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Sample records for association study implicates

  1. The estrogen hypothesis of Schizophrenia implicates glucose metabolism: Association study in three independent samples

    Directory of Open Access Journals (Sweden)

    Timm Sally

    2008-05-01

    Full Text Available Abstract Background Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness. Results We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects. Variants of the mitogen-activated protein kinase 14 gene (MAPK14 and the phosphoenolpyruvate carboxykinase 1 (PCK1 and fructose-1,6-biphosphatase (FBP1 were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2 consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender. Conclusion Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the

  2. A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

    Directory of Open Access Journals (Sweden)

    Cameron L. Randall

    2017-01-01

    Full Text Available Background. Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods. A genome-wide association study (GWAS; N=990 was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain of the Fear of Pain Questionnaire-9 (FPQ-9 were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p<5×10-8 for all near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

  3. A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

    Science.gov (United States)

    Randall, Cameron L; Wright, Casey D; Chernus, Jonathan M; McNeil, Daniel W; Feingold, Eleanor; Crout, Richard J; Neiswanger, Katherine; Weyant, Robert J; Shaffer, John R; Marazita, Mary L

    2017-01-01

    Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p pain total score and each of the FPQ-9 subscales. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

  4. Discovery of rare variants via sequencing: implications for the design of complex trait association studies.

    Directory of Open Access Journals (Sweden)

    Bingshan Li

    2009-05-01

    Full Text Available There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates.

  5. Genome-wide association study implicates PARD3B-based AIDS restriction

    NARCIS (Netherlands)

    Troyer, Jennifer L.; Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Li, Guan; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. European

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

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

  9. Association study in Alzheimer’s disease of single nucleotide polymorphisms implicated with coffee consumption

    Directory of Open Access Journals (Sweden)

    Victor Junji Yamamoto

    2015-06-01

    Full Text Available Background There is evidence from animal and in vitro models of the protective effects of caffeine in Alzheimer’s disease. The suggested mechanisms through which caffeine may protect neurons against Alzheimer’s disease pathology include the facilitation of beta-amyloid clearance, upregulation of cholinergic transmission, and increased neuronal plasticity and survival. Epidemiological studies support that Alzheimer’s disease patients consume smaller amounts of coffee beverages throughout their lives as compared to age-matched cognitively healthy individuals. Objective The aim of the present study was to determine whether the negative association between Alzheimer’s disease and coffee consumption may be influenced by a common genetic predisposition, given the fact that the pattern of coffee consumption is determined by both environmental and genetic factors. Method We conducted an in silico search addressing the association between genetic polymorphisms related to coffee consumption and the diagnosis of Alzheimer’s disease. We further investigated the interactions between genes located in regions bearing these polymorphisms. Results Our analysis revealed no evidence for a genetic association (nor interaction between related proteins involving coffee consumption and Alzheimer’s disease. Discussion The negative association between Alzheimer’s disease and coffee consumption suggested by epidemiological studies is most likely due to environmental factors that are not necessarily regulated by genetic background.

  10. A GENOME-WIDE ASSOCIATION STUDY OF BRONCHODILATOR RESPONSE IN LATINOS IMPLICATES RARE VARIANTS

    Science.gov (United States)

    Drake, Katherine A.; Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Oh, Sam S.; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D.; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; LeNoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R.; Hernandez, Ryan D.; Giacomini, Kathleen M.; Burchard, Esteban G.

    2013-01-01

    Rationale The primary rescue medication to treat acute asthma exacerbation is short-acting β2- adrenergic receptor (β2AR) agonists (SABAs), however there is variation in how well an individual responds to treatment. Although these differences may be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator drug response (BDR). Methods We performed a genome-wide association study (GWAS) for BDR in 1,782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified seven genetic variants associated with BDR at a genome-wide significant threshold (p<5×10−8), all of which had frequencies below 5%. Furthermore, we observed an excess of small p-values driven by rare variants (frequency < 5%), and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified five significant peaks; fine mapping within these peaks identified two rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Conclusion Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in solute carrier genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multi-ethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR. PMID:23992748

  11. Exploring health implications associated with irregular migration ...

    African Journals Online (AJOL)

    Although there have been several negative media reports on the plight of irregular migrants from Ghana, research on issues related to their health has been rather scanty. The study assesses health implications associated with irregular migration from Ghana using both the Techiman and Nkoranza Municipalities as a case ...

  12. Radiotracer dose reduction in integrated PET/MR: implications from national electrical manufacturers association phantom studies.

    Science.gov (United States)

    Oehmigen, Mark; Ziegler, Susanne; Jakoby, Bjoern W; Georgi, Jens-Christoph; Paulus, Daniel H; Quick, Harald H

    2014-08-01

    With the replacement of ionizing CT by MR imaging, integrated PET/MR in selected clinical applications may reduce the overall patient radiation dose when compared with PET/CT. Further potential for radiotracer dose reduction, while maintaining PET image quality (IQ) in integrated PET/MR, may be achieved by increasing the PET acquisition duration to match the longer time needed for MR data acquisition. To systematically verify this hypothesis under controlled conditions, this dose-reduction study was performed using a standardized phantom following the National Electrical Manufacturers Association (NEMA) IQ protocol. All measurements were performed on an integrated PET/MR whole-body hybrid system. The NEMA IQ phantom was filled with water and a total activity of 50.35 MBq of (18)F-FDG. The sphere-to-background activity ratio was 8:1. Multiple PET data blocks of 20-min acquisition time were acquired in list-mode format and were started periodically at multiples of the (18)F-FDG half-lives. Different sinograms (2, 4, 8, and 16 min in duration) were reconstructed. Attenuation correction of the filled NEMA phantom was performed using a CT-based attenuation map template. The attenuation-corrected PET images were then quantitatively evaluated following the NEMA IQ protocol, investigating contrast recovery, background variability, and signal-to-noise ratio. Image groups with half the activity and twice the acquisition time were evaluated. For better statistics, the experiment was repeated 3 times. Contrast recovery, background variability, and signal-to-noise ratio remained almost constant over 3 half-life periods when the decreasing radiotracer activity (100%, 50%, 25%, and 12.5%) was compensated by increasing acquisition time (2, 4, 8, and 16 min). The variation of contrast recovery over 3 half-life periods was small (-6% to +7%), with a mean variation of 2%, compared with the reference setting (100%, 2 min). The signal-to-noise ratio of the hot spheres showed only minor

  13. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D.

    2008-01-01

    ) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due...

  14. A Genome-wide Association Study of Dupuytren Disease Reveals 17 Additional Variants Implicated in Fibrosis.

    Science.gov (United States)

    Ng, Michael; Thakkar, Dipti; Southam, Lorraine; Werker, Paul; Ophoff, Roel; Becker, Kerstin; Nothnagel, Michael; Franke, Andre; Nürnberg, Peter; Espirito-Santo, Ana Isabel; Izadi, David; Hennies, Hans Christian; Nanchahal, Jagdeep; Zeggini, Eleftheria; Furniss, Dominic

    2017-09-07

    Individuals with Dupuytren disease (DD) are commonly seen by physicians and surgeons across multiple specialties. It is an increasingly common and disabling fibroproliferative disorder of the palmar fascia, which leads to flexion contractures of the digits, and is associated with other tissue-specific fibroses. DD affects between 5% and 25% of people of European descent and is the most common inherited disease of connective tissue. We undertook the largest GWAS to date in individuals with a surgically validated diagnosis of DD from the UK, with replication in British, Dutch, and German individuals. We validated association at all nine previously described signals and discovered 17 additional variants with p ≤ 5 × 10(-8). As a proof of principle, we demonstrated correlation of the high-risk genotype at the statistically most strongly associated variant with decreased secretion of the soluble WNT-antagonist SFRP4, in surgical specimen-derived DD myofibroblasts. These results highlight important pathways involved in the pathogenesis of fibrosis, including WNT signaling, extracellular matrix modulation, and inflammation. In addition, many associated loci contain genes that were hitherto unrecognized as playing a role in fibrosis, opening up new avenues of research that may lead to novel treatments for DD and fibrosis more generally. DD represents an ideal human model disease for fibrosis research. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-06-01

    Full Text Available We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE. We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes, we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6, CD14+ monocytes (P ≤ 2.74 × 10−4 and CD19+ B cells (P ≤ 2.00 × 10−6, and plasmacytoid dendritic cells (pDCs (P ≤ 9.00 × 10−6. We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44 and DNase I hypersensitivity sites (DHSs in CD14+ monocytes (q1/q0 = 1.41, P = 0.08. We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE.

  16. Clinical Implications of Associations between Headache and Gastrointestinal Disorders: A Study Using the Hallym Smart Clinical Data Warehouse

    Directory of Open Access Journals (Sweden)

    Sang-Hwa Lee

    2017-10-01

    gastritis was significantly higher in patients with TTH compared with controls (p < 0.001. However, no differences were observed in the prevalence of HP infection between the groups.ConclusionThe observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.

  17. Clinical Implications of Associations between Headache and Gastrointestinal Disorders: A Study Using the Hallym Smart Clinical Data Warehouse.

    Science.gov (United States)

    Lee, Sang-Hwa; Lee, Jae-June; Kwon, Youngsuk; Kim, Jong-Ho; Sohn, Jong-Hee

    2017-01-01

    higher in patients with TTH compared with controls ( p  < 0.001). However, no differences were observed in the prevalence of HP infection between the groups. The observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.

  18. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies.

    Science.gov (United States)

    Newell, M A; Cook, D; Tinker, N A; Jannink, J-L

    2011-02-01

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of a high-throughput, high-density marker system. The objectives of this research were to survey the level of population structure and the extent of LD in oat germplasm and determine their implications for GWAS. In total, 1,205 lines and 402 diversity array technology (DArT) markers were used to explore population structure. Principal component analysis and model-based cluster analysis of these data indicated that, for the lines used in this study, relatively weak population structure exists. To explore LD decay, map distances of 2,225 linked DArT marker pairs were compared with LD (estimated as r²). Results showed that LD between linked markers decayed rapidly to r² = 0.2 for marker pairs with a map distance of 1.0 centi-Morgan (cM). For GWAS, we suggest a minimum of one marker every cM, but higher densities of markers should increase marker-QTL association and therefore detection power. Additionally, it was found that LD was relatively consistent across the majority of germplasm clusters. These findings suggest that GWAS in oat can include germplasm with diverse origins and backgrounds. The results from this research demonstrate the feasibility of GWAS and related analyses in oat.

  19. Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials.

    Science.gov (United States)

    Biglan, Kevin Michael; Shoulson, Ira; Kieburtz, Karl; Oakes, David; Kayson, Elise; Shinaman, M Aileen; Zhao, Hongwei; Romer, Megan; Young, Anne; Hersch, Steven; Penney, Jack; Marder, Karen; Paulsen, Jane; Quaid, Kimberly; Siemers, Eric; Tanner, Caroline; Mallonee, William; Suter, Greg; Dubinsky, Richard; Gray, Carolyn; Nance, Martha; Bundlie, Scott; Radtke, Dawn; Kostyk, Sandra; Baic, Corrine; Caress, James; Walker, Francis; Hunt, Victoria; O'Neill, Christine; Chouinard, Sylvain; Factor, Stewart; Greenamyre, Timothy; Wood-Siverio, Cathy; Corey-Bloom, Jody; Song, David; Peavy, Guerry; Moskowitz, Carol; Wesson, Melissa; Samii, Ali; Bird, Thomas; Lipe, Hillary; Blindauer, Karen; Marshall, Frederick; Zimmerman, Carol; Goldstein, Jody; Rosas, Diana; Novak, Peter; Caviness, John; Adler, Charles; Duffy, Amy; Wheelock, Vicki; Tempkin, Teresa; Richman, David; Seeberger, Lauren; Albin, Roger; Chou, Kelvin L; Racette, Brad; Perlmutter, Joel S; Perlman, Susan; Bordelon, Yvette; Martin, Wayne; Wieler, Marguerite; Leavitt, Blair; Raymond, Lynn; Decolongon, Joji; Clarke, Lorne; Jankovic, Joseph; Hunter, Christine; Hauser, Robert A; Sanchez-Ramos, Juan; Furtado, Sarah; Suchowersky, Oksana; Klimek, Mary Lou; Guttman, Mark; Sethna, Rustom; Feigin, Andrew; Cox, Marie; Shannon, Barbara; Percy, Alan; Dure, Leon; Harrison, Madaline; Johnson, William; Higgins, Donald; Molho, Eric; Nickerson, Constance; Evans, Sharon; Hobson, Douglas; Singer, Carlos; Galvez-Jimenez, Nestor; Shannon, Kathleen; Comella, Cynthia; Ross, Christopher; Saint-Hilaire, Marie H; Testa, Claudia; Rosenblatt, Adam; Hogarth, Penelope; Weiner, William; Como, Peter; Kumar, Rajeev; Cotto, Candace; Stout, Julie; Brocht, Alicia; Watts, Arthur; Eberly, Shirley; Weaver, Christine; Foroud, Tatiana; Gusella, James; MacDonald, Marcy; Myers, Richard; Fahn, Stanley; Shults, Clifford

    2016-01-01

    Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials. To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS). A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion. Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years. Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions

  20. Gene-based association study for lipid traits in diverse cohorts implicates BACE1 and SIDT2 regulation in triglyceride levels

    Directory of Open Access Journals (Sweden)

    Angela Andaleon

    2018-01-01

    Full Text Available Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9.0 × 10−10 and rs1065853 upstream of APOE associated with LDL cholesterol (P = 6.6 × 10−9. The top SNP in the Filipino cohort associated with triglyceride levels (rs662799; P = 2.7 × 10−16 and has been previously implicated in other East Asian studies. While this SNP is located directly upstream of well known APOA5, we show it may also be involved in the regulation of BACE1 and SIDT2. Our gene-based association analysis, PrediXcan, revealed decreased expression of BACE1 and decreased expression of SIDT2 in several tissues, all driven by rs662799, significantly associate with increased triglyceride levels in Filipinos (FDR <0.1. In addition, our PrediXcan analysis implicated gene regulation as the mechanism underlying the associations of many other previously discovered lipid loci. Our novel BACE1 and SIDT2 findings were confirmed using summary statistics from the Global Lipids Genetic Consortium (GLGC meta-GWAS.

  1. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

    DEFF Research Database (Denmark)

    Anttila, Verneri; Stefansson, Hreinn; Kallela, Mikko

    2010-01-01

    1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10¿¿, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3...

  2. Physical landscape associations with mapped ecosystem values with implications for spatial value transfer: An empirical study from Norway

    OpenAIRE

    Brown, Greg; Hausner, Vera Helene; Lægreid, Eiliv Jenssen

    2015-01-01

    Accepted manuscript version. Published version available at http://dx.doi.org/10.1016/j.ecoser.2015.07.005 The identification of spatial associations between perceived ecosystem values and physical landscapes is confronted by a diversity of mapping methods, heterogeneous human populations, and variability in physical landscape classification systems. This study reviews previous research on spatial associations and reports new empirical findings from Norway to describe the potentia...

  3. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    Science.gov (United States)

    Sellgren, CM; Kegel, ME; Bergen, SE; Ekman, CJ; Olsson, S; Larsson, M; Vawter, MP; Backlund, L; Sullivan, PF; Sklar, P; Smoller, JW; Magnusson, PKE; Hultman, CM; Walther-Jallow, L; Svensson, CI; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:23459468

  4. A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

    NARCIS (Netherlands)

    Li, Xiang-Dong; Chang, Xiao; Connolly, John J.; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J; Robinson, Nora; Abrams, Debra; Li, Yun R.; Bradfield, Jonathan P.; Kim, Cecilia E.; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Cone, Roger; Li, Bingshan; Sleiman, Patrick M. A.; Hakonarson, Hakon; Kas, Martien J.H.

    2017-01-01

    We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1);

  5. A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

    NARCIS (Netherlands)

    Li, Dong; Chang, Xiao; Connolly, John J.; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J.; Robinson, Nora; Abrams, Debra; Li, Yun R.; Bradfield, Jonathan P.; Kim, Cecilia E.; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Cone, Roger; Li, Bingshan; Sleiman, Patrick A.; Hakonarson, Hakon; Perica, Vesna Boraska; Franklin, Christopher S.; Floyd, James A.B.; Thornton, Laura M.; Huckins, Laura M.; Southam, Lorraine; Rayner, William N; Tachmazidou, Ioanna; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger A.H.|info:eu-repo/dai/nl/096757191; Kas, Martien J.H.|info:eu-repo/dai/nl/185967019; Favaro, Angela; Santonastaso, Paolo; Fernánde-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori-Helkamaa, Anu; Furth, Eric F.Van; Slof-Opt Landt, Margarita C.T.; Hudson, James I.; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S.; Monteleone, Palmiero; Karwautz, Andreas; Berrettini, Wade H.; Schork, Nicholas J.; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Toñu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H.; DeSocio, Janiece E.; Hilliard, Christopher E.; O'Toole, Julie K.; Pantel, Jacques; Szatkiewicz, Jin P.; Zerwas, Stephanie; Davis, Oliver S P; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; De Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Danner, Unna N.; Hendriks, Judith; Koeleman, Bobby P.C.|info:eu-repo/dai/nl/157197468; Ophoff, Roel A.|info:eu-repo/dai/nl/16237299X; Strengman, Eric|info:eu-repo/dai/nl/304815195; 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 J; 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 W.; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Barrett, Jeff C.; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Zeggini, Eleftheria; Bulik, Cynthia M.; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M.; Halmi, Katherine A.; Johnson, Craig; Kaplan, Allan S.; La Via, Maria C.; Mitchell, James R.; Strober, Michael; Rotondo, Alessandro; Treasure, Janet; Woodside, D. Blake; Keel, Pamela K.; Klump, Kelly L.; Lilenfeld, Lisa; Bergen, Andrew W.|info:eu-repo/dai/nl/345481240; Kaye, Walter; Magistretti, Pierre

    2017-01-01

    We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P =

  6. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    Directory of Open Access Journals (Sweden)

    Jane E. Gallagher

    2016-07-01

    Full Text Available Abstract Background Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based health indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mortality, suggesting that self-reported health (SRH may be useful in screening-level community assessments. This paper evaluates whether SRH is an appropriate surrogate indicator of health status by evaluating relationships between SRH and sociodemographic, lifestyle, and health care factors as well as serological indicators of nutrition, health risk, and environmental exposures. Methods Data were combined from the 2003–2006 National Health and Nutrition Examination Surveys for 1372 nonsmoking 20–50 year olds. Ordinal and binary logistic regression was used to estimate odds ratios and 95 % confidence intervals of reporting poorer health based on measures of nutrition, health condition, environmental contaminants, and sociodemographic, health care, and lifestyle factors. Results Poorer SRH was associated with several serological measures of nutrition, health condition, and biomarkers of toluene, cadmium, lead, and mercury exposure. Race/ethnicity, income, education, access to health care, food security, exercise, poor mental and physical health, prescription drug use, and multiple health outcome measures (e.g., diabetes, thyroid problems, asthma were also associated with poorer SRH. Conclusion Based on the many significant associations between SRH and serological assays of health risk, sociodemographic measures, health care access and utilization, and lifestyle factors, SRH appears to be a useful health indicator with potential relevance for screening level community-based health and environmental studies.

  7. The use of common mitochondrial variants to detect and characterise population structure in the Australian population: implications for genome-wide association studies.

    Science.gov (United States)

    Byrne, Enda M; McRae, Allan F; Zhao, Zhen-Zhen; Martin, Nicholas G; Montgomery, Grant W; Visscher, Peter M

    2008-11-01

    There is an increasing recognition of the potential role of variants in mitochondrial DNA and nuclear-encoded mitochondrial proteins in modifying disease risk. This has led to a rise in the number of mitochondrial association studies being undertaken. The unique inheritance pattern of mitochondria makes mitochondrial DNA variation susceptible to having geographical structure. Such a structure may have a dramatic impact on mitochondrial association studies, particularly in heterogeneous populations. By combining self-reported ancestry data and mitochondrial genotype data for a sample of 3839 individuals from 1037 Australian families, population substructure is tested by looking for evidence of differences in mitochondrial haplogroup and single nucleotide polymorphism (SNP) frequencies between different ancestral groups in Australia. In addition, the substructure within ancestral groups is tested by comparing the similarity of mates to randomly drawn pairs of individuals from the same ancestral group. It is shown that there are significant differences in the frequency of variants both between European and non-European groups, and within Europe. This agrees with previous studies of European mitochondrial variation. No evidence was found for structure within ancestral groups. These results have implications for future association studies in the Australian population, and other populations of heterogeneous ancestry.

  8. Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

    Science.gov (United States)

    Gowans, L.J.J.; Adeyemo, W.L.; Eshete, M.; Mossey, P.A.; Busch, T.; Aregbesola, B.; Donkor, P.; Arthur, F.K.N.; Bello, S.A.; Martinez, A.; Li, M.; Augustine-Akpan, E.A.; Deressa, W.; Twumasi, P.; Olutayo, J.; Deribew, M.; Agbenorku, P.; Oti, A.A.; Braimah, R.; Plange-Rhule, G.; Gesses, M.; Obiri-Yeboah, S.; Oseni, G.O.; Olaitan, P.B.; Abdur-Rahman, L.; Abate, F.; Hailu, T.; Gravem, P.; Ogunlewe, M.O.; Buxó, C.J.; Marazita, M.L.; Adeyemo, A.A.; Murray, J.C.; Butali, A.

