connectivity of fracture systems. The field studies are complemented by systematic sampling to obtain the parameters Young's modulus, compressive and tensile strengths and elastic strain energy (also referred to as destruction work) from which we estimate rock and fracture toughnesses. The results show that in rocks with distinctive layering fractures are often restricted to individual layers, that is, stratabound. The probability of arrest seems to depend on the stiffness contrast between two single layers as well as on the thickness of the softer layer. The results also show that there are clear differences between fault zones in the different lithologies in terms of damage zone thicknesses and fracture system parameters. The results of laboratory analyses show that the mechanical properties vary considerably and for many samples there are clear directional differences. That is, samples taken perpendicular to layering commonly have higher stiffnesses and strengths than those taken parallel to layering. We combine the results of

  18. 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.

  19. 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

  20. 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

  1. Study on the atmospheric component with the scope of analyses on the environmental impact

    International Nuclear Information System (INIS)

    This work has been carried out following a specific request from Italian National Department for Environment and shows technical approaches and methodologies of analyses and forecasts set up for environmental impact studies referred to 'atmospheric environment'. This work is presented according to the general items and objectives fixed by the same Department in the wider operative system for the application in Italy of environmental impact procedures. (author)

  2. '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.

  3. 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...... 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...

  4. SNP analyses of growth factor genes EGF, TGFβ-1, and HGF reveal haplotypic association of EGF with autism

    International Nuclear Information System (INIS)

    Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-β (TGFβ) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFβ1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFβ1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism

  5. Disentangling the directions of associations between structural social capital and mental health: Longitudinal analyses of gender, civic engagement and depressive symptoms.

    Science.gov (United States)

    Landstedt, Evelina; Almquist, Ylva B; Eriksson, Malin; Hammarström, Anne

    2016-08-01

    The present paper analysed the directions of associations between individual-level structural social capital, in the form of civic engagement, and depressive symptoms across time from age 16-42 years in Swedish men and women. More specifically, we asked whether civic engagement was related to changes in depressive symptoms, if it was the other way around, or whether the association was bi-directional. This longitudinal study used data from a 26-year prospective cohort material of 1001 individuals in Northern Sweden (482 women and 519 men). Civic engagement was measured by a single-item question reflecting the level of engagement in clubs/organisations. Depressive symptoms were assessed by a composite index. Directions of associations were analysed by means of gender-separate cross-lagged structural equation models. Models were adjusted for parental social class, parental unemployment, parental health, and family type at baseline (age 16). Levels of both civic engagement and depressive symptoms were relatively stable across time. The model with the best fit to data showed that, in men, youth civic engagement was negatively associated with depressive symptoms in adulthood, thus supporting the hypothesis that involvement in social networks promotes health, most likely through provision of social and psychological support, perceived influence, and sense of belonging. Accordingly, interventions to promote civic engagement in young men could be a way to prevent poor mental health for men later on in life. No cross-lagged effects were found among women. We discuss this gender difference in terms of gendered experiences of civic engagement which in turn generate different meanings and consequences for men and women, such as civic engagement not being as positive for women's mental health as for that of men. We conclude that theories on structural social capital and interventions to facilitate civic engagement for health promoting purposes need to acknowledge gendered life

  6. Disentangling the directions of associations between structural social capital and mental health: Longitudinal analyses of gender, civic engagement and depressive symptoms.

    Science.gov (United States)

    Landstedt, Evelina; Almquist, Ylva B; Eriksson, Malin; Hammarström, Anne

    2016-08-01

    The present paper analysed the directions of associations between individual-level structural social capital, in the form of civic engagement, and depressive symptoms across time from age 16-42 years in Swedish men and women. More specifically, we asked whether civic engagement was related to changes in depressive symptoms, if it was the other way around, or whether the association was bi-directional. This longitudinal study used data from a 26-year prospective cohort material of 1001 individuals in Northern Sweden (482 women and 519 men). Civic engagement was measured by a single-item question reflecting the level of engagement in clubs/organisations. Depressive symptoms were assessed by a composite index. Directions of associations were analysed by means of gender-separate cross-lagged structural equation models. Models were adjusted for parental social class, parental unemployment, parental health, and family type at baseline (age 16). Levels of both civic engagement and depressive symptoms were relatively stable across time. The model with the best fit to data showed that, in men, youth civic engagement was negatively associated with depressive symptoms in adulthood, thus supporting the hypothesis that involvement in social networks promotes health, most likely through provision of social and psychological support, perceived influence, and sense of belonging. Accordingly, interventions to promote civic engagement in young men could be a way to prevent poor mental health for men later on in life. No cross-lagged effects were found among women. We discuss this gender difference in terms of gendered experiences of civic engagement which in turn generate different meanings and consequences for men and women, such as civic engagement not being as positive for women's mental health as for that of men. We conclude that theories on structural social capital and interventions to facilitate civic engagement for health promoting purposes need to acknowledge gendered life

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

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. Association of polypharmacy with fall-related fractures in older Taiwanese people: age- and gender-specific analyses

    OpenAIRE

    Pan, Hsueh-Hsing; Li, Chung-Yi; Chen, Tzeng-Ji; Su, Tung-ping; Wang, Kwua-Yun

    2014-01-01

    Objective To elucidate the associations between polypharmacy and age- and gender-specific risks of admission for fall-related fractures. Design Nested case–control study. Setting This analysis was randomly selected from all elderly beneficiaries in 2007–2008, and represents some 30% of the whole older insurers using Taiwan's National Health Insurance Research Database. Participants We identified 5933 cases newly admitted for fall-related fractures during 2007–2008, and 29 665 random controls ...

  10. Phylogenetic study on Shiraia bambusicola by rDNA sequence analyses.

    Science.gov (United States)

    Cheng, Tian-Fan; Jia, Xiao-Ming; Ma, Xiao-Hang; Lin, Hai-Ping; Zhao, Yu-Hua

    2004-01-01

    In this study, 18S rDNA and ITS-5.8S rDNA regions of four Shiraia bambusicola isolates collected from different species of bamboos were amplified by PCR with universal primer pairs NS1/NS8 and ITS5/ITS4, respectively, and sequenced. Phylogenetic analyses were conducted on three selected datasets of rDNA sequences. Maximum parsimony, distance and maximum likelihood criteria were used to infer trees. Morphological characteristics were also observed. The positioning of Shiraia in the order Pleosporales was well supported by bootstrap, which agreed with the placement by Amano (1980) according to their morphology. We did not find significant inter-hostal differences among these four isolates from different species of bamboos. From the results of analyses and comparison of their rDNA sequences, we conclude that Shiraia should be classified into Pleosporales as Amano (1980) proposed and suggest that it might be positioned in the family Phaeosphaeriaceae.

  11. Intercomparison study of NOx passive diffusion tubes with chemiluminescence analysers and evaluation of bias factors

    OpenAIRE

    Sánchez Jiménez, Araceli; Heal, Mathew R.; Beverland, Iain J.

    2011-01-01

    Passive diffusion tubes (PDTs) are an inexpensive and simple method to monitor air pollutants. Numerous studies have investigated the performance of PDTs for NO2 but little attention has been paid to PDTs for NOx. The aim of this study was to evaluate the performance of NOx PDTs in three different urban environments. Duplicate NOx and NO2 PDTs were co-located with chemiluminescence analysers at kerbside, urban centre and background sites in the city of Glasgow for twelve 1-week exposures. PDT...

  12. 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. PMID:25406801

  13. Decadal flood frequency analyses: Case study of station Litija on the Sava river

    Science.gov (United States)

    Bezak, Nejc; Brilly, Mitja; Sraj, Mojca

    2013-04-01

    The objective of the study was (1) to perform decadal flood frequency analyses for the nine 30 years long data series, (2) to compare some commonly used distribution functions, (3) to compare the method of moments and the method of L-moments, and (4) to evaluate changes in the Q-T curves for the different hydrological periods. Decadal flood frequency analyses can be useful in climate changes or climate variability assessment. Investigation of the influence of the selected period for flood frequency analyses is important for the observation of changes in the discharge data. To reach the optimal flood frequency analyses results one should choose the best fitting distribution function and appropriate parameter estimation technique. The hydrological station Litija on the river Sava is one of the oldest gauging stations in Slovenia. 116 years of the daily discharge data were used for decadal flood frequency analyses. Data was separated in nine parts, each part contained 30 years of annual maximums. The normal, log-normal, Pearson 3, log-Pearson 3, Gumbel, generalized extreme value (GEV) and generalized logistic (GL) distributions were used for flood frequency analyses. The method of moments and the method of L-moments were used for parameters estimation. The root mean square error (RMSE), mean absolute error (MAE), Probability plot correlation coefficient (PPCC), Kolmogorov-Smirnov (K-S), Anderson-Darling (A-D) and AIC (Akaike information criterion) tests were used to compare distribution functions and different data samples. The L-moments ratio diagram was also used to assess differences between distribution functions. The GEV, Pearson 3 and log-Pearson 3 distributions gave better results as the normal, log-normal, Gumbel and GL distributions. The Gumbel and log-normal distributions had larger dispersion of tests results as other considered distributions. When distribution parameters were estimated with the method of L-moments test results were better as in case of the

  14. Developing fair tests for mathematics curriculum comparison studies: the role of content analyses

    Science.gov (United States)

    Chávez, Óscar; Papick, Ira; Ross, Daniel J.; Grouws, Douglas A.

    2011-12-01

    This article describes the process of development of assessment instruments for a three-year longitudinal comparative study that focused on evaluating American high school students' mathematics learning from two distinct approaches to content organization: curriculum built around a sequence of three full-year courses (Algebra 1, Geometry, and Algebra 2) and a sequence of integrated mathematics courses (algebra and geometry content, together with functions, data analysis, and discrete mathematics is integrated each year). The study was conducted in six school districts in five states involving over 4,000 students from schools that were using both curricular approaches but with different groups of students. In order to develop assessment instruments that were not biased towards either of the two curriculum programs (Fair Tests), an iterative process of content analyses, identification of common topics, internal and external reviews, pilot tests, and revisions was followed, resulting in five tests that were used in the three years of the study. Results indicate that these tests have solid discrimination properties and address adequately mathematics content common to both secondary curriculum programs. The corresponding scoring rubrics are highly reliable, with interrater reliability above 94% for all tests. Mathematics education researchers involved in curriculum comparison studies need to conduct content analyses of the curriculum materials under study in order to identify salient relationships between curriculum programs and student outcomes.

  15. The importance of uncertainties in scenario analyses--A study on future ecosystem service delivery in Flanders.

    Science.gov (United States)

    Landuyt, Dries; Broekx, Steven; Engelen, Guy; Uljee, Inge; Van der Meulen, Maarten; Goethals, Peter L M

    2016-05-15

    Land use is rapidly changing and is significantly affecting ecosystem service delivery all around the world. The socio-economic context and political choices largely determine land use change. This land use change, driven by socio-economic pressures, will impact diverse elements of the environment including, for example, air quality, soil properties, water infiltration and food and wood production, impacts that can be linked to the provisioning of ecosystem services. To gain more insight into the effects of alternative socio-economic developments on ecosystem service delivery, land use change models are being coupled to ecosystem service delivery models to perform scenario analyses. Although the uncertainty of the results of these kind of scenario analyses are generally far from negligible, studies rarely take them into account. In this study, a cellular automaton land use change model is coupled to Bayesian belief network ecosystem service delivery models to facilitate the study of error propagation in scenario analysis. The proposed approach is applied to model the impact of alternative socio-economic developments on ecosystem service delivery in Flanders, Belgium and to assess the impact of land use allocation uncertainty on the uncertainty associated to future ecosystem service delivery. Results suggest that taking into account uncertainties may have an effect on policy recommendations that come out of the scenario analysis. However, in this study, uncertainties in the applied ecosystem service models were dominant, reducing the importance of accounting for land use allocation uncertainty. PMID:26930321

  16. [The effect of image analyser noises in studies of cell structure].

    Science.gov (United States)

    Shteĭn, G I

    2002-01-01

    Using image analysers, the influence of noises on the quality of images obtained from three types of digital CCD videocameras was studied. Algorithms for calculating the heterogeneity coefficient of cell structures have been proposed, which take into account the noises on the images. Application of procedures of image smoothing or averaging from a few shots, calculation of differences in heterogeneity coefficients of the object and a free field, and a combination of these methods have significantly reduced the influence of noises and increased the informativeness of texture features. PMID:11868456

  17. 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

    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...

  18. Comparing methods of analysing datasets with small clusters: case studies using four paediatric datasets.

    Science.gov (United States)

    Marston, Louise; Peacock, Janet L; Yu, Keming; Brocklehurst, Peter; Calvert, Sandra A; Greenough, Anne; Marlow, Neil

    2009-07-01

    Studies of prematurely born infants contain a relatively large percentage of multiple births, so the resulting data have a hierarchical structure with small clusters of size 1, 2 or 3. Ignoring the clustering may lead to incorrect inferences. The aim of this study was to compare statistical methods which can be used to analyse such data: generalised estimating equations, multilevel models, multiple linear regression and logistic regression. Four datasets which differed in total size and in percentage of multiple births (n = 254, multiple 18%; n = 176, multiple 9%; n = 10 098, multiple 3%; n = 1585, multiple 8%) were analysed. With the continuous outcome, two-level models produced similar results in the larger dataset, while generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) produced divergent estimates using the smaller dataset. For the dichotomous outcome, most methods, except generalised least squares multilevel modelling (ML GH 'xtlogit' in Stata) gave similar odds ratios and 95% confidence intervals within datasets. For the continuous outcome, our results suggest using multilevel modelling. We conclude that generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) should be used with caution when the dataset is small. Where the outcome is dichotomous and there is a relatively large percentage of non-independent data, it is recommended that these are accounted for in analyses using logistic regression with adjusted standard errors or multilevel modelling. If, however, the dataset has a small percentage of clusters greater than size 1 (e.g. a population dataset of children where there are few multiples) there appears to be less need to adjust for clustering.

  19. Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: meta-analyses of published studies

    OpenAIRE

    Kundu, Madan G.; Acharyya, Suddhasatta

    2016-01-01

    Purpose: PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR$_{OS}$ (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. Methods: A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatments effects on PFS were determined using hazard ratio (HR$_{PFS}$), increase in media...

  20. A review of published analyses of case-cohort studies and recommendations for future reporting.

    Directory of Open Access Journals (Sweden)

    Stephen J Sharp

    Full Text Available The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%. The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.

  1. Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana.

    Science.gov (United States)

    Kobayashi, Yuriko; Sadhukhan, Ayan; Tazib, Tanveer; Nakano, Yuki; Kusunoki, Kazutaka; Kamara, Mohamed; Chaffai, Radhouane; Iuchi, Satoshi; Sahoo, Lingaraj; Kobayashi, Masatomo; Hoekenga, Owen A; Koyama, Hiroyuki

    2016-04-01

    Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function. PMID:26667381

  2. A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

    Directory of Open Access Journals (Sweden)

    Kristina Gruden

    Full Text Available BACKGROUND: Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable. METHODOLOGY/PRINCIPAL FINDINGS: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics" analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4+T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset. CONCLUSIONS/SIGNIFICANCE: Our study shows that the intra-individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.

  3. The EU power plant conceptual study - neutronic design analyses for near term and advanced reactor models

    International Nuclear Information System (INIS)

    A power plant conceptual study (PPCS) has been conducted in the framework of the European fusion programme with the main objective to demonstrate the safety and environmental advantages and the economic viability of fusion power. Power plant models with limited (''near term concepts'') and advanced plasma physics and technological extrapolations (''advanced concepts'') were considered. Two near term plant models were selected, one employing a water cooled lithium-lead (WCLL), and the other one a helium cooled pebble bed (HCPB) blanket. Two variants were also considered for the advanced power plant models, one adopting a liquid metal blanket with a self-cooled lithium-lead breeder zone and a helium cooled steel structure (''dual coolant lithium lead'', DCLL), and the other one a self-cooled lithium-lead (SCLL) blanket with SiCf/SiC composite as structural material. This report provides a detailed documentation of the neutronics design analyses performed as part of the PPCS study for both the near term and advanced power plant models. Main issues are the assessment of the tritium breeding capability, the evaluation of the nuclear power generation and its spatial distribution, and the assessment and optimisation of the shielding performance. The analyses were based on three-dimensional Monte Carlo calculations with the MCNP code using suitable torus sector models developed for the different PPCS plant variants. (orig.)

  4. 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

    Full Text Available BACKGROUND: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS: Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis.

  5. Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    Science.gov (United States)

    Sung, Yun Ju; Pérusse, Louis; Sarzynski, Mark A.; Fornage, Myriam; Sidney, Steve; Sternfeld, Barbara; Rice, Treva; Terry, Gregg; Jacobs, David R.; Katzmarzyk, Peter; Curran, Joanne E; Carr, John Jeffrey; Blangero, John; Ghosh, Sujoy; Després, Jean-Pierre; Rankinen, Tuomo; Rao, D.C.; Bouchard, Claude

    2015-01-01

    Background To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). Subjects and Methods Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for BMI, and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2,513 subjects of European descent were available for the discovery phase. For replication, 2,171 European Americans and 772 African Americans were available. Results A total of 52 SNPs encompassing 7 loci showed suggestive evidence of association (p < 1.0 × 10−6) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; p= 1.10 × 10−7), an association that was replicated (p = 0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; p= 2.42 × 10−7). Our sex-specific analyses identified one genome-wide significant (p < 5.0 × 10−8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (p = 3.97 × 10−8 to 1.13 × 10−8). The THNSL2 gene previously associated with VAT in women was also replicated (p= 0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. Conclusions Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2

  6. A Comparative Study of Sparse Associative Memories

    Science.gov (United States)

    Gripon, Vincent; Heusel, Judith; Löwe, Matthias; Vermet, Franck

    2016-07-01

    We study various models of associative memories with sparse information, i.e. a pattern to be stored is a random string of 0s and 1s with about log N 1s, only. We compare different synaptic weights, architectures and retrieval mechanisms to shed light on the influence of the various parameters on the storage capacity.

  7. 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 the

  8. 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.

  9. Using multifractal and wavelet analyses to determine drought characteristics: a case study of Jilin province, China

    Science.gov (United States)

    Zhang, Qian; Lu, Wenxi; Chen, Sheming; Liang, Xiujuan

    2016-08-01

    Drought is a recurrent disaster that occurs in virtually all climatic zones of the world. However, drought characteristics vary substantially among different climatic regions. In this study, multifractal and wavelet analyses are used to characterize drought based on monthly precipitation. The rainfall data of 28 precipitation stations from 1958 to 2011 in Jilin province were collected to calculate the standardized precipitation index (SPI), and the negative monthly SPI time-series is used in a multiscaling approach to determine drought characteristics in Jilin province. Simple scaling and multiscaling analyses show significant variations in monthly droughts in the region. Morlet wavelet analysis also shows that significant cycles and multiple time-scales of drought exist in all stations. Cross wavelet analysis shows that drought occurrence in the region is mainly influenced by different climatic factor scales. However, different factors have different degrees of influence at different regions. The enduring influence of medium and long-term climatic patterns (such as El Niño events) may lead to the simple scaling behavior of drought for some regions.

  10. Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.

    Science.gov (United States)

    Nishimura, Yasuharu; Tomita, Yusuke; Yuno, Akira; Yoshitake, Yoshihiro; Shinohara, Masanori

    2015-05-01

    Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.

  11. Functional analysis of variance for association studies.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Greenwood, Mark C; Wei, Changshuai; Lu, Qing

    2014-01-01

    While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods - SKAT and a previously proposed method based on functional linear models (FLM), - especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity. PMID:25244256

  12. 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.

  13. 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

  14. Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors

    International Nuclear Information System (INIS)

    Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression. Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV. Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival. In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above

  15. In vivo biostability of polymeric spine implants: retrieval analyses from a United States investigational device exemption study.

    Science.gov (United States)

    Shen, Ming; Zhang, Kai; Koettig, Petra; Welch, William C; Dawson, John M

    2011-11-01

    The Dynesys System for stabilizing the lumbar spine was first surgically implanted in Europe in 1994. In 2003, a prospective, randomized, investigational device exemption clinical trial of the system for non-fusion dynamic stabilization began. Polycarbonate urethane (PCU) and polyethylene terephthalate (PET) components explanted from four patients who had participated in the study were analyzed for biostability. Components had been implanted 9-19 months. The explanted components were visually inspected and digitally photographed. Scanning electron microscopy was used to analyze the surface of the spacers. The chemical and molecular properties of the retrieved spacers and cords were quantitatively compared with lot-matched, shelf-aged, components that had not been implanted using attenuated total reflection Fourier transform infrared (FTIR) and gel permeation chromatography (GPC). FTIR analyses suggested that the explanted spacers exhibited slight surface chemical changes but were chemically unchanged below the surface and in the center. New peaks that could be attributed to biodegradation of PCU were not observed. The spectral analyses for the cords revealed that the PET cords were chemically unchanged at both the surface and the interior. Peaks associated with the PET biodegradation were not detected. GPC results did not identify changes to the distributions of molecular weights that might be attributed to biodegradation of either PCU spacers or PET cords. The explanted condition of the retrieved components demonstrated the biostability of both PCU spacers and PET cords that had been in vivo for up to 19 months. PMID:21538208

  16. Modeling seasonal leptospirosis transmission and its association with rainfall and temperature in Thailand using time-series and ARIMAX analyses

    Institute of Scientific and Technical Information of China (English)

    Sudarat Chadsuthi; Charin Modchang; Yongwimon Lenbury; Sopon Iamsirithaworn; Wannapong Triampo

    2012-01-01

    ABSTRACT Objective:To study the number of leptospirosis cases in relations to the seasonal pattern, and its association with climate factors.Methods:Time series analysis was used to study the time variations in the number of leptospirosis cases.TheAutoregressiveIntegratedMovingAverage (ARIMA) model was used in data curve fitting and predicting the next leptospirosis cases. Results:We found that the amount of rainfall was correlated to leptospirosis cases in both regions of interest, namely the northern and northeastern region ofThailand, while the temperature played a role in the northeastern region only.The use of multivariateARIMA(ARIMAX) model showed that factoring in rainfall(with an8 months lag) yields the best model for the northern region while the model, which factors in rainfall(with a10 months lag) and temperature(with an8 months lag) was the best for the northeastern region.Conclusions:The models are able to show the trend in leptospirosis cases and closely fit the recorded data in both regions.The models can also be used to predict the next seasonal peak quite accurately.

  17. 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].

  18. D Recording for 2d Delivering - the Employment of 3d Models for Studies and Analyses -

    Science.gov (United States)

    Rizzi, A.; Baratti, G.; Jiménez, B.; Girardi, S.; Remondino, F.