    2016-01-01

    Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10−3), 8q24 (rs987525, P = 1.22 × 10−3), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp

  9. A Pilot Genome-Wide Association Study in Postmenopausal Mexican-Mestizo Women Implicates the RMND1/CCDC170 Locus Is Associated with Bone Mineral Density

    Directory of Open Access Journals (Sweden)

    Marisela Villalobos-Comparán

    2017-01-01

    Full Text Available To identify genetic variants influencing bone mineral density (BMD in the Mexican-Mestizo population, we performed a GWAS for femoral neck (FN and lumbar spine (LS in Mexican-Mestizo postmenopausal women. In the discovery sample, 300,000 SNPs were genotyped in a cohort of 411 postmenopausal women and seven SNPs were analyzed in the replication cohort (n=420. The combined results of a meta-analysis from the discovery and replication samples identified two loci, RMND1 (rs6904364, P=2.77×10−4 and CCDC170 (rs17081341, P=1.62×10−5, associated with FN BMD. We also compared our results with those of the Genetic Factors for Osteoporosis (GEFOS Consortium meta-analysis. The comparison revealed two loci previously reported in the GEFOS meta-analysis: SOX6 (rs7128738 and PKDCC (rs11887431 associated with FN and LS BMD, respectively, in our study population. Interestingly, rs17081341 rare in Caucasians (minor allele frequency < 0.03 was found in high frequency in our population, which suggests that this association could be specific to non-Caucasian populations. In conclusion, the first pilot Mexican GWA study of BMD confirmed previously identified loci and also demonstrated the importance of studying variability in diverse populations and/or specific populations.

  10. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

    Science.gov (United States)

    Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

    2011-01-01

    Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

  11. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Saimul Islam

    Full Text Available Human papillomavirus (HPV causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT and Neo-adjuvant chemotherapy (NACT patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0% and NACT (71.0% cases with significant association with younger (20-45 yrs PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21, fibro adenomas (30%, 3/10 to tumors (64.8%, 203/313 samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0% followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839 in the LCR region and two (KT020836 and KT020837 in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314 and E6^E7*II (KU199315 fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

  12. Spatial and temporal associations of road traffic noise and air pollution in London: Implications for epidemiological studies.

    Science.gov (United States)

    Fecht, Daniela; Hansell, Anna L; Morley, David; Dajnak, David; Vienneau, Danielle; Beevers, Sean; Toledano, Mireille B; Kelly, Frank J; Anderson, H Ross; Gulliver, John

    2016-03-01

    Road traffic gives rise to noise and air pollution exposures, both of which are associated with adverse health effects especially for cardiovascular disease, but mechanisms may differ. Understanding the variability in correlations between these pollutants is essential to understand better their separate and joint effects on human health. We explored associations between modelled noise and air pollutants using different spatial units and area characteristics in London in 2003-2010. We modelled annual average exposures to road traffic noise (LAeq,24h, Lden, LAeq,16h, Lnight) for ~190,000 postcode centroids in London using the UK Calculation of Road Traffic Noise (CRTN) method. We used a dispersion model (KCLurban) to model nitrogen dioxide, nitrogen oxide, ozone, total and the traffic-only component of particulate matter ≤2.5μm and ≤10μm. We analysed noise and air pollution correlations at the postcode level (~50 people), postcodes stratified by London Boroughs (~240,000 people), neighbourhoods (Lower layer Super Output Areas) (~1600 people), 1km grid squares, air pollution tertiles, 50m, 100m and 200m in distance from major roads and by deprivation tertiles. Across all London postcodes, we observed overall moderate correlations between modelled noise and air pollution that were stable over time (Spearman's rho range: |0.34-0.55|). Correlations, however, varied considerably depending on the spatial unit: largest ranges were seen in neighbourhoods and 1km grid squares (both Spearman's rho range: |0.01-0.87|) and was less for Boroughs (Spearman's rho range: |0.21-0.78|). There was little difference in correlations between exposure tertiles, distance from road or deprivation tertiles. Associations between noise and air pollution at the relevant geographical unit of analysis need to be carefully considered in any epidemiological analysis, in particular in complex urban areas. Low correlations near roads, however, suggest that independent effects of road noise and

  13. A Systematic, Large-Scale Study of Synaesthesia: Implications for the Role of Early Experience in Lexical-Colour Associations

    Science.gov (United States)

    Rich, A. N.; Bradshaw, J. L.; Mattingley, J. B.

    2005-01-01

    For individuals with synaesthesia, stimuli in one sensory modality elicit anomalous experiences in another modality. For example, the sound of a particular piano note may be "seen" as a unique colour, or the taste of a familiar food may be "felt" as a distinct bodily sensation. We report a study of 192 adult synaesthetes, in…

  14. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    OpenAIRE

    Gallagher, Jane E.; Adrien A. Wilkie; Alissa Cordner; Hudgens, Edward E.; Ghio, Andrew J.; Birch, Rebecca J.; Wade, Timothy J

    2016-01-01

    Abstract Background Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based health indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mortality, suggesting that self-reported health (SRH) may be useful in screening-level community assessments. This paper evaluates whether SRH is an appropriate surrogate indicator of health status by evaluating ...

  15. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    OpenAIRE

    Gallagher, Jane E.; Adrien A. Wilkie; Cordner, Alissa; Hudgens, Edward E.; Ghio, Andrew J.; Birch, Rebecca J.; Wade, Timothy J

    2016-01-01

    Background Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based health indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mortality, suggesting that self-reported health (SRH) may be useful in screening-level community assessments. This paper evaluates whether SRH is an appropriate surrogate indicator of health status by evaluating relations...

  16. Genome-Wide Association Study Reveals Genetic Architecture of Eating Behaviors in Pigs and its Implications for Humans Obesity by Comparative Genome Mapping

    DEFF Research Database (Denmark)

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

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behaviors inDanish Duroc boars and its potential implications for eating behaviors in humans.Individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of dailyvisits to feeder (NVD), time spent to eat...

  17. Implication of P-glycoprotein in formation of depression-prone personality: association study between the C3435T MDR1 gene polymorphism and interpersonal sensitivity.

    Science.gov (United States)

    Enokido, Masanori; Suzuki, Akihito; Sadahiro, Ryoichi; Matsumoto, Yoshihiko; Shibuya, Naoshi; Goto, Kaoru; Otani, Koichi

    2014-01-01

    Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others. Previous studies suggested that interpersonal sensitivity is one of the vulnerable factors to depression, and that genetic factors and cortisol are involved in the formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active eliminator for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. In the present study, we examined the effects of the MDR1 C3435T polymorphism (rs1045642) on interpersonal sensitivity in healthy subjects. The subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM). The 2-factor analysis of covariance (ANCOVA) showed a significant main effect of the MDR1 genotype on the IPSM scores with a significant interaction between the genotype and gender. The subsequent 1-factor ANCOVA showed that in females the C/C genotype group had higher IPSM scores than the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and the C/T genotype group had higher IPSM scores than the T/T genotype group (p = 0.014). In males no significant association was found between the MDR1 genotype and the IPSM scores. In allelic analyses using the χ(2) tests, the C allele frequency in females was significantly higher (p < 0.001) in the high IPSM group than in the low IPSM group, while there was no significant difference in the C allele frequency between the high and low IPSM groups in total subjects and males. The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.

  18. Architectural Implications for Spatial Object Association Algorithms*

    Science.gov (United States)

    Kumar, Vijay S.; Kurc, Tahsin; Saltz, Joel; Abdulla, Ghaleb; Kohn, Scott R.; Matarazzo, Celeste

    2013-01-01

    Spatial object association, also referred to as crossmatch of spatial datasets, is the problem of identifying and comparing objects in two or more datasets based on their positions in a common spatial coordinate system. In this work, we evaluate two crossmatch algorithms that are used for astronomical sky surveys, on the following database system architecture configurations: (1) Netezza Performance Server®, a parallel database system with active disk style processing capabilities, (2) MySQL Cluster, a high-throughput network database system, and (3) a hybrid configuration consisting of a collection of independent database system instances with data replication support. Our evaluation provides insights about how architectural characteristics of these systems affect the performance of the spatial crossmatch algorithms. We conducted our study using real use-case scenarios borrowed from a large-scale astronomy application known as the Large Synoptic Survey Telescope (LSST). PMID:25692244

  19. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    NARCIS (Netherlands)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N.; Saleheen, Danish; Lehne, Benjamin; Leach, Irene Mateo; Drong, Alexander W.; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R.; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S.; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L.; Esko, Tonu; Go, Min Jin; Harris, Sarah E.; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E.; Li, Huaixing; Mok, Zuan Yu; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F. R.; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Alves, Alexessander Da Silva Couto; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C.; Kim, Yun Kyoung; Koivula, Robert W.; Luan, Jian'an; Lyytikainen, Leo-Pekka; Nguyen, Quang N.; Pereira, Mark A.; Postmus, Iris; Raitakari, Olli T.; Bryan, Molly Scannell; Scott, Robert A.; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S.; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Ines; Bjonnes, Andrew; Braun, Timothy R.; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D.; Doevendans, Pieter A.; Gansevoort, Ron T.; Gao, Yu-Tang; Grammer, Tanja B.; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S.; Hartikainen, Anna-Liisa; Hazen, Stanley L.; He, Jing; Heng, Chew-Kiat; Hixson, James E.; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L. N.; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M.; Katsuy, Tomohiro; Kibriya, Muhammad G.; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R.; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C. M.; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Mueller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T.; Pinidiyapathirage, Mohitha J.; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Rozario, Michelle Ann; Ruggiero, Daniela; Sala, Cinzia F.; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparso, Thomas; Spiering, Wilko; Starr, John M.; Stott, David J.; Stram, Daniel O.; Sugiyama, Takao; Szymczak, Silke; Tang, W. H. Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Vaino; Ueshima, Hirotsugu; Uitterlinden, Andre G.; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; Viikari, Jorma S.; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D.; Young, Terri L.; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W.; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W.; Franks, Steve; Friedlander, Yechiel; Gross, Myron D.; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jorgensen, Torben; Jukema, J. Wouter; Kahonen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimaki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J.; Sorensen, Thorkild I. A.; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J.; Franco, Oscar H.; Franke, Lude; Heijman, Bastiaan T.; Holbrook, Joanna D.; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; Maerz, Winfried; Metspalu, Andres; Mohlke, Karen L.; Sanghera, Dharambir K.; Shu, Xiao-Ou; van Meurs, Joyce B. J.; Vithana, Eranga; Wickremasinghe, Ananda R.; Wijmenga, Cisca; Wolffenbuttel, Bruce H. W.; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A.; Kleinjans, Jos C. S.; McCarthy, Mark I.; Soong, Richie; Gieger, Christian; Scott, James; Teo, Yik-Ying; He, Jiang; Elliott, Paul; Tai, E. Shyong; van der Harst, Pim; Kooner, Jaspal S.; Chambers, John C.

    2015-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x

  20. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    NARCIS (Netherlands)

    N. Kato (Norihiro); M. Loh (Marie); F. Takeuchi (Fumihiko); N. Verweij (Niek); X. Wang (Xu); W. Zhang (Weihua); T. NKelly (Tanika); D. Saleheen; B. Lehne (Benjamin); I.M. Leach (Irene Mateo); A. Drong (Alexander); J. Abbott (James); S. Wahl (Simone); S.-T. Tan (Sian-Tsung); W.R. Scott (William R.); G. Campanella (Gianluca); M. Chadeau-Hyam (Marc); U. Afzal (Uzma); T.S. Ahluwalia (Tarunveer Singh); M.J. Bonder (Marc); P. Chen (Ping); A. Dehghan (Abbas); T.L. Edwards (Todd L.); T. Esko (Tõnu); M.J. Go (Min Jin); S.E. Harris (Sarah); J. Hartiala (Jaana); S. Kasela (Silva); A. Kasturiratne (Anuradhani); C.C. Khor; M.E. Kleber (Marcus); H. Li (Huaixing); Z.Y. Mok (Zuan Yu); M. Nakatochi (Masahiro); N.S. Sapari (Nur Sabrina); R. Saxena (Richa); A.F. Stewart (Alexandre F.); L. Stolk (Lisette); Y. Tabara (Yasuharu); A.L. Teh (Ai Ling); Y. Wu (Ying); J.-Y. Wu (Jer-Yuarn); Y. Zhang (Yi); I. Aits (Imke); A. Da Silva Couto Alves (Alexessander); S. Das (Shikta); R. Dorajoo (Rajkumar); J. CHopewell (Jemma); Y.K. Kim (Yun Kyoung); R. WKoivula (Robert); J. Luan (Jian'An); L.-P. Lyytikäinen (Leo-Pekka); Q. NNguyen (Quang); M.A. Pereira (Mark A); D. Postmus (Douwe); O. TRaitakari (Olli); M. Scannell Bryan (Molly); R.A. Scott (Robert); R. Sorice; V. Tragante (Vinicius); M. Traglia (Michela); J. White (Jon); K. Yamamoto (Ken); Y. Zhang (Yonghong); L.S. Adair (Linda); A. Ahmed (Alauddin); K. Akiyama (Koichi); R. Asif (Rasheed); T. Aung (Tin); I. Barroso (Inês); A. Bjonnes (Andrew); T.R. Braun (Timothy R.); H. Cai (Hui); L.-C. Chang (Li-Ching); C.-H. Chen; C-Y. Cheng (Ching-Yu); Y.-S. Chong (Yap-Seng); F.S. Collins (Francis); R. Courtney (Regina); G. Davies (Gail); G. Delgado; L.D. Do (Loi D.); P.A. Doevendans (Pieter); R.T. Gansevoort (Ron); Y. Gao; T.B. Grammer (Tanja B); N. Grarup (Niels); J. Grewal (Jagvir); D. Gu (D.); G. SWander (Gurpreet); A.L. Hartikainen; S.L. Hazen (Stanley); J. He (Jing); C.K. Heng (Chew-Kiat); E.J.A. Hixso (E. James Ames); A. Hofman (Albert); C. Hsu (Chris); W. Huang (Wei); L.L.N. Husemoen (Lise Lotte); J.-Y. Hwang (Joo-Yeon); S. Ichihara (Sahoko); M. Igase (Michiya); M. Isono (Masato); J.M. Justesen (Johanne M.); T. Katsuya (Tomohiro); M. GKibriya (Muhammad); Y.J. Kim; M. Kishimoto (Miyako); W.-P. Koh (Woon-Puay); K. Kohara (Katsuhiko); M. Kumari (Meena); K. Kwek (Kenneth); N.R. Lee (Nanette); J. Lee (Jeannette); J. Liao (Jie); W. Lieb (Wolfgang); D.C. Liewald (David C.); T. Matsubara (Tatsuaki); Y. Matsushita (Yumi); T. Meitinger (Thomas); E. Mihailov (Evelin); L. Milani (Lili); R. Mills (Rebecca); K. Mononen (Kari); M. Müller-Nurasyid (Martina); T. Nabika (Toru); E. Nakashima (Eitaro); H.K. Ng (Hong Kiat); K. Nikus (Kjell); T. Nutile; T. Ohkubo (Takayoshi); K. Ohnaka (Keizo); S. Parish (Sarah); L. Paternoster (Lavinia); H. Peng (Hao); A. Peters (Annette); S. TPham (Son); M.J. Pinidiyapathirage (Mohitha J.); M. Rahman (Mahfuzar); H. Rakugi (Hiromi); O. Rolandsson (Olov); M.A. Rozario (Michelle Ann); D. Ruggiero; C. Sala (Cinzia); R. Sarju (Ralhan); K. Shimokawa (Kazuro); H. Snieder (Harold); T. Sparsø (Thomas); W. Spiering (Wilko); J.M. Starr (John); D.J. Stott (David J.); D. OStram (Daniel); T. Sugiyama (Takao); S. Szymczak (Silke); W.H.W. Tang (W.H. Wilson); L. Tong (Lin); S. Trompet (Stella); V. Turjanmaa (Väinö); H. Ueshima (Hirotsugu); A.G. Uitterlinden (André); S. Umemura (Satoshi); M. Vaarasmaki (Marja); R.M. Dam (Rob Mvan); W.H. van Gilst (Wiek); D.J. van Veldhuisen (Dirk); J. Viikari (Jorma); M. Waldenberger (Melanie); Y. Wang (Yiqin); A. Wang (Aili); R. Wilson (Rory); T.Y. Wong (Tien Yin); Y.-B. Xiang (Yong-Bing); S. Yamaguchi (Shuhei); X. Ye (Xingwang); R. Young (Robin); T.L. Young (Terri); J.-M. Yuan (Jian-Min); X. Zhou (Xueya); F.W. Asselbergs (Folkert); M. Ciullo; R. Clarke (Robert); P. Deloukas (Panagiotis); A. Franke (Andre); W.F. Paul (W. Frank); S. Franks (Steve); Y. Friedlander (Yechiel); M.D. Gross (Myron D.); Z. Guo (Zhirong); T. Hansen (T.); M.-R. Jarvelin (Marjo-Riitta); T. Jørgensen (Torben); J.W. Jukema (Jan Wouter); M. Kähönen (Mika); H. Kajio (Hiroshi); M. Kivimaki (Mika); J.-Y. Lee (Jong-Young); T. Lehtimäki (Terho); A. Linneberg (Allan); T. Miki (Tetsuro); O. Pedersen (Oluf); N.J. Samani (Nilesh); T.I.A. Sørensen (Thorkild); R. Takayanagi (Ryoichi); D. Toniolo (Daniela); H. Ahsan (Habibul); H. Allayee (Hooman); Y.-T. Chen (Yuan-Tsong); J. Danesh (John); I.J. Deary (Ian J.); O.H. Franco (Oscar); L. Franke (Lude); B. THeijman (Bastiaan); J.D. Holbrook (Joanna D.); A.J. Isaacs (Aaron); B.-J. Kim (Bong-Jo); X. Lin (Xu); J. Liu (Jianjun); W. März (Winfried); A. Metspalu (Andres); K.L. Mohlke (Karen); K. Sangher; D. Harambir (Dharambir); X.-O. Shu (Xiao-Ou); J.B.J. van Meurs (Joyce); E.N. Vithana (Eranga); A.R. Wickremasinghe (Ananda); C. Wijmenga (Cisca); B.H.W. Wolffenbuttel (Bruce H.W.); M. Yokota (Mitsuhiro); W. Zheng (Wei); D. Zhu (Dingliang); P. Vineis (Paolo); S.A. Kyrtopoulos (Soterios A.); J.C.S. Kleinjans (Jos C.S.); M.I. McCarthy (Mark); R. Soong (Richie); C. Gieger (Christian); J. Scott (James); Y.Y. Teo (Yik Ying); J. He (Jiang); P. Elliott (Paul); E.S. Tai (Shyong); P. van der Harst (Pim); J.S. Kooner (Jaspal S.); J.C. Chambers (John)

    2015-01-01

    textabstractWe carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to

  1. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    DEFF Research Database (Denmark)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko

    2015-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(...

  2. Association between Obesity, hsCRP ≥2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA)

    Science.gov (United States)

    Blaha, Michael J.; Rivera, Juan J.; Budoff, Matthew J.; Blankstein, Ron; Agatston, Arthur; O’Leary, Daniel H.; Cushman, Mary; Lakoski, Susan; Criqui, Michael H.; Szklo, Moyses; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Objective High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown. Methods and Results We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals. Conclusions High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status. PMID:21474823

  3. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

    Directory of Open Access Journals (Sweden)

    Dana B Hancock

    2009-08-01

    Full Text Available Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs. We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6 in the GWAS, located upstream of transducin-like enhancer of split 4 (TLE4, gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7. Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.

  4. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

    Science.gov (United States)

    Hancock, Dana B; Romieu, Isabelle; Shi, Min; Sienra-Monge, Juan-Jose; Wu, Hao; Chiu, Grace Y; Li, Huiling; del Rio-Navarro, Blanca Estela; Willis-Owen, Saffron A G; Willis-Owens, Saffron A G; Weiss, Scott T; Raby, Benjamin A; Gao, Hong; Eng, Celeste; Chapela, Rocio; Burchard, Esteban G; Tang, Hua; Sullivan, Patrick F; London, Stephanie J

    2009-08-01

    Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.

  5. Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases.

    Science.gov (United States)

    Ioannidis, John P A; Trikalinos, Thomas A; Khoury, Muin J

    2006-10-01

    Accumulated evidence from searching for candidate gene-disease associations of complex diseases can offer some insights as the field moves toward discovery-oriented approaches with massive genome-wide testing. Meta-analyses of 50 non-human lymphocyte antigen gene-disease associations with documented overall statistical significance (752 studies) show summary odds ratios with a median of 1.43 (interquartile range, 1.28-1.65). Many different biases may operate in this field, for both single studies and meta-analyses, and these biases could invalidate some of these seemingly "validated" associations. Studies with a sample size of >500 show a median odds ratio of only 1.15. The median sample size required to detect the observed summary effects in each population addressed in the 752 studies is estimated to be 3,535 (interquartile range, 1,936-9,119 for cases and controls combined). These estimates are steeply inflated in the presence of modest bias. Population heterogeneity, as well as gene-gene and gene-environment interactions, could steeply increase these estimates and may be difficult to address even by very large biobanks and observational cohorts. The one visible solution is for a large number of teams to join forces on the same research platforms. These collaborative studies ideally should be designed up front to also assess more complex gene-gene and gene-environment interactions.

  6. Corona Associations and Their Implications for Venus

    Science.gov (United States)

    Chapman, M.G.; Zimbelman, J.R.

    1998-01-01

    Geologic mapping principles were applied to determine genetic relations between coronae and surrounding geomorphologic features within two study areas in order to better understand venusian coronae. The study areas contain coronae in a cluster versus a contrasting chain and are (1) directly west of Phoebe Regio (quadrangle V-40; centered at latitude 15??S, longitude 250??) and (2) west of Asteria and Beta Regiones (between latitude 23??N, longitude 239?? and latitude 43??N, longitude 275??). Results of this research indicate two groups of coronae on Venus: (1) those that are older and nearly coeval with regional plains, and occur globally; and (2) those that are younger and occur between Beta, Atla, and Themis Regiones or along extensional rifts elsewhere, sometimes showing systematic age progressions. Mapping relations and Earth analogs suggest that older plains coronae may be related to a near-global resurfacing event perhaps initiated by a mantle superplume or plumes. Younger coronae of this study that show age progression may be related to (1) a tectonic junction of connecting rifts resulting from local mantle upwelling and spread of a quasi-stationary hotspot plume, and (2) localized spread of post-plains volcanism. We postulate that on Venus most of the young, post-resurfacing coronal plumes may be concentrated within an area defined by the bounds of Beta, Atla, and Themis Regiones. ?? 1998 Academic Press.

  7. Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China

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    Cheng-kun Yang

    2017-07-01

    Full Text Available Background/Aims: Hepatocellular carcinoma (HCC is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67 is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. Methods: A total of 195 hepatitis B virus (HBV-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers. An independent cohort (97 subjects validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. Results: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. Conclusion: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.

  8. Genome-wide pathway-based association study implicates complement system in the development of Kashin-Beck disease in Han Chinese.

    Science.gov (United States)

    Zhang, Feng; Wen, Yan; Guo, Xiong; Zhang, Yingang; Wang, Sen; Yang, Tielin; Shen, Hui; Chen, Xiangding; Tan, Lijun; Tian, Qing; Deng, Hong-Wen

    2015-02-01

    Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of KBD remains unknown. To identify relevant biological pathways for KBD, we conducted a genome-wide pathway-based association study (GWPAS) following by replication analysis, totally using 2743 Chinese Han adults. A modified gene set enrichment algorithm was used to detect association between KBD and 963 biological pathways. Cartilage gene expression analysis and serum complement measurement were performed to evaluate the functional relevance of identified pathway with KBD. We found that the Complement and Coagulation Cascades (CACC) pathway was significantly associated with KBD (P value=3.09×10(-5), false-discovery rate=0.042). Within the CACC pathway, the most significant association was observed at rs1656966 (P value=1.97×10(-4)) of KNG1 gene. Further replication study observed that rs1656966 (P value=0.037) was significantly associated with KBD in an independent validation sample of 1026 subjects. Gene expression analysis observed that CFD (ratio=3.39±2.68), A2M (ratio=3.67±5.63), C5 (ratio=2.65±2.52) and CD46 (ratio=2.29±137) genes of the CACC pathway were up-regulated in KBD articular cartilage compared to healthy articular cartilage. The serum level of complement C5 in KBD patients were significantly higher than that in healthy controls (P value=0.038). Our study is the first to suggest that complement system-related CACC pathway contributed to the development of KBD. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications.

    Science.gov (United States)

    Allen, Mariet; Zou, Fanggeng; Chai, High Seng; Younkin, Curtis S; Miles, Richard; Nair, Asha A; Crook, Julia E; Pankratz, V Shane; Carrasquillo, Minerva M; Rowley, Christopher N; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G; Bisceglio, Gina; Ortolaza, Alexandra I; Palusak, Ryan; Middha, Sumit; Maharjan, Sooraj; Georgescu, Constantin; Schultz, Debra; Rakhshan, Fariborz; Kolbert, Christopher P; Jen, Jin; Sando, Sigrid B; Aasly, Jan O; Barcikowska, Maria; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A; Petersen, Ronald C; Graff-Radford, Neill R; Dickson, Dennis W; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2012-04-11

    Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects). We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003). These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.

  10. Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications

    Directory of Open Access Journals (Sweden)

    Allen Mariet

    2012-04-01

    Full Text Available Abstract Background Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2, residing within an Alzheimer and Parkinson disease (AD and PD linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls and PD (678 PDs vs. 712 controls for association with disease risk (case-controls, age-at-diagnosis (cases and brain gene expression levels (autopsied subjects. Results We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038 in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034. There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27, but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003. Conclusion These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.

  11. Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility.

    Science.gov (United States)

    Lascorz, Jesús; Försti, Asta; Chen, Bowang; Buch, Stephan; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Schulmann, Karsten; Goecke, Timm; Kloor, Matthias; Engel, Cristoph; Büttner, Reinhard; Kunkel, Nelli; Weires, Marianne; Hoffmeister, Michael; Pardini, Barbara; Naccarati, Alessio; Vodickova, Ludmila; Novotny, Jan; Schreiber, Stefan; Krawczak, Michael; Bröring, Clemens D; Völzke, Henry; Schafmayer, Clemens; Vodicka, Pavel; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara; Propping, Peter; Hampe, Jochen; Hemminki, Kari

    2010-09-01

    Genetic susceptibility accounts for approximately 35% of all colorectal cancer (CRC). Ten common low-risk variants contributing to CRC risk have been identified through genome-wide association studies (GWASs). In our GWAS, 610 664 genotyped single-nucleotide polymorphisms (SNPs) passed the quality control filtering in 371 German familial CRC patients and 1263 controls, and replication studies were conducted in four additional case-control sets (4915 cases and 5607 controls). Known risk loci at 8q24.21 and 11q23 were confirmed, and a previously unreported association, rs12701937, located between the genes GLI3 (GLI family zinc finger 3) and INHBA (inhibin, beta A) [P = 1.1 x 10(-3), odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.23, dominant model in the combined cohort], was identified. The association was stronger in familial cases compared with unselected cases (P = 2.0 x 10(-4), OR 1.36, 95% CI 1.16-1.60, dominant model). Two other unreported SNPs, rs6038071, 40 kb upstream of CSNK2A1 (casein kinase 2, alpha 1 polypeptide) and an intronic marker in MYO3A (myosin IIIA), rs11014993, associated with CRC only in the familial CRC cases (P = 2.5 x 10(-3), recessive model, and P = 2.7 x 10(-4), dominant model). Three software tools successfully pointed to the overrepresentation of genes related to the mitogen-activated protein kinase (MAPK) signalling pathways among the 1340 most strongly associated markers from the GWAS (allelic P value < 10(-3)). The risk of CRC increased significantly with an increasing number of risk alleles in seven genes involved in MAPK signalling events (P(trend) = 2.2 x 10(-16), OR(per allele) = 1.34, 95% CI 1.11-1.61).

  12. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    Science.gov (United States)

    Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Yu Mok, Zuan; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W; Luan, Jian’an; Lyytikäinen, Leo-Pekka; Nguyen, Quang N; Pereira, Mark A; Postmus, Iris; Raitakari, Olli T; Bryan, Molly Scannell; Scott, Robert A; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Inês; Bjonnes, Andrew; Braun, Timothy R; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D; Doevendans, Pieter A; Gansevoort, Ron T; Gao, Yu-Tang; Grammer, Tanja B; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S; Hartikainen, Anna-Liisa; Hazen, Stanley L; He, Jing; Heng, Chew-Kiat; Hixson, James E; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L N; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M; Katsuya, Tomohiro; Kibriya, Muhammad G; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C M; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Müller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T; Pinidiyapathirage, Mohitha J; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Ann Rozario, Michelle; Ruggiero, Daniela; Sala, Cinzia F; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparsø, Thomas; Spiering, Wilko; Starr, John M; Stott, David J; Stram, Daniel O; Sugiyama, Takao; Szymczak, Silke; Tang, W H Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Väinö; Ueshima, Hirotsugu; Uitterlinden, André G; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M; van Gilst, Wiek H; van Veldhuisen, Dirk J; Viikari, Jorma S; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D; Young, Terri L; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W; Franks, Steve; Friedlander, Yechiel; Gross, Myron D; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jørgensen, Torben; Jukema, J Wouter; kähönen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimäki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J; Sørensen, Thorkild I A; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J; Franco, Oscar H; Franke, Lude; Heijman, Bastiaan T; Holbrook, Joanna D; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; März, Winfried; Metspalu, Andres; Mohlke, Karen L; Sanghera, Dharambir K; Shu, Xiao-Ou; van Meurs, Joyce B J; Vithana, Eranga; Wickremasinghe, Ananda R; Wijmenga, Cisca; Wolffenbuttel, Bruce H W; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A; Kleinjans, Jos C S; McCarthy, Mark I; Soong, Richie; Gieger, Christian; Scott, James

    2016-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. PMID:26390057

  13. Th17 response and autophagy - main pathways implicated in the development of inflammatory bowel disease by genome-wide association studies: new factors involved in inflammatory bowel disease susceptibility

    Directory of Open Access Journals (Sweden)

    Roberto Díaz-Peña

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is an entity that mainly includes ulcerative colitis (UC and Crohn's disease (CD. Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

  14. Gender-Associated Mitochondrial DNA Heteroplasmy in Somatic Tissues of the Endangered Freshwater Mussel Unio crassus (Bivalvia: Unionidae): Implications for Sex Identification and Phylogeographical Studies.

    Science.gov (United States)

    Mioduchowska, Monika; Kaczmarczyk, Agnieszka; Zając, Katarzyna; Zając, Tadeusz; Sell, Jerzy

    2016-11-01

    Some bivalve species possess two independent mitochondrial DNA lineages: maternally (F-type) and paternally (M-type) inherited. This phenomenon is called doubly uniparental inheritance. It is generally agreed that F-type mtDNA is typically present in female somatic and gonadal tissues as well as in male somatic tissues, whereas the M-type mtDNA occurs only in male germ line and gonadal tissue. In the present study, the mtDNA heteroplasmy (for both F and M genomes) in male somatic tissues of Unio crassus (Philipsson, 1788), species threatened with extinction, has been confirmed. Taking advantage from the presence of Mcox1 marker only in male somatic tissues, we developed a new method of sex identification in this endangered species, using nondestructive tissue sampling. Probability of correct sex identification was estimated at 97.5%. The present study is the first report on gender-associated mitochondrial DNA heteroplasmy in male somatic tissues of thick-shelled river mussel and first approach to U. crassus sex identification at molecular level. Our study also confirmed the utility of paternally inherited Mcox1 gene fragment as a complementary molecular tool for resolving phylogeographical relationships among populations of thick-shelled river mussel. © 2017 Wiley Periodicals, Inc.

  15. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.

    Science.gov (United States)

    Blaha, Michael J; Budoff, Matthew J; DeFilippis, Andrew P; Blankstein, Ron; Rivera, Juan J; Agatston, Arthur; O'Leary, Daniel H; Lima, Joao; Blumenthal, Roger S; Nasir, Khurram

    2011-08-20

    The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. 950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata. Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources. National Institutes of Health-National Heart, Lung, and Blood Institute. Copyright © 2011 Elsevier Ltd. All rights

  16. Association of neighbourhood residence and preferences with the built environment, work-related travel behaviours, and health implications for employed adults: findings from the URBAN study.

    Science.gov (United States)

    Badland, Hannah M; Oliver, Melody; Kearns, Robin A; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J; Batty, G David

    2012-10-01

    Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of

  17. Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

    Science.gov (United States)

    Cromwell, Ronita; Zanello, Susana; Yarbough, Patrice; Ploutz-Snyder, Robert; Taibbi, Giovanni; Vizzeri, Gianmarco

    2013-01-01

    time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

  18. Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

    Directory of Open Access Journals (Sweden)

    T Bernard Bigdeli

    Full Text Available Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects. These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted for each of five factor-derived scores based on the Operational Criteria Checklist for Psychotic Illness (delusions, hallucinations, mania, depression, and negative symptoms. Tests of association were conducted using the PDTPHASE and QPDTPHASE packages of UNPHASED. Empirical estimates of gene-wise significance were obtained by adaptive permutation of a the smallest observed P-value and b the threshold-truncated product of P-values for each locus.While no single variant was significant after LD-corrected Bonferroni-correction, our gene-dropping analyses identified loci which exceeded empirical significance criteria for both gene-based tests. Namely, R3HDML and C20orf39 are significantly associated with depressive symptoms of schizophrenia (P(emp<2×10⁻⁵ based on the minimum P-value and truncated-product methods, respectively.Using a gene-based approach to family-based association, R3HDML and C20orf39 were found to be significantly associated with clinical dimensions of schizophrenia. These findings demonstrate the efficacy of gene-based analysis and support previous evidence that chromosome 20 may harbor schizophrenia susceptibility or modifier loci.

  19. Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2

    NARCIS (Netherlands)

    Huang, Jie; Huffman, Jennifer E.; Yamkauchi, Munekazu; Trompet, Stella; Asselbergs, Folkert W.; Sabater-Lleal, Maria; Tregouet, David-Alexandre; Chen, Wei-Min; Smith, Nicholas L.; Kleber, Marcus E.; Shin, So-Youn; Becker, Diane M.; Tang, Weihong; Dehghan, Abbas; Johnson, Andrew D.; Vinh Truong, [No Value; Folkersen, Lasse; Yang, Qiong; Oudot-Mellkah, Tiphaine; Buckley, Brendan M.; Moore, Jason H.; Williams, Frances M. K.; Campbell, Harry; Silbernagel, Guenther; Vitart, Veronique; Rudan, Igor; Tofler, Geoffrey H.; Navis, Gerjan J.; DeStefano, Anita; Wright, Alan F.; Chen, Ming-Huei; de Craen, Anton J. M.; Worrall, Bradford B.; Rudnicka, Alicja R.; Rumley, Ann; Bookman, Ebony B.; Psaty, Bruce M.; Chen, Fang; Keene, Keith L.; Franco, Oscar H.; Boehm, Bernhard O.; Uitterlinden, Andre G.; Carter, Angela M.; Jukema, J. Wouter; Sattar, Naveed; Bis, Joshua C.; Ikram, Mohammad A.; Sale, Michele M.; McKnight, Barbara; Fornage, Myriam; Ford, Ian; Taylor, Kent; Slagboom, P. Eline; McArdle, Wendy L.; Hsu, Fang-Chi; Franco-Cereceda, Anders; Goodall, Alison H.; Yanek, Lisa R.; Furie, Karen L.; Cushman, Mary; Hofman, Albert; Witteman, Jacqueline C. M.; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Wilson, James F.; Westendorp, Rudi G. J.; Kathiresan, Sekar; Reilly, Muredach P.; Tracy, Russell P.; Polasek, Ozren; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Cambien, Francois; Stott, David J.; Lowe, Gordon D.; Spector, Timothy D.; Meigs, James B.; Marz, Winfried; Eriksson, Per; Becker, Lewis C.; Morange, Pierre-Emmanuel; Soranzo, Nicole; Williams, Scott M.; Hayward, Caroline; van der Harst, Pim; Hamsten, Anders; Lowenstein, Charles J.; Strachan, David P.; O'Donnell, Christopher J.

    Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular

  20. Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping

    DEFF Research Database (Denmark)

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

    2013-01-01

    1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results...... are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome...

  1. Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

    Directory of Open Access Journals (Sweden)

    Maria L Alcaide

    Full Text Available Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163, microbial translocation (LPS and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10 were evaluated.T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.

  2. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Directory of Open Access Journals (Sweden)

    Terje Raudsepp

    Full Text Available Impaired acrosomal reaction (IAR of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (PA and g.11040379C>A (p.166H>N in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44 and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  3. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Science.gov (United States)

    Raudsepp, Terje; McCue, Molly E; Das, Pranab J; Dobson, Lauren; Vishnoi, Monika; Fritz, Krista L; Schaefer, Robert; Rendahl, Aaron K; Derr, James N; Love, Charles C; Varner, Dickson D; Chowdhary, Bhanu P

    2012-01-01

    Impaired acrosomal reaction (IAR) of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (Phorse chromosome 13 in FK506 binding protein 6 (FKBP6). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of FKBP6 exons in cases and controls identified SNPs g.11040315G>A and g.11040379C>A (p.166H>N) in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44) and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  4. Mechanisms and implications of air pollution particle associations with chemokines.

    Science.gov (United States)

    Seagrave, Jeanclare

    2008-11-01

    Inflammation induced by inhalation of air pollutant particles has been implicated as a mechanism for the adverse health effects associated with exposure to air pollution. The inflammatory response is associated with upregulation of various pro-inflammatory cytokines and chemokines. We have previously shown that diesel exhaust particles (DEP), a significant constituent of air pollution particulate matter in many urban areas, bind and concentrate IL-8, an important human neutrophil-attracting chemokine, and that the chemokine remains biologically active. In this report, we examine possible mechanisms of this association and the effects on clearance of the chemokine. The binding appears to be the result of ionic interactions between negatively charged particles and positively charged chemokine molecules, possibly combined with intercalation into small pores in the particles. The association is not limited to diesel exhaust particles and IL-8: several other particle types also adsorb the chemokine and several other cytokines are adsorbed onto the diesel particles. However, there are wide ranges in the effectiveness of various particle types and various cytokines. Finally, male Fisher 344 rats were intratracheally instilled with chemokine alone or combined with diesel exhaust or silica particles under isofluorane anesthesia. In contrast to silica particles, which do not bind the chemokine, the presence of diesel exhaust particles, which bind the chemokine, prolonged the retention of the chemokine.

  5. A Genome-Wide Association Study Points out the Causal Implication of SOX9 in the Sex-Reversal Phenotype in XX Pigs

    Science.gov (United States)

    Rousseau, Sarah; Iannuccelli, Nathalie; Mercat, Marie-José; Naylies, Claire; Thouly, Jean-Claude; Servin, Bertrand; Milan, Denis; Pailhoux, Eric; Riquet, Juliette

    2013-01-01

    Among farm animals, pigs are known to show XX sex-reversal. In such cases the individuals are genetically female but exhibit a hermaphroditism, or a male phenotype. While the frequency of this congenital disease is quite low (less than 1%), the economic losses are significant for pig breeders. These losses result from sterility, urogenital infections and the carcasses being downgraded because of the risk of boar taint. It has been clearly demonstrated that the SRY gene is not involved in most cases of sex-reversal in pigs, and that autosomal recessive mutations remain to be discovered. A whole-genome scan analysis was performed in the French Large-White population to identify candidate genes: 38 families comprising the two non-affected parents and 1 to 11 sex-reversed full-sib piglets were genotyped with the PorcineSNP60 BeadChip. A Transmission Disequilibrium Test revealed a highly significant candidate region on SSC12 (most significant p-valueTesco. However, no causal mutations could be identified in either of the two sequenced regions. Further haplotype analyses did not identify a shared homozygous segment between the affected pigs, suggesting either a lack of power due to the SNP properties of the chip, or a second causative locus. Together with information from humans and mice, this study in pigs adds to the field of knowledge, which will lead to characterization of novel molecular mechanisms regulating sexual differentiation and dysregulation in cases of sex reversal. PMID:24223201

  6. An integrative study of Necremnus Thomson (Hymenoptera: Eulophidae) associated with invasive pests in Europe and North America: taxonomic and ecological implications

    Science.gov (United States)

    Gebiola, Marco; Bernardo, Umberto; Ribes, Antoni; Gibson, Gary A P

    2015-01-01

    The species of Necremnus attacking two invasive pests of tomato and canola in Europe and North America, respectively, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), have been revised using an integrative taxonomy approach. Molecular data from the mitochondrial cytochrome oxidase c subunit I and the nuclear D2 expansion region of the 28S ribosomal subunit and internal transcribed spacer 2, the discovery of new morphological features, and study of type material resulted in the delineation of three species groups, the Necremnus artynes, Necremnus cosconius, and Necremnus tidius groups, the discovery of four new species, and the resurrection of three taxa from synonymy. Lectotypes have been designated for 13 species originally described in Eulophus by Walker. Although Necremnus has not been revised, an illustrated key is given to differentiate 23 recognized European species. The key, type images, and treatments of the three species groups will enable more accurate identification of the valid species of Necremnus in the future. They will also benefit biological control practitioners of pest species. The ecological consequences of the new taxonomic concepts are discussed. PMID:25745268

  7. A genome-wide association study points out the causal implication of SOX9 in the sex-reversal phenotype in XX pigs.

    Directory of Open Access Journals (Sweden)

    Sarah Rousseau

    Full Text Available Among farm animals, pigs are known to show XX sex-reversal. In such cases the individuals are genetically female but exhibit a hermaphroditism, or a male phenotype. While the frequency of this congenital disease is quite low (less than 1%, the economic losses are significant for pig breeders. These losses result from sterility, urogenital infections and the carcasses being downgraded because of the risk of boar taint. It has been clearly demonstrated that the SRY gene is not involved in most cases of sex-reversal in pigs, and that autosomal recessive mutations remain to be discovered. A whole-genome scan analysis was performed in the French Large-White population to identify candidate genes: 38 families comprising the two non-affected parents and 1 to 11 sex-reversed full-sib piglets were genotyped with the PorcineSNP60 BeadChip. A Transmission Disequilibrium Test revealed a highly significant candidate region on SSC12 (most significant p-value<4.65.10(-10 containing the SOX9 gene. SOX9, one of the master genes involved in testis differentiation, was sequenced together with one of its main regulatory region Tesco. However, no causal mutations could be identified in either of the two sequenced regions. Further haplotype analyses did not identify a shared homozygous segment between the affected pigs, suggesting either a lack of power due to the SNP properties of the chip, or a second causative locus. Together with information from humans and mice, this study in pigs adds to the field of knowledge, which will lead to characterization of novel molecular mechanisms regulating sexual differentiation and dysregulation in cases of sex reversal.