    2011-09-01

    In the last years, thanks to the advances of surveying sensors and techniques, many heritage sites could be accurately replicated in digital form with very detailed and impressive results. The actual limits are mainly related to hardware capabilities, computation time and low performance of personal computer. Often, the produced models are not visible on a normal computer and the only solution to easily visualized them is offline using rendered videos. This kind of 3D representations is useful for digital conservation, divulgation purposes or virtual tourism where people can visit places otherwise closed for preservation or security reasons. But many more potentialities and possible applications are available using a 3D model. The problem is the ability to handle 3D data as without adequate knowledge this information is reduced to standard 2D data. This article presents some surveying and 3D modeling experiences within the APSAT project ("Ambiente e Paesaggi dei Siti d'Altura Trentini", i.e. Environment and Landscapes of Upland Sites in Trentino). APSAT is a multidisciplinary project funded by the Autonomous Province of Trento (Italy) with the aim documenting, surveying, studying, analysing and preserving mountainous and hill-top heritage sites located in the region. The project focuses on theoretical, methodological and technological aspects of the archaeological investigation of mountain landscape, considered as the product of sequences of settlements, parcelling-outs, communication networks, resources, and symbolic places. The mountain environment preserves better than others the traces of hunting and gathering, breeding, agricultural, metallurgical, symbolic activities characterised by different lengths and environmental impacts, from Prehistory to the Modern Period. Therefore the correct surveying and documentation of this heritage sites and material is very important. Within the project, the 3DOM unit of FBK is delivering all the surveying and 3D material to

  19. Evaluation of mixed dentition analyses in north Indian population: A comparative study

    Directory of Open Access Journals (Sweden)

    Ravi Kumar Goyal

    2014-01-01

    Full Text Available Introduction: Mixed dentition regression equations analyses (Moyers, Tanaka-Johnston are based on European population , reliability of these methods is questionable over other population. Materials and Methods: The present study was conducted on total 260 study models. This study was done in two phases. In the first phase, linear regression equations were made. In the second phase, comparison of actual values of sum of mesiodistal width of canine, first and second premolars with the predicted values proposed by Moyers, Tanaka-Johnston, and the new proposed mixed dentition analysis for North Indian population were made. Results: Set of four linear regression equations for predicting sum of mesiodistal width of permanent canine, first premolar and second premolar in North Indian population from sum of mesiodistal width of mandibular incisors and mandibular first molars, were proposed as ; (a for males, maxillary arch, Y = 2.9 + 0.40X, (b mandibular arch Y = 3.91 + 0.37X (c for females, maxillary arch Y = 0.56 + 0.45X (d mandibular arch Y = 1.14 + 0.42X. Moyers and Tanaka-Johnston, mixed dentition analysis , is found to be overestimating the mesiodistal width of unerupted canine and premolars in North Indian population.

  20. Studies on the determination of sulphur in thoria by thermal analyzer coupled with a quadrupole mass analyser

    International Nuclear Information System (INIS)

    Non-sintered thorium oxide powder is heated in the temperature range of 800 to 1200 deg C in a thermal analyser and the evolved gases were studied by a quadrupole mass analyser. Sulphur present in the thorium oxide matrix is started evolving in the form of sulphur dioxide when the sample is heated in argon atmosphere at around 850 to 900 deg C temperature. This paper highlights the detection of sulphur in the thorium oxide matrix by a quadrupole mass analyser coupled with a thermal analyser. (author)

  1. 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

  2. Identification of Phosphorylated Cyclin-Dependent Kinase 1 Associated with Colorectal Cancer Survival Using Label-Free Quantitative Analyses

    Science.gov (United States)

    Tyan, Yu-Chang; Hsiao, Eric S. L.; Chu, Po-Chen; Lee, Chung-Ta; Lee, Jenq-Chang; Chen, Yi-Ming Arthur; Liao, Pao-Chi

    2016-01-01

    Colorectal cancer is the most common form of cancer in the world, and the five-year survival rate is estimated to be almost 90% in the early stages. Therefore, the identification of potential biomarkers to assess the prognosis of early stage colorectal cancer patients is critical for further clinical treatment. Dysregulated tyrosine phosphorylation has been found in several diseases that play a significant regulator of signaling in cellular pathways. In this study, this strategy was used to characterize the tyrosine phosphoproteome of colorectal cell lines with different progression abilities (SW480 and SW620). We identified a total of 280 phosphotyrosine (pTyr) peptides comprising 287 pTyr sites from 261 proteins. Label-free quantitative analysis revealed the differential level of a total of 103 pTyr peptides between SW480 and SW620 cells. We showed that cyclin-dependent kinase I (CDK1) pTyr15 level in SW480 cells was 3.3-fold greater than in SW620 cells, and these data corresponded with the label-free mass spectrometry-based proteomic quantification analysis. High level CDK1 pTyr15 was associated with prolonged disease-free survival for stage II colorectal cancer patients (n = 79). Taken together, our results suggest that the CDK1 pTyr15 protein is a potential indicator of the progression of colorectal cancer. PMID:27383761

  3. Multigenic Control of Pod Shattering Resistance in Chinese Rapeseed Germplasm Revealed by Genome-Wide Association and Linkage Analyses.

    Science.gov (United States)

    Liu, Jia; Wang, Jun; Wang, Hui; Wang, Wenxiang; Zhou, Rijin; Mei, Desheng; Cheng, Hongtao; Yang, Juan; Raman, Harsh; Hu, Qiong

    2016-01-01

    The 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 an 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 a 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 that 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. PMID:27493651

  4. 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 ca

  5. Association of polypharmacy with fall-related fractures in older Taiwanese people: age- and gender-specific analyses

    Science.gov (United States)

    Pan, Hsueh-Hsing; Li, Chung-Yi; Chen, Tzeng-Ji; Su, Tung-Ping; Wang, Kwua-Yun

    2014-01-01

    Objective To elucidate the associations between polypharmacy and age- and gender-specific risks of admission for fall-related fractures. Design Nested case–control study. Setting This analysis was randomly selected from all elderly beneficiaries in 2007–2008, and represents some 30% of the whole older insurers using Taiwan's National Health Insurance Research Database. Participants We identified 5933 cases newly admitted for fall-related fractures during 2007–2008, and 29 665 random controls free from fracture. Primary and secondary outcome measures Polypharmacy was defined as the use of fall-related drugs of four or more categories of medications and prescribed related to fall within a 1-year period. Logistic regression models were employed to estimate the ORs and related 95% CIs. The interaction of polypharmacy with age and sex was assessed separately. Results Compared with those who consumed no category of medication, older people who consumed 1, 2, 3 and ≥4 categories of medications were all at significantly increased odds of developing fall-related fractures, with a significant dose–gradient pattern (β=0.7953; p for trend <0.0001). There were significant interactions between polypharmacy and age, but no significant interactions between polypharmacy and gender. The dose–gradient relationship between number of medications category and risk of fall-related fractures was more obvious in women than in men (β=0.1962 vs β=0.1873). Additionally, it was most evident in older people aged 75–84 years (β=0.2338). Conclusions This population-based study in Taiwan confirms the link between polypharmacy and increased risk of fall-related fractures in older people; and highlights that elderly women and older people aged 75–84 years will be the targeted participants for further prevention from fall-related fractures caused by polypharmacy. PMID:24682575

  6. Identification of proteasome subunit beta type 6 (PSMB6) associated with deltamethrin resistance in mosquitoes by proteomic and bioassay analyses.

    Science.gov (United States)

    Sun, Linchun; Ye, Yuting; Sun, Haibo; Yu, Jing; Zhang, Li; Sun, Yan; Zhang, Donghui; Ma, Lei; Shen, Bo; Zhu, Changliang

    2013-01-01

    Deltamethrin (DM) insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6) is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.

  7. Identification of proteasome subunit beta type 6 (PSMB6 associated with deltamethrin resistance in mosquitoes by proteomic and bioassay analyses.

    Directory of Open Access Journals (Sweden)

    Linchun Sun

    Full Text Available Deltamethrin (DM insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE and mass spectrometry (MS. Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6 is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:22171549

  9. 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.

  10. Wind Power Forecasting Error Frequency Analyses for Operational Power System Studies: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Florita, A.; Hodge, B. M.; Milligan, M.

    2012-08-01

    The examination of wind power forecasting errors is crucial for optimal unit commitment and economic dispatch of power systems with significant wind power penetrations. This scheduling process includes both renewable and nonrenewable generators, and the incorporation of wind power forecasts will become increasingly important as wind fleets constitute a larger portion of generation portfolios. This research considers the Western Wind and Solar Integration Study database of wind power forecasts and numerical actualizations. This database comprises more than 30,000 locations spread over the western United States, with a total wind power capacity of 960 GW. Error analyses for individual sites and for specific balancing areas are performed using the database, quantifying the fit to theoretical distributions through goodness-of-fit metrics. Insights into wind-power forecasting error distributions are established for various levels of temporal and spatial resolution, contrasts made among the frequency distribution alternatives, and recommendations put forth for harnessing the results. Empirical data are used to produce more realistic site-level forecasts than previously employed, such that higher resolution operational studies are possible. This research feeds into a larger work of renewable integration through the links wind power forecasting has with various operational issues, such as stochastic unit commitment and flexible reserve level determination.

  11. Application of the CALUX bioassay for epidemiological study. Analyses of Belgian human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Wouwe, N. van; Debacker, N.; Sasse, A. [Scientific Institute of Public Health, Brussels (BE)] (and others)

    2004-09-15

    The CALUX bioassay is a promising screening method for the detection of dioxin-like compounds. The observed good sensitivity, low number of false negative results as well as the good correlations with the GC-HRMS TEQ-values in case of feed and food analyses allow this method to climb in the first assessment methods' scale. The low amount of sample needed in addition to those latest advantages suggest that the CALUX bioassay could be a good screening method for epidemiological studies. The Belgian epidemiological study concerning the possible effect of the dioxin incident on the body burden of the Belgian population was an opportunity to test this method in comparison to the gold reference one: the GC-HRMS. The first part of this abstract presents epidemiological parameters (sensibility, specificity,) of the CALUX bioassay using CALUX TEQ-values as estimators of the TEQ-values of the 17 PCDD/Fs. The second part examines epidemiological determinants observed for CALUX and GCHRMS TEQ-values.

  12. 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.

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

    Science.gov (United States)

    Graham, Hillary T.; Rotroff, Daniel M.; Marvel, Skylar W.; Buse, John B.; Havener, Tammy M.; Wilson, Alyson G.; Wagner, Michael J.; Motsinger-Reif, Alison A.; Friedewald, W.T.

    2016-01-01

    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.

  14. 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.

  15. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    OpenAIRE

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilep...

  16. 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.

  17. Parametric Study of Control Rod Exposure for PWR Burnup Credit Criticality Safety Analyses

    International Nuclear Information System (INIS)

    The Interim Staff Guidance on burnup credit (ISG-8) for pressurized water reactor (PWR) spent nuclear fuel (SNF), issued by the Nuclear Regulatory Commission's (NRC) Spent Fuel Project Office, recommends the use of analyses that provide an ''adequate representation of the physics'' and notes particular concern with the ''need to consider the more reactive actinide compositions of fuels burned with fixed absorbers or with control rods fully or partly inserted.'' In the absence of readily available information on the extent of control rod (CR) usage in U.S. PWRs and the subsequent reactivity effect of CR exposure on discharged SNF, NRC staff have indicated a need for greater understanding in these areas. In response, this paper presents results of a parametric study of the effect of CR exposure on the reactivity of discharged SNF for various CR designs (including Axial Power Shaping Rods), fuel enrichments, and exposure conditions (i.e., burnup and axial insertion). The study is performed in two parts. In the first part, two-dimensional calculations are performed, effectively assuming full axial CR insertion. These calculations are intended to bound the effect of CR exposure and facilitate comparisons of the various CR designs. In the second part, three-dimensional calculations are performed to determine the effect of various axial insertion conditions and gain a better understanding of reality. The results from the study demonstrate that the reactivity effect increases with increasing CR exposure (e.g., burnup) and decreasing initial fuel enrichment (for a fixed burnup). Additionally, the results show that even for significant burnup exposures, minor axial CR insertions (e.g., eff of a spent fuel cask

  18. Elemental analyses of pine bark and wood in an environmental study

    Energy Technology Data Exchange (ETDEWEB)

    Saarela, K.-E.; Harju, L.; Rajander, J. [Laboratory of Analytical Chemistry, Process Chemistry Group, AAbo Akademi University, Biskopsg. 8, FIN-20500 AAbo (Finland); Lill, J.-O.; Heselius, S.-J. [Turku PET Centre, Accelerator Laboratory, AAbo Akademi University, Porthansg. 3, FIN-20500 AAbo (Finland); Lindroos, A. [Department of Geology and Mineralogy, AAbo Akademi University, Domkyrkotorget 1, FIN-20500 AAbo (Finland); Mattsson, K. [Department of Biology, AAbo Akademi University, BioCity, Artillerig. 6, FIN-20500 AAbo (Finland)

    2005-05-01

    Bark and wood samples were taken from the same individuals of Scots pine (Pinus sylvestris L.) from a polluted area close to a Cu-Ni smelter in Harjavalta and from some relatively unpolluted areas in western Finland. The samples were analysed by thick-target particle induced X-ray emission (PIXE) after preconcentration by dry ashing at 550 {sup o}C. The elemental contents of pine bark and wood were compared to study the impact of heavy metal pollution on pine trees. By comparison of the elemental contents in ashes of bark and wood, a normalisation was obtained. For the relatively clean areas, the ratios of the concentration in bark ash to the concentration in wood ash for different elements were close to 1. This means that the ashes of Scots Pine wood and bark have quite similar elemental composition. For the samples from the polluted area the mean concentration ratios for some heavy metals were elevated (13-28), reflecting the effect of direct atmospheric contamination. The metal contents in the ashes of pine bark and wood were also compared to recommendations for ashes to be recycled back to the forest environment. Bark from areas close to emission sources of heavy metal pollution should be considered with caution if aiming at recycling the ash. Burning of bark fuel of pine grown within 6 km of the Cu-Ni smelter is shown to generate ashes with high levels of Cu, Ni as well as Cd, As and Pb. (author)

  19. Levee reliability analyses for various flood return periods – a case study in Southern Taiwan

    Directory of Open Access Journals (Sweden)

    W.-C. Huang

    2015-01-01

    Full Text Available In recent years, heavy rainfall conditions have caused damages around the world. To prevent damages by floods, levees have often been constructed in prone-to-inundation areas. This study performed reliability analyses for the Chiuliao 1st Levee located in southern Taiwan. The failure-related parameters were the water level, the scouring depth, and the in-situ friction angle. Three major failure mechanisms were considered, including the slope sliding failure of the levee, and the sliding and overturning failures of the retaining wall. When the variabilities of the in-situ friction angle and the scouring depth are considered for various flood return periods, the variations of the factor of safety (FS for the different failure mechanisms show that the retaining wall sliding and overturning failures are more sensitive to the variability of the friction angle. When the flood return period is greater than 2 years, the levee can undergo slope sliding failure for all values of the water level difference. The results for levee stability analysis considering the variability of different parameters could assist engineers in designing the levee cross sections, especially with potential failure mechanisms in mind.

  20. 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.

  1. 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.

  2. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing.

    Directory of Open Access Journals (Sweden)

    Guo Li

    Full Text Available BACKGROUND: Rapidly growing evidence suggests that microRNAs (miRNAs are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC. METHODS: The differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models. RESULTS: 50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501, 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323 and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1 and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1. CONCLUSIONS: Our study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance.

  3. Evaluating variations of genotype calling: a potential source of spurious associations in genome-wide association studies

    Indian Academy of Sciences (India)

    Xuixiao Hong; Zhenqiang Su; Weigong Ge; Leming Shi; Roger Perkins; Hong Fang; Donna Mendrick; Weida Tong

    2010-04-01

    Genome-wide association studies (GWAS) examine the entire human genome with the goal of identifying genetic variants (usually single nucleotide polymorphisms (SNPs)) that are associated with phenotypic traits such as disease status and drug response. The discordance of significantly associated SNPs for the same disease identified from different GWAS indicates that false associations exist in such results. In addition to the possible sources of spurious associations that have been investigated and discussed intensively, such as sample size and population stratification, an accurate and reproducible genotype calling algorithm is required for concordant GWAS results from different studies. However, variations of genotype calling of an algorithm and their effects on significantly associated SNPs identified in downstream association analyses have not been systematically investigated. In this paper, the variations of genotype calling using the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM) algorithm and the resulting influence on the lists of significantly associated SNPs were evaluated using the raw data of 270 HapMap samples analysed with the Affymetrix Human Mapping 500K Array Set (Affy500K) by changing algorithmic parameters. Modified were the Dynamic Model (DM) call confidence threshold (threshold) and the number of randomly selected SNPs (size). Comparative analysis of the calling results and the corresponding lists of significantly associated SNPs identified through association analysis revealed that algorithmic parameters used in BRLMM affected the genotype calls and the significantly associated SNPs. Both the threshold and the size affected the called genotypes and the lists of significantly associated SNPs in association analysis. The effect of the threshold was much larger than the effect of the size. Moreover, the heterozygous calls had lower consistency compared to the homozygous calls.

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

    Institute of Scientific and Technical Information of China (English)

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

    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 ageand 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.

  5. Indoor carbon dioxide concentrations and sick building syndrome symptoms in the BASE study revisited: Analyses of the 100 building dataset

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, Christine A.; Steiner, Kate C.; Apte, Michael G.

    2002-02-01

    In previously published analyses of the 41-building 1994-1996 USEPA Building Assessment Survey and Evaluation (BASE) dataset, higher workday time-averaged indoor minus outdoor CO{sub 2} concentrations (dCO{sub 2}) were associated with increased prevalence of certain mucous membrane and lower respiratory sick building syndrome (SBS) symptoms, even at peak dCO{sub 2} concentrations below 1,000 ppm. For this paper, similar analyses were performed using the larger 100-building 1994-1998 BASE dataset. Multivariate logistic regression analyses quantified the associations between dCO{sub 2} and the SBS symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. Adjusted dCO{sub 2} prevalence odds ratios for sore throat and wheeze were 1.17 and 1.20 per 100-ppm increase in dCO{sub 2} (p <0.05), respectively. These new analyses generally support our prior findings. Regional differences in climate, building design, and operation may account for some of the differences observed in analyses of the two datasets.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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 sin

  7. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

    DEFF Research Database (Denmark)

    Croft, Laurence J; Szklarczyk, Damian; Jensen, Lars J;

    2012-01-01

    reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3'UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes...

  8. 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...

  9. 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. PMID:27440295

  10. A genome-wide association study of anorexia nervosa.

    Science.gov (United States)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-10-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

  11. A genome-wide association study of anorexia nervosa

    Science.gov (United States)

    Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

    2015-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

  12. A whole-genome association study for pig reproductive traits.

    Science.gov (United States)

    Onteru, S K; Fan, B; Du, Z-Q; Garrick, D J; Stalder, K J; Rothschild, M F

    2012-02-01

    A whole-genome association study was performed for reproductive traits in commercial sows using the PorcineSNP60 BeadChip and Bayesian statistical methods. The traits included total number born (TNB), number born alive (NBA), number of stillborn (SB), number of mummified foetuses at birth (MUM) and gestation length (GL) in each of the first three parities. We report the associations of informative QTL and the genes within the QTL for each reproductive trait in different parities. These results provide evidence of gene effects having temporal impacts on reproductive traits in different parities. Many QTL identified in this study are new for pig reproductive traits. Around 48% of total genes located in the identified QTL regions were predicted to be involved in placental functions. The genomic regions containing genes important for foetal developmental (e.g. MEF2C) and uterine functions (e.g. PLSCR4) were associated with TNB and NBA in the first two parities. Similarly, QTL in other foetal developmental (e.g. HNRNPD and AHR) and placental (e.g. RELL1 and CD96) genes were associated with SB and MUM in different parities. The QTL with genes related to utero-placental blood flow (e.g. VEGFA) and hematopoiesis (e.g. MAFB) were associated with GL differences among sows in this population. Pathway analyses using genes within QTL identified some modest underlying biological pathways, which are interesting candidates (e.g. the nucleotide metabolism pathway for SB) for pig reproductive traits in different parities. Further validation studies on large populations are warranted to improve our understanding of the complex genetic architecture for pig reproductive traits.

  13. Study of the type of gamma radioactivity in platform carbonaceous rocks: analyses and environmental, diagenetic and geodynamical interpretations

    International Nuclear Information System (INIS)

    In well-logging, values of gamma-activity are measured by scintillometry. A conventional paradigm is to link high γ-activity to Potassium (K) and Thorium (Th) isotopes present in clays and to Uranium isotopes present either in detrital sediments (typically in zircon or monazite minerals) or to sediments rich in organic matter. In shallow-water carbonates platforms, high γ-activities are interpreted in the same way. However, in a first γ-scintillometer survey of the Gorges du Nan section (sub-alpine Vercors massif), we found inconsistencies between lithologies and their expected γ-responses: the highest radioactive beds do not correspond to high argillaceous or detrital limestones and marls, but to some low content argillaceous or 'pure' limestones beds. The aim of this study was to identify the radioactive isotopes associated to different types of carbonates, their localisation, their abundance and their respective contribution to the total gamma response in order to propose a new method for the interpretation of gamma-ray logs in shallow-water carbonates. This study was focused on two intervals: - The first one corresponds to the Ba3 depositional sequence (Upper Barremian) which is composed essentially of limestones. This sequence was studied in the Vercors and Chartreuse sub-alpine massifs near Grenoble and in the Swiss Jura near Neuchatel; - The second one corresponds to the 'Lower Oritolina marls' interval. This interval was studied in the Vercors and Chartreuse sub-alpine massifs near Grenoble, in Spain (Organya basin) and in central Tunisia near Kairouan. We carried out detailed sedimentological, diagenetic and isotopic studies of all these sections. Oxygen and carbon stable isotopes analyses allowed us to establish some large scale correlations between sections in the French Alps, in the Pyrenees and in central Tunisia. The good correlation between Oxygen and Carbon stable isotopes curves of the Lower Orbitolina marls in all the

  14. Bursty reconnection modulating the substorm current wedge, a substorm case study re-analysed by ECLAT tools.

    Science.gov (United States)

    Opgenoorth, Hermann; Palin, Laurianne; Ågren, Karin; Zivkovic, Tatjana; Facsko, Gabor; Sergeev, Victor; Kubyshkina, Marina; Nikolaev, Alexander; Milan, Steve; Imber, Suzanne; Kauristie, Kirsti; Palmroth, Minna; van de Kamp, Max; Nakamura, Rumi; Boakes, Peter

    2015-04-01

    Multi-instrumental data mining and interpretation can be tedious and complicated. In this context, the ECLAT (European Cluster Assimilation Technology) project was created to « provide a novel and unique data base and tools for space scientists, by providing an upgrade of the European Space Agency's Cluster Active Archive (CAA). » How can this new tool help the space plasma physics community? Here we demonstrate the power of coordinated global and meso-scale ground-based data to put satellite data into the proper context. We re-analyse a well-isolated substorm with a strong growth phase, which starts right overhead the Scandinavian network of instruments on 8 September 2002. This event was previously studied in detail by Sergeev et al (2005), based on a THEMIS-like configuration near-midnight using a unique radial constellation of LANL (~6.6Re), Geotail and Polar (~9Re), and Cluster (~16Re). In this new study we add detailed IMAGE spacecraft and ground-based network data. Magnetospheric models are specially adapted using solar wind conditions and in-situ observations. Simulation results are compared to the in-situ observations and discussed. We show how - both before and after substorm onset - bursty reconnection in the tail modulates the localised field aligned current flow associated with the substorm current wedge.

  15. 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

  16. Disorganized Systematic Reviews and Meta-analyses: Time to Systematize the Conduct and Publication of These Study Overviews?

    Science.gov (United States)

    Riaz, Irbaz Bin; Khan, Muhammad Shahzeb; Riaz, Haris; Goldberg, Robert J

    2016-03-01

    The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this "runaway train" back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing "popularity." The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study. PMID:26522792

  17. Disorganized Systematic Reviews and Meta-analyses: Time to Systematize the Conduct and Publication of These Study Overviews?

    Science.gov (United States)

    Riaz, Irbaz Bin; Khan, Muhammad Shahzeb; Riaz, Haris; Goldberg, Robert J

    2016-03-01

    The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this "runaway train" back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing "popularity." The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study.

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

    Science.gov (United States)

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

    2016-10-01

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

  19. Correlation Analyses Between the Characteristic Times of Gradual Solar Energetic Particle Events and the Properties of Associated Coronal Mass Ejections

    Science.gov (United States)

    Pan, Z. H.; Wang, C. B.; Wang, Yuming; Xue, X. H.