  8. Dermatomyositis and myastenia gravis: An uncommon association with therapeutic implications.

    Science.gov (United States)

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Méndez Perles, Clara; Barbadillo, Carmen; Godoy, Hildegarda; Andréu, José Luis

    2015-01-01

    The association of dermatomyositis with myasthenia gravis (MG) is uncommon, having been reported so far in only 26 cases. We report the case of a 69 year-old man diagnosed with MG two years ago and currently treated with piridostigmyne. The patient developed acute proximal weakness, shoulder pain and elevated creatine-kinase (CK). He also developed generalized facial erythema and Gottron's papules. Laboratory tests showed positive antinuclear and anti-Mi2 antibodies. Further analysis confirmed CK levels above 1000 U/l. The clinical management of the patient and the therapeutic implications derived from the coexistence of both entities are discusssed. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Sex Differences: Implications for the Obesity-Asthma Association

    Science.gov (United States)

    Sood, Akshay

    2011-01-01

    We have demonstrated in several studies that obesity and adipokines are more strongly associated with asthma in women than in men. The reason for this controversial sex difference is not known. Based on our prior studies, we hypothesize that sex-related difference in ectopic fat may explain the obesity-asthma association in women. PMID:21088605

  10. Multidrug resistance-associated proteins and implications in drug development.

    Science.gov (United States)

    Liu, Ya-He; Di, Yuan-Ming; Zhou, Zhi-Wei; Mo, Sui-Lin; Zhou, Shu-Feng

    2010-01-01

    1. The multidrug resistance-associated proteins (MRPs) belong to the ATP-binding cassette superfamily (ABCC family) of transporters that are expressed differentially in the liver, kidney, intestine and blood-brain barrier. There are nine human MRPs that transport a structurally diverse array of endo- and xenobiotics as well as their conjugates. 2. Multidrug resistance-associated protein 1 can be distinguished from MRP2 and MRP3 by its higher affinity for leukotriene C(4). Unlike MRP1, MRP2 functions in the extrusion of endogenous organic anions, such as bilirubin glucuronide and certain anticancer agents. In addition to the transport of glutathione and glucuronate conjugates, MRP3 has the additional capability of mediating the transport of monoanionic bile acids. 3. Both MRP4 and MRP5 are able to mediate the transport of cyclic nucleotides and confer resistance to certain antiviral and anticancer nucleotide analogues. Hereditary deficiency of MRP6 results in pseudoxanthoma elasticum. In the body, MRP6 is involved in the transport of glutathione conjugates and the cyclic pentapeptide BQ123. 4. Various MRPs show considerable differences in tissue distribution, substrate specificity and proposed physiological function. These proteins play a role in drug disposition and excretion and thus are implicated in drug toxicity and drug interactions. Increased efflux of natural product anticancer drugs and other anticancer agents mediated by MRPs from cancer cells is associated with tumour resistance. 5. A better understanding of the function and regulating mechanisms of MRPs could help minimize and avoid drug toxicity and unfavourable drug-drug interactions, as well as help overcome drug resistance.

  11. Associations of sleep disturbance with ADHD: implications for treatment

    OpenAIRE

    Hvolby, Allan

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; inc...

  12. Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene.

    Science.gov (United States)

    Nievergelt, Caroline M; Maihofer, Adam X; Mustapic, Maja; Yurgil, Kate A; Schork, Nicholas J; Miller, Mark W; Logue, Mark W; Geyer, Mark A; Risbrough, Victoria B; O'Connor, Daniel T; Baker, Dewleen G

    2015-01-01

    Research on the etiology of post-traumatic stress disorder (PTSD) has rapidly matured, moving from candidate gene studies to interrogation of the entire human genome in genome-wide association studies (GWAS). Here we present the results of a GWAS performed on samples from combat-exposed U.S. Marines and Sailors from the Marine Resiliency Study (MRS) scheduled for deployment to Iraq and/or Afghanistan. The MRS is a large, prospective study with longitudinal follow-up designed to identify risk and resiliency factors for combat-induced stress-related symptoms. Previously implicated PTSD risk loci from the literature and polygenic risk scores across psychiatric disorders were also evaluated in the MRS cohort. Participants (N=3494) were assessed using the Clinician-Administered PTSD Scale and diagnosed using the DSM-IV diagnostic criterion. Subjects with partial and/or full PTSD diagnosis were called cases, all other subjects were designated controls, and study-wide maximum CAPS scores were used for longitudinal assessments. Genomic DNA was genotyped on the Illumina HumanOmniExpressExome array. Individual genetic ancestry was determined by supervised cluster analysis for subjects of European, African, Hispanic/Native American, and other descent. To test for association of SNPs with PTSD, logistic regressions were performed within each ancestry group and results were combined in meta-analyses. Measures of childhood and adult trauma were included to test for gene-by-environment (GxE) interactions. Polygenic risk scores from the Psychiatric Genomic Consortium were used for major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). The array produced >800K directly genotyped and >21M imputed markers in 3494 unrelated, trauma-exposed males, of which 940 were diagnosed with partial or full PTSD. The GWAS meta-analysis identified the phosphoribosyl transferase domain containing 1 gene (PRTFDC1) as a genome-wide significant PTSD locus (rs6482463; OR=1

  13. RNAi screening in primary human hepatocytes of genes implicated in genome-wide association studies for roles in type 2 diabetes identifies roles for CAMK1D and CDKAL1, among others, in hepatic glucose regulation.

    Directory of Open Access Journals (Sweden)

    Steven Haney

    Full Text Available Genome-wide association (GWA studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D. In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.

  14. Associations between perceived social environment and neighborhood safety: Health implications.

    Science.gov (United States)

    De Jesus, Maria; Puleo, Elaine; Shelton, Rachel C; Emmons, Karen M

    2010-09-01

    This study examined the associations between social networks, social support, social cohesion, and perceived neighborhood safety among an ethnically diverse sample of 1352 residents living in 12 low-income public housing sites in Boston, Massachusetts. For males and females, social cohesion was associated with perceived safety. For males, a smaller social network was associated with greater feelings of safety. Social support was not a significant predictor of perceived safety. The findings reported here are useful in exploring a potential pathway through which social environmental factors influence health and in untangling the complex set of variables that may influence perceived safety. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.

    Science.gov (United States)

    Travis, William D; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G; Geisinger, Kim; Yatabe, Yasushi; Ishikawa, Yuichi; Wistuba, Ignacio; Flieder, Douglas B; Franklin, Wilbur; Gazdar, Adi; Hasleton, Philip S; Henderson, Douglas W; Kerr, Keith M; Petersen, Iver; Roggli, Victor; Thunnissen, Erik; Tsao, Ming

    2013-05-01

    The new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification provides, for the first time, standardized terminology for lung cancer diagnosis in small biopsies and cytology; this was not primarily addressed by previous World Health Organization classifications. Until recently there have been no therapeutic implications to further classification of NSCLC, so little attention has been given to the distinction of adenocarcinoma and squamous cell carcinoma in small tissue samples. This situation has changed dramatically in recent years with the discovery of several therapeutic options that are available only to patients with adenocarcinoma or NSCLC, not otherwise specified, rather than squamous cell carcinoma. This includes recommendation for use of special stains as an aid to diagnosis, particularly in the setting of poorly differentiated tumors that do not show clear differentiation by routine light microscopy. A limited diagnostic workup is recommended to preserve as much tissue for molecular testing as possible. Most tumors can be classified using a single adenocarcinoma marker (eg, thyroid transcription factor 1 or mucin) and a single squamous marker (eg, p40 or p63). Carcinomas lacking clear differentiation by morphology and special stains are classified as NSCLC, not otherwise specified. Not otherwise specified carcinomas that stain with adenocarcinoma markers are classified as NSCLC, favor adenocarcinoma, and tumors that stain only with squamous markers are classified as NSCLC, favor squamous cell carcinoma. The need for every institution to develop a multidisciplinary tissue management strategy to obtain these small specimens and process them, not only for diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, is emphasized.

  16. Behavioral Implications of Risk-Return Associations: An Application of

    Directory of Open Access Journals (Sweden)

    Ranjan Dasgupta

    2017-09-01

    Full Text Available This study primarily investigates the risk attitudes of the fifty CNX NIFTY companies from a behavioral perspective as proposed by Kahneman and Tversky (1979 and Tversky and Kahneman (1992. It hypothesizes that for below target returns, a large majority of Indian companies would be risk-seeking, and for above target returns, most of them would be risk-averse. To fulfil its objectives, this study uses rates of return on assets and equity and the capital ratios of fifty CNX NIFTY companies over the period 2009-2013. It also uses Kendall’s (1938 test to measure the correlations between above variables within the relevant groups (all companies and each sub group [under Size and Industry]. Results show that bigger and smaller Indian companies and their managers are mostly risk-seeking and risk-averse respectively and shareholders-centric in regard to their attitude. These results will have important implications for the Indian companies and managers in evaluating their risk attitudes from the behavioral perspective.

  17. Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis).

    Science.gov (United States)

    Nasir, Khurram; Bittencourt, Marcio S; Blaha, Michael J; Blankstein, Ron; Agatson, Arthur S; Rivera, Juan J; Miedema, Michael D; Miemdema, Michael D; Sibley, Christopher T; Shaw, Leslee J; Blumenthal, Roger S; Budoff, Matthew J; Krumholz, Harlan M

    2015-10-13

    The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy. This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not. MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years. Significant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Trapeziometacarpal Ligaments Biomechanical Study: Implications in Arthroscopy

    Science.gov (United States)

    Esplugas, Mireia; Lluch-Bergada, Alex; Mobargha, Nathalie; Llusa-Perez, Manuel; Hagert, Elisabet; Garcia-Elias, Marc

    2016-01-01

    Purpose In the presence of early osteoarthritis, changes to the trapeziometacarpal joint (TMJ) often result in pain and is associated with joint instability and a tendency of dorsoradial subluxation. In these instances, arthroscopy may be indicated to: (1) assess the extent of cartilage disease and the laxity of ligaments and to (2) treat TMJ instability. The purpose of our study was to biomechanically analyze which ligaments are the primary stabilizers of the TMJ. Methods Overall, 11 fresh-frozen human cadaver specimens were dissected and attached to a testing device with the thumb positioned in neutral abduction, neutral flexion, and neutral opposition. The four extrinsic and five intrinsic muscle tendons acting on the TMJ were simultaneously loaded with weights proportional to their physiological cross-sectional area. The dorsal, volar, and ulnar groups of ligaments were dissected. A motion-tracking device, FasTrak (Polhemus Inc., Colchester, VT), was used to study the spatial position of the base of the first metacarpal bone (MC1), before and after random sectioning of each of the ligaments. Statistical analysis of the MC1 translation along the transverse XY plane was performed using one-way analysis of variance and a paired t-test, with a significance level of p ligaments, the MC1 moved dorsoradially with an average of 0.150 mm (standard deviation [SD]: 0.072) and 0.064 mm (SD: 0.301), respectively. By contrast, the destabilization of the MC1 after sectioning of the dorsal ligaments was substantially larger (0.523 mm; SD: 0.0512; p = 0.004). Conclusion Sectioning of the dorsal ligament group resulted in the greatest dorsoradial translation of the MC1. Consequently, the dorsal ligaments may be regarded as the primary TMJ stabilizers. Clinical Relevance This study suggests that stabilizing arthroscopic shrinkage of the TMJ should be targeted toward the dorsal TMJ ligaments. PMID:27777818

  19. Awareness in Alzheimer's disease and associated dementias: theoretical framework and clinical implications.

    Science.gov (United States)

    Clare, Linda; Marková, Ivana S; Roth, Ilona; Morris, Robin G

    2011-11-01

    Awareness can be defined as a reasonable or realistic perception or appraisal of a given aspect of one's situation, functioning or performance, or of the resulting implications, expressed explicitly or implicitly. Disturbances of awareness have significant implications for people with dementia and their caregivers. The construction of awareness has been extensively studied in dementia, but a lack of conceptual and methodological clarity in this area means that few clear findings have emerged. This article presents a framework for conceptualizing awareness in people with Alzheimer's disease and associated dementias that can guide research and influence practice. This article begins by considering the general concept of awareness and the ways in which neurological damage can place constraints on awareness. Within an integrative biopsychosocial model that acknowledges the influence of neurocognitive, psychological, and social variables on awareness, challenges for empirical research on awareness in dementia are addressed, and a 'levels of awareness' framework is presented within which awareness operates at four levels of increasing complexity, providing a means of differentiating among awareness phenomena. Approaches to mapping awareness phenomena are discussed, and directions for future research and clinical practice are outlined. The levels of awareness framework should act as a stimulus to further research in this area, resulting in a more coherent understanding of the nature of awareness deficits, the implications of these for people with dementia and their caregivers, and the possibilities for targeted and effective interventions.

  20. Clinical implication for endometriosis associated with ovarian cancer

    Directory of Open Access Journals (Sweden)

    Pao-Ling Torng

    2017-11-01

    Full Text Available We reviewed current literature regarding the association of endometriosis and epithelial ovarian cancer based on epidemiology studies, molecular researches and clinical observations. Our methods include a review of literature research of MEDLINE, PubMed, Cochrane Library of Systematic Reviews and reference search in selected papers. The life time risk of epithelial ovarian cancer in women with endometriosis is low, yet there might be a cluster of individuals who have higher risk of developing epithelial ovarian cancer from endometriosis. Endometriosis associated ovarian cancer (EAOC is predominant in particular histological subtypes of epithelial ovarian carcinoma and are related to some specific molecular aberrations. Clinical observations showed age as an important variable to the development of EAOC. Rapid growth of tumor and solid components in sonography are key features to detect malignant transformation of endometriosis. Evidence is not clear about prophylactic oophorectomy in preventing EAOC in patients with endometriosis. This review provided rationale data for identifying, monitoring, counseling and management of women with endometriosis who are potentially high risk for malignant transformation. Keywords: Endometriosis, Epithelial ovarian cancer, Malignant transformation

  1. Cluster formation in liverwort-associated methylobacteria and its implications

    Science.gov (United States)

    Kutschera, U.; Thomas, J.; Hornschuh, M.

    2007-08-01

    Pink-pigmented methylotropic bacteria of the genus Methylobacterium inhabit the surfaces of plant organs. In bryophytes, these methylobacteria enhance cell growth, but the nature of this plant-microbe interaction is largely unknown. In this study, methylobacteria were isolated from the upper surface of the free-living thalli of the liverwort Marchantia polymorpha L. Identification of one strain by 16S ribosomal RNA (rRNA) gene-targeted polymerase chain reaction (PCR) and other data show that these microbes represent an undescribed species of the genus Methylobacterium ( Methylobacterium sp.). The growth-promoting activity of these wild-type methylobacteria was tested and compared with that of the type strain Methylobacterium mesophilicum. Both types of methylobacteria stimulated surface expansion of isolated gemmae from Marchantia polymorpha by about 350%. When suspended in water, the liverwort-associated bacteria ( Methylobacterium sp.) formed dense clusters of up to 600 cells. In liquid cultures of Methylobacterium mesophilicum, single cells were observed, but no clustering occurred. We suggest that the liverwort-associated methylobacteria are co-evolved symbionts of the plants: Cluster formation may be a behavior that enhances the survival of the epiphytic microbes during periods of drought of these desiccation-tolerant lower plants.

  2. Factors associated with self-reported health: implications for ...

    Science.gov (United States)

    BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mortality, suggesting that self-reported health (SRH) may be useful in screening-level community assessments. This paper evaluates whether SRH is an appropriate surrogate indicator of health status by evaluating relationships between SRH and sociodemographic, lifestyle, and health care factors as well as serological indicators of nutrition, health risk, and environmental exposures.METHODS: Data were combined from the 2003-2006 National Health and Nutrition Examination Surveys for 1372 nonsmoking 20-50 year olds. Ordinal and binary logistic regression was used to estimate odds ratios and 95 % confidence intervals of reporting poorer health based on measures of nutrition, health condition, environmental contaminants, and sociodemographic, health care, and lifestyle factors.RESULTS: Poorer SRH was associated with several serological measures of nutrition, health condition, and biomarkers of toluene, cadmium, lead, and mercury exposure. Race/ethnicity, income, education, access to health care, food security, exercise, poor mental and physical health, prescription drug use, and multiple health outcome measures (e.g., diabetes, thyroid problems, asthma) were also associated with poorer SRH.CONCLUS

  3. Tumor-associated macrophages: implications in cancer immunotherapy.

    Science.gov (United States)

    Petty, Amy J; Yang, Yiping

    2017-03-01

    Tumor-associated macrophages (TAMs), representing most of the leukocyte population in solid tumors, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of the local tumor microenvironment. These anti-inflammatory and protumorigenic macrophages modulate the local microenvironment to facilitate tumor growth and metastasis. In this review, we examine the origin of TAMs and the complex regulatory networks within the tumor microenvironment that facilitate the polarization of TAMs toward a protumoral phenotype. More extensively, we evaluate the mechanisms by which TAMs mediate angiogenesis, metastasis, chemotherapeutic resistance and immune evasion. Lastly, we will highlight novel interventional strategies targeting TAMs in preclinical studies and in early clinical trials that have significant potential in improving efficacy of current chemotherapeutic and/or immunotherapeutic approaches.

  4. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

    DEFF Research Database (Denmark)

    Turcot, Valérie; Lu, Yingchang; Highland, Heather M

    2018-01-01

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734...

  5. Food Avoidance and Food Modification Practices of Older Rural Adults: Association with Oral Health Status and Implications for Service Provision

    Science.gov (United States)

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A.; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A.

    2010-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for…

  6. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

    NARCIS (Netherlands)

    Turcot, Valérie; Lu, Yingchang; Highland, Heather M.; Schurmann, Claudia; Justice, Anne E.; Fine, Rebecca S.; Bradfield, Jonathan P.; Esko, Tõnu; Giri, Ayush; Graff, Mariaelisa; Guo, Xiuqing; Hendricks, Audrey E.; Karaderi, Tugce; Lempradl, Adelheid; Locke, Adam E.; Mahajan, Anubha; Marouli, Eirini; Sivapalaratnam, Suthesh; Young, Kristin L.; Alfred, Tamuno; Feitosa, Mary F.; Masca, Nicholas G. D.; Manning, Alisa K.; Medina-Gomez, Carolina; Mudgal, Poorva; Ng, Maggie C. Y.; Reiner, Alex P.; Vedantam, Sailaja; Willems, Sara M.; Winkler, Thomas W.; Abecasis, Gonçalo; Aben, Katja K.; Alam, Dewan S.; Alharthi, Sameer E.; Allison, Matthew; Amouyel, Philippe; Asselbergs, Folkert W.; Auer, Paul L.; Balkau, Beverley; Bang, Lia E.; Barroso, Inês; Bastarache, Lisa; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F.; Blüher, Matthias; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A.; Bork-Jensen, Jette; Bots, Michiel L.; Bottinger, Erwin P.; Bowden, Donald W.; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H.; Broer, Linda; Brumat, Marco; Burt, Amber A.; Butterworth, Adam S.; Campbell, Peter T.; Cappellani, Stefania; Carey, David J.; Catamo, Eulalia; Caulfield, Mark J.; Chambers, John C.; Chasman, Daniel I.; Chen, Yii-der I.; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y.; Cocca, Massimiliano; Collins, Francis S.; Cook, James P.; Corley, Janie; Corominas Galbany, Jordi; Cox, Amanda J.; Crosslin, David S.; Cuellar-Partida, Gabriel; D'Eustacchio, Angela; Danesh, John; Davies, Gail; Bakker, Paul I. W.; Groot, Mark C. H.; Mutsert, Renée; Deary, Ian J.; Dedoussis, George; Demerath, Ellen W.; Heijer, Martin; Hollander, Anneke I.; Ruijter, Hester M.; Dennis, Joe G.; Denny, Josh C.; Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dubé, Marie-Pierre; Dunning, Alison M.; Easton, Douglas F.; Edwards, Todd L.; Ellinghaus, David; Ellinor, Patrick T.; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Farooqi, I. Sadaf; Faul, Jessica D.; Fauser, Sascha; Feng, Shuang; Ferrannini, Ele; Ferrieres, Jean; Florez, Jose C.; Ford, Ian; Fornage, Myriam; Franco, Oscar H.; Franke, Andre; Franks, Paul W.; Friedrich, Nele; Frikke-Schmidt, Ruth; Galesloot, Tessel E.; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Gibson, Jane; Giedraitis, Vilmantas; Gjesing, Anette P.; Gordon-Larsen, Penny; Gorski, Mathias; Grabe, Hans-Jörgen; Grant, Struan F. A.; Grarup, Niels; Griffiths, Helen L.; Grove, Megan L.; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeff; Hakonarson, Hakon; Hammerschlag, Anke R.; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B.; Hattersley, Andrew T.; Have, Christian T.; Hayward, Caroline; He, Liang; Heard-Costa, Nancy L.; Heath, Andrew C.; Heid, Iris M.; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W.; Holmen, Oddgeir L.; Hovingh, G. Kees; Howson, Joanna M. M.; Hu, Yao; Huang, Paul L.; Huffman, Jennifer E.; Ikram, M. Arfan; Ingelsson, Erik; Jackson, Anne U.; Jansson, Jan-Håkan; Jarvik, Gail P.; Jensen, Gorm B.; Jia, Yucheng; Johansson, Stefan; Jørgensen, Marit E.; Jørgensen, Torben; Jukema, J. Wouter; Kahali, Bratati; Kahn, René S.; Kähönen, Mika; Kamstrup, Pia R.; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon L. R.; Karpe, Fredrik; Kathiresan, Sekar; Kee, Frank; Kiemeney, Lambertus A.; Kim, Eric; Kitajima, Hidetoshi; Komulainen, Pirjo; Kooner, Jaspal S.; Kooperberg, Charles; Korhonen, Tellervo; Kovacs, Peter; Kuivaniemi, Helena; Kutalik, Zoltán; Kuulasmaa, Kari; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lamparter, David; Lange, Ethan M.; Lange, Leslie A.; Langenberg, Claudia; Larson, Eric B.; Lee, Nanette R.; Lehtimäki, Terho; Lewis, Cora E.; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Keng-Hung; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Ching-Ti; Liu, Dajiang J.; Liu, Yongmei; Lo, Ken S.; Lophatananon, Artitaya; Lotery, Andrew J.; Loukola, Anu; Luan, Jian'an; Lubitz, Steven A.; Lyytikäinen, Leo-Pekka; Männistö, Satu; Marenne, Gaëlle; Mazul, Angela L.; McCarthy, Mark I.; McKean-Cowdin, Roberta; Medland, Sarah E.; Meidtner, Karina; Milani, Lili; Mistry, Vanisha; Mitchell, Paul; Mohlke, Karen L.; Moilanen, Leena; Moitry, Marie; Montgomery, Grant W.; Mook-Kanamori, Dennis O.; Moore, Carmel; Mori, Trevor A.; Morris, Andrew D.; Morris, Andrew P.; Müller-Nurasyid, Martina; Munroe, Patricia B.; Nalls, Mike A.; Narisu, Narisu; Nelson, Christopher P.; Neville, Matt; Nielsen, Sune F.; Nikus, Kjell; Njølstad, Pål R.; Nordestgaard, Børge G.; Nyholt, Dale R.; O'Connel, Jeffrey R.; O'Donoghue, Michelle L.; Olde Loohuis, Loes M.; Ophoff, Roel A.; Owen, Katharine R.; Packard, Chris J.; Padmanabhan, Sandosh; Palmer, Colin N. A.; Palmer, Nicholette D.; Pasterkamp, Gerard; Patel, Aniruddh P.; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L.; Peloso, Gina M.; Pennell, Craig E.; Perola, Markus; Perry, James A.; Perry, John R. B.; Pers, Tune H.; Person, Thomas N.; Peters, Annette; Petersen, Eva R. B.; Peyser, Patricia A.; Pirie, Ailith; Polasek, Ozren; Polderman, Tinca J.; Puolijoki, Hannu; Raitakari, Olli T.; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F.; Renström, Frida; Rheinberger, Myriam; Ridker, Paul M.; Rioux, John D.; Rivas, Manuel A.; Roberts, David J.; Robertson, Neil R.; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S.; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Sapkota, Yadav; Sattar, Naveed; Schoen, Robert E.; Schreiner, Pamela J.; Schulze, Matthias B.; Scott, Robert A.; Segura-Lepe, Marcelo P.; Shah, Svati H.; Sheu, Wayne H.-H.; Sim, Xueling; Slater, Andrew J.; Small, Kerrin S.; Smith, Albert V.; Southam, Lorraine; Spector, Timothy D.; Speliotes, Elizabeth K.; Starr, John M.; Stefansson, Kari; Steinthorsdottir, Valgerdur; Stirrups, Kathleen E.; Strauch, Konstantin; Stringham, Heather M.; Stumvoll, Michael; Sun, Liang; Surendran, Praveen; Swift, Amy J.; Tada, Hayato; Tansey, Katherine E.; Tardif, Jean-Claude; Taylor, Kent D.; Teumer, Alexander; Thompson, Deborah J.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Thuesen, Betina H.; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P.; Uher, Rudolf; Uitterlinden, André G.; Uusitupa, Matti; Laan, Sander W.; Duijn, Cornelia M.; Leeuwen, Nienke; van Setten, Jessica; Vanhala, Mauno; Varbo, Anette; Varga, Tibor V.; Varma, Rohit; Velez Edwards, Digna R.; Vermeulen, Sita H.; Veronesi, Giovanni; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F.; Völker, Uwe; Vuckovic, Dragana; Wagenknecht, Lynne E.; Walker, Mark; Wallentin, Lars; Wang, Feijie; Wang, Carol A.; Wang, Shuai; Wang, Yiqin; Ware, Erin B.; Wareham, Nicholas J.; Warren, Helen R.; Waterworth, Dawn M.; Wessel, Jennifer; White, Harvey D.; Willer, Cristen J.; Wilson, James G.; Witte, Daniel R.; Wood, Andrew R.; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M.; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhou, Wei; Zondervan, Krina T.; Rotter, Jerome I.; Pospisilik, John A.; Rivadeneira, Fernando; Borecki, Ingrid B.; Deloukas, Panos; Frayling, Timothy M.; Lettre, Guillaume; North, Kari E.; Lindgren, Cecilia M.; Hirschhorn, Joel N.; Loos, Ruth J. F.

    2018-01-01

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734

  7. Persistent primitive hypoglossal artery associated with Chiari II malformation: Diagnosis and clinical implications

    Directory of Open Access Journals (Sweden)

    Gupta Mudit

    2010-01-01

    Full Text Available We present a case of persistent primitive hypoglossal artery (PPHA associated with Chiari II malformation and discuss the clinical implications. There has been one reported case of PPHA associated with Chiari 1 malformation, but none in association with Chiari II. Our patient also had a widened hypoglossal canal, with cerebrospinal fluid (CSF sac herniation through it.

  8. Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings.

    Science.gov (United States)

    Victoroff, Jeff; Lin, Feng V; Coburn, Kerry L; Shillcutt, Samuel D; Voon, Valerie; Ducharme, Simon

    2017-09-06

    Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.

  9. Nitrogen fixation associated with sago (Metroxylon sagu) and some implications.

    Science.gov (United States)

    Shipton, W A; Baker, A; Blaney, B J; Horwood, P F; Warner, J M; Pelowa, D; Greenhill, A R

    2011-01-01

    To determine the presence and contribution of diazotrophic bacteria to nitrogen concentrations in edible starch derived from the sago palm (Metroxylon sagu). Isolation of diazotrophic bacteria and analysis of nitrogen fixation were conducted on pith, root and sago starch samples. Acetylene reduction showed that five of ten starch samples were fixing nitrogen. Two presumptive nitrogen-fixing bacteria from starch fixed nitrogen in pure culture and five isolates were positive for the nif H gene. Nitrogen concentrations in 51 starch samples were low (37 samples sago starch, which undoubtedly plays a role in fermentation ecology. Nitrogen levels are considered too low to be of nutritional benefit and to protect against nutritional-associated illnesses. Sago starch does not add significantly to the protein calorie intake and may be associated with susceptibility to nutritional-associated illness. © 2010 The Authors. Letters in Applied Microbiology © 2010 The Society for Applied Microbiology.

  10. Implications of Error Analysis Studies for Academic Interventions

    Science.gov (United States)

    Mather, Nancy; Wendling, Barbara J.

    2017-01-01

    We reviewed 13 studies that focused on analyzing student errors on achievement tests from the Kaufman Test of Educational Achievement-Third edition (KTEA-3). The intent was to determine what instructional implications could be derived from in-depth error analysis. As we reviewed these studies, several themes emerged. We explain how a careful…

  11. Discursive Study of Religion : Approaches, Definitions, Implications

    NARCIS (Netherlands)

    von Stuckrad, Kocku

    2013-01-01

    The article explores recent approaches to historical analysis of discourse that have been developed in disciplines such as the sociology of knowledge and historical epistemology. These approaches have only sporadically been taken seriously in the academic study of religion, although they have a

  12. Clinical implications and pathological associations of circulating mitochondrial DNA.

    Science.gov (United States)

    Tuboly, Eszter; Mcllroy, Daniel; Briggs, Gabrielle; Lott, Natalie; Balogh, Zsolt J

    2017-01-01

    Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytosis of a-proteobacteria. There are several characteristic features which refer to its prokaryotic ancestors including its independent sets of double-stranded mitochondrial DNA, which is uniquely circular in form and contains a significant amount of unmethylated DNA as CpG islands. Resent research has proven that free mitochondrial DNA found in blood was associated with innate immunomodulation in a broad-range of clinical conditions. Upon release, mitochondrial DNA acts as a danger-associated molecular pattern in the circulation, it is recognized by pattern recognition receptors and it facilitates inflammatory responses. Besides its high receptor activation potential, mitochondrial DNA is likely to perform direct crosstalk with activated leukocytes and to be contributed to other anti-microbial activities. Here we highlight the pathological conditions where cell free mtDNA is involved, describe the potential sources and mechanisms of extracellular mtDNA release and explore evidence for its mechanism of action after being excreted and potential therapeutic strategies.

  13. Clinical implications of a phenomenological study: Being regarded ...

    African Journals Online (AJOL)

    Clinical implications of a phenomenological study: Being regarded as a threat while attempting to do one's best. Norma Cole. Abstract. Cultural messages promote putting forward one's best effort, and yet any level of success, or the effort itself, can lead to being regarded as a threat. People forming everyday social ...

  14. 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, ...

  15. Medication-wide association studies

    NARCIS (Netherlands)

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

    2013-01-01

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

  16. Population structure and linkage disequilibrium in Lupinus albus L. germplasm and its implication for association mapping.

    Science.gov (United States)

    Iqbal, Muhammad Javed; Mamidi, Sujan; Ahsan, Rubina; Kianian, Shahryar F; Coyne, Clarice J; Hamama, Anwar A; Narina, Satya S; Bhardwaj, Harbans L

    2012-08-01

    White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized for its ability to grow on poor soils and application as green manure in addition to seed harvest. The seed has very high levels of protein (33-47 %) and oil (6-13 %). It also has many secondary metabolites that are potentially of nutraceutical value to animals and humans. Despite such a great potential, lupins role in modern agriculture began only in the twentieth century. Although a large collection of Lupinus germplasm accessions is available worldwide, rarely have they been genetically characterized. Additionally, scarce genomic resources in terms of recombinant populations and genome information have been generated for L. albus. With the advancement in association mapping methods, the natural populations have the potential to replace the recombinant populations in gene mapping and marker-trait associations. Therefore, we studied the genetic similarity, population structure and marker-trait association in a USDA germplasm collection for their current and future application in this crop improvement. A total of 122 PI (Plant Inventory) lines were screened with 18 AFLP primer pairs that generated 2,277 fragments. A subset of 892 polymorphic markers with MAF >0.05 (minor allele frequency) were used for association mapping. The cluster analysis failed to group accessions on the basis of their passport information, and a weak structure and low linkage disequilibrium (LD) were observed indicating the usefulness of the collection for association mapping. Moreover, we were also able to identify two markers (a p value of 1.53 × 10(-4) and 2.3 × 10(-4)) that explained 22.69 and 20.5 % of seed weight variation determined using R (LR) (2) . The implications of lack of geographic clustering, population structure, low LD and the ability of AFLP to map seed weight trait using association mapping and the usefulness of the PI collections in breeding programs are discussed.

  17. Farmers’ Awareness of Ecosystem Services and the Associated Policy Implications

    Directory of Open Access Journals (Sweden)

    Fangfang Xun

    2017-09-01

    Full Text Available This study analyzes the primary factors influencing farmers’ awareness of ecosystem services. This study, through questionnaires, conducts research on farmers’ awareness of and demand for ecosystem service functions. The research encapsulates 156 households from 21 groups of villagers in the Guangxi Karst Ecological Immigration District in China. The results of the factors influencing farmers’ awareness of ecosystem services, analyzed using a regression model, show that: (1 Farmers are concerned with ecosystem service functions that directly benefit them; however, they do not sufficiently understand the ecosystem’s ecological security maintenance or cultural landscape functions; (2 Farmers’ awareness of ecosystem service functions is not consistent with their corresponding demand, including the ecosystem’s leisure and entertainment, social security, disaster prevention and water purification services; (3 Education level, land area cultivated by the household, proportion of the household’s income from agriculture and immigration status directly affect farmers’ awareness of ecosystem services; (4 Farmers’ personal characteristics, family characteristics and subjective attitudes have different effects on the level of ecological service cognition. Understanding farmers’ awareness of ecosystem services, and the influencing factors can help policymakers and development managers plan local development and policies, and enable harmonious development of the human-earth system in immigration regions of China.

  18. Student Identity Considerations and Implications Associated with Socioscientific Issues Instruction

    Science.gov (United States)

    Ruzek, Mitchel James

    The purpose of this investigation was to explore how aspects of identity, perceived levels of controversy, and the strength of a student's attachment to their controversial identity relate to conceptual understanding and knowledge acquisition during socioscientific issues (SSI) based instruction in a biology classroom. The knowledge gained from this study will have the capacity to enhance our understanding of the role that attachment to identity plays during SSI negotiation. Additionally, insight was gained into the role played by aspects of identity in conceptual understanding of scientifically controversial topics during SSI based instruction. This study contributed to the existing knowledge base in science education by illuminating processes involved in socioscientific issue navigation among students of differing perceptions of controversy as well as students who held aspects of controversial identity that may or may not interact with the specific issues chosen. Students demonstrated evidence of variations of reasoning, justification, perception of controversy, and aspects of knowledge gain as they negotiated the issues of marijuana safety and fast food legality. Additionally, evidence was provided that showed general knowledge gain throughout the group during socioscientific issues instruction. It has been said that one of the appeals of the SSI instructional model is that is serves not only as a context for the delivery of content, but acts as a catalyst for various forms of epistemological beliefs and research into the development of conceptual and psychological knowledge structures (Zeidler, 2013). This investigation supports the deeper understanding of the contribution of controversy perception to epistemology as well as conceptual and psychological knowledge structures during SSI navigation.

  19. Misuse of "study drugs:" prevalence, consequences, and implications for policy

    Directory of Open Access Journals (Sweden)

    Spruijt-Metz Donna

    2006-06-01

    Full Text Available Abstract Background Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. Results Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. Conclusion Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts.

  20. Biomechanical and organisational stressors and associations with employment withdrawal among pregnant workers: evidence and implications.

    Science.gov (United States)

    Guendelman, Sylvia; Gemmill, Alison; MacDonald, Leslie A

    2016-12-01

    The distribution of exposure to biomechanical and organisational job stressors (BOJS) and associations with employment withdrawal (antenatal leave, unemployment) was examined in a case-control study of 1114 pregnant workers in California. We performed descriptive and multivariate logistic and multinomial regression analyses. At pregnancy onset, 57% were exposed to one or more biomechanical stressors, including frequent bending, heavy lifting and prolonged standing. One-third were simultaneously exposed to BOJS. Exposure to biomechanical stressors declined as pregnancy progressed and cessation often (41%) coincided with employment withdrawal (antenatal leave and unemployment). In multivariate modelling, whether we adjusted for or considered organisational stressors as coincident exposures, results showed that pregnant workers exposed to biomechanical stressors had increased employment withdrawal compared to the unexposed. Work schedule accommodations moderate this association. Paid antenatal leave, available to few US women, was an important strategy for mitigating exposure to BOJS. Implications for science and policy are discussed. Practitioner Summary: This case-control study showed that exposure to biomechanical stressors decline throughout pregnancy. Antenatal leave was an important strategy used for mitigating exposure among sampled California women with access to paid benefits. Employment withdrawal among workers exposed to BJOS may be reduced by proactive administrative and engineering efforts applied early in pregnancy.

  1. Geochemical Implications of CO2 Leakage Associated with Geologic Storage: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, Omar R.; Qafoku, Nikolla; Cantrell, Kirk J.; Brown, Christopher F.

    2012-07-09

    Leakage from deep storage reservoirs is a major risk factor associated with geologic sequestration of carbon dioxide (CO2). Different scientific theories exist concerning the potential implications of such leakage for near-surface environments. The authors of this report reviewed the current literature on how CO2 leakage (from storage reservoirs) would likely impact the geochemistry of near surface environments such as potable water aquifers and the vadose zone. Experimental and modeling studies highlighted the potential for both beneficial (e.g., CO2 re sequestration or contaminant immobilization) and deleterious (e.g., contaminant mobilization) consequences of CO2 intrusion in these systems. Current knowledge gaps, including the role of CO2-induced changes in redox conditions, the influence of CO2 influx rate, gas composition, organic matter content and microorganisms are discussed in terms of their potential influence on pertinent geochemical processes and the potential for beneficial or deleterious outcomes. Geochemical modeling was used to systematically highlight why closing these knowledge gaps are pivotal. A framework for studying and assessing consequences associated with each factor is also presented in Section 5.6.

  2. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    Science.gov (United States)

    Tafti, Mehdi; Lammers, Gert J.; Dauvilliers, Yves; Overeem, Sebastiaan; Mayer, Geert; Nowak, Jacek; Pfister, Corinne; Dubois, Valérie; Eliaou, Jean-François; Eberhard, Hans-Peter; Liblau, Roland; Wierzbicka, Aleksandra; Geisler, Peter; Bassetti, Claudio L.; Mathis, Johannes; Lecendreux, Michel; Khatami, Ramin; Heinzer, Raphaël; Haba-Rubio, José; Feketeova, Eva; Baumann, Christian R.; Kutalik, Zoltán; Tiercy, Jean-Marie

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18–1.87] P = 7.0*10−4), C*04:01 (OR = 1.34 [1.10–1.63] P = 3.23*10−3), and B*35:01 (OR = 1.46 [1.13–1.89] P = 3.64*10−3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15–1.52] P = 6.95*10−5) and HLA-C-Ser11 (OR = 1.34 [1.15–1.57] P = 2.43*10−4). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons. Citation: Tafti M, Lammers GJ, Dauvilliers Y, Overeem S, Mayer G, Nowak J, Pfister C, Dubois V, Eliaou JF, Eberhard HP, Liblau R, Wierzbicka A, Geisler P, Bassetti CL, Mathis J, Lecendreux M, Khatami R, Heinzer R, Haba-Rubio J, Feketeova E, Baumann CR, Kutalik Z, Tiercy JM. Narcolepsy-associated HLA class I alleles implicate cell-mediated cytotoxicity. SLEEP 2016;39(3):581–587. PMID:26518595

  3. Associations between Gun Violence Exposure, Gang Associations, and Youth Aggression: Implications for Prevention and Intervention Programs

    Directory of Open Access Journals (Sweden)

    Myriam Forster

    2015-01-01

    Full Text Available Using cross-sectional data collected from three middle schools in Southeast Los Angeles, we assessed the association of neighborhood violence exposure, gang associations, and social self-control with past week aggression in a sample of minority youth (n=164. Results from Poisson and logistic regression models showed that direct exposure to gun violence, having friends in gangs, and low social self control were all positively associated with past week aggression. Among girls, having gang affiliated family members was positively associated with aggression, whereas among boys having friends in gangs was associated with past week aggression. Subjective expectations of engagement in future interpersonal violence were associated with being male, having friends in gangs, and fear of neighborhood gun violence. We recommend that youth violence prevention and intervention programs address the impact of family, peers, and gun violence on student coping and identify students with low social self-control who could benefit from social and emotional skills training.

  4. Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications.

    Science.gov (United States)

    Chia, Ruth; Chiò, Adriano; Traynor, Bryan J

    2018-01-01

    The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS. Since 2014, seven additional genes have been associated with ALS (MATR3, CHCHD10, TBK1, TUBA4A, NEK1, C21orf2, and CCNF), all of which were identified by genome-wide association studies, whole genome studies, or exome sequencing technologies. Each of the seven novel genes code for proteins associated with one or more molecular pathways known to be involved in ALS. These pathways include dysfunction in global protein homoeostasis resulting from abnormal protein aggregation or a defect in the protein clearance pathway, mitochondrial dysfunction, altered RNA metabolism, impaired cytoskeletal integrity, altered axonal transport dynamics, and DNA damage accumulation due to defective DNA repair. Because these novel genes share common disease pathways with other genes implicated in ALS, therapeutics targeting these pathways could be useful for a broad group of patients stratified by genotype. However, the effects of these novel genes have not yet been investigated in animal models, which will be a key step to translating these findings into clinical practice. WHERE NEXT?: The identification of these seven novel genes has been important in unravelling the molecular mechanisms underlying ALS. However, our understanding of what causes ALS is not complete, and further genetic research will provide additional detail about its causes. Increased genetic knowledge will

  5. Prodromal symptoms of Parkinson's disease: Implications for epidemiological studies of disease etiology.

    Science.gov (United States)

    Elbaz, A

    In recent years, there has been a major shift in our understanding of the course of Parkinson's disease (PD) from a disease of the brain to a disease of long latency, characterized by the progressive emergence of multiple non-motor symptoms, including hyposmia, constipation, depression, anxiety, rapid eye movement (REM) sleep behavior disorder and excessive daytime sleepiness, as well as subtle motor signs, before the typical motor signs appear. Epidemiological studies have made major contributions by allowing better characterization of subsequent PD risk in relation to non-motor symptoms. Such findings have profound implications for the conduct of epidemiological studies examining risk and protective factors in PD, and the interpretation of their findings. Given the length of the prodromal period, reverse causation in particular is a major concern with many reported associations. One striking feature of PD etiology, compared with other diseases, is the presence of numerous inverse associations. If these associations are truly causal, they would have major implications for disease prevention and for slowing disease progression. However, whether these associations are truly causal remains to be demonstrated in future studies. Experimental studies play an important role by offering a better understanding of the underlying mechanisms. Well-designed epidemiological studies using innovative approaches will also be key in elucidating whether these intriguing associations are causal or a consequence of reverse causation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Implications of patient-borne costs associated with pediatric neurosurgical care in eastern Africa.

    Science.gov (United States)

    Awori, Jonathan; Strahle, Jennifer; Okechi, Humphrey; Davis, Matthew C

    2016-07-01

    OBJECTIVE Pediatric neurosurgery can be highly cost-effective even in the developing world, but delivery of these services is hampered by resource limitations at the levels of both health care infrastructure and individual patients. Few studies have evaluated costs borne by neurosurgical patients in the developing world and their potential implications for efficient and effective delivery of care in this population. METHODS The families of 40 pediatric neurosurgery patients were surveyed in February 2015 at the AIC Kijabe Hospital in Kijabe, Kenya. Costs associated with obtaining inpatient care were assessed. RESULTS Patient families were charged an average of US $539.44 for neurosurgical services, representing 132% of their annual income. Indirect expenses (transport, food and lodging, lost wages) constituted US $79.37, representing 14.7% of the overall cost and 19.5% of their annual income. CONCLUSIONS Expansion of pediatric neurosurgical services throughout the developing world necessitates increased attention to seemingly insignificant expenses that are absorbed by patients and their families. Even when all direct costs are covered at the institutional or national level, without additional assistance, some patients may be too poor to obtain even "free" neurosurgical care.