    2011-06-01

    It is generally believed that gradual solar energetic particles (SEPs) are accelerated by shocks associated with coronal mass ejections (CMEs). Using an ice-cream cone model, the radial speed and angular width of 95 CMEs associated with SEP events during 1998 - 2002 are calculated from SOHO/LASCO observations. Then, we investigate the relationships between the kinematic properties of these CMEs and the characteristic times of the intensity-time profile of their accompanied SEP events observed at 1 AU. These characteristic times of SEP are i) the onset time from the accompanying CME eruption at the Sun to the SEP arrival at 1 AU, ii) the rise time from the SEP onset to the time when the SEP intensity is one-half of peak intensity, and iii) the duration over which the SEP intensity is within a factor of two of the peak intensity. It is found that the onset time has neither significant correlation with the radial speed nor with the angular width of the accompanying CME. For events that are poorly connected to the Earth, the SEP rise time and duration have no significant correlation with the radial speed and angular width of the associated CMEs. However, for events that are magnetically well connected to the Earth, the SEP rise time and duration have significantly positive correlations with the radial speed and angular width of the associated CMEs. This indicates that a CME event with wider angular width and higher speed may more easily drive a strong and wide shock near to the Earth-connected interplanetary magnetic field lines, may trap and accelerate particles for a longer time, and may lead to longer rise time and duration of the ensuing SEP event.

  20. Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies: Controversies in Meta-Analyses Results on Cardiac Cell-Based Regenerative Studies.

    Science.gov (United States)

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Navarese, Eliano P; Moye, Lemuel À

    2016-04-15

    In contrast to multiple publication-based meta-analyses involving clinical cardiac regeneration therapy in patients with recent myocardial infarction, a recently published meta-analysis based on individual patient data reported no effect of cell therapy on left ventricular function or clinical outcome. A comprehensive review of the data collection, statistics, and the overall principles of meta-analyses provides further clarification and explanation for this controversy. The advantages and pitfalls of different types of meta-analyses are reviewed here. Each meta-analysis approach has a place when pivotal clinical trials are lacking and sheds light on the magnitude of the treatment in a complex healthcare field.

  1. Bragg prism monochromator and analyser for super ultra-small angle neutron scattering studies

    Indian Academy of Sciences (India)

    Apoorva G Wagh; Sohrab Abbas; Markus Strobl; Wolfgang Treimer

    2008-11-01

    We have designed, fabricated and operated a novel Bragg prism monochromator–analyser combination. With a judicious choice of the Bragg reflection, its asymmetry and the apex angle of the silicon single crystal prism, the monochromator has produced a neutron beam with sub-arcsec collimation. A Bragg prism analyser with the opposite asymmetry has been tailored to accept a still sharper angular profile. With this optimized monochromator–analyser pair, we have attained the narrowest and sharpest neutron angular profile to date. At this facility, we have recorded the first SUSANS spectra spanning wave vector transfers ∼ 10−6 Å-1 to characterize samples containing agglomerates up to tens of micrometres in size.

  2. An efficient empirical Bayes method for genomewide association studies.

    Science.gov (United States)

    Wang, Q; Wei, J; Pan, Y; Xu, S

    2016-08-01

    Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits. PMID:26582716

  3. Are Gene Expression Microarray Analyses Reliable? A Review of Studies of Retinoic Acid Responsive Genes

    Institute of Scientific and Technical Information of China (English)

    Peter J. van der Spek; Andreas Kremer; Lynn Murry; Michael G. Walker

    2003-01-01

    Microarray analyses of gene expression are widely used, but reports of the same analyses by different groups give widely divergent results, and raise questions regarding reproducibility and reliability. We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes. These reports show substantial differences in their results. In this article, we review the methodology, results, and potential causes of differences in these applications of microarrays. Finally, we suggest practices to improve the reliability and reproducibility of microarray experiments.

  4. Are Gene Expression Microarray Analyses Reliable? A Review of Studies of Retinoic Acid Responsive Genes

    Institute of Scientific and Technical Information of China (English)

    PeterJ.vanderSpek; AndreasKremer; LynnMurry; MichaelG.Walker

    2003-01-01

    Microarray analyses of gene expression are widely used,but reports of the same analyses by different groups give widely divergent results,and raise questions regarding reproducibility and reliability.We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes.These reports show substantial differences in their results.In this article,we review the methodology,results,and potential causes of differences in these applications of microarrays.Finally,we suggest practices to improve the reliability and reproducibility of microarray experiments.

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

    International Nuclear Information System (INIS)

    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

  6. 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

  7. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    Science.gov (United States)

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  8. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan;

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  9. A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

    OpenAIRE

    Calboli, F. C. F.; Tozzi, F.; Galwey, N. W.; Antoniades, A.; Mooser, V.; Preisig, M.; Vollenweider, P; Waterworth, D.; Waeber, G.; Johnson, M. R.; Muglia, P; Balding, D. J.

    2010-01-01

    Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 mi...

  10. 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…

  11. 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...... 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...

  12. 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

    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 in......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...

  13. 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...

  14. Case Study Analyses of the SUCCESS DC-8 Scanning Lidar Database

    Science.gov (United States)

    Uthe, Edward E.

    2000-01-01

    Under project SUCCESS (Subsonic Aircraft Contrail and Cloud Effects Special Study) funded by the Atmospheric Effects of Aviation Program, SRI International (SRI) developed an angular scanning backscatter lidar for operation on the NASA DC-8 research aircraft and deployed the scanning lidar during the SUCCESS field campaign. The primary purpose of the lidar was to generate real-time video displays of clouds and contrails above, ahead of, and below the DC-8 as a means to help position the aircraft for optimum cloud and contrail sampling by onboard in situ sensors, and to help extend the geometrical domain of the in situ sampling records. A large, relatively complex lidar database was collected and several data examples were processed to illustrate the value of the lidar data for interpreting the other data records collected during SUCCESS. These data examples were used to develop a journal publication for the special SUCCESS Geophysical Research Letters issue. The data examples justified data analyses of a larger part of the DC-8 lidar database and is the objective of the current study. Efficient processing of the SUCCESS DC-8 scanning lidar database required substantial effort to enhance hardware and software components of the data system that was used for the initial analyses. MATLAB instructions are used to generate altitude and distance color-coded lidar displays corrected for effects introduced by aircraft pitch and forward movement during an angular scan time interval. Onboard in situ sensor atmospheric measurements are propagated to distances ahead of the DC-8 using recorded aircraft velocity so that they can be plotted on the lidar displays for comparison with lidar remotely observed aerosol distributions. Resulting lidar and in situ sensor polar scan displays over extended sampling intervals are integrated into a time series movie format for 36 case studies. Contrails and clouds were detected to ranges of 15 km by the forward-viewing angular scanning lidar

  15. 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. PMID:27567713

  16. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  17. Audio-visual perception of 3D cinematography: an fMRI study using condition-based and computation-based analyses.

    Directory of Open Access Journals (Sweden)

    Akitoshi Ogawa

    Full Text Available The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion. Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround, 3D with monaural sound (3D-Mono, 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG. The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life

  18. Audio-visual perception of 3D cinematography: an fMRI study using condition-based and computation-based analyses.

    Science.gov (United States)

    Ogawa, Akitoshi; Bordier, Cecile; Macaluso, Emiliano

    2013-01-01

    The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG). The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life-like stimuli. PMID

  19. Models and analyses for inertial-confinement fusion-reactor studies

    Energy Technology Data Exchange (ETDEWEB)

    Bohachevsky, I.O.

    1981-05-01

    This report describes models and analyses devised at Los Alamos National Laboratory to determine the technical characteristics of different inertial confinement fusion (ICF) reactor elements required for component integration into a functional unit. We emphasize the generic properties of the different elements rather than specific designs. The topics discussed are general ICF reactor design considerations; reactor cavity phenomena, including the restoration of interpulse ambient conditions; first-wall temperature increases and material losses; reactor neutronics and hydrodynamic blanket response to neutron energy deposition; and analyses of loads and stresses in the reactor vessel walls, including remarks about the generation and propagation of very short wavelength stress waves. A discussion of analytic approaches useful in integrations and optimizations of ICF reactor systems concludes the report.

  20. Models and analyses for inertial-confinement fusion-reactor studies

    International Nuclear Information System (INIS)

    This report describes models and analyses devised at Los Alamos National Laboratory to determine the technical characteristics of different inertial confinement fusion (ICF) reactor elements required for component integration into a functional unit. We emphasize the generic properties of the different elements rather than specific designs. The topics discussed are general ICF reactor design considerations; reactor cavity phenomena, including the restoration of interpulse ambient conditions; first-wall temperature increases and material losses; reactor neutronics and hydrodynamic blanket response to neutron energy deposition; and analyses of loads and stresses in the reactor vessel walls, including remarks about the generation and propagation of very short wavelength stress waves. A discussion of analytic approaches useful in integrations and optimizations of ICF reactor systems concludes the report

  1. Study design, methodology and statistical analyses in the clinical development of sparfloxacin.

    Science.gov (United States)

    Genevois, E; Lelouer, V; Vercken, J B; Caillon, R

    1996-05-01

    Many publications in the past 10 years have emphasised the difficulties of evaluating anti-infective drugs and the need for well-designed clinical trials in this therapeutic field. The clinical development of sparfloxacin in Europe, involving more than 4000 patients in ten countries, provided the opportunity to implement a methodology for evaluation and statistical analyses which would take into account actual requirements and past insufficiencies. This methodology focused on a rigorous and accurate patient classification for evaluability, subgroups of particular interest, efficacy assessment based on automation (algorithm) and individual case review by expert panel committees. In addition, the statistical analyses did not use significance testing but rather confidence intervals to determine whether sparfloxacin was therapeutically equivalent to the reference comparator antibacterial agents. PMID:8737126

  2. ESPRESSO: taking into account assessment errors on outcome and exposures in power analysis for association studies

    OpenAIRE

    Gaye, Amadou; Burton, Thomas W. Y.; Burton, Paul R

    2015-01-01

    Motivation: Very large studies are required to provide sufficiently big sample sizes for adequately powered association analyses. This can be an expensive undertaking and it is important that an accurate sample size is identified. For more realistic sample size calculation and power analysis, the impact of unmeasured aetiological determinants and the quality of measurement of both outcome and explanatory variables should be taken into account. Conventional methods to analyse power use closed-...

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

    OpenAIRE

    Krägeloh, Christian U

    2011-01-01

    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 ...

  4. Radiological analyses of France Telecom surge arresters. Study performed for the CGT FAPT Cantal

    International Nuclear Information System (INIS)

    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

  5. Seismic criteria studies and analyses. Quarterly progress report No. 3. [LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    1975-01-03

    Information is presented concerning the extent to which vibratory motions at the subsurface foundation level might differ from motions at the ground surface and the effects of the various subsurface materials on the overall Clinch River Breeder Reactor site response; seismic analyses of LMFBR type reactors to establish analytical procedures for predicting structure stresses and deformations; and aspects of the current technology regarding the representation of energy losses in nuclear power plants as equivalent viscous damping.

  6. Methodical study of cost-benefit analyses of the liquid metal fast breeder reactor

    International Nuclear Information System (INIS)

    Six American cost-benefit analyses (CBA) of nuclear energy and, in particular, of the Liquid Metal Fast Breeder Reactor (LMFBR) were analysed under the aspect of their methodical difficulties. Two different methodical approaches can be discerned which are related to two completely different applications, according to which the advantages and disadvantages of the breeder reactor are estimated in line with the basic concept of cost-benefit analysis. The analytical methods used to justify the continuation of the breeder-related research programme reveal that the specific energy-related technological and economic conditions of the geographic region considered have to be taken into account. The results of a CBA performed for the USA can therefore not be transferred to the Federal Republic of Germany. Due to the in part strongly differing quantitative results the analyses reviewed do not suggest a clear and final decision in favour of the continuation of the American LMFBR research programme to the extent envisaged. In addition, neither by a positive nor by a negative overall result of the analysis can it be concluded that no other advanced electricity generating technology would have a more favourable cost-benefit ratio, or that the breeder-related research activities, which have been pursued for several years already, should be discontinued. (orig.)

  7. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Science.gov (United States)

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W B; de Klerk, Nicholas H; Hui, Jennie; Beilby, John; James, Alan L; Creaney, Jenette; Robinson, Bruce W; Mukherjee, Sutapa; Palmer, Lyle J; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. PMID:23626673

  8. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Giuseppe Matullo

    Full Text Available Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM, a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes, causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14. Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28. These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

  9. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    NARCIS (Netherlands)

    A.D. Børglum; D. Demontis; J. Grove (Jakob); J. Pallesen (J.); M.V. Hollegaard (Mads V); C.B. Pedersen (C.); A. Hedemand (A.); M. Mattheisen (Manuel); A.G. Uitterlinden (André); M. Nyegaard (M.); T.F. Orntoft (Torben); C. Wiuf (Carsten); M. Didriksen (Michael); M. Nordentoft (M.); M.M. Nö then (M.); M. Rietschel (M.); R.A. Ophoff (Roel); S. Cichon (Sven); R.H. Yolken (Robert); D.M. Hougaard (David); P.B. Mortensen; O. Mors

    2014-01-01

    textabstractGenetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all indi

  10. Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

  11. Dietary supplement use and colorectal cancer risk: A systematic review and meta-analyses of prospective cohort studies

    NARCIS (Netherlands)

    Heine-Bröring, R.C.; Winkels, R.M.; Renkema, J.M.S.; Kragt, L.; Orten-Luiten, van A.C.B.; Tigchelaar, E.F.; Chan, D.S.M.; Norat, T.; Kampman, E.

    2015-01-01

    Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta-analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up

  12. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

    Science.gov (United States)

    Mattheisen, M; Samuels, J F; Wang, Y; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Qin, H-D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Liang, K-Y; Goes, F S; Maher, B; Pulver, A E; Shugart, Y Y; Valle, D; Lange, C; Nestadt, G

    2015-03-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples. PMID:24821223

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

    Science.gov (United States)

    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; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-03-01

    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. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  14. 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

  15. Case Control Analyses of Acute Endophthalmitis after Cataract Surgery in South India Associated with Technique, Patient Care, and Socioeconomic Status

    Directory of Open Access Journals (Sweden)

    Taraprasad Das

    2012-01-01

    Full Text Available Purpose. We investigated acute endophthalmitis incidence following cataract surgery vis-a-vis the current technological and postoperative care changes in higher and lower socioeconomic categories of patients in South India. Methods. In a retrospective case control study, we analyzed 62 cases of acute endophthalmitis and 5 controls for each endophthalmitis case from 46,095 cataract surgeries done between years 1993 and 1998. The time period covered the transition of surgical technique and after care. In addition, we analyzed systemic diseases, surgeon factor, habitat, and socioeconomic status. Results. Clinical and culture positive endophthalmitis incidence were 0.13% and 0.07%, respectively. Differential incidence of 0.10% and 0.17% for in- and ambulatory care surgeries, respectively, was close to statistical significance (=0.054. Lower economy category ambulatory patients had higher risk of infection. Conclusion. Ambulatory cataract surgery carried additional risk for post-operative infection in lower socioeconomic group. Improved health education could ensure greater safety.

  16. 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. M

  17. 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

    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....

  18. Eine Re-Analyse der Blue Mountains Eye Study zum Kataraktrisiko durch inhalative Kortikoide: Ein Beitrag zur Objektivierung der Diskussion

    OpenAIRE

    Hartung, Joachim; Knapp, Guido

    1999-01-01

    In einer Re-Analyse der Blue Mountains Eye Study von Cumming, Mitchell und Leeder (1997) wird gezeigt, daß diese Studie keinen Beitrag zur Klärung des Kataraktrisikos von inhalativen Kortikoiden leistet. Akzeptiert man die Schlußweisen der Studie, so ergibt sich ein diffuses und zugleich aber auch interessantes Bild von diversen Aussagen zu Kataraktrisiken bei inhalativen Kortikoiden, systemisch verabreichten Kortikoiden bzw. einer Kombination von inhalativen und systemisch verabreichten Kort...

  19. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

    Directory of Open Access Journals (Sweden)

    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  20. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

    Science.gov (United States)

    Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

    2016-01-01

    Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. Design Systematic review and meta-analysis. Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was

  1. 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.

  2. 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.

  3. 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

    2014-12-01

    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.

  4. The Danish Association for Science and Technology Studies

    DEFF Research Database (Denmark)

    A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments.......A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments....

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

    OpenAIRE

    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 ...

  6. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors : a case-control study using spontaneous reports

    NARCIS (Netherlands)

    Schillevoort, I; van Puijenbroek, E P; de Boer, A; Roos, R A C; Jansen, Paul A F; Leufkens, H G M

    2002-01-01

    The aim of this study was to assess whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with extrapyramidal syndromes (EPS). We analysed the spontaneous reports of adverse drug reactions (ADRs) collected by The Netherlands Pharmacovigilance Foundation Lareb in the period 198

  7. 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

  8. Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

    Science.gov (United States)

    Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

    2015-04-01

    This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

  9. 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.

  10. Associations between School-Related Factors and Depressive Symptoms among Children: A Comparative Study, Finland and Norway

    Science.gov (United States)

    Minkkinen, Jaana

    2014-01-01

    This study compares school-related associations in depressive symptoms among children aged between 9-13 years from four schools in Finland and Norway. A total of 523 pupils participated in the cross-sectional survey. The connections between depressive symptoms and school factors were analysed using hierarchical regression analyses. School…

  11. 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.

  12. 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.

  13. Epigenome-Wide Association Studies for common human diseases

    OpenAIRE

    Rakyan, Vardhman K; Down, Thomas A; Balding, David J.; Beck, Stephan

    2011-01-01

    Despite the success of genome-wide association studies (GWAS) in identifying loci associated with common diseases, a significant proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation (DNAm). Such Epigenome-Wide Association Studies (EWAS) present novel opportunities but also create new challenges that are not...

  14. A Candidate Gene Association Study of 77 Polymorphisms in Migraine

    OpenAIRE

    Schürks, Markus; Kurth, Tobias; Buring, Julie E.; Zee, Robert Y.L.

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association....

  15. Comparative study of the electronic structure of natural and synthetic rubies using XAFS and EDAX analyses

    Indian Academy of Sciences (India)

    P Parikh; D M Bhardwaj; R P Gupta; N L Saini; S Fernandes; R K Singhal; D C Jain; K B Garg

    2002-12-01

    We have studied the Cr–K-edge XANES and EXAFS in natural Indian rubies from two sources and a synthetic ruby at ESRF. Weight % of various constituents in them is determined using EDAX measurements. Taking the results from the three techniques together we are able to demonstrate their feasibility in quantitative study of precious stones.

  16. Structured multiplicity and confirmatory statistical analyses in pharmacodynamic studies using the quantitative electroencephalogram.

    Science.gov (United States)

    Ferber, Georg; Staner, Luc; Boeijinga, Peter

    2011-09-30

    Pharmacodynamic (PD) clinical studies are characterised by a high degree of multiplicity. This multiplicity is the result of the design of these studies that typically investigate effects of a number of biomarkers at various doses and multiple time points. Measurements are taken at many or all points of a "hyper-grid" that can be understood as the cross-product of a number of dimensions each of which has typically 3-30 discrete values. This exploratory design helps understanding the phenomena under investigation, but has made a confirmatory statistical analysis of these studies difficult, so that such an analysis is often missing in this type of studies. In this contribution we show that the cross-product structure of PD studies allows to combine several well-known techniques to address multiplicity in an effective way, so that a confirmatory analysis of these studies becomes feasible without unrealistic loss of power. We demonstrate the application of this technique in two studies that use the quantitative EEG (qEEG) as biomarker for drug activity at the GABA-A receptor. QEEG studies suffer particularly from the curse of multiplicity, since, in addition to the common dimensions like dose and time, the qEEG is measured at many locations over the scalp and in a number of frequency bands which inflate the multiplicity by a factor of about 250.

  17. CO{sub 2} Sequestration Capacity and Associated Aspects of the Most Promising Geologic Formations in the Rocky Mountain Region: Local-Scale Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Laes, Denise; Eisinger, Chris; Morgan, Craig; Rauzi, Steve; Scholle, Dana; Scott, Phyllis; Lee, Si-Yong; Zaluski, Wade; Esser, Richard; Matthews, Vince; McPherson, Brian

    2013-07-30

    The purpose of this report is to provide a summary of individual local-­scale CCS site characterization studies conducted in Colorado, New Mexico and Utah. These site-­ specific characterization analyses were performed as part of the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project. The primary objective of these local-­scale analyses is to provide a basis for regional-­scale characterization efforts within each state. Specifically, limits on time and funding will typically inhibit CCS projects from conducting high-­ resolution characterization of a state-­sized region, but smaller (< 10,000 km{sup 2}) site analyses are usually possible, and such can provide insight regarding limiting factors for the regional-­scale geology. For the RMCCS project, the outcomes of these local-­scale studies provide a starting point for future local-­scale site characterization efforts in the Rocky Mountain region.

  18. CO{sub 2} Sequestration Capacity and Associated Aspects of the Most Promising Geologic Formations in the Rocky Mountain Region: Local-Scale Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Laes, Denise; Eisinger, Chris; Morgan, Craig; Rauzi, Steve; Scholle, Dana; Scott, Phyllis; Lee, Si-Yong; Zaluski, Wade; Esser, Richard; Matthews, Vince; McPherson, Brian

    2013-07-30

    The purpose of this report is to provide a summary of individual local-­‐scale CCS site characterization studies conducted in Colorado, New Mexico and Utah. These site-­‐ specific characterization analyses were performed as part of the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project. The primary objective of these local-­‐scale analyses is to provide a basis for regional-­‐scale characterization efforts within each state. Specifically, limits on time and funding will typically inhibit CCS projects from conducting high-­‐ resolution characterization of a state-­‐sized region, but smaller (< 10,000 km{sup 2}) site analyses are usually possible, and such can provide insight regarding limiting factors for the regional-­‐scale geology. For the RMCCS project, the outcomes of these local-­‐scale studies provide a starting point for future local-­‐scale site characterization efforts in the Rocky Mountain region.

  19. 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)

  20. 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.

  1. 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.

  2. Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults

    DEFF Research Database (Denmark)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Varbo, Anette;

    2015-01-01

    BACKGROUND: Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely...... was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure. CONCLUSION: Milk intake was not associated with risk of IHD or MI, observationally or genetically....

  3. Hierarchical Linear Modeling Analyses of NEO-PI-R Scales In the Baltimore Longitudinal Study of Aging

    OpenAIRE

    Terracciano, Antonio; McCrae, Robert R.; Brant, Larry J; Costa, Paul T.

    2005-01-01

    We examined age trends in the five factors and 30 facets assessed by the Revised NEO Personality Inventory in Baltimore Longitudinal Study of Aging data (N = 1,944; 5,027 assessments) collected between 1989 and 2004. Consistent with cross-sectional results, Hierarchical Linear Modeling analyses showed gradual personality changes in adulthood: a decline up to age 80 in Neuroticism, stability and then decline in Extraversion, decline in Openness, increase in Agreeableness, and increase up to ag...

  4. 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

    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....

  5. 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.

  6. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  7. Comparative study of three Plumbago L. species (Plumbaginaceae) by microscopy, UPLC–UV and HPTLC analyses

    Science.gov (United States)

    This paper presents a comparative study of anatomy of leaves, stems and roots of three species of Plumbago, namely P. auriculata Lam., P. indica L. and P. zeylanica L. by light microscopy. The paper also provides qualitative and quantitative analysis of the naphthoquinone, plumbagin, a major constit...

  8. A Prospective Study of Stimulant Response in Preschool Children: Insights from ROC Analyses

    Science.gov (United States)

    Short, Elizabeth J.; Manos, Michael J.; Findling, Robert L.; Schubel, Emily A.

    2004-01-01

    Objective: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. Method: Twenty-eight preschoolers (ages 4.0-5.9) participated in the present investigation. They were obtained…

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

    DEFF Research Database (Denmark)

    Tybjærg-Hansen, Anne

    2009-01-01

    -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...