  7. Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility.

    Science.gov (United States)

    Asa, Cheryl S; Bauman, Karen L; Devery, Sarah; Zordan, Martín; Camilo, Gerardo R; Boutelle, Sally; Moresco, Anneke

    2014-01-01

    The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated. © 2013 Wiley Periodicals, Inc.

  8. Understanding Driving Forces and Implications Associated with the Land Use and Land Cover Changes in Portugal

    Directory of Open Access Journals (Sweden)

    Bruno M. Meneses

    2017-02-01

    Full Text Available Understanding the processes of land use and land cover changes (LUCC and the associated driving forces is important for achieving sustainable development. This paper presents the LUCC in Portugal at the regional level (NUTS II from 1995 to 2010 and discusses the main driving forces and implications associated with these LUCC. The main objectives of this work are: (a to quantify the land use and land cover (LUC types (level I of LUC cartography by NUT II in Portugal for the years 1995, 2007 and 2010; (b to assess the spatio-temporal LUCC; and (c to identify and discuss the main driving forces of LUCC and corresponding implications based on correlations and Principal Components Analysis. The results revealed large regional and temporal LUCC and further highlighted the different and sometimes opposite time trends between neighboring regions. By associating driving forces to LUCC, different influences at the regional level were observed, namely LUCC into agriculture land derived from the construction of dams (Alentejo region, or the conversion of coniferous forest into eucalypt forest (Centre region associated with increased gross value added (GVA and employment in industry and forestry. Temporal differentiation was also observed, particularly in the settlements that expanded between 1995 and 2007 due to the construction of large infrastructures (e.g., highways, industrial complexes, or buildings, which is reflected on employment in industry and construction and respective GVA. However, certain LUCC have implications, particularly in energy consumption, for which different behavior between regions can be highlighted in this analysis, but also on land-use sustainability.

  9. IMPLICATIONS OF THE TENTATIVE ASSOCIATION BETWEEN GW150914 AND A FERMI -GBM TRANSIENT

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang; Yuan, Qiang; Jin, Zhi-Ping; Fan, Yi-Zhong; Liu, Si-Ming; Wei, Da-Ming [Key Laboratory of dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Science, Nanjing 210008 (China); Zhang, Fu-Wen, E-mail: yzfan@pmo.ac.cn, E-mail: dmwei@pmo.ac.cn, E-mail: fwzhang@glut.edu.cn [College of Science, Guilin University of Technology, Guilin 541004 (China)

    2016-08-10

    The merger-driven gamma-ray bursts (GRBs) and their associated gravitational-wave (GW) radiation, if both are successfully detected, have some far-reaching implications, including, for instance: (i) the statistical comparison of the physical properties of the short/long-short GRBs with and without GW detection can test the general origin model; (ii) revealing the physical processes taking place at the central engine; (iii) measuring the velocity of the gravitational wave directly/accurately. In this work, we discuss these implications in the case of a possible association of GW150914/Gamma-ray Burst Monitor (GBM) transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event may be a distinct outlier in some statistical diagrams, possibly due to its specific binary black hole merger origin. However, the presence of a “new” group of SGRBs with “unusual” physical parameters is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, the magnetic activity rather than the neutrino process is likely responsible for the energy extraction, and the accretion disk mass is estimated to be ∼10{sup −5} M {sub ⊙}. The GW150914/GBM transient 150914 association, if confirmed, would provide the first opportunity to directly measure the GW velocity, and its departure from the speed of the light should be within a factor of ∼10{sup −17}.

  10. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

    Science.gov (United States)

    Turcot, Valérie; Lu, Yingchang; Highland, Heather M; Schurmann, Claudia; Justice, Anne E; Fine, Rebecca S; Bradfield, Jonathan P; Esko, Tõnu; Giri, Ayush; Graff, Mariaelisa; Guo, Xiuqing; Hendricks, Audrey E; Karaderi, Tugce; Lempradl, Adelheid; Locke, Adam E; Mahajan, Anubha; Marouli, Eirini; Sivapalaratnam, Suthesh; Young, Kristin L; Alfred, Tamuno; Feitosa, Mary F; Masca, Nicholas G D; Manning, Alisa K; Medina-Gomez, Carolina; Mudgal, Poorva; Ng, Maggie C Y; Reiner, Alex P; Vedantam, Sailaja; Willems, Sara M; Winkler, Thomas W; Abecasis, Gonçalo; Aben, Katja K; Alam, Dewan S; Alharthi, Sameer E; Allison, Matthew; Amouyel, Philippe; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Bang, Lia E; Barroso, Inês; Bastarache, Lisa; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Brumat, Marco; Burt, Amber A; Butterworth, Adam S; Campbell, Peter T; Cappellani, Stefania; Carey, David J; Catamo, Eulalia; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der I; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Corominas Galbany, Jordi; Cox, Amanda J; Crosslin, David S; Cuellar-Partida, Gabriel; D'Eustacchio, Angela; Danesh, John; Davies, Gail; Bakker, Paul I W; Groot, Mark C H; Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; Heijer, Martin; Hollander, Anneke I; Ruijter, Hester M; Dennis, Joe G; Denny, Josh C; Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dubé, Marie-Pierre; Dunning, Alison M; Easton, Douglas F; Edwards, Todd L; Ellinghaus, David; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Farooqi, I Sadaf; Faul, Jessica D; Fauser, Sascha; Feng, Shuang; Ferrannini, Ele; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franco, Oscar H; Franke, Andre; Franks, Paul W; Friedrich, Nele; Frikke-Schmidt, Ruth; Galesloot, Tessel E; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Gibson, Jane; Giedraitis, Vilmantas; Gjesing, Anette P; Gordon-Larsen, Penny; Gorski, Mathias; Grabe, Hans-Jörgen; Grant, Struan F A; Grarup, Niels; Griffiths, Helen L; Grove, Megan L; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeff; Hakonarson, Hakon; Hammerschlag, Anke R; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Have, Christian T; Hayward, Caroline; He, Liang; Heard-Costa, Nancy L; Heath, Andrew C; Heid, Iris M; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Holmen, Oddgeir L; Hovingh, G Kees; Howson, Joanna M M; Hu, Yao; Huang, Paul L; Huffman, Jennifer E; Ikram, M Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jia, Yucheng; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon L R; Karpe, Fredrik; Kathiresan, Sekar; Kee, Frank; Kiemeney, Lambertus A; Kim, Eric; Kitajima, Hidetoshi; Komulainen, Pirjo; Kooner, Jaspal S; Kooperberg, Charles; Korhonen, Tellervo; Kovacs, Peter; Kuivaniemi, Helena; Kutalik, Zoltán; Kuulasmaa, Kari; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A; Lamparter, David; Lange, Ethan M; Lange, Leslie A; Langenberg, Claudia; Larson, Eric B; Lee, Nanette R; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Keng-Hung; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Ching-Ti; Liu, Dajiang J; Liu, Yongmei; Lo, Ken S; Lophatananon, Artitaya; Lotery, Andrew J; Loukola, Anu; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Männistö, Satu; Marenne, Gaëlle; Mazul, Angela L; McCarthy, Mark I; McKean-Cowdin, Roberta; Medland, Sarah E; Meidtner, Karina; Milani, Lili; Mistry, Vanisha; Mitchell, Paul; Mohlke, Karen L; Moilanen, Leena; Moitry, Marie; Montgomery, Grant W; Mook-Kanamori, Dennis O; Moore, Carmel; Mori, Trevor A; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Narisu, Narisu; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Nyholt, Dale R; O'Connel, Jeffrey R; O'Donoghue, Michelle L; Olde Loohuis, Loes M; Ophoff, Roel A; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin N A; Palmer, Nicholette D; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John R B; Pers, Tune H; Person, Thomas N; Peters, Annette; Petersen, Eva R B; Peyser, Patricia A; Pirie, Ailith; Polasek, Ozren; Polderman, Tinca J; Puolijoki, Hannu; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Renström, Frida; Rheinberger, Myriam; Ridker, Paul M; Rioux, John D; Rivas, Manuel A; Roberts, David J; Robertson, Neil R; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sapkota, Yadav; Sattar, Naveed; Schoen, Robert E; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati H; Sheu, Wayne H-H; Sim, Xueling; Slater, Andrew J; Small, Kerrin S; Smith, Albert V; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Stefansson, Kari; Steinthorsdottir, Valgerdur; Stirrups, Kathleen E; Strauch, Konstantin; Stringham, Heather M; Stumvoll, Michael; Sun, Liang; Surendran, Praveen; Swift, Amy J; Tada, Hayato; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Uusitupa, Matti; Laan, Sander W; Duijn, Cornelia M; Leeuwen, Nienke; van Setten, Jessica; Vanhala, Mauno; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Velez Edwards, Digna R; Vermeulen, Sita H; Veronesi, Giovanni; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Völker, Uwe; Vuckovic, Dragana; Wagenknecht, Lynne E; Walker, Mark; Wallentin, Lars; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Ware, Erin B; Wareham, Nicholas J; Warren, Helen R; Waterworth, Dawn M; Wessel, Jennifer; White, Harvey D; Willer, Cristen J; Wilson, James G; Witte, Daniel R; Wood, Andrew R; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhou, Wei; Zondervan, Krina T; Rotter, Jerome I; Pospisilik, John A; Rivadeneira, Fernando; Borecki, Ingrid B; Deloukas, Panos; Frayling, Timothy M; Lettre, Guillaume; North, Kari E; Lindgren, Cecilia M; Hirschhorn, Joel N; Loos, Ruth J F

    2018-01-01

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  11. Cross-sectional study of morbidity, morbidity-associated factors and cost of treatment in Ngaoundere, Cameroon, with implications for health policy in developing countries and development assistance policy

    Directory of Open Access Journals (Sweden)

    Holtedahl Knut

    2002-04-01

    Full Text Available Abstract Background In a population-based epidemiological study in Ngaoundere, Cameroon, we studied cross-sectional child morbidity and the cost of necessary investigation and treatment. Methods Three teams of two to three health workers visited haphazardly selected households in all major housing quarters. We asked permission to enter for a health survey. Children with cough, fever or weight loss as well as sick adults were offered free-of-charge local hospital examination and treatment. Results From 177 households with 1777 persons, 51 (2.9% persons were referred. Thirty-five of them had an undiagnosed disease threatening individual health and in many cases also public health. Seven were hospitalised, including three adults with tuberculosis. Malnutrition was diagnosed in nine small children. Four patients had AIDS, seven had malaria. Average total cost for ambulant patients was 15 USD, for hospitalised patients 110 USD. In the households, almost half of the women 16–50 years of age had no schooling. Two per cent of women and nine per cent of men were daily smokers. Coughing children were more likely than non-coughing children to live in a household with at least one smoker (OR = 3.58, 95% CI 1.72 to 7.46, and they generally lived in more poor households (P = 0.018. Twelve of 16 children with weight loss were referred from households with a high poverty score. Conclusions Adult smoking and poverty affect children's health. The cost of hospitalisation or long-lasting therapy is beyond the means of most ordinary families. Diseases with severe consequences for public health, like tuberculosis, AIDS and malaria should have national programs with free, decentralised examination and treatment. Access to generic drugs is important. A major educational effort is needed to improve public health.

  12. The association between aerobic fitness and language processing in children: implications for academic achievement.

    Science.gov (United States)

    Scudder, Mark R; Federmeier, Kara D; Raine, Lauren B; Direito, Artur; Boyd, Jeremy K; Hillman, Charles H

    2014-06-01

    Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children's aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance. Published by Elsevier Inc.

  13. Studies on the environmental implications of ants (Hymenoptera ...

    African Journals Online (AJOL)

    A study of ants associated wh two synanthropcenvironments in Awka was carried out in 2008 using pitfall and bait traps. The study yelded a total of 561 ants wth 409 obtaned from the hemisynanthrophic environment while 192 ants were collected from the endophilic environment. The percentage occurrence, total dstribution ...

  14. 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. © 2016 Society for Endocrinology.

  15. Migraine Associated with Gastrointestinal Disorders: Review of the Literature and Clinical Implications

    NARCIS (Netherlands)

    Hemert, van S.; Breedveld, A.C.; Rovers, J.M.P.; Vermeiden, J.P.W.; Witteman, B.J.M.; Smits, M.; Roos, de N.M.

    2014-01-01

    Recent studies suggest that migraine may be associated with gastrointestinal (GI) disorders, including irritable bowel syndrome (IBS), inflammatory bowel syndrome, and celiac disease. Here, an overview of the associations between migraine and GI disorders is presented, as well as possible

  16. Statin-associated immune-mediated myopathy: biology and clinical implications.

    Science.gov (United States)

    Christopher-Stine, Lisa; Basharat, Pari

    2017-04-01

    In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

  17. 77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

    Science.gov (United States)

    2012-02-21

    ... on Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling... entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling... availability of a revised draft guidance for industry entitled ``Drug Interaction Studies--Study Design, Data...

  18. [Food addiction: Definition, measurement and limits of the concept, associated factors, therapeutic and clinical implications].

    Science.gov (United States)

    Cathelain, Sarah; Brunault, Paul; Ballon, Nicolas; Réveillère, Christian; Courtois, Robert

    2016-12-01

    Addictions, which are characterized by the inability to control a behavior despite existence of physical or psychological consequences, have biological, psychological and social determinants. Although the possibility of developing an addiction to some psychoactive substances (e.g. alcohol, tobacco, cannabis) and to gambling (i.e., gambling disorder) is now well demonstrated, the possibility to develop a non-drug addiction (i.e., behavioral addiction) to certain behaviors which provide pleasure (e.g. eating, having sex, buying things) is still in debate. The concept of food addiction, which refers to people who exhibit substance dependence criteria in relation to some high-fat and high-sugar foods, was recently proposed by applying substance dependence DSM criteria to eating behavior. To assess food addiction, the Yale Food Addiction Scale is now the only self-administered questionnaire (diagnosis and estimate of the number of symptoms of food addiction). Prevalence for food addiction is higher in overweight and obese patients, and in patients with certain psychopathological characteristics (i.e., depression, Attention Deficit Hyperactivity Disorder, high impulsivity), in patients who are single and in patients with neurobiological alterations in the reward system. However, it is still unclear whether food addiction is necessary associated with subsequent increase in body weight and/or obesity. An increasing number of studies demonstrated that drug addiction and food addiction shares some similar clinical, neurobiological and psychopathological and sociocultural risk factors. To test the pertinence to include food addiction as an addiction, it would be interesting to conduct future studies in patients who may experience harms related to their food addiction, including not only patients with obesity, but also patients with metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, stroke, or coronary heart disease. Food addiction is a clinical

  19. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.

    Science.gov (United States)

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-10-13

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.

  20. Epigenome-wide association studies identify DNA methylation associated with kidney function.

    Science.gov (United States)

    Chu, Audrey Y; Tin, Adrienne; Schlosser, Pascal; Ko, Yi-An; Qiu, Chengxiang; Yao, Chen; Joehanes, Roby; Grams, Morgan E; Liang, Liming; Gluck, Caroline A; Liu, Chunyu; Coresh, Josef; Hwang, Shih-Jen; Levy, Daniel; Boerwinkle, Eric; Pankow, James S; Yang, Qiong; Fornage, Myriam; Fox, Caroline S; Susztak, Katalin; Köttgen, Anna

    2017-11-03

    Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.

  1. Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications.

    Science.gov (United States)

    Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

    2011-01-01

    There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS). The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS. The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14-19 years) from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia), Bahrain, Dubai (United Arab Emirates), Kuwait, Amman (Jordan), Mosel (Iraq), Muscat (Oman), Tunisia (Tunisia) and Kenitra (Morocco). Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits. The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention.

  2. Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.

    Science.gov (United States)

    Ransohoff, Katherine J; Wu, Wenting; Cho, Hyunje G; Chahal, Harvind C; Lin, Yuan; Dai, Hong-Ji; Amos, Christopher I; Lee, Jeffrey E; Tang, Jean Y; Hinds, David A; Han, Jiali; Wei, Qingyi; Sarin, Kavita Y

    2017-03-14

    Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 x 10-8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.

  3. 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....

  4. 2-D structure of the A region of Xist RNA and its implication for PRC2 association.

    Directory of Open Access Journals (Sweden)

    Sylvain Maenner

    2010-01-01

    Full Text Available In placental mammals, inactivation of one of the X chromosomes in female cells ensures sex chromosome dosage compensation. The 17 kb non-coding Xist RNA is crucial to this process and accumulates on the future inactive X chromosome. The most conserved Xist RNA region, the A region, contains eight or nine repeats separated by U-rich spacers. It is implicated in the recruitment of late inactivated X genes to the silencing compartment and likely in the recruitment of complex PRC2. Little is known about the structure of the A region and more generally about Xist RNA structure. Knowledge of its structure is restricted to an NMR study of a single A repeat element. Our study is the first experimental analysis of the structure of the entire A region in solution. By the use of chemical and enzymatic probes and FRET experiments, using oligonucleotides carrying fluorescent dyes, we resolved problems linked to sequence redundancies and established a 2-D structure for the A region that contains two long stem-loop structures each including four repeats. Interactions formed between repeats and between repeats and spacers stabilize these structures. Conservation of the spacer terminal sequences allows formation of such structures in all sequenced Xist RNAs. By combination of RNP affinity chromatography, immunoprecipitation assays, mass spectrometry, and Western blot analysis, we demonstrate that the A region can associate with components of the PRC2 complex in mouse ES cell nuclear extracts. Whilst a single four-repeat motif is able to associate with components of this complex, recruitment of Suz12 is clearly more efficient when the entire A region is present. Our data with their emphasis on the importance of inter-repeat pairing change fundamentally our conception of the 2-D structure of the A region of Xist RNA and support its possible implication in recruitment of the PRC2 complex.

  5. Arab Teens Lifestyle Study (ATLS: objectives, design, methodology and implications

    Directory of Open Access Journals (Sweden)

    Musaiger AO; ATLS Research Group

    2011-12-01

    Full Text Available Hazzaa M Al-Hazzaa1,2, Abdulrahman O Musaiger3, ATLS Research Group1Exercise Physiology Laboratory, Department of Physical Education and Movement Sciences, College of Education, King Saud University, 2Scientific Board, Obesity Research Chair, King Saud University, Riyadh, Saudi Arabia; 3Arab Center for Nutrition, Manama, Bahrain, and Nutrition and Health Studies Unit, Deanship of Scientific Research, University of Bahrain, BahrainBackground: There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS. The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS.Design/Methods: The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14–19 years from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia, Bahrain, Dubai (United Arab Emirates, Kuwait, Amman (Jordan, Mosel (Iraq, Muscat (Oman, Tunisia (Tunisia and Kenitra (Morocco. Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits.Discussion: The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will

  6. Survival Implications Associated with Variation in Mastectomy Rates for Early-Staged Breast Cancer

    Directory of Open Access Journals (Sweden)

    John M. Brooks

    2012-01-01

    Full Text Available Despite a 20-year-old guideline from the National Institutes of Health (NIH Consensus Development Conference recommending breast conserving surgery with radiation (BCSR over mastectomy for woman with early-stage breast cancer (ESBC because it preserves the breast, recent evidence shows mastectomy rates increasing and higher-staged ESBC patients are more likely to receive mastectomy. These observations suggest that some patients and their providers believe that mastectomy has advantages over BCSR and these advantages increase with stage. These beliefs may persist because the randomized controlled trials (RCTs that served as the basis for the NIH guideline were populated mainly with lower-staged patients. Our objective is to assess the survival implications associated with mastectomy choice by patient alignment with the RCT populations. We used instrumental variable methods to estimate the relationship between surgery choice and survival for ESBC patients based on variation in local area surgery styles. We find results consistent with the RCTs for patients closely aligned to the RCT populations. However, for patients unlike those in the RCTs, our results suggest that higher mastectomy rates are associated with reduced survival. We are careful to interpret our estimates in terms of limitations of our estimation approach.

  7. The Study of Nevi in Children: Principles Learned and Implications for Melanoma Diagnosis

    Science.gov (United States)

    Scope, Alon; Marchetti, Michael A.; Marghoob, Ashfaq A.; Dusza, Stephen W.; Geller, Alan C.; Satagopan, Jaya M.; Weinstock, Martin A.; Berwick, Marianne; Halpern, Allan C.

    2016-01-01

    Melanocytic nevi are a strong phenotypic marker of cutaneous melanoma risk. Changes in nevi during childhood and adolescence make these prime periods for studying nevogenesis. Insights gained by the study of nevi in childhood have implications for melanoma detection in both adults and children. A more comprehensive understanding of the morphologic characteristics of nevi in different anatomic locations, in association with the patient’s age and pigmentary phenotype may aid in the identification of melanomas. When monitoring melanocytic lesions over time, it is essential to differentiate normal from abnormal change. In this review, we summarize the rapidly expanding body of literature, particularly in the context of our experience with the Study of Nevi in Children (SONIC) Project. PMID:27320410

  8. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    NARCIS (Netherlands)

    Tafti, M.; Lammers, G.J.; Dauvilliers, Y.; Overeem, S.; Mayer, G.; Nowak, J.; Pfister, C.; Dubois, V.; Eliaou, J.F.; Eberhard, H.P.; Liblau, R.; Wierzbicka, A.; Geisler, P.; Bassetti, C.L.; Mathis, J.; Lecendreux, M.; Khatami, R.; Heinzer, R.; Haba-Rubio, J.; Feketeova, E.; Baumann, C.R.; Kutalik, Z.; Tiercy, J.M.