  10. 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…

  11. Colorado Community College System Financial Aid Services: Cost Analyses and Cost Efficiency Study

    Science.gov (United States)

    Beckmann, Dale

    2004-01-01

    This study was conducted in two phases. One, the Cost Analysis, reports on inventory and analysis of actual estimated costs for delivering financial aid services to students and potential students in thirteen Colorado Community College System (CCCS) community colleges in Fiscal Year 2003. Additionally, an assessment of services and functions is…

  12. LA GESTION ASSOCIATIVE DE LA PÊCHE EN FRANCE : UNE ANALYSE ÉCONOMIQUE À PARTIR DU CAS DES SALMONIDÉS

    Directory of Open Access Journals (Sweden)

    LE GOFFE P.

    2004-07-01

    Full Text Available L’analyse économique et l’examen des quelques données empiriques disponibles en France incitent à se demander si la gestion associative permet de tirer suffisamment de bien-être de la pêche de loisir en eau douce. Notre analyse s’appuie sur le cas des salmonidés. D’une part, l’effort de pêche est probablement trop important sur les bons parcours faciles d’accès, ce qui peut entraîner des pertes de bien-être dues à la congestion. D’autre part, les propriétaires riverains ne sont pas suffisamment incités à améliorer la qualité de l’environnement, alors que les pêcheurs ont un consentement à payer pour des améliorations. Ces inefficacités s’expliquent par la conjonction de trois phénomènes. Tout d’abord, les droits de propriété, privés, sont atténués par des dispositions législatives. Ensuite, les associations ne contrôlent pas suffisamment l’effort de pêche individuel et collectif. Finalement, les politiques halieutiques sont centrées sur la protection de la ressource et sont, bien que nécessaires, insuffisantes pour maximiser la rente sociale tirée de la pêche. La régulation de l’effort de pêche et la négociation de certains services environnementaux sur la base du principe bénéficiaire-payeur permettraient d’améliorer le bien-être collectif. Des tarifs sociaux permettraient de maintenir l’équité dans l’accès.

  13. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai;

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  14. Analysing Repeat Visitation on Country Level with Passive Mobile Positioning Method: an Estonian Case Study

    Directory of Open Access Journals (Sweden)

    Andres Kuusik

    2013-01-01

    Full Text Available The purpose of this paper is to investigate the capabilities and limits of the passive mobile positioning (PMP method in studying loyalty of tourists on the macro level. The repeat visitors were identified using database of call activities of roaming phones in Estonia since 25.04.2005 till 31.01.2009. For this purpose was developed model which selected repeat visits on the basis of time interval. The findings of the study revealed that it is possible to observe the duration, density, seasonality and dynamics of repeat visitations. In addition the local destinations and events most loved by repeat visitors and the trajectory they are using could be also identified. Another important finding revealed that repeat visitors stay longer in destination than first time visitors. The results presented in this paper could be used by Estonian Ministry of Economic Affairs and Communications and by Enterprise Estonia developing the Estonian tourism policy

  15. The Process of Designing and Analysing a Qualitative Study into Multiple WIL Experiences

    OpenAIRE

    Ward, Lisa J.; McAdie, Tina M.; Bravington, Alison; King, Nigel

    2012-01-01

    Title: Designing a Qualitative Study into Multiple Work Integrated Learning (WIL) Experiences. Authors: Lisa Ward, Dr Tina McAdie, Alison Bravington, Professor Nigel King Group / institution: University of Huddersfield. Conference theme(s) covered: Challenges and Innovations in the design and delivery of WIL Sub-theme: Impacts of WIL on graduate outcomes and employability Background / context: Universities are forever looking for the perfect Work Integrated Learning (WIL) model: t...

  16. An empirical study analysing the dynamics of two International Strategic Alliances in the Indian hotel industry

    OpenAIRE

    Rathore, Abhijeet

    2009-01-01

    This report undertakes a significant study in the field of Indian hotel industry, which has witnessed some major strategic co-marketing alliances with renowned International hospitality players that have become more prominent especially after the liberalisation of Indian economy in early nineties. The rationale behind this report is to critically examine the dynamics of two well known international joint ventures namely, Hotel Leelaventure-Kempinski Hotels and East India Hotels limited - Hilt...

  17. Special studies and analyses for the Assistant Secretary for Policy, Safety, and Environment. Final report

    International Nuclear Information System (INIS)

    The report identifies major tasks accomplished, details plans for the orderly completion of all work in process, and provides a complete listing of deliverables (reports, briefings, letters, etc.) provided under the contract. Purpose of this contract was to provide environmental studies, analytical planning, evaluation, and other technical assistance and support to the DOE Office of the Assistant Secretary for Environmental Protection, Safety and Emergency Preparedness (EP) and designated EP offices and divisions

  18. A mycogeographical study of Norwegian macrofungi based on GLM analyses of herbarium data

    OpenAIRE

    2007-01-01

    ABSTRACT This study focuses on the mycogeography of 83 selected macrofungi in Norway. The fungi’s distribution patterns were related to a dataset of 81 environmental variables through GLM in order to reveal which factors that accounts for the species distributions. The GLM models for the 83 species were generally dominated by variables in the categories ‘Temperature’, ‘Energy’, ‘Humidity’ and ‘Topography’, plus the variable Geology richness, confirming established knowledge about which en...

  19. Case study: readiness and total ownership cost analyses for new fighter aircraft, F-XX

    OpenAIRE

    Kang, Keebom; Doerr, Kenneth H.

    2012-01-01

    Approved for public release; distribution in unlimited. Acquisition Research Case Study Disclaimer: The views represented in this report are those of the author and do not reflect the official policy position of the Navy, the Department of Defense, or the Federal Government. This case is intended to illustrate key trade-offs in planning the acquisition of a major weapon system. In particular, the impact of logistics and maintenance decisions on life-cycle costs and readiness ar...

  20. Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

    OpenAIRE

    Jackson, Dan; White, Ian R.; Riley, Richard D.

    2012-01-01

    Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the rando...

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

    OpenAIRE

    Aschemann-Witzel Jessica; Perez-Cueto Federico JA; Niedzwiedzka Barbara; Verbeke Wim; Bech-Larsen Tino

    2012-01-01

    Abstract Background Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaig...

  2. A comparative case study of indoor soundscape approach on objective analyses and subjective evaluations of libraries

    OpenAIRE

    Dökmeci, Papatya; Kang, Jian

    2012-01-01

    International audience In this study indoor soundscaping approaches were used to evaluate 3 different libraries in Sheffield, United Kingdom. Acoustic measurement and recordings as well as social survey on indoor soundscapes were carried out in each library. Usage, time spent, evaluation of physical conditions, demographics, sound perception, noise annoyance, and sound preferences were included in the survey. In addition, established frameworks were used for examining the architectural cha...

  3. Robotic pilot study for analysing spasticity: clinical data versus healthy controls

    OpenAIRE

    Seth, Nitin; Johnson, Denise; Taylor, Graham W.; Allen, O. Brian; Abdullah, Hussein A

    2015-01-01

    Background Spasticity is a motor disorder that causes significant disability and impairs function. There are no definitive parameters that assess spasticity and there is no universally accepted definition. Spasticity evaluation is important in determining stages of recovery. It can determine treatment effectiveness as well as how treatment should proceed. This paper presents a novel cross sectional robotic pilot study for the primary purpose of assessment. The system collects force and positi...

  4. Neutronics analyses for fast spectrum nuclear systems and scenario studies for advanced nuclear fuel cycles

    OpenAIRE

    Grasso, Giacomo

    2010-01-01

    The present PhD thesis summarizes the three-years study about the neutronic investigation of a new concept nuclear reactor aiming at the optimization and the sustainable management of nuclear fuel in a possible European scenario. A new generation nuclear reactor for the nuclear reinassance is indeed desired by the actual industrialized world, both for the solution of the energetic question arising from the continuously growing energy demand together with the corresponding reduction of oil ava...

  5. Trace element contamination in Slovakian part of Carpathian mountains studied by moss monitoring and foliar analyses

    International Nuclear Information System (INIS)

    The use of terrestrial mosses as biomonitors in large-scale-multielement studies of heavy metal deposition from the atmosphere is a well established technique in Europe. In such studies it is advantageous to determine as many elements as possible in order to distinguish different source categories. A combination of INAA and AAS has been found very useful in this respect, in particular when epithermal activation is used for instrumental neutron activation analysis. A total of 44 elements in Pleurozium schreberi and Hylocomium splendens moss samples from the Slovakian part of Carpathian Mts. and a background area in Central Norway were identified. The highest concentrations of the majority of trace elements were found in mosses growing in the second European Black Triangle (Poland - Czech-Slovak border) and hot spots Central Spis in Slovakia. These results are in conformity with the load of trace elements in the foliage of white fir (abies alba), Norway spruce (Picea abies) and common beech (Fagus sylvatica) from 5 sites of the Carpathian Mts. forests. Foliage surfaces of three forest tree species contained Al, Si, Ca, Fe, Mg, K, Cl, Mn, Na, Ni, and Ti in all studied localities. Anthropogenic and geogenic influences are being discussed on the basis of the results. Warimax rotated principal component analysis was used to identify and characterize different pollution sources and to point out the most polluted areas

  6. 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.

  7. Studies on Aries River (Apuseni Mountains) pollution using factorial analyses (in Romanian)

    OpenAIRE

    Forray Ferenc La̒za̒r

    2001-01-01

    In the present study we try to use factor analysis in the characterisation of river water chemistry between the municipalities of Cheia and Muncel along a 54-km stretch of the Aries River (NW Romania). The results show that 4 factors can explain 88% of the water chemistry. The first factor explains 39% of the total data variance, and represents the water-rock interactions. This high percent indicates the importance of water rock interactions in defining the chemistry of surface waters. The se...

  8. Study of parameters important to soil-structure interaction in seismic analyses of nuclear power plants

    International Nuclear Information System (INIS)

    The development of state-of-the-art techniques for analyzing the effects of soil-structure interaction (SSI) on structures during earthquakes is outlined. Emphasis is placed on methods to account for energy dissipation as a result of both wave propagation away from the structure's foundation and hysteretic soil response. Solution techniques are grouped into two major types: substructure methods, which break the problem into a series of steps; and direct methods, which analyze the soil-structure model in one step. In addition to theoretical and historical development of SSI methodology, case studies are presented illustrating the application of these solution techniques. 94 references

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

    Directory of Open Access Journals (Sweden)

    Aschemann-Witzel Jessica

    2012-02-01

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

  10. Study of parameters important to soil-structure interaction in seismic analyses of nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, T.A.

    1983-12-01

    The development of state-of-the-art techniques for analyzing the effects of soil-structure interaction (SSI) on structures during earthquakes is outlined. Emphasis is placed on methods to account for energy dissipation as a result of both wave propagation away from the structure's foundation and hysteretic soil response. Solution techniques are grouped into two major types: substructure methods, which break the problem into a series of steps; and direct methods, which analyze the soil-structure model in one step. In addition to theoretical and historical development of SSI methodology, case studies are presented illustrating the application of these solution techniques. 94 references.

  11. A Karyological Study on Johrenia dichotoma DC. (Apiaceae by Image Analysing System

    Directory of Open Access Journals (Sweden)

    Esra Martın

    2014-05-01

    Full Text Available In this study Karyotype Analysis was defined in Johrenia dichotoma DC. This taxa contained diploid chromosome number of as 2n=22. The total haploid chromosome lengths 29.84 μm with average chromosome lengths from 2.25 to 3.47 μm. The karyotype formulae of this taxa consisted of eleven pairs of median chromosome. Also, the chromosome morphology of J. dichotoma was identified by calculating arm and centromeric index, the ratio length of its chromosome arms, and its ideogram was done. Chromosome morphology is new for science world. The research has made contribution to the cytotaxonomic revision of the genus Johrenia in Turkey.

  12. A Karyological Study on Johrenia dichotoma DC. (Apiaceae) by Image Analysing System

    OpenAIRE

    Esra Martın; Yavuz Bagcı; Muhittin Dinc; Fahim Altınordu; Ahmet Duran

    2014-01-01

    In this study Karyotype Analysis was defined in Johrenia dichotoma DC. This taxa contained diploid chromosome number of as 2n=22. The total haploid chromosome lengths 29.84 μm with average chromosome lengths from 2.25 to 3.47 μm. The karyotype formulae of this taxa consisted of eleven pairs of median chromosome. Also, the chromosome morphology of J. dichotoma was identified by calculating arm and centromeric index, the ratio length of its chromosome arms, and its ideogram was done. Chromosome...

  13. Suprathermal helium associated with corotating interaction regions: A case study

    Science.gov (United States)

    Yu, J.; Berger, L.; Wimmer-Schweingruber, R. F.; Hilchenbach, M.; Kallenbach, R.; Klecker, B.; Guo, J.

    2016-03-01

    Enhancements of suprathermal particles observed at 1AU often can be related to Corotating Interaction Regions (CIRs). The compression regions associated with CIRs and their driven shocks which typically form at a few AU distance to the Sun can efficiently accelerate particles. If accelerated at the trailing edge of a CIR these particles can travel sunward along the ambient magnetic field and thus enhanced fluxes can be observed even if the acceleration region has passed over the spacecraft. We have analysed a CIR that has been observed at L1 by ACE/SWICS and SOHO/CELIAS/STOF on days 207 and 208 in 2003. The combination of SWICS and STOF data allowed us to study suprathermal Helium ranging from its onset at solar wind bulk energies up to 330 keV/nuc. Here we present our results for the temporal evolution of the flux, energy spectra and the He+/He++ ratio. In particular we present observational evidence for a turnover of the energy spectra at lower energies after the CIR passage which has been theoretically predicted but never been observed so far.

  14. Analysing soil degradation through hydric erosion. Case study - Ialomita County, Romania

    Directory of Open Access Journals (Sweden)

    ADRIANA BIANCA OVREIU

    2015-12-01

    Full Text Available Analy sing soil degradation through hydric erosion. Case study – Ialomița County, Romania. Landscape degradation through different processes has intensified and extended spatially to all geographical regions at global level, irrespective of the social, economic or political background. The main process which contributes to soil degradation is hydric erosion. Surface drainage, which is the most common form of erosion, affects hundreds of thousands of hectares worldwide. Surface runoff therefore demands more attent ion, as it can produce advanced land degradation, up to the stage when it cannot be used any more for agricultural purposes. In our country, hydric erosion affects nearly 50% of all agricultural and arable land, with an annual estimated damage of about 126 million tonnes of rich soil [1] [2]. The Ialomița county is located on the lower reach of the homonymous river, in a landscape dominated by lowlands, having more than 80% of its administrative area used for agricultural purposes. Soil degradation through different hydric processes would therefore have major implications on agricultural yields, as it would reduce the productivity potential of the soil land cover. Consequently, the main goal of the present research was to quantify the amount of soil loss thr ough hydric erosion for the Ialomița county’s territory, using the Universal Soil Loss Equation (USLE and GIS - based techniques. This study also relies on many scientific references, field observations and in - depth analysis of thematic maps

  15. 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.

  16. Statistical Approaches to Analyse Gene Bank Data Using a Lentil Germplasm Collection as a Case Study

    Directory of Open Access Journals (Sweden)

    Gabriella Sonnante

    2008-09-01

    Full Text Available Normally in a plant gene bank a large number of accessions per each crop and/ or taxon is stored. During their characterization and preliminary evaluation, several quantitative and qualitative data are recorded and, usually, a wide intra accession variation is observed. Th e management of all this information becomes very difficult without effective statistical methods combining these different types of data. At the Institute of Plant Genetics, CNR, in Bari (Italy this problem has been tackled by testing many statistical approaches. The present contribution describes one of these approaches, which to date has proven to be highly adequate; a case study describing a lentil germplasm collection has been used for demonstration. A valuable application of this method is the determination of core subsets important to increase the utilization and accessibility of plant genetic resources. In the presented case study a subset of the lentil germplasm collection was chosen to perform molecular analysis based on ISSR markers. The samples were selected on the basis of both morpho-agronomic evaluation and geographical origin. These markers proved to be useful for distinguishing among closely related genotypes and for possibly substantiating the genetic peculiarity of some interesting material.

  17. Ion collision cross section analyses in quadrupole ion traps using the filter diagonalization method: a theoretical study.

    Science.gov (United States)

    Jiang, Ting; He, Miyi; Guo, Dan; Zhai, Yanbing; Xu, Wei

    2016-04-28

    Previously, we have demonstrated the feasibility of measuring ion collision cross sections (CCSs) within a quadrupole ion trap by performing time-frequency analyses of simulated ion trajectories. In this study, an improved time-frequency analysis method, the filter diagonalization method (FDM), was applied for data analyses. Using the FDM, high resolution could be achieved in both time- and frequency-domains when calculating ion time-frequency curves. Owing to this high-resolution nature, ion-neutral collision induced ion motion frequency shifts were observed, which further cause the intermodulation of ion trajectories and thus accelerate image current attenuation. Therefore, ion trap operation parameters, such as the ion number, high-order field percentage and buffer gas pressure, were optimized for ion CCS measurements. Under optimized conditions, simulation results show that a resolving power from 30 to more than 200 could be achieved for ion CCS measurements. PMID:27066889

  18. [Study of the Sporothrix schenkii (yeast forms) extract. Electrophoretic and immunoelectrophoretic analyses: characterization of enzymatic activities].

    Science.gov (United States)

    Walbaum, S; Duriez, T; Dujardin, L; Biguet, J

    1978-07-28

    An extract from living yeast forms of S. schenckii was prepared. The yeasts originated from a shake culture in B.H.I. broth (Difco) incubated for 3 days at 35 degrees C in darkness; they were harvested, washed and disrupted with glass beads in a model MSK Braun mechanical cell homogenizer; a freezing-thawing was added to improve the extract. After electrophoretic separation in agarose gel, the extract's components were characterized by their enzymic activity; with this technique, 30 bands were revealed. These enzymic activities were also investigated on the antigenic fractions of the extract revealed by a rabbit hyperimmunserum: 16 among 22 immunoprecipitates are identified by their catalytic properties. Study of the earliest precipitating antibodies (appearing-order and enzymic caracterization) in rabbits just immunized completes this work. How to ameliorate the quality of the extract by culture and extraction conditions is also specified. PMID:692628

  19. 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.

  20. 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.

  1. Analyses of archaeological pottery samples using X-ray fluorescence technique for provenance study

    International Nuclear Information System (INIS)

    Archaeological artifacts reveal information on past human activities, artifact preparation technology, art and possible trade. Ceramics are the most stable and abundant material in archaeological context. Pottery is the most abundant tracers in all archaeological excavations. Compared to major elements, elements present at trace concentrations levels are source specific and they maintain same concentration levels in source clay as well as finished products e.g., fired clay potteries. As it is difficult to find out exact source or origin, provenance study is carried out first to establish whether objects under study are from the same or different sources/origin. Various analytical techniques like instrumental neutron activation analysis (INAA), Ion beam analysis (IBA) and X-ray fluorescence (XRF) have been used for obtaining elemental concentrations in archaeological potteries. Portable X-ray fluorescence (pXRF) spectrometry provides a non-destructive means for elemental characterization of a wide range of archaeological materials. Ten archaeological pottery samples were collected from Kottapuram, Kerala under the supervision of archaeological survey of India. Portable X-ray fluorescence (pXRF) spectrometry using a handheld Olympus Innov-X Delta XRF device, ACD BARC, has been used for chemical characterization of the pottery samples. The instrument is equipped with the Delta Rhodium (Rh) anode X-Ray tube and uses a Silicon Drift Detector (resolution <200 eV at 5.95 keV Mn Kα X-ray). NIST 2781 SRM was analyzed for quality control purpose. Ten elements namely Fe, Ti, Mn, Co, Cu, Zn, Pb, Zr, Mo and Se were chosen for cluster analysis and their concentration values were utilized for multivariate statistical analysis using WinSTAT 9.0

  2. 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.

  3. Simultaneous Analyses and Applications of Multiple Fluorobenzoate and Halide Tracers in Hydrologic Studies

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Q; Moran, J E

    2004-01-22

    An analytical method that employs ion chromatography has been developed to more fully exploit the use of fluorobenzoic acids (FBAs) and halides as hydrologic tracers. In a single run, this reliable, sensitive, and robust method can simultaneously separate and quantify halides (fluoride, chloride, bromide, and iodide) and up to seven FBAs from other common groundwater constituents (e.g., nitrate and sulfate). The usefulness of this ion chromatographic (IC) analytical method is demonstrated in both field and laboratory tracer experiments. Field experiments in unsaturated tuff featuring fractures or a fault show that this efficient and cost-effective method helps achieve the objectives of tracer studies that use multiple FBAs and/or diffusivity tracers (simultaneous use of one or more FBA and halide). The field study examines the hydrologic response of fractures and the matrix to different flow rates and the contribution of matrix diffusion in chemical transport. Laboratory tracer experiments with eight geologic media from across the United States--mostly from Department of Energy facilities where groundwater contamination is prevalent and where subsurface characterization employing tracers has been ongoing or is in need--reveal several insights about tracer transport behavior: (1) Bromide and FBAs are not always transported conservatively. (2) The delayed transport of these anionic tracers is likely related to geologic media characteristics, such as organic matter, pH, iron oxide content, and clay mineralogy. (3) Any use of iodine as a hydrologic tracer should take into account the different sorption behaviors of iodide and iodate and the possible conversion of iodine's initial chemical form. (4) The transport behavior of potential FBA and halide tracers under relevant geochemical conditions should be evaluated before beginning ambitious, large-scale field tracer experiments.

  4. Design/cost tradeoff studies. Appendix A. Supporting analyses and tradeoffs, book 2. Earth Observatory Satellite system definition study (EOS)

    Science.gov (United States)

    1974-01-01

    Attitude reference systems for use with the Earth Observatory Satellite (EOS) are described. The systems considered are fixed and gimbaled star trackers, star mappers, and digital sun sensors. Covariance analyses were performed to determine performance for the most promising candidate in low altitude and synchronous orbits. The performance of attitude estimators that employ gyroscopes which are periodically updated by a star sensor is established by a single axis covariance analysis. The other systems considered are: (1) the propulsion system design, (2) electric power and electrical integration, (3) thermal control, (4) ground data processing, and (5) the test plan and cost reduction aspects of observatory integration and test.

  5. 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 death.

  6. Phred-Phrap package to analyses tools: a pipeline to facilitate population genetics re-sequencing studies

    Directory of Open Access Journals (Sweden)

    Machado Moara

    2011-02-01

    Full Text Available Abstract Background Targeted re-sequencing is one of the most powerful and widely used strategies for population genetics studies because it allows an unbiased screening for variation that is suitable for a wide variety of organisms. Examples of studies that require re-sequencing data are evolutionary inferences, epidemiological studies designed to capture rare polymorphisms responsible for complex traits and screenings for mutations in families and small populations with high incidences of specific genetic diseases. Despite the advent of next-generation sequencing technologies, Sanger sequencing is still the most popular approach in population genetics studies because of the widespread availability of automatic sequencers based on capillary electrophoresis and because it is still less prone to sequencing errors, which is critical in population genetics studies. Two popular software applications for re-sequencing studies are Phred-Phrap-Consed-Polyphred, which performs base calling, alignment, graphical edition and genotype calling and DNAsp, which performs a set of population genetics analyses. These independent tools are the start and end points of basic analyses. In between the use of these tools, there is a set of basic but error-prone tasks to be performed with re-sequencing data. Results In order to assist with these intermediate tasks, we developed a pipeline that facilitates data handling typical of re-sequencing studies. Our pipeline: (1 consolidates different outputs produced by distinct Phred-Phrap-Consed contigs sharing a reference sequence; (2 checks for genotyping inconsistencies; (3 reformats genotyping data produced by Polyphred into a matrix of genotypes with individuals as rows and segregating sites as columns; (4 prepares input files for haplotype inferences using the popular software PHASE; and (5 handles PHASE output files that contain only polymorphic sites to reconstruct the inferred haplotypes including polymorphic and

  7. Dating gasoline releases using ground-water chemical analyses: Case studies

    International Nuclear Information System (INIS)

    This paper presents case studies where geochemical data were analyzed in spatial and temporal relation to documented gasoline releases at typical service station sites. In particular, the authors present ground-water analytical data for sites where (1) the date of the gasoline release is known with a good degree of confidence, (2) the release is confined to a relatively short period of time so as to be considered essentially instantaneous, (3) antecedent geochemical condition are known or can be reasonably expected to have been either unaffected by previous hydrocarbon impacts or minor in comparison to known release events, and (4) where geologic materials can be classified as to structure and composition. The authors' intent is to provide empirical data regarding the hydrogeological fate of certain gasoline components, namely the compounds benzene, toluene, ethylbenzene and xylene isomers (BTEX) and methyl-tertiary-butyl ether (MTBE). Particular emphasis is placed on analysis of gasoline weathering as a means of comparing releases in given hydrogeologic environments. Trends seen in a variety of comparative hydrocarbon compound ratios may provide a basis for evaluating relative release dates

  8. Studies on Aries River (Apuseni Mountains pollution using factorial analyses (in Romanian

    Directory of Open Access Journals (Sweden)

    Forray Ferenc La̒za̒r

    2001-04-01

    Full Text Available In the present study we try to use factor analysis in the characterisation of river water chemistry between the municipalities of Cheia and Muncel along a 54-km stretch of the Aries River (NW Romania. The results show that 4 factors can explain 88% of the water chemistry. The first factor explains 39% of the total data variance, and represents the water-rock interactions. This high percent indicates the importance of water rock interactions in defining the chemistry of surface waters. The second factor explains 23% of the data variation and represents the influence of mining effluents. The influence of the mine tailings on water chemistry is represented by the third factor. The sum of the second and the third factor can explain 40% of the total data variance, which confirms that the Arieş River is highly polluted by the mining industry. The last factor, which explains 8% of data variation represents the influence of the agricultural and domestic effluents.

  9. 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.

  10. A CLINICAL STUDY TO ANALYSE THE SPECTRUM OF PERITONITIS DUE TO HOLLOW VISCUS PERFORATION

    Directory of Open Access Journals (Sweden)

    Sai Datta

    2015-07-01

    Full Text Available Perforation peritonitis is the one of the common abdominal surgical emergency . The spectrum of etiology of perforation in Tropical countries continues to be different from its Western counterpart. The objective of the study was to highlight the spectrum of perforation peritonitis as encountered at K aturi M edical C ollege and H ospital , G untur. A.P. Hundred consec utive cases of perforation peritonitis over a period of 26 months . (June 2010 - July 2012 were reviewed in terms of clinical presentation, operative findings and postoperative course retrospectively. The most common type of perforation in our series was per forated duodenal ulcer (56 cases followed by Appendicular (16 cases, Ileal (12 cases, Colonic ( 6 cases, Gastric ( 4 cases, Jejunal (2 cases, Gall bladder (2 cases, Anastomotic ulcer ( 2 cases were reported . Despite delay in seeking medical treatment (32%, the overall mortality (11% , favorably comparable with other published series though the overall morbidity (29% was favorable. In contrast to western literature, where lower gastrointestinal tract perforations predominate, upper gastrointestinal tr act perforations constitute the majority of cases in India. Mostly males and elderly people are affected due to injudicious usage of NSAIDS, alcohol, smoking. ( 11 Withdrawal from these habits and using of proton pump inhibitors and H - Pylori eradication which warrant early recognition and prompt treatment to avoid serious complications and death.

  11. Gene network analyses of first service conception in Brangus heifers: use of genome and trait associations, hypothalamic-transcriptome information, and transcription factors.

    Science.gov (United States)

    Fortes, M R S; Snelling, W M; Reverter, A; Nagaraj, S H; Lehnert, S A; Hawken, R J; DeAtley, K L; Peters, S O; Silver, G A; Rincon, G; Medrano, J F; Islas-Trejo, A; Thomas, M G

    2012-09-01

    Measures of heifer fertility are economically relevant traits for beef production systems and knowledge of candidate genes could be incorporated into future genomic selection strategies. Ten traits related to growth and fertility were measured in 890 Brangus heifers (3/8 Brahman × 5/8 Angus, from 67 sires). These traits were: BW and hip height adjusted to 205 and 365 d of age, postweaning ADG, yearling assessment of carcass traits (i.e., back fat thickness, intramuscular fat, and LM area), as well as heifer pregnancy and first service conception (FSC). These fertility traits were collected from controlled breeding seasons initiated with estrous synchronization and AI targeting heifers to calve by 24 mo of age. The BovineSNP50 BeadChip was used to ascertain 53,692 SNP genotypes for ∼802 heifers. Associations of genotypes and phenotypes were performed and SNP effects were estimated for each trait. Minimally associated SNP (P < 0.05) and their effects across the 10 traits formed the basis for an association weight matrix and its derived gene network related to FSC (57.3% success and heritability = 0.06 ± 0.05). These analyses yielded 1,555 important SNP, which inferred genes linked by 113,873 correlations within a network. Specifically, 1,386 SNP were nodes and the 5,132 strongest correlations (|r| ≥ 0.90) were edges. The network was filtered with genes queried from a transcriptome resource created from deep sequencing of RNA (i.e., RNA-Seq) from the hypothalamus of a prepubertal and a postpubertal Brangus heifer. The remaining hypothalamic-influenced network contained 978 genes connected by 2,560 edges or predicted gene interactions. This hypothalamic gene network was enriched with genes involved in axon guidance, which is a pathway known to influence pulsatile release of LHRH. There were 5 transcription factors with 21 or more connections: ZMAT3, STAT6, RFX4, PLAGL1, and NR6A1 for FSC. The SNP that identified these genes were intragenic and were on chromosomes

  12. The study of association Phyllitidi-Fagetum in Codru-Moma Mountains (North-Western Romania

    Directory of Open Access Journals (Sweden)

    Călin-Gheorghe PĂŞCUŢ

    2010-11-01

    Full Text Available In the present study we aimed to analyse the phytocoenoses that take part in the association Phyllitidi-Fagetum Vida (1959 1963, in the area of the Codru-Moma Mountains.The phytocoenoses of association Phyllitidi-Fagetum Vida (1959 1963 were analyzed from the point of view of floristic diversity, of the life forms spectrum, of the floristic elements spectrum and the diagram of the ecological indices. The presence of this association in Codru-Moma Mountains was signaled following 10 phytocoenological relevées done during the period 2008-2010.

  13. Association between arterial stiffness and atherosclerosis: the Rotterdam Study

    NARCIS (Netherlands)

    N.M-L. van Popele (Nicole); D.E. Grobbee (Diederick); M.L. Bots (Michiel); R. Asmar (Roland); J. Topouchian; R.S. Reneman; A.P.G. Hoeks; D.A. van der Kuip (Deirdre); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted w

  14. Validation study for crediting chlorine in criticality analyses for spent nuclear fuel disposition

    Energy Technology Data Exchange (ETDEWEB)

    Sobes, Vladimir [ORNL; Scaglione, John M [ORNL; Wagner, John C [ORNL; Dunn, Michael E [ORNL

    2015-01-01

    Spent nuclear fuel (SNF) management practices in the United States rely on dry storage systems that include both canister- and cask-based systems. The United States Department of Energy Used Fuel Disposition Campaign is examining the feasibility of direct disposal of dual-purpose (storage and transportation) canisters (DPCs) in a geological repository. One of the major technical challenges for direct disposal is the ability to demonstrate the subcriticality of the DPCs loaded with SNF for the repository performance period (e.g., 10,000 years or more) as the DPCs may undergo degradation over time. Specifically, groundwater ingress into the DPC (i.e., flooding) could allow the system to achieve criticality in scenarios where the neutron absorber plates in the DPC basket have degraded. However, as was shown by Banerjee et al., some aqueous species in the groundwater provide noticeable reactivity reduction for these systems. For certain amounts of particular aqueous species (e.g., chlorine, lithium) in the groundwater, subcriticality can be demonstrated even for DPCs with complete degradation of the neutron absorber plates or a degraded fuel basket configuration. It has been demonstrated that chlorine is the leading impurity, as indicated by significant neutron absorption in the water that is available in reasonable quantities for the deep geological repository media under consideration. This paper presents the results of an investigation of the available integral experiments worldwide that could be used to validate DPC disposal criticality evaluations, including credit for chlorine. Due to the small number of applicable critical configurations, validation through traditional trending analysis was not possible. The bias in the eigenvalue of the application systems due only to the chlorine was calculated using TSURFER analysis and found to be on the order of 100 percent mille (1 pcm = 10-5 keff). This study investigated the design of a series of

  15. Validation Study for Crediting Chlorine in Criticality Analyses for US Spent Nuclear Fuel Disposition

    Energy Technology Data Exchange (ETDEWEB)

    Sobes, Vladimir [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Scaglione, John M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wagner, John C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dunn, Michael E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    Spent nuclear fuel (SNF) management practices in the United States rely on dry storage systems that include both canister- and cask-based systems. The United States Department of Energy Used Fuel Disposition Campaign is examining the feasibility of direct disposal of dual-purpose (storage and transportation) canisters (DPCs) in a geological repository. One of the major technical challenges for direct disposal is the ability to demonstrate the subcriticality of the DPCs loaded with SNF for the repository performance period (e.g., 10,000 years or more) as the DPCs may undergo degradation over time. Specifically, groundwater ingress into the DPC (i.e., flooding) could allow the system to achieve criticality in scenarios where the neutron absorber plates in the DPC basket have degraded. However, as was shown by Banerjee et al., some aqueous species in the groundwater provide noticeable reactivity reduction for these systems. For certain amounts of particular aqueous species (e.g., chlorine, lithium) in the groundwater, subcriticality can be demonstrated even for DPCs with complete degradation of the neutron absorber plates or a degraded fuel basket configuration. It has been demonstrated that chlorine is the leading impurity, as indicated by significant neutron absorption in the water that is available in reasonable quantities for the deep geological repository media under consideration. This paper presents the results of an investigation of the available integral experiments worldwide that could be used to validate DPC disposal criticality evaluations, including credit for chlorine. Due to the small number of applicable critical configurations, validation through traditional trending analysis was not possible. The bias in the eigenvalue of the application systems due only to the chlorine was calculated using TSURFER analysis and found to be on the order of 100 percent mille (1 pcm = 10-5 keff). This study investigated the design of a series of

  16. Validation Study for Crediting Chlorine in Criticality Analyses for US Spent Nuclear Fuel Disposition

    International Nuclear Information System (INIS)

    Spent nuclear fuel (SNF) management practices in the United States rely on dry storage systems that include both canister- and cask-based systems. The United States Department of Energy Used Fuel Disposition Campaign is examining the feasibility of direct disposal of dual-purpose (storage and transportation) canisters (DPCs) in a geological repository. One of the major technical challenges for direct disposal is the ability to demonstrate the subcriticality of the DPCs loaded with SNF for the repository performance period (e.g., 10,000 years or more) as the DPCs may undergo degradation over time. Specifically, groundwater ingress into the DPC (i.e., flooding) could allow the system to achieve criticality in scenarios where the neutron absorber plates in the DPC basket have degraded. However, as was shown by Banerjee et al., some aqueous species in the groundwater provide noticeable reactivity reduction for these systems. For certain amounts of particular aqueous species (e.g., chlorine, lithium) in the groundwater, subcriticality can be demonstrated even for DPCs with complete degradation of the neutron absorber plates or a degraded fuel basket configuration. It has been demonstrated that chlorine is the leading impurity, as indicated by significant neutron absorption in the water that is available in reasonable quantities for the deep geological repository media under consideration. This paper presents the results of an investigation of the available integral experiments worldwide that could be used to validate DPC disposal criticality evaluations, including credit for chlorine. Due to the small number of applicable critical configurations, validation through traditional trending analysis was not possible. The bias in the eigenvalue of the application systems due only to the chlorine was calculated using TSURFER analysis and found to be on the order of 100 percent mille (1 pcm = 10-5 keff). This study investigated the design of a series of critical configurations

  17. 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.

  18. Case-control genome-wide association study of attention-deficit/hyperactivity disorder

    OpenAIRE

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard JL; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotvped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affy...

  19. CCNA Cisco Certified Network Associate Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Learn from the Best - Cisco Networking Authority Todd LammleWritten by Cisco networking authority Todd Lammle, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Todd's straightforward style provides lively examples, hands on and written labs, easy-to-understand analogies, and real-world scenarios that will not only help you prepare for the exam, but also give you a solid foundation as a Cisco networking professional.This Study Guide teaches you how toDescribe how a network worksConfigure, verify and troubleshoot a switch with VLANs and interswitch co

  20. Study of the production mechanism of the η meson in proton-proton collisions by means of analysing power measurements

    International Nuclear Information System (INIS)

    The analysing power measurements for the #vector#pp→ppη reaction studied in this dissertation are used in the determination of the reaction mechanism of the η meson production in nucleon-nucleon collisions. Measurements have been performed in the close-to-threshold energy region at beam momenta of pbeam=2.010 and 2.085 GeV/c, corresponding to the excess energies of Q=10 and 36 MeV, respectively. The experiments were realised by means of a cooler synchrotron and storage ring COSY along with a cluster jet target. For registration of the reaction products the COSY-11 facility has been used. The identification of the η meson has been performed with the missing mass method. The results for the angular dependence of the analysing power combined with the hitherto determined isospin dependence of the total cross section for the η meson production in the nucleon-nucleon collisions, reveal a statistically significant indication that the excitation of the nucleon to the S11 resonance, the process which intermediates the production of the η meson, is predominantly due to the exchange of a π meson between the colliding nucleons. The determined values of the analysing power at both excess energies are consistent with zero implying that the η meson is produced predominantly in the s-wave at both excess energies. (orig.)

  1. The 2012/2013 ABRF Proteomic Research Group Study: Assessing Longitudinal Intralaboratory Variability in Routine Peptide Liquid Chromatography Tandem Mass Spectrometry Analyses.

    Science.gov (United States)

    Bennett, Keiryn L; Wang, Xia; Bystrom, Cory E; Chambers, Matthew C; Andacht, Tracy M; Dangott, Larry J; Elortza, Félix; Leszyk, John; Molina, Henrik; Moritz, Robert L; Phinney, Brett S; Thompson, J Will; Bunger, Maureen K; Tabb, David L

    2015-12-01

    Questions concerning longitudinal data quality and reproducibility of proteomic laboratories spurred the Protein Research Group of the Association of Biomolecular Resource Facilities (ABRF-PRG) to design a study to systematically assess the reproducibility of proteomic laboratories over an extended period of time. Developed as an open study, initially 64 participants were recruited from the broader mass spectrometry community to analyze provided aliquots of a six bovine protein tryptic digest mixture every month for a period of nine months. Data were uploaded to a central repository, and the operators answered an accompanying survey. Ultimately, 45 laboratories submitted a minimum of eight LC-MSMS raw data files collected in data-dependent acquisition (DDA) mode. No standard operating procedures were enforced; rather the participants were encouraged to analyze the samples according to usual practices in the laboratory. Unlike previous studies, this investigation was not designed to compare laboratories or instrument configuration, but rather to assess the temporal intralaboratory reproducibility. The outcome of the study was reassuring with 80% of the participating laboratories performing analyses at a medium to high level of reproducibility and quality over the 9-month period. For the groups that had one or more outlying experiments, the major contributing factor that correlated to the survey data was the performance of preventative maintenance prior to the LC-MSMS analyses. Thus, the Protein Research Group of the Association of Biomolecular Resource Facilities recommends that laboratories closely scrutinize the quality control data following such events. Additionally, improved quality control recording is imperative. This longitudinal study provides evidence that mass spectrometry-based proteomics is reproducible. When quality control measures are strictly adhered to, such reproducibility is comparable among many disparate groups. Data from the study are

  2. Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

    Directory of Open Access Journals (Sweden)

    Binod Neupane

    Full Text Available In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when

  3. Comparative study of bridge plate associated to the intramedullary pin and the dynamic compression plate on the experimental osteotomy fixation of femoral in rabbits (Oryctolagus cuniculus). Clinical, radiographic, histological and scintigraphy analyses; Estudo comparativo da placa em ponte associada ao pino intramedular e da placa de compressao dinamica na fixacao de osteotomia experimental em femur de coelhos (Oryctolagus cuniculus). Analises clinica, radiografica, histologica e cintilografica

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Natalie Ferreira

    2011-07-01

    The objectives were to benchmark and monitor the fracture healing of femoral osteotomy in rabbits after fixation with dynamic compression plate and bridge plate associated with intramedullary pin. Were used 14 New Zealand rabbits, four months old with mean weight of 3.5 pounds, from the Experimental Farm Professor Helio Barbosa of the Veterinary School of Minas Gerais Federal Univ. (UFMG). The animals were randomly divided into two groups (I and II). All rabbits underwent osteotomy across the middle third of right femur. In the group I was made to fix the osteotomy with the bridge plate (BP) associated with intramedullary pin, introduced the technique of minimal invasion. In group II, we used dynamic compression plate (DCP) via the conventional approach. Both groups were evaluated clinical, radiographic, histologic and scintigraphic findings. Clinical assessments were performed weekly until the 12{sup th} postoperative week and radiographic examinations were performed before, immediately after, at 15, 30, 45, 60 and 90 days. The bone scintigraphy were performed before and at 20, 50 and 90 days after surgery to monitor the bone metabolism qualitatively and quantitatively. Observed perfusion and bone healing process. After 90 days of study, there was histopathologic evaluation of the osteotomized area and the insertion of screws. In the region of the osteotomy was observed predominance of trabecular bone in group I and group II, the predominance of bone osteons, compatible with the original bone. On insertion of the screws did not differ between groups and there was cortical discontinuity, little necrosis and local hemorrhage. The two types of fixation have led to consolidation within the scheduled period, maturing in early fixation with DCP fixation compared with BP. Scintigraphy demonstrated by the indices of activity and image characteristics, the process of bone healing was significantly greater in animals undergoing early fixation with DCP. (author)

  4. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  5. Genomic analyses of cherry rusty mottle group and cherry twisted leaf-associated viruses reveal a possible new genus within the family betaflexiviridae.

    Science.gov (United States)

    Villamor, D E V; Susaimuthu, J; Eastwell, K C

    2015-03-01

    It is demonstrated that closely related viruses within the family Betaflexiviridae are associated with a number of diseases that affect sweet cherry (Prunus avium) and other Prunus spp. Cherry rusty mottle-associated virus (CRMaV) is correlated with the appearance of cherry rusty mottle disease (CRMD), and Cherry twisted leaf-associated virus (CTLaV) is linked to cherry twisted leaf disease (CTLD) and apricot ringpox disease (ARPD). Comprehensive analysis of previously reported full genomic sequences plus those determined in this study representing isolates of CTLaV, CRMaV, Cherry green ring mottle virus, and Cherry necrotic rusty mottle virus revealed segregation of sequences into four clades corresponding to distinct virus species. High-throughput sequencing of RNA from representative source trees for CRMD, CTLD, and ARPD did not reveal additional unique virus sequences that might be associated with these diseases, thereby further substantiating the association of CRMaV and CTLaV with CRMD and CTLD or ARPD, respectively. Based on comparison of the nucleotide and amino acid sequence identity values, phylogenetic relationships with other triple-gene block-coding viruses within the family Betaflexiviridae, genome organization, and natural host range, a new genus (Robigovirus) is suggested. PMID:25496302

  6. Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia

    DEFF Research Database (Denmark)

    Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio;

    2012-01-01

    Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem......, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs)....

  7. Gene network analyses of first service conception in Brangus heifers: use of genome and trait associations, hypothalamic-transcriptome information, and transcription factors.

    Science.gov (United States)

    Fortes, M R S; Snelling, W M; Reverter, A; Nagaraj, S H; Lehnert, S A; Hawken, R J; DeAtley, K L; Peters, S O; Silver, G A; Rincon, G; Medrano, J F; Islas-Trejo, A; Thomas, M G

    2012-09-01

    Measures of heifer fertility are economically relevant traits for beef production systems and knowledge of candidate genes could be incorporated into future genomic selection strategies. Ten traits related to growth and fertility were measured in 890 Brangus heifers (3/8 Brahman × 5/8 Angus, from 67 sires). These traits were: BW and hip height adjusted to 205 and 365 d of age, postweaning ADG, yearling assessment of carcass traits (i.e., back fat thickness, intramuscular fat, and LM area), as well as heifer pregnancy and first service conception (FSC). These fertility traits were collected from controlled breeding seasons initiated with estrous synchronization and AI targeting heifers to calve by 24 mo of age. The BovineSNP50 BeadChip was used to ascertain 53,692 SNP genotypes for ∼802 heifers. Associations of genotypes and phenotypes were performed and SNP effects were estimated for each trait. Minimally associated SNP (P Brangus heifer. The remaining hypothalamic-influenced network contained 978 genes connected by 2,560 edges or predicted gene interactions. This hypothalamic gene network was enriched with genes involved in axon guidance, which is a pathway known to influence pulsatile release of LHRH. There were 5 transcription factors with 21 or more connections: ZMAT3, STAT6, RFX4, PLAGL1, and NR6A1 for FSC. The SNP that identified these genes were intragenic and were on chromosomes 1, 5, 9, and 11. Chromosome 5 harbored both STAT6 and RFX4. The large number of interactions and genes observed with network analyses of multiple sources of genomic data (i.e., GWAS and RNA-Seq) support the concept of FSC being a polygenic trait. PMID:22739780

  8. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha;

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this ...

  9. Association of airborne moisture-indicating microorganisms withbuilding-related symptoms and water damage in 100 U.S. office buildings:Analyses of the U.S. EPA BASE data

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, Mark J.; Lei, Quanhong; Cozen, Myrna O.; Shendell, DerekG.; Macher, Janet M.; Tsai, Feng C.

    2003-10-01

    Metrics of culturable airborne microorganisms for either total organisms or suspected harmful subgroups have generally not been associated with symptoms among building occupants. However, the visible presence of moisture damage or mold in residences and other buildings has consistently been associated with respiratory symptoms and other health effects. This relationship is presumably caused by adverse but uncharacterized exposures to moisture-related microbiological growth. In order to assess this hypothesis, we studied relationships in U.S. office buildings between the prevalence of respiratory and irritant symptoms, the concentrations of airborne microorganisms that require moist surfaces on which to grow, and the presence of visible water damage. For these analyses we used data on buildings, indoor environments, and occupants collected from a representative sample of 100 U.S. office buildings in the U.S. Environmental Protection Agency's Building Assessment Survey and Evaluation (EPA BASE) study. We created 19 alternate metrics, using scales ranging from 3-10 units, that summarized the concentrations of airborne moisture-indicating microorganisms (AMIMOs) as indicators of moisture in buildings. Two were constructed to resemble a metric previously reported to be associated with lung function changes in building occupants; the others were based on another metric from the same group of Finnish researchers, concentration cutpoints from other studies, and professional judgment. We assessed three types of associations: between AMIMO metrics and symptoms in office workers, between evidence of water damage and symptoms, and between water damage and AMIMO metrics. We estimated (as odds ratios (ORs) with 95% confidence intervals) the unadjusted and adjusted associations between the 19 metrics and two types of weekly, work-related symptoms--lower respiratory and mucous membrane--using logistic regression models. Analyses used the original AMIMO metrics and were

  10. A study of association between dental health status and pregnancy

    OpenAIRE

    Bhavana Gupta; Attiuddin Siddique

    2013-01-01

    Background: To study the association between dental health status and pregnancy in rural India. Methods: The cohort study was carried out in the department of Obstetrics and Gynecology at Integral Institute of Medical Sciences and Research, Lucknow from March 2012 to April 2013, for the period of 1year. The dental health statuses of 600 antenatal cases were studied. The prevalence of gingivitis, dental caries and periodontal disease were studied. The association between poor oral hygiene, ...