    2016-01-01

    STUDY OBJECTIVES: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an

  9. Venous thromboembolism in overt hyperthyroidism - a direct association with clinical implications?

    NARCIS (Netherlands)

    Elbers, L. P. B.; van Zaane, B.; Gerdes, V. E. A.; Coutinho, J. M.; Bisschop, P. H.; Fliers, E.

    2014-01-01

    Hyperthyroidism is associated with procoagulant changes in the haemostatic system. At present, it is uncertain whether this leads to an increased risk of venous and/or arterial thrombosis. Only a few small studies have investigated this association but due to methodological limitations it is not

  10. Periodontal Systemic Connections-Novel Associations-A Review of the Evidence with Implications for Medical Practitioners

    Science.gov (United States)

    Kalakonda, Butchibabu; Koppolu, Pradeep; Baroudi, Kusai; Mishra, Ashank

    2016-01-01

    Periodontal diseases, considered as inflammatory diseases have proved to have a spectrum of systemic implications. Earliest research has associated periodontal disease with common systemic aliments such as hypertension, diabetes, osteoporosis, rheumatoid arthritis to name a few. The evolution of advanced diagnostic aids let researchers make vast inroads in linking periodontal diseases to systemic diseases like Alzheimer’s disease (AD) and even Schizophrenia. Our aim was to review and critically evaluate comprehensive literature and provide knowledge to medical practitioners on these associations so as to pave way for closer interactions between medical and dental practitioners in implementing better health care. Electronic databases such as PubMed, Google Scholar and Cochrane databases were used as source of the data for relevant studies published from 2005 up to 2015 with the following keywords, “‘Periodontal disease”, “systemic conditions”, “periodontal disease and Alzheimer’s”, “Periodontal disease and Schizophrenia”, “Periodontal disease and Psoriasis” and “Periodontal disease and erectile dysfunction”. The evidence presented ascertains that a reasonable and modest association does exist between Periodontal disease and Alzheimer’s, Schizophrenia, Erectile dysfunction, as well as Psoriasis and thus establishes periodontal disease as a potential risk factor. PMID:27103910

  11. Tax Revenue Implications of Devaluations : A Case Study of Bangladesh

    OpenAIRE

    Nitai C. Nag

    1999-01-01

    A small macroeconomics model is used to estimate empirically the real tax revenue implications of devaluation. Overall effect of devaluation on tax revenue id found to be negative, which contrasts with the theoretical presumption that devaluation improves the government revenue position. According to our estimation a 10 percent devaluation lowers equilibrium output by 1.04 percent and overall tax revenue by 4.2 percent. Import is dependent on output in the model. Contractionary output effect,...

  12. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

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

  13. Factors associated with female genital mutilation in Burkina Faso and its policy implications

    Directory of Open Access Journals (Sweden)

    Chung Donna

    2011-05-01

    Full Text Available Abstract Background Female genital mutilation (FGM usually undertaken between the ages of 1-9 years and is widely practised in some part of Africa and by migrants from African countries in other parts of the world. Laws prohibit FGM in almost every country. FGM can cause immediate complications (pain, bleeding and infection and delayed complications (sexual, obstetric, psychological problems. Several factors have been associated with an increased likelihood of FGM. In Burkina Faso, the prevalence of FGM appears to have increased in recent years. Methods We investigated social, demographic and economic factors associated with FGM in Burkina Faso using the 2003 Demographic Health Survey (DHS. The DHS is a nationally representative cross-sectional survey (multistage stratified random sampling of households of women of reproductive age (15-49 years. Associations between potential risk factors and the prevalence of FGM were explored using χ2 and t-tests and Mann Whitney U-test as appropriate. Logistic regression modelling was used to investigate social, demographic and economic risk factors associated with FGM. Main outcome measures i whether a woman herself had had FGM; ii whether she had one or more daughters with FGM. Results Data were available on 12,049 women. Response rates by region were at least 90%. Women interviewed were representative of the underlying populations of the different regions of Burkina Faso. Seventy seven percent (9267 of the women interviewed had had FGM. 7336 women had a daughter of whom 2216 (30.2% had a daughter with FGM and 334 (4.5% said that they intended that their daughter should have it. Univariate analysis showed that age, religion, wealth, ethnicity, literacy, years of education, household affluence, region and who had responsibility for health care decisions in the household had (RHCD were all significantly related to the two outcomes (p Conclusions and Policy implications Factors associated with FGM are varied

  14. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

    Science.gov (United States)

    Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Glendon, Gord; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hart, Steven N; Hartman, Mikael; Hooning, Maartje J; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; James, Paul A; John, Esther M; Johnson, Nichola; Jones, Michael; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lambrechts, Diether; Li, Na; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Meindl, Alfons; Mitchell, Gillian; Muir, Kenneth; Nevelsteen, Ines; van den Ouweland, Ans; Peterlongo, Paolo; Phuah, Sze Yee; Pylkäs, Katri; Rowley, Simone M; Sangrajrang, Suleeporn; Schmutzler, Rita K; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Verhoef, Senno; Wong-Brown, Michelle; Zheng, Wei; Zheng, Ying; Nevanlinna, Heli; Scott, Rodney J; Andrulis, Irene L; Wu, Anna H; Hopper, John L; Couch, Fergus J; Winqvist, Robert; Burwinkel, Barbara; Sawyer, Elinor J; Schmidt, Marjanka K; Rudolph, Anja; Dörk, Thilo; Brauch, Hiltrud; Hamann, Ute; Neuhausen, Susan L; Milne, Roger L; Fletcher, Olivia; Pharoah, Paul D P; Campbell, Ian G; Dunning, Alison M; Le Calvez-Kelm, Florence; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia

    2016-01-01

    Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. PMID:26921362

  15. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    Science.gov (United States)

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models.

  16. Depression and Apathy Among People Living with HIV: Implications for Treatment of HIV Associated Neurocognitive Disorders.

    Science.gov (United States)

    Bryant, Vaughn E; Whitehead, Nicole E; Burrell, Larry E; Dotson, Vonetta M; Cook, Robert L; Malloy, Paul; Devlin, Kathryn; Cohen, Ronald A

    2015-08-01

    Depression and apathy are common among people living with HIV (PLWH). However, in PLWH, it is unclear whether depression and apathy are distinct conditions, which contribute to different patterns of disruption to cognitive processing and brain systems. Understanding these conditions may enable the development of prognostic indicators for HIV associated neurocognitive disorders (HAND). The present study examined substance use behavior and cognitive deficits, associated with depression and apathy, in 120 PLWH, using hierarchical regression analyses. Higher levels of depression were associated with a history of alcohol dependence and greater deficits in processing speed, motor and global cognitive functioning. Higher levels of apathy were associated with a history of cocaine dependence. It is recommended that PLWH get screened appropriately for apathy and depression, in order to receive the appropriate treatment, considering the comorbidities associated with each condition. Future research should examine the neurological correlates of apathy and depression in PLWH.

  17. [Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

    Science.gov (United States)

    Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

    2012-06-01

    The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  18. The implications of trade liberalization for diet and health: a case study from Central America

    Directory of Open Access Journals (Sweden)

    Hawkes Corinna

    2009-07-01

    Full Text Available Abstract Background Central America has undergone extensive trade liberalization over the past two decades, and has recently signed a Free Trade Agreement with the United States. The region is also experiencing a dual burden of malnutrition with the growth of dietary patterns associated with the global 'nutrition transition'. This study describes the relationship between trade liberalization policies and food imports and availability, and draws implications for diet and health, using Central America as a case study region. Methods Changes in tariff and non-tariff barriers for each country were documented, and compared with time-series graphs of import, production and availability data to show the outcome of changes in trade policy in relation to food imports and food availability. Results Changes in trade policy in Central America have directly affected food imports and availability via three avenues. First, the lowering of trade barriers has promoted availability by facilitating higher imports of a wide range of foods. Second, trade liberalization has affected food availability through promoting domestic meat production. Third, reductions in barriers to investment appear to be critical in expansion of processed food markets. This suggests that changes in trade policies have facilitated rising availability and consumption of meat, dairy products, processed foods and temperate (imported fruits in Central America. Conclusion This study indicates that the policies of trade liberalization in Central American countries over the past two decades, particularly in relation to the United States, have implications for health in the region. Specifically, they have been a factor in facilitating the "nutrition transition", which is associated with rising rates of obesity and chronic diseases such as cardiovascular disease and cancer. Given the significant cost of chronic disease for the health care system, individuals and the wider community, it is critical

  19. Implication of kinematic dynamo studies for the geodynamo

    Science.gov (United States)

    Gubbins, David

    2008-04-01

    In the kinematic dynamo problem Maxwell's equations are solved for the magnetic field given a prescribed fluid velocity. Although no dynamic equations are involved, it does provide an accurate link between the magnetic field and fluid velocity and can therefore be used to infer something about the flow underlying the observed geomagnetic field. In this sense it complements the commonly used frozen-flux theory for inverting secular variation for core flow, in which electrical diffusion is neglected, and can be used to show up some of the strengths and weaknesses of the frozen-flux approximation. It might be thought that kinematic models have been superceded by dynamic models that include the momentum and heat equations, but this is not the case. Even the biggest numerical simulation cannot approach the correct parameters for the Earth's core, and the classes of flows that result are, in fact, quite restricted as well as being too complex for simple physical interpretation. A variety of simple flows have been studied for dynamo action; of particular interest here are a broad class of flows, based loosely on extensions of the early simple choice of Bullard & Gellman and to some extent representative of what might be generated by convection in the Earth's rapidly rotating core: this paper reviews the implications of the solutions for geomagnetism. The non-axisymmetric flows mimic convection rolls in a rotating sphere, the axisymmetric poloidal flows describe meridional circulation, a likely secondary flow, and the axisymmetric toroidal flow is a simple differential rotation. Helicity, which seems to be important for dynamo action, is related to spiralling of the rolls. Dipole, rather than quadrupole, fields are preferred when spiralling is eastward and differential rotation westward at the surface. Magnetic flux tends to be concentrated at stagnation points of the flow, and dynamo action fails when this concentration becomes so intense that steep gradients develop so

  20. Fluid retention associated with imatinib treatment in patients with gastroenterol stromal: Quantitative radiologic assessment and implications for management

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikihil H. [Dept. of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Pyo, Jun Hee [The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston (United States)

    2015-04-15

    We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

  1. DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases.

    Science.gov (United States)

    Searles Quick, V B; Davis, J M; Olincy, A; Sikela, J M

    2015-12-15

    The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species.

  2. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  3. Associates of an Elevated Natriuretic Peptide Level in Stable Heart Failure Patients: Implications for Targeted Management

    Directory of Open Access Journals (Sweden)

    Aftab Jan

    2013-01-01

    Full Text Available Background. Persistently elevated natriuretic peptide (NP levels in heart failure (HF patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP in a stable HF population. Methods. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF, left atrial volume index (LAVI, and E/e prime (E/e′ was measured. Results. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e′, creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e′ and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Conclusion. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

  4. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  5. Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

    Science.gov (United States)

    Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

    2013-10-01

    Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Entrepreneurship Education at Tertiary Education Level: Implication to Historical Studies

    Directory of Open Access Journals (Sweden)

    Salahu Mohammed Lawal

    2012-07-01

    Full Text Available Nigeria is richly endowed with both human and material resources that when well utilized can make her one of the richest and developed nation in the world.  But poor utilization of the resources, corruption and dwindling fortune in her education system made her among the first twenty five poorest nations in the world.  Similarly, report shows that 26% of the employable population remained unemployed.  This called for the need for entrepreneurship education most especially at tertiary level where high level manpower is supposed to be trained.  It is on this premise that the paper attempts to examine entrepreneurship education and its implication to history students and graduates.

  7. Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry

    NARCIS (Netherlands)

    Wischnewski, M.; Schutter, D.J.L.G.

    2016-01-01

    Objective: Paired associative stimulation (PAS) has been used to study normal and abnormal cortical plasticity. However, a normative review of PAS effects has not been provided so far. To this end, the magnitude and time course of PAS protocols was systematically evaluated here. Methods: A

  8. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Directory of Open Access Journals (Sweden)

    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  9. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  10. Highly drug-resistant pathogens implicated in burn-associated bacteremia in an Iraqi burn care unit.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Ronat

    Full Text Available OBJECTIVE: In low- and middle-income countries, bloodstream infections are an important cause of mortality in patients with burns. Increasingly implicated in burn-associated infections are highly drug-resistant pathogens with limited treatment options. We describe the epidemiology of bloodstream infections in patients with burns in a humanitarian surgery project in Iraq. METHODS: We performed a retrospective, descriptive study of blood culture isolates identified between July 2008 and September 2009 among patients with burns in a single hospital in Iraq who developed sepsis. RESULTS: In 1169 inpatients admitted to the burn unit during the study period, 212 (18% had suspected sepsis, and 65 (6% had confirmed bacteremia. Sepsis was considered the primary cause of death in 198 patients (65%; 95% CI 65-70 of the 304 patients that died. The most commonly isolated organisms were Pseudomonas aeruginosa (22 isolates [34%], Staphylococcus aureus (17 [26%], Klebsiella pneumoniae (8 [12%], Staphylococcus epidermidis (7 [11%], Acinetobacter baumannii (6 [9%], and Enterobacter cloacae (5 [8%]. A high proportion of Enterobacteriaceae strains produced extended-spectrum beta-lactamase and S. aureus isolates were uniformly methicillin-resistant. For gram-negative bacteria, the most reliably active antibiotics were imipenen and amikacin. CONCLUSIONS: Burn patients with sepsis in Iraq were commonly found to have bloodstream pathogens resistant to most antibiotics available locally. Effective empirical therapy of burn sepsis in this region of Iraq would consist of vancomycin or teicoplanin and a carbapenem-class antibiotic with antipseudomonal activity.

  11. Multiple Intelligences (MI of Associate in Hotel and Restaurant Management Students & Its Implication to the Teaching of Oral Communication

    Directory of Open Access Journals (Sweden)

    Juvy G. Mojares

    2015-11-01

    Full Text Available A number of educators argue that MI helps students build positive attitudes toward learning in English class. A study says that “Students who are using their areas of strength to learn feel more competent and confident and enjoy the challenge of acquiring new information”. This study sought to find out the MI of selected Associate in Hotel and Restaurant Management (AHRMstudents. It also delved on the implication of MI to the teaching of the subject. The research design used was basically a descriptive method employing an adopted MI survey form administered to Oral Communication students. There were five sections of second year AHRM students. Out of 196 students, 111 were selected to answer the survey questions by the use of the combination of stratified random sampling and the Slovin’s formula. Results showed that the top three intelligences the respondents have based on their scores are intrapersonal, followed by bodily/kinesthetic and logical/mathematical intelligences; least of the intelligences are verbal/linguistic and visual/spatial.This implied that teaching of Oral Communication should nurture the intrapersonal intelligence and more importantly should enhance and develop the verbal strength of the AHRM students. Teaching should focus more on improving communication skills with others, and not just within themselves.

  12. Pedagogical implications of approaches to study in distance learning: developing models through qualitative and quantitative analysis.

    Science.gov (United States)

    Carnwell, R

    2000-05-01

    The need for flexibility in the delivery of nurse education has been identified by various initiatives including: widening the entry gate; continuous professional development; and the specialist practitioner. Access to degree level programmes is creating the need to acquire academic credit through flexible learning. The aim of this study was to further develop relationships between the need for guidance, materials design and learning styles and strategies and how these impact upon the construction of meaning. The study is based on interviews of 20 female community nurses purposively selected from the 96 respondents who had previously completed a survey questionnaire. The interviews were underpinned by theories relating to learning styles and approaches to study. Of particular concern was how these variables are mediated by student context, personal factors and materials design, to influence the need for support and guidance. The interview transcripts were first analysed using open and axial coding. Three approaches to study emerged from the data - systematic waders, speedy-focusers and global dippers - which were linked to other concepts and categories. Categories were then assigned numerical codes and subjected to logistical regression analysis. The attributes of the three approaches to study, arising from both qualitative and quantitative analysis, are explained in detail. The pedagogical implications of the three approaches to study are explained by their predicted relationships to other variables, such as support and guidance, organization of study, materials design and role of the tutor. The global dipper approach is discussed in more detail due to its association with a variety of predictor variables, not associated with the other two approaches to study. A feedback model is then developed to explore the impact of guidance on the global dipper approach. The paper makes recommendations for guidance to students using different approaches to study in distance

  13. Abdominal fat mass is associated with adaptive immune activation: the CODAM study

    NARCIS (Netherlands)

    Thewissen, M.M.; Damoiseaux, J.G.; Duijvestijn, A.M.; Greevenbroek, M.M.; Kallen, van der C.J.H.; Feskens, E.J.M.; Blaak, E.E.; Schalkwijk, C.G.; Stehouwer, C.D.A.; Cohen Tervaert, J.W.; Ferreira, I.

    2011-01-01

    Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist

  14. Associative Visual Agnosia: A Case Study

    OpenAIRE

    A. Charnallet; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  15. 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.

  16. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Farida El-Baz Mohamed

    2016-03-10

    Mar 10, 2016 ... Study of obesity associated proopiomelanocortin ... Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth ... Cases were compared to fifty age-, sex- and pubertal stage-matched healthy non obese children and adolescents as a control group. The work was carried ...

  17. 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

  18. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    Jane

    2011-09-28

    Sep 28, 2011 ... We wanted to determine the association between alcohol addiction and ethanol metabolizing genes and neurotransmitter related genes. MATERIALS AND METHODS. Study population. A total of 332 DNA samples from unrelated Chinese Han population in Yunnan region were obtained (214 controls and ...

  19. Periodontal Systemic Connections-Novel Associations-A Review of the Evidence with Implications for Medical Practitioners

    OpenAIRE

    Kalakonda, Butchibabu; Koppolu, Pradeep; Baroudi, Kusai; Mishra, Ashank

    2016-01-01

    Periodontal diseases, considered as inflammatory diseases have proved to have a spectrum of systemic implications. Earliest research has associated periodontal disease with common systemic aliments such as hypertension, diabetes, osteoporosis, rheumatoid arthritis to name a few. The evolution of advanced diagnostic aids let researchers make vast inroads in linking periodontal diseases to systemic diseases like Alzheimer’s disease (AD) and even Schizophrenia. Our aim was to review and critical...

  20. Chapter 11: Genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    William S Bush

    Full Text Available Genome-wide association studies (GWAS have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

  1. Gendered Risk Perceptions Associated with Human-Wildlife Conflict: Implications for Participatory Conservation

    Science.gov (United States)

    Gore, Meredith L.; Kahler, Jessica S.

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities. PMID:22403722

  2. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    Directory of Open Access Journals (Sweden)

    Meredith L Gore

    Full Text Available This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1 gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC in a participatory conservation context, and (2 highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2 to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38 to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities.

  3. Diagnostic implications of associated defects in patients with typical orofacial clefts

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    Isabella L. Monlleó

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVES: To describe prevalence of associated defects and clinical-genetic characteristics of patients with typical orofacial clefts seen at a reference genetic service. METHODS: Descriptive study conducted between September of 2009 and July of 2014. Two experienced dysmorphologists personally collected and coded clinical data using a validated, standard multicenter protocol. Syndromic cases were defined by the presence of four or more minor defects, one or more major defects, or recognition of a specific syndrome. Fisher's exact and Kruskal-Wallis tests were used for statistics. RESULTS: Among 141 subjects, associated defects were found in 133 (93%, and 84 (59.5% were assigned as syndromic. Cleft palate was statistically associated with a greater number of minor defects (p < 0.0012 and syndromic assignment (p < 0.001. Syndromic group was associated with low birth weight (p < 0.04 and less access to surgical treatment (p < 0.002. There was no statistical difference between syndromic and non-syndromic groups regarding gender (p < 0.55, maternal age of 35 years and above (p < 0.50, alcohol (p < 0.50 and tobacco consumption (p < 0.11, consanguinity (p < 0.59, recurrence (p < 0.08, average number of pregnancies (p < 0.32, and offspring (p < 0.35. CONCLUSIONS: There is a lack of information on syndromic clefts. The classification system for phenotype assignment adopted in this study has facilitated recognition of high prevalence of associated defects and syndromic cases. This system may be a useful strategy to gather homogeneous samples, to elect appropriate technologies for etiologic and genotype-phenotype approaches, and to assist with multiprofessional care and genetic counseling.

  4. Mutations in presenilin 2 and its implications in Alzheimer’s disease and other dementia-associated disorders

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    Cai Y

    2015-07-01

    Full Text Available Yan Cai,1 Seong Soo A An,1 SangYun Kim2 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, 2Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea Abstract: Alzheimer’s disease (AD is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1, presenilin 2 (PSEN2, and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson’s disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders. Keywords: mutations in presenilin 2, Alzheimer’s disease

  5. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP Proteins with Implications for Human Disease

    Directory of Open Access Journals (Sweden)

    Marshall V. Williams

    2016-12-01

    Full Text Available The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase, as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer.

  6. Multiple factors are involved in the dysarthria associated with Parkinson's disease: a review with implications for clinical practice and research.

    Science.gov (United States)

    Sapir, Shimon

    2014-08-01

    Motor speech abnormalities are highly common and debilitating in individuals with idiopathic Parkinson's disease (IPD). These abnormalities, collectively termed hypokinetic dysarthria (HKD), have been traditionally attributed to hypokinesia and bradykinesia secondary to muscle rigidity and dopamine deficits. However, the role of rigidity and dopamine in the development of HKD is far from clear. The purpose of the present study was to offer an alternative view of the factors underlying HKD. The authors conducted an extensive, but not exhaustive, review of the literature to examine the evidence for the traditional view versus the alternative view. The review suggests that HKD is a highly complex and variable phenomenon including multiple factors, such as scaling and maintaining movement amplitude and effort; preplanning and initiation of movements; internal cueing; sensory and temporal processing; automaticity; emotive vocalization; and attention to action (vocal vigilance). Although not part of the dysarthria, nonmotor factors, such as depression, aging, and cognitive-linguistic abnormalities, are likely to contribute to the overall speech symptomatology associated with IPD. These findings have important implications for clinical practice and research.