  11. A protocol for a systematic review on the impact of unpublished studies and studies published in the gray literature in meta-analyses

    OpenAIRE

    Schmucker, Christine; Bluemle, Annette; Briel, Matthias; Portalupi, Susan; Lang, Britta; Motschall, Edith; Schwarzer, Guido; Bassler, Dirk; Mueller, Katharina F; von Elm, Erik; Meerpohl, Joerg J

    2013-01-01

    BACKGROUND: Meta-analyses are particularly vulnerable to the effects of publication bias. Despite methodologists' best efforts to locate all evidence for a given topic the most comprehensive searches are likely to miss unpublished studies and studies that are published in the gray literature only. If the results of the missing studies differ systematically from the published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention's effects.As part of the OPEN pr...

  12. Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

    Science.gov (United States)

    Jing, Jiaojiao; Pattaro, Cristian; Hoppmann, Anselm; Okada, Yukinori; Fox, Caroline S; Köttgen, Anna

    2016-10-01

    Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. PMID:27263491

  13. permGPU: Using graphics processing units in RNA microarray association studies

    Directory of Open Access Journals (Sweden)

    George Stephen L

    2010-06-01

    Full Text Available Abstract Background Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. Results We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. Conclusions permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

  14. Association analyses of oxidative stress, aerobic capacity, daily physical activity, and body composition parameters in patients with mild to moderate COPD

    OpenAIRE

    Genç, Abdurrahman; ÜÇOK, Kağan; ŞENER, Ümit; KOYUNCU, Tülay; AKAR, Olcay; ÇELİK, Sefa; Ünlü, Mehmet

    2014-01-01

    To investigate total oxidant and antioxidant status, maximal aerobic capacity, daily physical activity, pulmonary functions, and body composition changes, as well as the associations among these parameters, in patients with mild to moderate chronic obstructive pulmonary disease (COPD) versus healthy controls. Materials and methods: The study included 30 male patients newly diagnosed with COPD and 30 body mass index-matched, nonsmoker male controls. Maximal aerobic capacity, daily physical ac...

  15. Efficacy of levomilnacipran extended-release in improving functional impairment associated with major depressive disorder: pooled analyses of five double-blind, placebo-controlled trials

    OpenAIRE

    Sambunaris, Angelo; Gommoll, Carl; Chen, ChangZheng; Greenberg, William M

    2014-01-01

    Major depressive disorder (MDD) is characterized by increased rates of impaired function and disability. During antidepressant treatment, functional improvement often lags behind symptomatic resolution, and residual impairment is associated with an increased risk for relapse. When evaluating MDD treatments, it is important to assess not only depressive symptoms but also functional outcomes. In this post-hoc analysis, data from five studies were pooled to examine the effect of levomilnacipran ...

  16. A Genomewide Association Study of Early Spontaneous Preterm Delivery

    Science.gov (United States)

    Zhang, Heping; Baldwin, Don A.; Bukowski, Radek K.; Parry, Samuel; Xu, Yaji; Song, Chi; Andrews, William W.; Saade, George R.; Esplin, M. Sean; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John; Varner, Michael; Biggio, Joseph R.

    2015-01-01

    Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment. Genotyping was performed using Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare allele occurrence rates between case and control groups, and incorporated quality control and multiple-testing adjustments. We analyzed DNA samples from mother-infant pairs from early SPTB cases (200/7 to 336/7 weeks, 959 women and 979 neonates) and term delivery controls (390/7 to 416/7 weeks, 960 women and 985 neonates). For validation purposes, we included an independent validation cohort consisting of early SPTB cases (293 mothers and 243 infants) and term controls (200 mothers and 149 infants). Clustering analysis revealed no population stratification. Multiple maternal SNPs were identified with association p-values between 10E-5 and 10E-6. The most significant maternal SNP was rs17053026 on chromosome 3 with an odds ratio (OR) 0.44 with a p-value of 1.0E-06. Two neonatal SNPs reached the genome-wide significance threshold, including rs17527054 on chromosome 6p22 with a p-value of 2.7E-12 and rs3777722 on chromosome 6q27 with a p-value of 1.4E-10. However, we could not replicate these findings after adjusting for multiple comparisons in a validation cohort. This is the first report of a genomewide case-control study to identify single nucleotide polymorphisms (SNPs) that correlate with SPTB. PMID:25599974

  17. Genetic association studies in drug-induced liver injury.

    Science.gov (United States)

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  18. Socio-economic inequality in childhood and beyond: an overview of challenges and findings from comparative analyses of cohort studies*

    Science.gov (United States)

    Waldfogel, Jane

    2016-01-01

    The growing number of countries with large child cohort studies offers an unprecedented opportunity for comparative research. A topic of central interest in my research is, to what extent the sizable gaps in development that exist between children from different socioeconomic status (SES) groups in the US are also present in other countries, and to what extent the mechanisms explaining these gaps are similar or different across countries. This overview draws on the results of comparative analyses of birth cohort study data collected in Australia, Canada, the United Kingdom, and the United States, to illustrate the challenges that arise in carrying out this kind of research and the way these challenges were met – in particular those having to do with data access and comparability, and those having to do with causal inference. I conclude that this type of research also offers great promise as shown by findings on SES gaps in child development in the four countries.

  19. Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study

    OpenAIRE

    Shea, M. Kyla; Booth, Sarah L.; Massaro, Joseph M.; Jacques, Paul F.; D’Agostino, Ralph B.; Dawson-Hughes, Bess; Ordovas, José M; O’Donnell, Christopher J.; Kathiresan, Sekar; Keaney, John F.; Vasan, Ramachandran S.; Emelia J Benjamin

    2007-01-01

    In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, we used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, lipid lowering and hormone replacement medications, season, and menopausal status. Participants were from the Framingham Offspring Study (n=1381; mean age 59 years; 52% women). Vitamin K status, measured by plasma p...

  20. Shearing microscopy using polarized optical microscope with shear stage and spectral analyser to study liquid crystalline polymers.

    Science.gov (United States)

    Tanaka, K; Yonetake, K; Masuko, T; Akiyama, R

    2002-01-01

    In-situ polarized optical microscopy using a shear stage and a spectral analyser as well as a CCD camera were applied to study the phase transition under shear flow for a thermotropic and side-chain-type liquid crystalline polysiloxane. The onset of the appearance of anisotropic texture of the polysiloxane was observed under shear flow using the CCD camera at temperatures much higher than the isotropic-liquid crystalline phase transition temperature if the polysiloxane was cooled from the isotropic phase in the quiescent state. Both the onset temperature and the temperature for full development of the anisotropic texture across the field of view became higher as the shear rate increased. The transmitted light intensity was also measured using a spectral analyser with crossed polarisers at wavelengths from 300 nm to 800 nm, and the integrated intensity of the spectrum was calculated. Changes in the spectrum and the integrated intensity against temperature in the cooling process were compared with observation using the CCD camera. Temperature dependence of the integrated intensity showed that the onset of the appearance of the anisotropic texture under high shear rates was detected at temperatures slightly higher than that observed using the CCD camera. PMID:11856377

  1. Is the relationship between common mental disorder and adiposity bidirectional? Prospective analyses of a UK general population-based study

    OpenAIRE

    Fezeu, L.K.; Batty, G D; Gale, C R; Kivimaki, M.; Hercberg, S; Czernichow, S.

    2015-01-01

    The direction of the association between mental health and adiposity is poorly understood. Our objective was to empirically examine this link in a UK study. This is a prospective cohort study of 3 388 people (men) aged ? 18 years at study induction who participated in both the UK Health and Lifestyle Survey at baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both survey examinations, body mass index, waist circumference and self-reported common mental disorder (the 30-it...

  2. An association study between the norepinephrine transporter gene and depression

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Jacobsen, Iben S; Grynderup, Matias B;

    2013-01-01

    A2 for solute carrier 6 family member 2). The gene is responsible for the reuptake of norepinephrine and dopamine into presynaptic nerve terminals and the norepinephrine system appears to play an important role in depression. We therefore analyzed genetic variants within SLC6A2 for association......A potential approach for identification of candidate genes for depression is characterization of chromosomal rearrangements. Through analysis of a chromosome translocation in an individual with recurrent depression, we identified a potential candidate gene: the norepinephrine transporter (NET; SLC6...... with depression in 408 affected and 559 control individuals from Denmark. After quality control of the genotypes, 31 of 45 single nucleotide polymorphisms (SNPs) were left for analyses. One SNP showed a nominal association with depression but did not survive correction for multiple testing. The results from our...

  3. Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington’s Disease

    Science.gov (United States)

    Scarpa, Joseph R.; Jiang, Peng; Losic, Bojan; Readhead, Ben; Dudley, Joel T.; Vitaterna, Martha H.; Turek, Fred W.

    2016-01-01

    Recent systems-based analyses have demonstrated that sleep and stress traits emerge from shared genetic and transcriptional networks, and clinical work has elucidated the emergence of sleep dysfunction and stress susceptibility as early symptoms of Huntington's disease. Understanding the biological bases of these early non-motor symptoms may reveal therapeutic targets that prevent disease onset or slow disease progression, but the molecular mechanisms underlying this complex clinical presentation remain largely unknown. In the present work, we specifically examine the relationship between these psychiatric traits and Huntington's disease (HD) by identifying striatal transcriptional networks shared by HD, stress, and sleep phenotypes. First, we utilize a systems-based approach to examine a large publicly available human transcriptomic dataset for HD (GSE3790 from GEO) in a novel way. We use weighted gene coexpression network analysis and differential connectivity analyses to identify transcriptional networks dysregulated in HD, and we use an unbiased ranking scheme that leverages both gene- and network-level information to identify a novel astrocyte-specific network as most relevant to HD caudate. We validate this result in an independent HD cohort. Next, we computationally predict FOXO3 as a regulator of this network, and use multiple publicly available in vitro and in vivo experimental datasets to validate that this astrocyte HD network is downstream of a signaling pathway important in adult neurogenesis (TGFβ-FOXO3). We also map this HD-relevant caudate subnetwork to striatal transcriptional networks in a large (n = 100) chronically stressed (B6xA/J)F2 mouse population that has been extensively phenotyped (328 stress- and sleep-related measurements), and we show that this striatal astrocyte network is correlated to sleep and stress traits, many of which are known to be altered in HD cohorts. We identify causal regulators of this network through Bayesian network

  4. Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.

    Science.gov (United States)

    Scarpa, Joseph R; Jiang, Peng; Losic, Bojan; Readhead, Ben; Gao, Vance D; Dudley, Joel T; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2016-07-01

    Recent systems-based analyses have demonstrated that sleep and stress traits emerge from shared genetic and transcriptional networks, and clinical work has elucidated the emergence of sleep dysfunction and stress susceptibility as early symptoms of Huntington's disease. Understanding the biological bases of these early non-motor symptoms may reveal therapeutic targets that prevent disease onset or slow disease progression, but the molecular mechanisms underlying this complex clinical presentation remain largely unknown. In the present work, we specifically examine the relationship between these psychiatric traits and Huntington's disease (HD) by identifying striatal transcriptional networks shared by HD, stress, and sleep phenotypes. First, we utilize a systems-based approach to examine a large publicly available human transcriptomic dataset for HD (GSE3790 from GEO) in a novel way. We use weighted gene coexpression network analysis and differential connectivity analyses to identify transcriptional networks dysregulated in HD, and we use an unbiased ranking scheme that leverages both gene- and network-level information to identify a novel astrocyte-specific network as most relevant to HD caudate. We validate this result in an independent HD cohort. Next, we computationally predict FOXO3 as a regulator of this network, and use multiple publicly available in vitro and in vivo experimental datasets to validate that this astrocyte HD network is downstream of a signaling pathway important in adult neurogenesis (TGFβ-FOXO3). We also map this HD-relevant caudate subnetwork to striatal transcriptional networks in a large (n = 100) chronically stressed (B6xA/J)F2 mouse population that has been extensively phenotyped (328 stress- and sleep-related measurements), and we show that this striatal astrocyte network is correlated to sleep and stress traits, many of which are known to be altered in HD cohorts. We identify causal regulators of this network through Bayesian network

  5. Australian and South Pacific External Studies Association: Odlaa's Regional Predecessor

    Science.gov (United States)

    Bewley, Donald

    2008-01-01

    The Australian and South Pacific External Studies Association (ASPESA)-- the predecessor of the Open and Distance Learning Association of Australia, Inc. (ODLAA)--was founded in 1973. From the outset, ASPESA adopted a broader-than-Australia focus for open and distance learning that included New Zealand, Papua New Guinea, and the member countries…

  6. A meta-analytic review of life cycle assessment and flow analyses studies of palm oil biodiesel.

    Science.gov (United States)

    Manik, Yosef; Halog, Anthony

    2013-01-01

    This work reviews and performs a meta-analysis of the recent life cycle assessment and flow analyses studies palm oil biodiesel. The best available data and information are extracted, summarized, and discussed. Most studies found palm oil biodiesel would produce positive energy balance with an energy ratio between 2.27 and 4.81, and with a net energy production of 112 GJ ha(-1) y(-1). With the exception of a few studies, most conclude that palm oil biodiesel is a net emitter of greenhouse gases (GHG). The origin of oil palm plantation (planted area) is the foremost determinant of GHG emissions and C payback time (CPBT). Converting peatland forest results in GHG emissions up to 60 tons CO(2) equivalent (eq) ha(-1) y(-1) leading to 420 years of CPBT. In contrast, converting degraded land or grassland for plantation can positively offset the system to become a net sequester of 5 tons CO(2) eq ha(-1) y(-1). Few studies have discussed cradle-to-grave environmental impacts such as acidification, eutrophication, toxicity, and biodiversity, which open opportunity for further studies. PMID:22941969

  7. Hierarchical Linear Modeling Analyses of NEO-PI-R Scales In the Baltimore Longitudinal Study of Aging

    Science.gov (United States)

    Terracciano, Antonio; McCrae, Robert R.; Brant, Larry J.; Costa, Paul T.

    2009-01-01

    We examined age trends in the five factors and 30 facets assessed by the Revised NEO Personality Inventory in Baltimore Longitudinal Study of Aging data (N = 1,944; 5,027 assessments) collected between 1989 and 2004. Consistent with cross-sectional results, Hierarchical Linear Modeling analyses showed gradual personality changes in adulthood: a decline up to age 80 in Neuroticism, stability and then decline in Extraversion, decline in Openness, increase in Agreeableness, and increase up to age 70 in Conscientiousness. Some facets showed different curves from the factor they define. Birth cohort effects were modest, and there were no consistent Gender × Age interactions. Significant non-normative changes were found for all five factors; they were not explained by attrition but might be due to genetic factors, disease, or life experience. PMID:16248708

  8. Study on dynamic response of embedded long span corrugated steel culverts using scaled model shaking table tests and numerical analyses

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A series of scaled-model shaking table tests and its simulation analyses using dynamic finite element method were performed to clarify the dynamic behaviors and the seismic stability of embedded corrugated steel culverts due to strong earthquakes like the 1995 Hyogoken-nanbu earthquake. The dynamic strains of the embedded culvert models and the seismic soil pressure acting on the models due to sinusoidal and random strong motions were investigated. This study verified that the corrugated culvert model was subjected to dynamic horizontal forces (lateral seismic soil pressure) from the surrounding ground,which caused the large bending strains on the structure; and that the structures do not exceed the allowable plastic deformation and do not collapse completely during strong earthquake like Hyogoken-nanbu earthquake. The results obtained are useful for design and construction of embedded long span corrugated steel culverts in seismic regions.

  9. Acquisition, Analyses and Interpretation of fMRI Data: A Study on the Effective Connectivity in Human Primary Auditory Cortices

    International Nuclear Information System (INIS)

    A study on the effective connectivity characteristics in auditory cortices was conducted on five healthy Malay male subjects with the age of 20 to 40 years old using functional magnetic resonance imaging (fMRI), statistical parametric mapping (SPM5) and dynamic causal modelling (DCM). A silent imaging paradigm was used to reduce the scanner sound artefacts on functional images. The subjects were instructed to pay attention to the white noise stimulus binaurally given at intensity level of 70 dB higher than the hearing level for normal people. Functional specialisation was studied using Matlab-based SPM5 software by means of fixed effects (FFX), random effects (RFX) and conjunction analyses. Individual analyses on all subjects indicate asymmetrical bilateral activation between the left and right auditory cortices in Brodmann areas (BA)22, 41 and 42 involving the primary and secondary auditory cortices. The three auditory areas in the right and left auditory cortices are selected for the determination of the effective connectivity by constructing 9 network models. The effective connectivity is determined on four out of five subjects with the exception of one subject who has the BA22 coordinates located too far from BA22 coordinates obtained from group analysis. DCM results showed the existence of effective connectivity between the three selected auditory areas in both auditory cortices. In the right auditory cortex, BA42 is identified as input centre with unidirectional parallel effective connectivities of BA42→BA41and BA42→BA22. However, for the left auditory cortex, the input is BA41 with unidirectional parallel effective connectivities of BA41→BA42 and BA41→BA22. The connectivity between the activated auditory areas suggests the existence of signal pathway in the auditory cortices even when the subject is listening to noise. (author)

  10. Assessing models of speciation under different biogeographic scenarios; An empirical study using multi-locus and RNA-seq analyses

    Science.gov (United States)

    Edwards, Taylor; Tollis, Marc; Hsieh, PingHsun; Gutenkunst, Ryan N.; Liu, Zhen; Kusumi, Kenro; Culver, Melanie; Murphy, Robert W.

    2016-01-01

    Evolutionary biology often seeks to decipher the drivers of speciation, and much debate persists over the relative importance of isolation and gene flow in the formation of new species. Genetic studies of closely related species can assess if gene flow was present during speciation, because signatures of past introgression often persist in the genome. We test hypotheses on which mechanisms of speciation drove diversity among three distinct lineages of desert tortoise in the genus Gopherus. These lineages offer a powerful system to study speciation, because different biogeographic patterns (physical vs. ecological segregation) are observed at opposing ends of their distributions. We use 82 samples collected from 38 sites, representing the entire species' distribution and generate sequence data for mtDNA and four nuclear loci. A multilocus phylogenetic analysis in *BEAST estimates the species tree. RNA-seq data yield 20,126 synonymous variants from 7665 contigs from two individuals of each of the three lineages. Analyses of these data using the demographic inference package ∂a∂i serve to test the null hypothesis of no gene flow during divergence. The best-fit demographic model for the three taxa is concordant with the *BEAST species tree, and the ∂a∂i analysis does not indicate gene flow among any of the three lineages during their divergence. These analyses suggest that divergence among the lineages occurred in the absence of gene flow and in this scenario the genetic signature of ecological isolation (parapatric model) cannot be differentiated from geographic isolation (allopatric model).

  11. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H;

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  12. Current approaches of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Xu

    2008-01-01

    @@ With rapid advances in high-throughput genotyping technology and the great increase in information available on SNPs throughout the genuine, genuine-wide association(GWA) studies have now become feasible.

  13. Genetic association study of common mitochondrial variants on body fat mass.

    Directory of Open Access Journals (Sweden)

    Tie-Lin Yang

    Full Text Available Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³ and body fat mass (adjusted P = 5.67×10⁻⁴ Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.

  14. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv;

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs......7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of [Formula: see text]O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher...

  15. Families or Unrelated: The Evolving Debate in Genetic Association Studies

    OpenAIRE

    Fardo, David W.; Charnigo, Richard; Epstein, Michael P.

    2012-01-01

    To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then de...

  16. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Hansel, Nadia N; Paré, Peter D; Rafaels, Nicholas; Sin, Don D; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W Mark; Pascoe, Chris D; Arsenault, Bryna A; Postma, Dirkje S; Boezen, H Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S; Cho, Michael H; Litonjua, Augusto A; Sparrow, David; Ober, Carole; Wise, Robert A; Connett, John; Neptune, Enid R; Beaty, Terri H; Ruczinski, Ingo; Mathias, Rasika A; Barnes, Kathleen C

    2015-08-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10(-8)). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10(-8) < P ≤ 4.6 × 10(-6)). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10(-9)) and MYH15 (P = 1.62 × 10(-6)), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

  17. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Paré, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, H. Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10−8). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10−8 < P ≤ 4.6 × 10−6). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10−9) and MYH15 (P = 1.62 × 10−6), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

  18. A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC, triglycerides (TG, low-density lipoprotein cholesterol (LDL and high-density lipoprotein cholesterol (HDL in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16, 1.38 × 10(-6 and 5.59 × 10(-9, respectively. These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

  19. Evidence for the selective reporting of analyses and discrepancies in clinical trials: a systematic review of cohort studies of clinical trials.

    Directory of Open Access Journals (Sweden)

    Kerry Dwan

    2014-06-01

    Full Text Available Most publications about selective reporting in clinical trials have focussed on outcomes. However, selective reporting of analyses for a given outcome may also affect the validity of findings. If analyses are selected on the basis of the results, reporting bias may occur. The aims of this study were to review and summarise the evidence from empirical cohort studies that assessed discrepant or selective reporting of analyses in randomised controlled trials (RCTs.A systematic review was conducted and included cohort studies that assessed any aspect of the reporting of analyses of RCTs by comparing different trial documents, e.g., protocol compared to trial report, or different sections within a trial publication. The Cochrane Methodology Register, Medline (Ovid, PsycInfo (Ovid, and PubMed were searched on 5 February 2014. Two authors independently selected studies, performed data extraction, and assessed the methodological quality of the eligible studies. Twenty-two studies (containing 3,140 RCTs published between 2000 and 2013 were included. Twenty-two studies reported on discrepancies between information given in different sources. Discrepancies were found in statistical analyses (eight studies, composite outcomes (one study, the handling of missing data (three studies, unadjusted versus adjusted analyses (three studies, handling of continuous data (three studies, and subgroup analyses (12 studies. Discrepancy rates varied, ranging from 7% (3/42 to 88% (7/8 in statistical analyses, 46% (36/79 to 82% (23/28 in adjusted versus unadjusted analyses, and 61% (11/18 to 100% (25/25 in subgroup analyses. This review is limited in that none of the included studies investigated the evidence for bias resulting from selective reporting of analyses. It was not possible to combine studies to provide overall summary estimates, and so the results of studies are discussed narratively.Discrepancies in analyses between publications and other study documentation

  20. Body mass index, exercise, and other lifestyle factors in relation to age at natural menopause: analyses from the breakthrough generations study.

    Science.gov (United States)

    Morris, Danielle H; Jones, Michael E; Schoemaker, Minouk J; McFadden, Emily; Ashworth, Alan; Swerdlow, Anthony J

    2012-05-15

    The authors examined the effect of women's lifestyles on the timing of natural menopause using data from a cross-sectional questionnaire used in the United Kingdom-based Breakthrough Generations Study in 2003-2011. The analyses included 50,678 women (21,511 who had experienced a natural menopause) who were 40-98 years of age at study entry and did not have a history of breast cancer. Cox competing risks proportional hazards models were fitted to examine the relation of age at natural menopause to lifestyle and anthropometric factors. Results were adjusted for age at reporting, smoking status at menopause, parity, and body mass index at age 40 years, as appropriate. All P values were 2-sided. High adult weight (P(trend) vegetarian (P < 0.001) were associated with older age at menopause. Neither height nor history of an eating disorder was associated with menopausal age. These findings show the importance of lifestyle factors in determining menopausal age. PMID:22494951

  1. Genome-wide association studies and contribution to cardiovascular physiology.

    Science.gov (United States)

    Munroe, Patricia B; Tinker, Andrew

    2015-09-01

    The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology.

  2. The relationship of bone and blood lead to hypertension: Further analyses of the normative aging study data

    Energy Technology Data Exchange (ETDEWEB)

    Hu, H.; Kim, Rokho; Korrick, S. [Harvard Medical School, Boston, MA (United States)]|[Harvard Health of Public Health, Boston, MA (United States); Rotnitzky, A. [Harvard School of Public Health, Boston, MA (United States)] [and others

    1996-12-31

    In an earlier report based on participants in the Veterans Administration Normative Aging Study, we found a significant association between the risk of hypertension and lead levels in tibia. To examine the possible confounding effects of education and occupation, we considered in this study five levels of education and three levels of occupation as independent variables in the statistical model. Of 1,171 active subjects seen between August 1991 and December 1994, 563 provided complete data for this analysis. In the initial logistic regression model, acre and body mass index, family history of hypertension, and dietary sodium intake, but neither cumulative smoking nor alcohol ingestion, conferred increased odds ratios for being hypertensive that were statistically significant. When the lead biomarkers were added separately to this initial logistic model, tibia lead and patella lead levels were associated with significantly elevated odds ratios for hypertension. In the final backward elimination logistic regression model that included categorical variables for education and occupation, the only variables retained were body mass index, family history of hypertension, and tibia lead level. We conclude that education and occupation variables were not confounding the association between the lead biomarkers and hypertension that we reported previously. 27 refs., 3 tabs.

  3. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    Science.gov (United States)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; M. Maloney, Cliona; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P.R.; Mehta, Amar; van Iperen, Erik P.A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M.A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; Boer, Anthonius de; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E.K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; J. Meyer, Nuala; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W.M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I.W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; D. Christie, Jason; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F.A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. PMID:21194676

  4. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

    Science.gov (United States)

    Gottlieb, D J; Hek, K; Chen, T-H; Watson, N F; Eiriksdottir, G; Byrne, E M; Cornelis, M; Warby, S C; Bandinelli, S; Cherkas, L; Evans, D S; Grabe, H J; Lahti, J; Li, M; Lehtimäki, T; Lumley, T; Marciante, K D; Pérusse, L; Psaty, B M; Robbins, J; Tranah, G J; Vink, J M; Wilk, J B; Stafford, J M; Bellis, C; Biffar, R; Bouchard, C; Cade, B; Curhan, G C; Eriksson, J G; Ewert, R; Ferrucci, L; Fülöp, T; Gehrman, P R; Goodloe, R; Harris, T B; Heath, A C; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, D J; Jensen, M K; Johnson, A D; Kähönen, M; Kao, L; Kraft, P; Larkin, E K; Lauderdale, D S; Luik, A I; Medici, M; Montgomery, G W; Palotie, A; Patel, S R; Pistis, G; Porcu, E; Quaye, L; Raitakari, O; Redline, S; Rimm, E B; Rotter, J I; Smith, A V; Spector, T D; Teumer, A; Uitterlinden, A G; Vohl, M-C; Widen, E; Willemsen, G; Young, T; Zhang, X; Liu, Y; Blangero, J; Boomsma, D I; Gudnason, V; Hu, F; Mangino, M; Martin, N G; O'Connor, G T; Stone, K L; Tanaka, T; Viikari, J; Gharib, S A; Punjabi, N M; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H

    2015-10-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. PMID:25469926

  5. Association analyses of large-scale glycan microarray data reveal novel host-specific substructures in influenza A virus binding glycans

    Science.gov (United States)

    Zhao, Nan; Martin, Brigitte E.; Yang, Chun-Kai; Luo, Feng; Wan, Xiu-Feng

    2015-10-01

    Influenza A viruses can infect a wide variety of animal species and, occasionally, humans. Infection occurs through the binding formed by viral surface glycoprotein hemagglutinin and certain types of glycan receptors on host cell membranes. Studies have shown that the α2,3-linked sialic acid motif (SA2,3Gal) in avian, equine, and canine species; the α2,6-linked sialic acid motif (SA2,6Gal) in humans; and SA2,3Gal and SA2,6Gal in swine are responsible for the corresponding host tropisms. However, more detailed and refined substructures that determine host tropisms are still not clear. Thus, in this study, we applied association mining on a set of glycan microarray data for 211 influenza viruses from five host groups: humans, swine, canine, migratory waterfowl, and terrestrial birds. The results suggest that besides Neu5Acα2-6Galβ, human-origin viruses could bind glycans with Neu5Acα2-8Neu5Acα2-8Neu5Ac and Neu5Gcα2-6Galβ1-4GlcNAc substructures; Galβ and GlcNAcβ terminal substructures, without sialic acid branches, were associated with the binding of human-, swine-, and avian-origin viruses; sulfated Neu5Acα2-3 substructures were associated with the binding of human- and swine-origin viruses. Finally, through three-dimensional structure characterization, we revealed that the role of glycan chain shapes is more important than that of torsion angles or of overall structural similarities in virus host tropisms.

  6. Genetic association studies in lumbar disc degeneration: a systematic review.

    Directory of Open Access Journals (Sweden)

    Pasi J Eskola

    Full Text Available OBJECTIVE: 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. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576. CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

  7. 3D RECORDING FOR 2D DELIVERING – THE EMPLOYMENT OF 3D MODELS FOR STUDIES AND ANALYSES

    Directory of Open Access Journals (Sweden)

    A. Rizzi

    2012-09-01

    Full Text Available In the last years, thanks to the advances of surveying sensors and techniques, many heritage sites could be accurately replicated in digital form with very detailed and impressive results. The actual limits are mainly related to hardware capabilities, computation time and low performance of personal computer. Often, the produced models are not visible on a normal computer and the only solution to easily visualized them is offline using rendered videos. This kind of 3D representations is useful for digital conservation, divulgation purposes or virtual tourism where people can visit places otherwise closed for preservation or security reasons. But many more potentialities and possible applications are available using a 3D model. The problem is the ability to handle 3D data as without adequate knowledge this information is reduced to standard 2D data. This article presents some surveying and 3D modeling experiences within the APSAT project ("Ambiente e Paesaggi dei Siti d’Altura Trentini", i.e. Environment and Landscapes of Upland Sites in Trentino. APSAT is a multidisciplinary project funded by the Autonomous Province of Trento (Italy with the aim documenting, surveying, studying, analysing and preserving mountainous and hill-top heritage sites located in the region. The project focuses on theoretical, methodological and technological aspects of the archaeological investigation of mountain landscape, considered as the product of sequences of settlements, parcelling-outs, communication networks, resources, and symbolic places. The mountain environment preserves better than others the traces of hunting and gathering, breeding, agricultural, metallurgical, symbolic activities characterised by different lengths and environmental impacts, from Prehistory to the Modern Period. Therefore the correct surveying and documentation of this heritage sites and material is very important. Within the project, the 3DOM unit of FBK is delivering all the surveying

  8. A comparative study between xerographic, computer-assisted overlay generation and animated-superimposition methods in bite mark analyses.

    Science.gov (United States)

    Tai, Meng Wei; Chong, Zhen Feng; Asif, Muhammad Khan; Rahmat, Rabiah A; Nambiar, Phrabhakaran

    2016-09-01

    This study was to compare the suitability and precision of xerographic and computer-assisted methods for bite mark investigations. Eleven subjects were asked to bite on their forearm and the bite marks were photographically recorded. Alginate impressions of the subjects' dentition were taken and their casts were made using dental stone. The overlays generated by xerographic method were obtained by photocopying the subjects' casts and the incisal edge outlines were then transferred on a transparent sheet. The bite mark images were imported into Adobe Photoshop® software and printed to life-size. The bite mark analyses using xerographically generated overlays were done by comparing an overlay to the corresponding printed bite mark images manually. In computer-assisted method, the subjects' casts were scanned into Adobe Photoshop®. The bite mark analyses using computer-assisted overlay generation were done by matching an overlay and the corresponding bite mark images digitally using Adobe Photoshop®. Another comparison method was superimposing the cast images with corresponding bite mark images employing the Adobe Photoshop® CS6 and GIF-Animator©. A score with a range of 0-3 was given during analysis to each precision-determining criterion and the score was increased with better matching. The Kruskal Wallis H test showed significant difference between the three sets of data (H=18.761, p<0.05). In conclusion, bite mark analysis using the computer-assisted animated-superimposition method was the most accurate, followed by the computer-assisted overlay generation and lastly the xerographic method. The superior precision contributed by digital method is discernible despite the human skin being a poor recording medium of bite marks.

  9. A comparative study between xerographic, computer-assisted overlay generation and animated-superimposition methods in bite mark analyses.

    Science.gov (United States)

    Tai, Meng Wei; Chong, Zhen Feng; Asif, Muhammad Khan; Rahmat, Rabiah A; Nambiar, Phrabhakaran

    2016-09-01

    This study was to compare the suitability and precision of xerographic and computer-assisted methods for bite mark investigations. Eleven subjects were asked to bite on their forearm and the bite marks were photographically recorded. Alginate impressions of the subjects' dentition were taken and their casts were made using dental stone. The overlays generated by xerographic method were obtained by photocopying the subjects' casts and the incisal edge outlines were then transferred on a transparent sheet. The bite mark images were imported into Adobe Photoshop® software and printed to life-size. The bite mark analyses using xerographically generated overlays were done by comparing an overlay to the corresponding printed bite mark images manually. In computer-assisted method, the subjects' casts were scanned into Adobe Photoshop®. The bite mark analyses using computer-assisted overlay generation were done by matching an overlay and the corresponding bite mark images digitally using Adobe Photoshop®. Another comparison method was superimposing the cast images with corresponding bite mark images employing the Adobe Photoshop® CS6 and GIF-Animator©. A score with a range of 0-3 was given during analysis to each precision-determining criterion and the score was increased with better matching. The Kruskal Wallis H test showed significant difference between the three sets of data (H=18.761, p<0.05). In conclusion, bite mark analysis using the computer-assisted animated-superimposition method was the most accurate, followed by the computer-assisted overlay generation and lastly the xerographic method. The superior precision contributed by digital method is discernible despite the human skin being a poor recording medium of bite marks. PMID:27591538

  10. Loci associated with N-glycosylation of human IgG are not associated with rheumatoid arthritis: a Mendelian randomisation study

    Science.gov (United States)

    Yarwood, Annie; Okada, Yukinori; Plenge, Robert; Yamamoto, Kazuhiko; Barton, Anne; Symmons, Deborah; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter; Worthington, Jane; Eyre, Steve

    2016-01-01

    Objectives A recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with autoimmune disease (AID) susceptibility, suggesting there may be pleiotropy (genetic sharing) between loci controlling both N-glycosylation and AIDs. We investigated this by testing variants associated with levels of IgG N-glycosylation for association with rheumatoid arthritis (RA) susceptibility using a Mendelian randomisation study, and testing a subset of these variants in a less well-powered study of treatment response and severity. Methods SNPs showing association with IgG N-glycosylation were analysed for association with RA susceptibility in 14 361 RA cases and 43 923 controls. Five SNPs were tested for association with response to anti-tumour necrosis factor (TNF) therapy in 1081 RA patient samples and for association with radiological disease severity in 342 patients. Results Only one SNP (rs9296009) associated with N-glycosylation showed an association (p=6.92×10–266) with RA susceptibility, although this was due to linkage disequilibrium with causal human leukocyte antigen (HLA) variants. Four regions of the genome harboured SNPs associated with both traits (shared loci); although statistical analysis indicated that the associations observed for the two traits are independent. No SNPs showed association with response to anti-TNF therapy. One SNP rs12342831 was modestly associated with Larsen score (p=0.05). Conclusions In a large, well-powered cohort of RA patients, we show SNPs driving levels of N-glycosylation have no association with RA susceptibility, indicating colocalisation of associated SNPs are not necessarily indicative of a shared genetic background or a role for glycosylation in disease susceptibility. PMID:26386125

  11. A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

    OpenAIRE

    Zhou, Li; He, Meian; Mo, Zengnan; Wu, Chen; Handong YANG; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue

    2013-01-01

    Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome w...

  12. Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania.

    Directory of Open Access Journals (Sweden)

    Siana Nkya Mtatiro

    Full Text Available BACKGROUND: Fetal hemoglobin (HbF is an important modulator of sickle cell disease (SCD. HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered. METHODS AND FINDINGS: We conducted a genome-wide association study (GWAS in 1,213 SCA (HbSS/HbSβ0 patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP, including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with P<10(-6. These associations could not be replicated in a SCA population in the UK. CONCLUSIONS: This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

  13. Academic and Social Functioning Associated with Attention-Deficit/Hyperactivity Disorder: Latent Class Analyses of Trajectories from Kindergarten to Fifth Grade.

    Science.gov (United States)

    DuPaul, George J; Morgan, Paul L; Farkas, George; Hillemeier, Marianne M; Maczuga, Steve

    2016-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are known to exhibit significantly lower academic and social functioning than other children. Yet the field currently lacks knowledge about specific impairment trajectories experienced by children with ADHD, which may constrain early screening and intervention effectiveness. Data were analyzed from a nationally representative U.S. cohort in the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K) for 590 children (72.7 % male) whose parents reported a formal diagnosis of ADHD. Children's math, reading, and interpersonal skills were assessed at 5 time points between kindergarten and fifth grade. Growth mixture model analyses indicated 4 latent trajectory classes for reading, 8 classes for math, and 4 classes for interpersonal skills. Membership in reading and math trajectory classes was strongly related; overlaps with interpersonal skills classes were weaker. Trajectory class membership was correlated with demographic characteristics and behavioral functioning. Children with ADHD display substantial heterogeneity in their reading, math, and interpersonal growth trajectories, with some groups of children especially likely to display relatively severe levels of academic and social impairment over time. Early screening and intervention to address impairment, particularly reading difficulties, among kindergarten students with ADHD is warranted. PMID:26750108

  14. Academic and Social Functioning Associated with Attention-Deficit/Hyperactivity Disorder: Latent Class Analyses of Trajectories from Kindergarten to Fifth Grade.

    Science.gov (United States)

    DuPaul, George J; Morgan, Paul L; Farkas, George; Hillemeier, Marianne M; Maczuga, Steve

    2016-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are known to exhibit significantly lower academic and social functioning than other children. Yet the field currently lacks knowledge about specific impairment trajectories experienced by children with ADHD, which may constrain early screening and intervention effectiveness. Data were analyzed from a nationally representative U.S. cohort in the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K) for 590 children (72.7 % male) whose parents reported a formal diagnosis of ADHD. Children's math, reading, and interpersonal skills were assessed at 5 time points between kindergarten and fifth grade. Growth mixture model analyses indicated 4 latent trajectory classes for reading, 8 classes for math, and 4 classes for interpersonal skills. Membership in reading and math trajectory classes was strongly related; overlaps with interpersonal skills classes were weaker. Trajectory class membership was correlated with demographic characteristics and behavioral functioning. Children with ADHD display substantial heterogeneity in their reading, math, and interpersonal growth trajectories, with some groups of children especially likely to display relatively severe levels of academic and social impairment over time. Early screening and intervention to address impairment, particularly reading difficulties, among kindergarten students with ADHD is warranted.

  15. Associations of socioeconomic factors with inadequate dietary intake in food aid users in France (the ABENA study 2004–2005)

    OpenAIRE

    Méjean, Caroline; Deschamps, V.; Bellin-Lestienne, C.; Oleko, A.; Darmon, Nicole; Serge, H.; Katia, C.

    2010-01-01

    Background/Objectives: Few studies in Europe have examined the relationship of sociodemographic and economic factors with diet in deprived populations. We analysed the association between socioeconomic characteristics and consumption of different food groups in food aid users. Subjects/Methods: A cross-sectional study was conducted among food aid users in four urban French zones (n=1664). Associations of sociodemographic and economic factors and food aid use with frequency of consumption of t...

  16. A comparative study of first and all-author co-citation counting, and two different matrix generation approaches applied for author co-citation analyses

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Larsen, Birger; Ingwersen, Peter

    2009-01-01

    Aim: The present article contributes to the current methodological debate concerning author co-citation analyses. (ACA) The study compares two different units of analyses, i.e. first- versus inclusive all-author co-citation counting, as well as two different matrix generation approaches, i...... for the seemingly advantages of the Drexel approach....

  17. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  18. Atomistic analyses of competition between site-selective segregation and association of point defects at grain boundary in Y2O3-doped ZrO2

    International Nuclear Information System (INIS)

    The site-selective occupation of point defects, Y3+ ions (Y′Zr) and O2- vacancies (VÖ), and their associations at a symmetric tilt grain boundary (GB) are studied to understand their competitive contribution to energetically favorable atomic arrangements by using atomistic simulations. It is found that at the GB there are the favorable sites for segregation of an isolated Y′Zr and VÖ. This indicates that the driving force for the site-selective segregation is present. Moreover, our results of Y′Zr-VÖ association at the GB show that the lattice energies are very dispersed despite that a second-nearest neighbor (SNN) vacancy to Y′Zr is favored for bulk Y2O3-doped ZrO2. The result suggests that the site-selective segregation has significant effects on the favorable point defect arrangement at the GB core, competing with the point defect associations. For more realistic cases, Monte Carlo simulations are performed to reveal favorable atomic arrangements for a high dopant concentration, where point defects are crowded at the GB. The results show that the region of GB segregation can be classified with respect to O2- coordination to cation species; at the GB core the favorable configuration is not necessarily a SNN O2- vacancy relative to Y3+. On the other hand, eight-fold O2- coordination is sustained for Y3+ ions more than ∼3 Å distant from the GB plane. The difference in O2- coordination may play an important role in O2- ionic conductivity at GBs via the energetics for O2- migration. (author)

  19. Realising the Value of Linked Data to Health Economic Analyses of Cancer Care: A Case Study of Cancer 2015.

    Science.gov (United States)

    Lorgelly, Paula K; Doble, Brett; Knott, Rachel J

    2016-02-01

    There is a growing appetite for large complex databases that integrate a range of personal, socio-demographic, health, genetic and financial information on individuals. It has been argued that 'Big Data' will provide the necessary catalyst to advance both biomedical research and health economics and outcomes research. However, it is important that we do not succumb to being data rich but information poor. This paper discusses the benefits and challenges of building Big Data, analysing Big Data and making appropriate inferences in order to advance cancer care, using Cancer 2015 (a prospective, longitudinal, genomic cohort study in Victoria, Australia) as a case study. Cancer 2015 has been linked to State and Commonwealth reimbursement databases that have known limitations. This partly reflects the funding arrangements in Australia, a country with both public and private provision, including public funding of private healthcare, and partly the legislative frameworks that govern data linkage. Additionally, linkage is not without time delays and, as such, achieving a contemporaneous database is challenging. Despite these limitations, there is clear value in using linked data and creating Big Data. This paper describes the linked Cancer 2015 dataset, discusses estimation issues given the nature of the data and presents panel regression results that allow us to make possible inferences regarding which patient, disease, genomic and treatment characteristics explain variation in health expenditure. PMID:26547307

  20. Implications of different approaches for characterizing ambient air pollutant concentrations within the urban airshed for time-series studies and health benefits analyses

    Directory of Open Access Journals (Sweden)

    Winquist Andrea

    2011-05-01

    Full Text Available Abstract Background In time-series studies of the health effects of urban air pollutants, decisions must be made about how to characterize pollutant levels within the airshed. Methods Emergency department visits for pediatric asthma exacerbations were collected from Atlanta hospitals. Concentrations of carbon monoxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter less than 10 microns in diameter (PM10, particulate matter less than 2.5 microns in diameter (PM2.5, and the PM2.5 components elemental carbon, organic carbon, and sulfate were obtained from networks of ambient air quality monitors. For each pollutant we created three different daily metrics. For one metric we used the measurements from a centrally-located monitor; for the second we averaged measurements across the network of monitors; and for the third we estimated the population-weighted average concentration using an isotropic spatial model. Rate ratios for each of the metrics were estimated from time-series models. Results For pollutants with relatively homogeneous spatial distributions we observed only small differences in the rate ratio across the three metrics. Conversely, for spatially heterogeneous pollutants we observed larger differences in the rate ratios. For a given pollutant, the strength of evidence for an association (i.e., chi-square statistics tended to be similar across metrics. Conclusions Given that the chi-square statistics were similar across the metrics, the differences in the rate ratios for the spatially heterogeneous pollutants may seem like a relatively small issue. However, these differences are important for health benefits analyses, where results from epidemiological studies on the health effects of pollutants (per unit change in concentration are used to predict the health impacts of a reduction in pollutant concentrations. We discuss the relative merits of the different metrics as they pertain to time-series studies and health benefits

  1. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    DEFF Research Database (Denmark)

    Børglum, A D; Demontis, D; Grove, J;

    2014-01-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144...... in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10...

  2. Sialolithiasis is associated with nephrolithiasis: a case-control study.

    Science.gov (United States)

    Wu, Chuan-Chang; Hung, Shih-Han; Lin, Herng-Ching; Lee, Cha-Ze; Lee, Hsin-Chien; Chung, Shiu-Dong

    2016-05-01

    Conclusions This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis. Objective Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset. Methods Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis. Results Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p < 0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use. PMID:26808906

  3. Joint Analysis of Multiple Traits in Rare Variant Association Studies.

    Science.gov (United States)

    Wang, Zhenchuan; Wang, Xuexia; Sha, Qiuying; Zhang, Shuanglin

    2016-05-01

    The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant-by-variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single-TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single-TOW and WSRR. PMID:26990300

  4. Analysing customer requirements and satisfaction in the furniture industry according to ISO 9000 certification: a case study

    Directory of Open Access Journals (Sweden)

    Laura Martínez Caro

    2010-12-01

    Full Text Available The need to identify customer requirements and to satisfy them has become the main objective of companies. To manage that activity, that it is commonly associated to the marketing department, is the aim of every quality system, and therefore is a task that comprises the remaining departments of the organization. Through a case study, this paper seeks to identify which are the usual marketing practices in the furniture industry, and to outline an appropriate performance framework in agreement with the procedures settled down in the ISO 9000:2000 standards.

  5. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study

    DEFF Research Database (Denmark)

    Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio;

    2009-01-01

    remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS : The cohort...... includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28...

  6. Empowered teams : case-study analyses of the process of introducing empowered teams into organisations with a poor industrial relations history

    OpenAIRE

    Scott-Lennon, Frank

    2001-01-01

    This research focuses on case-study analyses of the process of introducing empowered teams into organisations with a poor industrial relations history. The chosen research methodology is in the ethnographic mode and analogous to grounded theory; data was collected in five case-study organisations. The respondent data is presented for each case study in turn and then analysed in a cross-case manner, highlighting some critical themes/issues identified by respondents who were k...

  7. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. PMID:27492634

  8. Generalization of Rare Variant Association Tests for Longitudinal Family Studies.

    Science.gov (United States)

    Chien, Li-Chu; Hsu, Fang-Chi; Bowden, Donald W; Chiu, Yen-Feng

    2016-02-01

    Given the functional relevance of many rare variants, their identification is frequently critical for dissecting disease etiology. Functional variants are likely to be aggregated in family studies enriched with affected members, and this aggregation increases the statistical power to detect rare variants associated with a trait of interest. Longitudinal family studies provide additional information for identifying genetic and environmental factors associated with disease over time. However, methods to analyze rare variants in longitudinal family data remain fairly limited. These methods should be capable of accounting for different sources of correlations and handling large amounts of sequencing data efficiently. To identify rare variants associated with a phenotype in longitudinal family studies, we extended pedigree-based burden (BT) and kernel (KS) association tests to genetic longitudinal studies. Generalized estimating equation (GEE) approaches were used to generalize the pedigree-based BT and KS to multiple correlated phenotypes under the generalized linear model framework, adjusting for fixed effects of confounding factors. These tests accounted for complex correlations between repeated measures of the same phenotype (serial correlations) and between individuals in the same family (familial correlations). We conducted comprehensive simulation studies to compare the proposed tests with mixed-effects models and marginal models, using GEEs under various configurations. When the proposed tests were applied to data from the Diabetes Heart Study, we found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes.

  9. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Murabito, Joanne M; White, Charles C; Kavousi, Maryam;

    2012-01-01

    BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based coh......BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population...... additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery...

  10. Epigenome-wide association study identifies TXNIP gene associated with type 2 diabetes mellitus and sustained hyperglycemia.

    Science.gov (United States)

    Soriano-Tárraga, Carolina; Jiménez-Conde, Jordi; Giralt-Steinhauer, Eva; Mola-Caminal, Marina; Vivanco-Hidalgo, Rosa M; Ois, Angel; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Sayols-Baixeras, Sergi; Elosua, Roberto; Roquer, Jaume

    2016-02-01

    Type 2 diabetes mellitus (DM) is an established risk factor for a wide range of vascular diseases, including ischemic stroke (IS). Glycated hemoglobin A1c (HbA1c), a marker for average blood glucose levels over the previous 12 weeks, is used as a measure of glycemic control and also as a diagnostic criterion for diabetes (HbA1c levels ≥ 6.5%). Epigenetic mechanisms, such as DNA methylation, may be associated with aging processes and with modulation of the risk of various pathologies, such as DM. Specifically, DNA methylation could be one of the mechanisms mediating the relation between DM and environmental exposures. Our goal was to identify new CpG methylation sites associated with DM. We performed a genome-wide methylation study in whole-blood DNA from an IS patient cohorts. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. All statistical analyses were adjusted for sex, age, hyperlipidemia, body mass index (BMI), smoking habit and cell count. Findings were replicated in two independent cohorts, an IS cohort and a population-based cohort, using the same array. In the discovery phase (N = 355), we identified a CpG site, cg19693031 (located in the TXNIP gene) that was associated with DM (P = 1.17 × 10(-12)); this CpG was replicated in two independent cohorts (N = 167 and N = 645). Methylation of TXNIP was inversely and intensely associated with HbA1c levels (P = 7.3 × 10(-16)), specifically related to diabetic patients with poor control of glucose levels. We identified an association between the TXNIP gene and DM through epigenetic mechanisms, related to sustained hyperglycemia levels (HbA1c ≥ 7%). PMID:26643952

  11. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

    Directory of Open Access Journals (Sweden)

    Wayland Hsiao

    2009-01-01

    Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

  12. Associations of heart failure with sleep quality: The rotterdam study

    NARCIS (Netherlands)

    L.A. Zuurbier (Lisette); A.I. Luik (Annemarie); M.J.G. Leening (Maarten); A. Hofman (Albert); R. Freak-Poli (Rosanne); O.H. Franco (Oscar); B.H. Stricker; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractStudy Objectives: The prevalence of sleep disturbances and heart failure increases with age. We aimed to evaluate the associations of incident heart failure and cardiac dysfunction with changes in sleep quality. Methods: This prospective population-based study was conducted in the Rotter

  13. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countri

  14. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  15. Genome-Wide Association Studies of the Human Gut Microbiota.

    Science.gov (United States)

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  16. Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study

    Science.gov (United States)

    Orozco, Gisela; Eyre, Steve; Hinks, Anne; Ke, Xiayi; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane

    2010-01-01

    Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. Methods A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ2 test using Stata. Results Association to the CD40 gene was robustly replicated (p=2×10−4, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8×10−8, OR 0.87 (95% CI 0.83 to 0.92). Conclusion In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus. PMID:19435719

  17. Defining a minimal clinically important difference for endometriosis-associated pelvic pain measured on a visual analog scale: analyses of two placebo-controlled, randomized trials

    Directory of Open Access Journals (Sweden)

    Schmitz Heinz

    2010-11-01

    Full Text Available Abstract Background When comparing active treatments, a non-inferiority (or one-sided equivalence study design is often used. This design requires the definition of a non-inferiority margin, the threshold value of clinical relevance. In recent studies, a non-inferiority margin of 15 mm has been used for the change in endometriosis-associated pelvic pain (EAPP on a visual analog scale (VAS. However, this value was derived from other chronic painful conditions and its validation in EAPP was lacking. Methods Data were analyzed from two placebo-controlled studies of active treatments in endometriosis, including 281 patients with laparoscopically-confirmed endometriosis and moderate-to-severe EAPP. Patients recorded EAPP on a VAS at baseline and the end of treatment. Patients also assessed their satisfaction with treatment on a modified Clinical Global Impression scale. Changes in VAS score were compared with patients' self-assessments to derive an empirically validated non-inferiority margin. This anchor-based value was compared to a non-inferiority margin derived using the conventional half standard deviation rule for minimal clinically important difference (MCID in patient-reported outcomes. Results Anchor-based and distribution-based MCIDs were-7.8 mm and-8.6 mm, respectively. Conclusions An empirically validated non-inferiority margin of 10 mm for EAPP measured on a VAS is appropriate to compare treatments in endometriosis.

  18. Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.

    Directory of Open Access Journals (Sweden)

    Elisa Alonso-Perez

    Full Text Available INTRODUCTION: Systemic Lupus Erythematosus (SLE shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. METHODS: European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR classification criteria (except ANAs and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. RESULTS: THERE WERE THREE NEW ASSOCIATIONS: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR=0.76 and 1.30, P(corr =0.007 and 0.03, respectively and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. CONCLUSION: Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.

  19. Genome-wide association study identifies three novel loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Hara, Kazuo; Fujita, Hayato; Johnson, Todd A;

    2014-01-01

    genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases...... (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.......Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly...

  20. Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis: A Prospective Clinical Study.

    Science.gov (United States)

    Kennedy, James I C; Askelund, Kathryn J; Premkumar, Rakesh; Phillips, Anthony R J; Murphy, Rinki; Windsor, John A; Petrov, Maxim S

    2016-02-01

    Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity.Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders.A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021).Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity.

  1. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.

    Science.gov (United States)

    Chahal, Harvind S; Wu, Wenting; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Hinds, David A; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  2. A study on the seismic behavior of a retrofitted building based on nonlinear static and dynamic analyses

    Institute of Scientific and Technical Information of China (English)

    Esra Mete Güneyisi; Gülay Altay

    2005-01-01

    This study describes the seismic performance of an existing five storey reinforced concrete building which represents the typical properties of low-rise non-ductile buildings in Turkey. The effectiveness of shear walls and the steel bracings in retrofitting the building was examined through nonlinear static and dynamic analyses. By using the nonlinear static analysis, retrofitted buildings seismic performances under lateral seismic load were compared with each other.Moreover, the performance points and response levels of the existing and retrofitting cases were determined by way of the capacity-spectrum method described in ATC-40 (1996). For the nonlinear dynamic analysis the records were selected to represent wide ranges of duration and frequency content. Considering the change in the stiffness and the energy dissipation capacities, the performance of the existing and retrofitted buildings were evaluated in terms of story drifts and damage states.It was found that each earthquake record exhibited its own peculiarities, dictated by frequency content, duration, sequence of peaks and their amplitude. The seismic performance of retrofitted buildings resulted in lower displacements and higher energy dissipation capacity depending mainly on the properties of the ground motions and the retrofitting strategies. Moreover,severe structural damage (irreparable or collapse) was observed for the existing building. However, buildings with retrofit alternatives exhibited lower damage levels changing from no damage to irreparable damage states.

  3. Sources of variability and comparability between salmonid stomach contents and isotopic analyses: study design lessons and recommendations

    Science.gov (United States)

    Vinson, M.R.; Budy, P.

    2011-01-01

    We compared sources of variability and cost in paired stomach content and stable isotope samples from three salmonid species collected in September 2001–2005 and describe the relative information provided by each method in terms of measuring diet overlap and food web study design. Based on diet analyses, diet overlap among brown trout, rainbow trout, and mountain whitefish was high, and we observed little variation in diets among years. In contrast, for sample sizes n ≥ 25, 95% confidence interval (CI) around mean δ15Ν and δ13C for the three target species did not overlap, and species, year, and fish size effects were significantly different, implying that these species likely consumed similar prey but in different proportions. Stable isotope processing costs were US$12 per sample, while stomach content analysis costs averaged US$25.49 ± $2.91 (95% CI) and ranged from US$1.50 for an empty stomach to US$291.50 for a sample with 2330 items. Precision in both δ15Ν and δ13C and mean diet overlap values based on stomach contents increased considerably up to a sample size of n = 10 and plateaued around n = 25, with little further increase in precision.

  4. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    Science.gov (United States)

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  5. Genome-wide and candidate gene association study of cigarette smoking behaviors.

    Directory of Open Access Journals (Sweden)

    Neil Caporaso

    Full Text Available The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO Trial, and 2,282 women from the Nurses' Health Study (NHS. We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years, and three binary (ever versus never smoking, 10 cigarettes per day [CPDBI], and current versus former smoking. Association testing for each single nucleotide polymorphism (SNP was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10(-7 in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10(-5 for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10(-3, including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4x10(-5, our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.

  6. Association between Soy Isoflavone Intake and Breast Cancer Risk for Pre- and Post-Menopausal Women: A Meta-Analysis of Epidemiological Studies

    OpenAIRE

    Meinan Chen; Yanhua Rao; Yi Zheng; Shiqing Wei; Ye Li; Tong Guo; Ping Yin

    2014-01-01

    BACKGROUND: Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intak...

  7. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao;

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, ...

  8. Genome-wide association study reveals regions associated with gestation length in two pig populations

    NARCIS (Netherlands)

    Hidalgo, A.M.; Lopes, M.S.; Harlizius, B.; Bastiaansen, J.W.M.

    2016-01-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available

  9. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    D.J. Gottlieb (Daniel J); K. Hek (Karin); T.-H. Chen; N.F. Watson; G. Eiriksdottir (Gudny); E.M. Byrne; M. Cornelis (Marilyn); S.C. Warby; S. Bandinelli; L. Cherkas (Lynn); D.S. Evans (Daniel); H.J. Grabe (Hans Jörgen); J. Lahti (Jari); M. Li (Man); T. Lehtimäki (Terho); T. Lumley (Thomas); K. Marciante (Kristin); L. Perusse (Louis); B.M. Psaty (Bruce); J. Robbins; G.J. Tranah (Gregory); J.M. Vink; J.B. Wilk; J.M. Stafford; C. Bellis (Claire); R. Biffar; C. Bouchard (Claude); B. Cade; G.C. Curhan (Gary); J. Eriksson; R. Ewert; L. Ferrucci (Luigi); T. Fülöp; P.R. Gehrman (Philip); R. Goodloe (Robert); T.B. Harris (Tamara B.); A.C. Heath (Andrew C.); D.G. Hernandez (Dena); A. Hofman (Albert); J.J. Hottenga (Jouke Jan); D. Hunter (David); M.K. Jensen (Majken K.); A.D. Johnson (Andrew); M. Kähönen (Mika); W.H.L. Kao (Wen); P. Kraft (Peter); E.K. Larkin; D.S. Lauderdale; A.I. Luik (Annemarie I); M. Medici; G.W. Montgomery (Grant W.); A. Palotie; S.R. Patel (Sanjay); G. Pistis (Giorgio); E. Porcu; L. Quaye (Lydia); O. Raitakari (Olli); S. Redline (Susan); E.B. Rimm (Eric B.); J.I. Rotter; A.V. Smith; T.D. Spector (Timothy); A. Teumer (Alexander); A.G. Uitterlinden (André); M.-C. Vohl (Marie-Claude); E. Widen; G.A.H.M. Willemsen (Gonneke); T.L. Young (Terri L.); X. Zhang; Y. Liu; J. Blangero (John); D.I. Boomsma (Dorret); V. Gudnason (Vilmundur); F. Hu; M. Mangino; N.G. Martin (Nicholas); G.T. O'Connor (George); K.L. Stone (Katie L); T. Tanaka; J. Viikari (Jorma); S.A. Gharib (Sina); N.M. Punjabi (Naresh); K. Räikkönen (Katri); H. Völzke (Henry); E. Mignot; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractUsual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 popula

  10. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  11. Metagenome-wide association studies: fine-mining the microbiome.

    Science.gov (United States)

    Wang, Jun; Jia, Huijue

    2016-08-01

    Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease. PMID:27396567

  12. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  13. Genome Wide Association Study:Searching for Genes Underlying Body Mass Index in the Chinese

    Institute of Scientific and Technical Information of China (English)

    YANG Fang; CHEN Xiang Ding; TAN Li Jun; SHEN Jie; LI Ding You; ZHANG Fang; SHA Bao Yong; DENG Hong Wen

    2014-01-01

    Objective Obesity is becoming a worldwide health problem. The genome wide association (GWA) study particularly for body mass index (BMI) has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate (FDR) correction (P=5.45×10-7-7.26×10-6, FDR q=0.033-0.048). Two adjacent SNPs (rs4432245 &rs711906) in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene were significantly associated with BMI (P=6.38×10-6&4.39×10-6, FDR q=0.048). In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene (P=0.03&0.01, respectively). Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be‘ethnic specific’ in the Chinese.

  14. Study of CP Violation in Dalitz-Plot Analyses of B-Meson Decays to Three Kaons

    Energy Technology Data Exchange (ETDEWEB)

    Lindquist, Brian [Stanford Univ., CA (United States)

    2012-02-01

    The Standard Model (SM) explains CP violation in terms of the CKM matrix. The BABAR experiment was designed mainly to test the CKM model in B decays. B decays that proceed through b → s loop diagrams, of which B {yields} KKK decays are an example, are sensitive to new physics effects that could lead to deviations from the CKM predictions for CP violation. We present studies of CP violation in the decays B+ → K+K-K+, B+ → KS0KS0K+, and B0 → K+K-KS0, using a Dalitz plot amplitude analysis. These studies are based on approximately 470 million B$\\bar{B}$ decays collected by BABAR at the PEP-II collider at SLAC. We perform measurements of time-dependent CP violation in B0 → K+K-KS0, including B0 → ΦKS0. We measure a CP-violating phase βeff (ΦKS0) = 0.36 ± 0.11 ± 0.04 rad., in agreement with the SM. This is the world's most precise measurement of this quantity. We also measure direct CP asymmetries in all three decay modes, including the direct CP asymmetry ACP (ΦK+) = (12.8 ± 4.4 ± 1.3)%, which is 2.8 sigma away from zero. This measurement is in tension with the SM, which predicts an asymmetry of a few percent. We also study the resonant and nonresonant features in the B → KKK Dalitz plots. We find that the hypothetical scalar fX(1500) resonance, introduced by prior analyses to explain an unknown peak in the mKK spectrum, cannot adequately describe the data. We conclude instead that the fX(1500) can be explained as the sum of the f0(1500), f'2(1525), and f0(1710) resonances, removing the need for the hypothetical fX(1500). We also find that an exponential

  15. Association studies using random and "candidate" microsatellite loci in two infectious goat diseases

    Directory of Open Access Journals (Sweden)

    Obexer-Ruff Gabriela

    2003-06-01

    Full Text Available Abstract We established a set of 30 microsatellites of Bovidae origin for use in a biodiversity study in Swiss and Creole goats. Additional microsatellites located within or next to "candidate" genes of interest, such as cytokine genes (IL4, INF-gamma and MHC class II genes (DRB, DYA were tested in the caprine species in order to detect possible associations with two infectious caprine diseases. Microsatellite analysis was undertaken using automated sequencers (ABI373 & 3100. In the first study, a total of 82 unrelated Creole goats, 37 resistant and 45 susceptible to Heartwater disease (Cowdriosis were analysed. In this study, the two microsatellite loci DRBP1 (MHCII and BOBT24 (IL4 were positively associated with disease susceptibility, demonstrating a corrected P-value of 0.002 and 0.005, respectively. In a second investigation, we tested 36 goats, naturally infected with the nematode parasite Trichostrongylus colubriformis. These animals were divided into a "low" and "high" excreting group on the basis of two independently recorded fecal egg counts. For this nematode resistance study, we detected a significant association of one of the alleles of the microsatellite locus SPS113 with "low" excretion (resistance. The MHC class II locus DYA (P19, was weakly associated with susceptibility in both diseases (Pc = 0.05. In future experiments, we will extend the sample size in order to verify the described associations.

  16. Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

    NARCIS (Netherlands)

    Wilk, Jemma B; Shrine, Nick R G; Loehr, Laura R; Zhao, Jing Hua; Manichaikul, Ani; Lopez, Lorna M; Smith, Albert Vernon; Heckbert, Susan R; Smolonska, Joanna; Tang, Wenbo; Loth, Daan W; Curjuric, Ivan; Hui, Jennie; Cho, Michael H; Latourelle, Jeanne C; Henry, Amanda P; Aldrich, Melinda; Bakke, Per; Beaty, Terri H; Bentley, Amy R; Borecki, Ingrid B; Brusselle, Guy G; Burkart, Kristin M; Chen, Ting-hsu; Couper, David; Crapo, James D; Davies, Gail; Dupuis, Josée; Franceschini, Nora; Gulsvik, Amund; Hancock, Dana B; Harris, Tamara B; Hofman, Albert; Imboden, Medea; James, Alan L; Khaw, Kay-Tee; Lahousse, Lies; Launer, Lenore J; Litonjua, Augusto; Liu, Yongmei; Lohman, Kurt K; Lomas, David A; Lumley, Thomas; Marciante, Kristin D; McArdle, Wendy L; Meibohm, Bernd; Morrison, Alanna C; Musk, Arthur W; Myers, Richard H; North, Kari E; Postma, Dirkje S; Psaty, Bruce M; Rich, Stephen S; Rivadeneira, Fernando; Rochat, Thierry; Rotter, Jerome I; Artigas, María Soler; Starr, John M; Uitterlinden, André G; Wareham, Nicholas J; Wijmenga, Cisca; Zanen, Pieter; Province, Michael A; Silverman, Edwin K; Deary, Ian J; Palmer, Lyle J; Cassano, Patricia A; Gudnason, Vilmundur; Barr, R Graham; Loos, Ruth J F; Strachan, David P; London, Stephanie J; Boezen, Hendrika; Probst-Hensch, Nicole; Gharib, Sina A; Hall, Ian P; O'Connor, George T; Tobin, Martin D; Stricker, Bruno H

    2012-01-01

    RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD asses

  17. Study of Single Top Quarks in Association with Vector Bosons

    CERN Document Server

    Leggat, Duncan Alexander

    2015-01-01

    The search for single top production in association with a massive electroweak vector bosonusing data collected by the CMS detector at the Large Hadron Collider is presented. Twoanalyses are discussed: the search for a single top produced in association with a W boson(tW production) and the search for t-channel single top production with a radiated Zboson (tZq production). Both analyses make use of proton-proton collision data at acentre-of-mass energy of 8 TeV, and focus on the leptonic decays of the vector bosons. Acut and count based approach is employed for the tW search, searching for a final statecontaining two leptons, two neutrinos and a jet originating from the decay of a b-quark.The main backgrounds to be understood and controlled in this analysis are those arisingfrom the production of top quark pairs and Z bosons with one or more jets. Using a set ofdata corresponding to an integrated luminosity of 12.2 fb−1 , a production cross section of33.9 ± 8.6 pb was measured for the process. This corres...

  18. Mechanical and thermo-mechanical analyses of the tapered plug for plugging of deposition tunnels. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Faelth, Billy (Clay Technology AB, Lund (Sweden)); Gatter, Patrik (Vattenfall Power Consultant AB, Stockholm (Sweden))

    2009-09-15

    This report presents results from a study that was carried out in order to examine the applicability of the tapered plug concept for plugging of deposition tunnels in the deep repository for spent nuclear fuel. The report presents results from mechanical and thermo-mechanical models of the tapered plug. The models were analyzed with 3DEC. The models included a portion of a deposition tunnel and its intersection with a main tunnel. In the deposition tunnel, a tapered concrete plug was installed. The plug was subjected to the combined load from the swelling backfill material and from pore pressure inside the deposition tunnel. The thermo-mechanical effects due to the heat generation in the spent fuel were also included in the analyses. Generic material parameter values for the concrete were used. The following items were studied: - Stresses and displacements in the plug. - Shear stresses and shear displacements in the rock-concrete interface. - Stress additions in the rock due to the loads. The sensitivity of the results to changes of constitutive models, to changes of the plug geometry and to pore water pressure in the rock-concrete interface was examined. The results indicate that the displacements in the plug will be within reasonable ranges but the stresses may locally be high enough that they exceed acceptable levels. However, they can be reduced by choice of advantageous plug geometry and by having a good rock-concrete bond. The results also show that the stress additions in the rock due to the thermal load may yield stresses that locally exceed the spalling strength of the rock. At most locations, however, the rock stresses will amount at lower levels. It was concluded that, with choice of an appropriate design, the tapered plug seems to be an applicable concept for plugging of deposition tunnels. It was also concluded that further studies of the tapered plug concept should use material properties parameter values for low-pH concrete. Further, they should also

  19. Genome-wide association study reveals regions associated with gestation length in two pig populations.

    Science.gov (United States)

    Hidalgo, A M; Lopes, M S; Harlizius, B; Bastiaansen, J W M

    2016-04-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE.

  20. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    Science.gov (United States)

    Dijkstra, Akkelies E.; Smolonska, Joanna; van den Berge, Maarten; Wijmenga, Ciska; Zanen, Pieter; Luinge, Marjan A.; Platteel, Mathieu; Lammers, Jan-Willem; Dahlback, Magnus; Tosh, Kerrie; Hiemstra, Pieter S.; Sterk, Peter J.; Spira, Avi; Vestbo, Jorgen; Nordestgaard, Borge G.; Benn, Marianne; Nielsen, Sune F.; Dahl, Morten; Verschuren, W. Monique; Picavet, H. Susan J.; Smit, Henriette A.; Owsijewitsch, Michael; Kauczor, Hans U.; de Koning, Harry J.; Nizankowska-Mogilnicka, Eva; Mejza, Filip; Nastalek, Pawel; van Diemen, Cleo C.; Cho, Michael H.; Silverman, Edwin K.; Crapo, James D.; Beaty, Terri H.; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Bossé, Yohan; Obeidat, M. A.; Loth, Daan W.; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Andre; Stricker, Bruno H.; Brusselle, Guy G.; van Duijn, Cornelia M.; Brouwer, Uilke; Koppelman, Gerard H.; Vonk, Judith M.; Nawijn, Martijn C.; Groen, Harry J. M.; Timens, Wim; Boezen, H. Marike; Postma, Dirkje S.

    2014-01-01

    Background Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH. PMID:24714607

  1. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available BACKGROUND: Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP. RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  2. Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study

    DEFF Research Database (Denmark)

    Prompers, L.; Huijberts, M.; Schaper, N.;

    2008-01-01

    Aims/hypothesis The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection. Methods Data....... In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease Udgivelsesdato: 2008/10...

  3. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  4. Association between Dietary Intake and Bone Mineral Density in Japanese Postmenopausal Women: The Yokogoshi Cohort Study.

    Science.gov (United States)

    Hirata, Harumi; Kitamura, Kaori; Saito, Toshiko; Kobayashi, Ryosaku; Iwasaki, Masanori; Yoshihara, Akihiro; Watanabe, Yumi; Oshiki, Rieko; Nishiwaki, Tomoko; Nakamura, Kazutoshi

    2016-01-01

    Diet and food intake play an important role in the development of osteoporosis. However, apart from calcium and vitamin D, how nutrients affect bone status is not fully understood. The purpose of this study was to determine cross-sectional and longitudinal associations between dietary intake and bone mineral density (BMD) in Japanese postmenopausal women. This 5-year cohort study included 600 community-dwelling women aged 55-74 years at baseline in 2005. Information on demographics, nutrition, and lifestyle was obtained through interviews, and nutritional and dietary intake was assessed using a validated food frequency questionnaire. BMD measurements were performed by dual energy X-ray absorptiometry. In 2010, 498 women underwent follow-up BMD examinations. Multiple linear regression analysis was performed to determine associations of predictor variables with BMD, adjusting for confounders. In cross-sectional analyses, coffee or black tea consumption was positively associated with lumbar spine (P = 0.004) and total hip (P = 0.003) BMD, and alcohol intake was positively associated with femoral neck (P = 0.005) and total hip (P = 0.001) BMD. In longitudinal analyses, vitamin K (P = 0.028) and natto (fermented soybeans) (P = 0.023) were positively associated with lumbar spine BMD, and meat or meat product consumption was inversely associated with total hip (P = 0.047) BMD. In conclusion, dietary factors other than calcium and vitamin D intake are predictors of bone mass and bone loss in Japanese postmenopausal women. In particular, natto intake is recommended for preventing postmenopausal bone loss on the basis of current evidence.

  5. Whole Genome Association Studies of Residual Feed Intake and Rel