  7. Conditional associative memory for musical stimuli in nonmusicians: implications for absolute pitch.

    Science.gov (United States)

    Bermudez, Patrick; Zatorre, Robert J

    2005-08-24

    A previous positron emission tomography (PET) study of musicians with and without absolute pitch put forth the hypothesis that the posterior dorsolateral prefrontal cortex is involved in the conditional associative aspect of the identification of a pitch. In the work presented here, we tested this hypothesis by training eight nonmusicians to associate each of four different complex musical sounds (triad chords) with an arbitrary number in a task designed to have limited analogy to absolute-pitch identification. Each subject under-went a functional magnetic resonance imaging scanning procedure both before and after training. Active condition (identification of chords)-control condition (amplitude-matched noise bursts) comparisons for the pretraining scan showed no significant activation maxima. The same comparison for the posttraining scan revealed significant peaks of activation in posterior dorsolateral prefrontal, ventrolateral prefrontal, and parietal areas. A conjunction analysis was performed to show that the posterior dorsolateral prefrontal activity in this study is similar to that observed in the aforementioned PET study. We conclude that the posterior dorsolateral prefrontal cortex is selectively involved in the conditional association aspect of our task, as it is in the attribution of a verbal label to a note by absolute-pitch musicians.

  8. A NOS1 variant implicated in cognitive performance influences evoked neural responses during a high density EEG study of early visual perception.

    LENUS (Irish Health Repository)

    O'Donoghue, Therese

    2012-05-01

    The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear.

  9. Epigenome-Wide Association Study of Wellbeing.

    Science.gov (United States)

    Baselmans, Bart M L; van Dongen, Jenny; Nivard, Michel G; Lin, Bochao D; Zilhão, Nuno R; Boomsma, Dorret I; Bartels, Meike

    2015-12-01

    Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10(-8) and cg01940273, p = 2.34 * 10(-8)) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10(-7); cg09716613, p = 3.23 * 10(-7); cg04387347, p = 3.95 * 10(-7); and cg02290168, p = 5.23 * 10(-7)) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

  10. Postnatal paternal depressive symptoms associated with fathers' subsequent parenting: findings from the Millennium Cohort Study.

    Science.gov (United States)

    Nath, Selina; Russell, Ginny; Ford, Tamsin; Kuyken, Willem; Psychogiou, Lamprini

    2015-12-01

    Impaired parenting may lie on the causal pathway between paternal depression and children's outcomes. We use the first four surveys of the Millennium Cohort Study to investigate the association between paternal depressive symptoms and fathers' parenting (negative, positive and involvement). Findings suggest that postnatal paternal depressive symptoms are associated with fathers' negative parenting. This has implications for the design of intervention programmes for parents with depression and young children. © The Royal College of Psychiatrists 2015.

  11. A norovirus outbreak associated with consumption of NSW oysters: implications for quality assurance systems.

    Science.gov (United States)

    Huppatz, Clare; Munnoch, Sally A; Worgan, Tory; Merritt, Tony D; Dalton, Craig; Kelly, Paul M; Durrheim, David N

    2008-03-01

    Norovirus is a common cause of gastroenteritis outbreaks associated with raw shellfish consumption. In Australia there have been several reports of norovirus outbreaks associated with oysters despite the application of regulatory measures recommended by Food Standards Australia New Zealand. This study describes an outbreak of norovirus gastroenteritis following the consumption of New South Wales oysters. In September 2007, OzFoodNet conducted a cohort study of a gastroenteritis outbreak amongst people that had dined at a Port Macquarie restaurant. Illness was strongly associated with oyster consumption, with all cases having eaten oysters from the same lease (RR undefined, p Norovirus was detected in a faecal specimen. Although no pathogen was identified during the environmental investigation, the source oyster lease had been closed just prior to harvesting due to sewage contamination. Australian quality assurance programs do not routinely test oysters for viral contamination that pose a risk to human health. It is recommended that the feasibility of testing oysters for norovirus, particularly after known faecal contamination of oyster leases, be assessed.

  12. Genome-Wide Association Studies of Cancer

    Science.gov (United States)

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  13. Race, Ethnicity, Class and Identity: Implications for Study Abroad

    Science.gov (United States)

    Goldoni, Federica

    2017-01-01

    This study addresses study abroad and second language acquisition. The number of U.S. students studying abroad is increasing. However, students' cultural and linguistic immersion experiences abroad can be disconcerting, challenging their sociocultural identities, values, learning objectives, and expectations. This study employed critical race…

  14. 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].

  15. Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture

    Science.gov (United States)

    Baker, Lauren A.; Kirkpatrick, Brian; Rosa, Guilherme J. M.; Gianola, Daniel; Valente, Bruno; Sumner, Julia P.; Baltzer, Wendy; Hao, Zhengling; Binversie, Emily E.; Volstad, Nicola; Piazza, Alexander; Sample, Susannah J.

    2017-01-01

    Anterior cruciate ligament (ACL) rupture is a common condition that can be devastating and life changing, particularly in young adults. A non-contact mechanism is typical. Second ACL ruptures through rupture of the contralateral ACL or rupture of a graft repair is also common. Risk of rupture is increased in females. ACL rupture is also common in dogs. Disease prevalence exceeds 5% in several dog breeds, ~100 fold higher than human beings. We provide insight into the genetic etiology of ACL rupture by genome-wide association study (GWAS) in a high-risk breed using 98 case and 139 control Labrador Retrievers. We identified 129 single nucleotide polymorphisms (SNPs) within 99 risk loci. Associated loci (P<5E-04) explained approximately half of phenotypic variance in the ACL rupture trait. Two of these loci were located in uncharacterized or non-coding regions of the genome. A chromosome 24 locus containing nine genes with diverse functions met genome-wide significance (P = 3.63E-0.6). GWAS pathways were enriched for c-type lectins, a gene set that includes aggrecan, a gene set encoding antimicrobial proteins, and a gene set encoding membrane transport proteins with a variety of physiological functions. Genotypic risk estimated for each dog based on the risk contributed by each GWAS locus showed clear separation of ACL rupture cases and controls. Power analysis of the GWAS data set estimated that ~172 loci explain the genetic contribution to ACL rupture in the Labrador Retriever. Heritability was estimated at 0.48. We conclude ACL rupture is a moderately heritable highly polygenic complex trait. Our results implicate c-type lectin pathways in ACL homeostasis. PMID:28379989

  16. Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture.

    Directory of Open Access Journals (Sweden)

    Lauren A Baker

    Full Text Available Anterior cruciate ligament (ACL rupture is a common condition that can be devastating and life changing, particularly in young adults. A non-contact mechanism is typical. Second ACL ruptures through rupture of the contralateral ACL or rupture of a graft repair is also common. Risk of rupture is increased in females. ACL rupture is also common in dogs. Disease prevalence exceeds 5% in several dog breeds, ~100 fold higher than human beings. We provide insight into the genetic etiology of ACL rupture by genome-wide association study (GWAS in a high-risk breed using 98 case and 139 control Labrador Retrievers. We identified 129 single nucleotide polymorphisms (SNPs within 99 risk loci. Associated loci (P<5E-04 explained approximately half of phenotypic variance in the ACL rupture trait. Two of these loci were located in uncharacterized or non-coding regions of the genome. A chromosome 24 locus containing nine genes with diverse functions met genome-wide significance (P = 3.63E-0.6. GWAS pathways were enriched for c-type lectins, a gene set that includes aggrecan, a gene set encoding antimicrobial proteins, and a gene set encoding membrane transport proteins with a variety of physiological functions. Genotypic risk estimated for each dog based on the risk contributed by each GWAS locus showed clear separation of ACL rupture cases and controls. Power analysis of the GWAS data set estimated that ~172 loci explain the genetic contribution to ACL rupture in the Labrador Retriever. Heritability was estimated at 0.48. We conclude ACL rupture is a moderately heritable highly polygenic complex trait. Our results implicate c-type lectin pathways in ACL homeostasis.

  17. Association of heterotrophic bacteria with aggregated Arthrospira platensis exopolysaccharides: implications in the induction of axenic cultures.

    Science.gov (United States)

    Shiraishi, Hideaki

    2015-01-01

    Inducing an axenic culture of the edible cyanobacterium Arthrospira (Spirulina) platensis using differential filtration alone is never successful; thus, it has been thought that, in non-axenic cultures, a portion of contaminating bacteria is strongly associated with Arthrospira cells. However, examination of the behavior of these bacteria during filtration revealed that they were not associated with Arthrospira cells but with aggregates of exopolysaccharides present in the medium away from the Arthrospira cells. Based on this finding, a rapid and reliable method for preparing axenic trichomes of A. platensis was established. After verifying the axenicity of the resulting trichomes on enriched agar plates, they were individually transferred to fresh sterile medium using a handmade tool, a microtrowel, to produce axenic cultures. With this technique, axenic cultures of various A. platensis strains were successfully produced. The technique described in this study is potentially applicable to a wider range of filamentous cyanobacteria.

  18. Community College Study Abroad: Implications for Student Success

    Science.gov (United States)

    Raby, Rosalind Latiner; Rhodes, Gary M.; Biscarra, Albert

    2014-01-01

    The aim of this research is to explore whether participation in study abroad by community college students impacts levels of engagement and if there is a connection between studying abroad and academic achievement. While university-level studies have a history in exploring these questions, the same is not true for community colleges. The…

  19. Cartilage lesions in feline stifle joints - Associations with articular mineralizations and implications for osteoarthritis.

    Science.gov (United States)

    Leijon, Alexandra; Ley, Charles J; Corin, Antonia; Ley, Cecilia

    2017-10-01

    Feline stifle osteoarthritis (OA) is common, however little is known about the early stages of the disease. Furthermore, the importance of small articular mineralizations (AMs) in feline stifle OA is controversial. This study aimed to describe microscopic articular cartilage lesions and to investigate associations between cartilage lesions and AMs, synovitis, osteochondral junction findings and subchondral bone sclerosis. Stifles of 29 cats, aged 1-23years and euthanized for reasons other than stifle disease, were examined. Osteochondral tissue and synovial membrane changes were histologically evaluated. Computed tomography and radiography were used for evaluation of AMs. Global cartilage scores (GCS, n=28) were summarized and joints assigned a histologic OA grade. Minimal to mild histologic OA was seen in 24/28 joints. In 27/29 joints tibial cartilage lesions were seen, whereas femoral lesions were only seen in two joints. Articular mineralizations were detected in 13/29 joints, 11 were small and 12 were located entirely within the medial meniscus. There was no association between GCS and presence or volumes of AMs. However, higher GCS was associated with synovitis (P=0.001) and age (P<0.0005). Presence of subchondral bone sclerosis (P<0.0005) and disruption of the calcified cartilage or tidemark (P<0.0005) were associated with cartilage lesions. We conclude that the tibial articular cartilage is a common location for histologic OA lesions in cats. Synovitis and changes in the subchondral bone and calcified cartilage may be important in the pathogenesis of feline stifle OA, whereas small AMs likely represent incidental findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition.

    Science.gov (United States)

    Kavle, Justine A; Flax, Valerie L; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods. © 2015 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

  1. Association between the serotonin transporter and cytokines: Implications for the pathophysiology of bipolar disorder.

    Science.gov (United States)

    Chou, Yuan-Hwa; Hsieh, Wen-Chi; Chen, Li-Chi; Lirng, Jiing-Feng; Wang, Shyh-Jen

    2016-02-01

    Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD. Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay. SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1β, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD. While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    Science.gov (United States)

    Espinoza, Mario; Cappo, Mike; Heupel, Michelle R; Tobin, Andrew J; Simpfendorfer, Colin A

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches.

  3. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    Directory of Open Access Journals (Sweden)

    Mario Espinoza

    Full Text Available Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS along the entire Great Barrier Reef Marine Park (GBRMP over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances. Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation

  4. Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS.

    Science.gov (United States)

    Whyte, Michael P; Griffith, Malachi; Trani, Lee; Mumm, Steven; Gottesman, Gary S; McAlister, William H; Krysiak, Kilannin; Lesurf, Robert; Skidmore, Zachary L; Campbell, Katie M; Rosman, Ilana S; Bayliss, Susan; Bijanki, Vinieth N; Nenninger, Angela; Van Tine, Brian A; Griffith, Obi L; Mardis, Elaine R

    2017-08-01

    Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient's mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using four algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS

  5. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Proteomic studies associated with Parkinson's disease.

    Science.gov (United States)

    Kasap, Murat; Akpinar, Gurler; Kanli, Aylin

    2017-03-01

    Parkinson's disease (PD) is an insidious disorder affecting more than 1-2% of the population over the age of 65. Understanding the etiology of PD may create opportunities for developing new treatments. Genomic and transcriptomic studies are useful, but do not provide evidence for the actual status of the disease. Conversely, proteomic studies deal with proteins, which are real time players, and can hence provide information on the dynamic nature of the affected cells. The number of publications relating to the proteomics of PD is vast. Therefore, there is a need to evaluate the current proteomics literature and establish the connections between the past and the present to foresee the future. Areas covered: PubMed and Web of Science were used to retrieve the literature associated with PD proteomics. Studies using human samples, model organisms and cell lines were selected and reviewed to highlight their contributions to PD. Expert commentary: The proteomic studies associated with PD achieved only limited success in facilitating disease diagnosis, monitoring and progression. A global system biology approach using new models is needed. Future research should integrate the findings of proteomics with other omics data to facilitate both early diagnosis and the treatment of PD.

  7. 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.

  8. effective study habits in educational sector: counselling implications.

    African Journals Online (AJOL)

    Emeka Egbochuku

    attitudes towards learning, one of the reasons for having a good study programme in the school environment. Providing a study programme is an important strategy for school management. In actual fact it helps a child to make intelligent choice and adjustment. As we all know, adolescence is a turbulent stage of growth and.

  9. Implications of Common Core State Standards on the Social Studies

    Science.gov (United States)

    Kenna, Joshua L.; Russell, William B., III.

    2014-01-01

    Social studies teachers have often been on the outside looking in during much of the era billed as the standards-based educational reform (SBER), but with the adoption and implementation of the Common Core State Standards (CCSS), social studies teachers seem to have been invited back inside. Yet, how will the standards impact social studies…

  10. Association of bacteria with marine invertebrates: Implications for ballast water management

    Digital Repository Service at National Institute of Oceanography (India)

    Khandeparker, L.; Anil, A.C.

    phytoplankton, and their implications for ballast water risk management. Marine Pollution Bulletin (In press) Colwell RR (1996) Global climate and infectious disease: the cholera paradigm. Science 274: 2025- 2031 Conway DVP, White RG, Hugues-Dit-Ciles J... that threaten naturally evolved biodiversity, the consequences of which are increasingly being realized (Anil et al. 2002). The unintentional introduction of disease causing pathogenic bacteria, which are transported from the place of origin or formed during...

  11. Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease.

    Science.gov (United States)

    Burns, J C; Shimizu, C; Shike, H; Newburger, J W; Sundel, R P; Baker, A L; Matsubara, T; Ishikawa, Y; Brophy, V A; Cheng, S; Grow, M A; Steiner, L L; Kono, N; Cantor, R M

    2005-08-01

    Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(-589)T allele (P=0.03). Asymmetric transmission of the IL-4 C(-589)T was replicated in a second, independent cohort of 60 trios (P=0.05, combined P=0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCepsilonR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility.

  12. Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Caroline Perronnet

    2010-01-01

    Full Text Available Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD, which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression.

  13. Emotion regulatory function of parent attention to child pain and associated implications for parental pain control behaviour.

    Science.gov (United States)

    Vervoort, Tine; Trost, Zina; Sütterlin, Stefan; Caes, Line; Moors, Agnes

    2014-08-01

    We investigated the function of parental attention to child pain in regulating parental distress and pain control behaviour when observing their child performing a painful (cold pressor) task (CPT); we also studied the moderating role of parental state anxiety. Participants were 62 schoolchildren and one of their parents. Parental attention towards or away from child pain (ie, attend to pain vs avoid pain) was experimentally manipulated during a viewing task pairing unfamiliar children's neutral and pain faces. Before and after the viewing task, parental distress regulation was assessed by heart rate (HR) and heart rate variability (HRV). In a subsequent phase, parents observed their own child perform a CPT task, allowing assessment of parental pain control behaviour (indexed by latency to stop their child's CPT performance) and parental distress, which was assessed via self-report before and after observation of child CPT performance. Eye tracking during the viewing task and self-reported attention to own child's pain confirmed successful attention manipulation. Further, findings indicated that the effect of attentional strategy on parental emotion regulation (indexed by HR, self-report) and pain control behaviour depended on parents' state anxiety. Specifically, whereas low anxious parents reported more distress and demonstrated more pain control behaviour in the Attend to Pain condition, high anxious parents reported more distress and showed more pain control behaviour in the Avoid Pain condition. This inverse pattern was likewise apparent in physiological distress indices (HR) in response to the initial viewing task. Theoretical/clinical implications and further research directions are discussed. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  14. SYSTEMIC INFLAMMATION IMPAIRS ATTENTION AND COGNITIVE FLEXIBILITY BUT NOT ASSOCIATIVE LEARNING IN AGED RATS: Possible Implications for Delirium

    Directory of Open Access Journals (Sweden)

    Deborah J Culley

    2014-06-01

    Full Text Available Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 ug/kg or saline and were tested on the attentional shifting task (AST, an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly 3-fold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

  15. Identification of cancer risk and associated behaviour: implications for social marketing campaigns for cancer prevention.

    Science.gov (United States)

    Kippen, Rebecca; James, Erica; Ward, Bernadette; Buykx, Penny; Shamsullah, Ardel; Watson, Wendy; Chapman, Kathy

    2017-08-17

    Community misconception of what causes cancer is an important consideration when devising communication strategies around cancer prevention, while those initiating social marketing campaigns must decide whether to target the general population or to tailor messages for different audiences. This paper investigates the relationships between demographic characteristics, identification of selected cancer risk factors, and associated protective behaviours, to inform audience segmentation for cancer prevention social marketing. Data for this cross-sectional study (n = 3301) are derived from Cancer Council New South Wales' 2013 Cancer Prevention Survey. Descriptive statistics and logistic regression models were used to investigate the relationship between respondent demographic characteristics and identification of each of seven cancer risk factors; demographic characteristics and practice of the seven 'protective' behaviours associated with the seven cancer risk factors; and identification of cancer risk factors and practising the associated protective behaviours, controlling for demographic characteristics. More than 90% of respondents across demographic groups identified sun exposure and smoking cigarettes as moderate or large cancer risk factors. Around 80% identified passive smoking as a moderate/large risk factor, and 40-60% identified being overweight or obese, drinking alcohol, not eating enough vegetables and not eating enough fruit. Women and older respondents were more likely to identify most cancer risk factors as moderate/large, and to practise associated protective behaviours. Education was correlated with identification of smoking as a moderate/large cancer risk factor, and with four of the seven protective behaviours. Location (metropolitan/regional) and country of birth (Australia/other) were weak predictors of identification and of protective behaviours. Identification of a cancer risk factor as moderate/large was a significant predictor for five out

  16. Implications of Queer Theory for the Study of Religion and Gender: Entering the Third Decade

    Directory of Open Access Journals (Sweden)

    Claudia Schippert

    2011-08-01

    Full Text Available This essay explores the conceptual and contextual shifts in queer theoretical work as it is entering into its third decade of articulation. The essay reviews important recent themes in, and examines implications of, queer theoretical scholarship for the study of religion and gender. I suggest that among the implications are a (more undisciplined study of religion (and secularism that takes seriously shifts resulting from transnational and diasporic queer scholarship, shifts in conceptions of agency and resistance resulting from analyses  and critique of homonormative positions, and can critically intervene in homonationalism and Islamophobia.

  17. Association Between Sleep Timing, Obesity, Diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Cohort Study.

    Science.gov (United States)

    Knutson, Kristen L; Wu, Donghong; Patel, Sanjay R; Loredo, Jose S; Redline, Susan; Cai, Jianwen; Gallo, Linda C; Mossavar-Rahmani, Yasmin; Ramos, Alberto R; Teng, Yanping; Daviglus, Martha L; Zee, Phyllis C

    2017-04-01

    Recent studies implicate inadequate sleep duration and quality in metabolic disease. Fewer studies have examined the timing of sleep, which may be important because of its potential impact on circadian rhythms of metabolic function. We examined the association between sleep timing and metabolic risk among Hispanic/Latino adults. Cross-sectional data from community-based study of 13429 participants aged 18-74 years. People taking diabetic medications were excluded. Sleep timing was determined from self-reported bedtimes and wake times. Chronotype was defined as the midpoint of sleep on weekends adjusted for sleep duration on weekdays. Other measurements included body mass index (BMI), fasting glucose levels, estimated insulin resistance (HOMA-IR), glucose levels 2 hours post oral glucose ingestion, and hemoglobin A1c. Survey linear regression models tested associations between sleep timing and metabolic measures. Analyses were stratified by diabetes status and age-group when significant interactions were observed. Among participants with diabetes, fasting glucose levels were positively associated with bedtime (approximately +3%/hour later, p sleep (approximately +2%/hour later, p sleep (+1.5%/hr later, p sleep timing was associated with lower BMI, lower fasting glucose, and lower HbA1c, but the opposite association was observed among older participants. Later sleep timing was associated with higher estimated insulin resistance across all groups. Some associations between sleep timing and metabolic measures may be age-dependent.

  18. Study of the factors associated with substance use in adolescence using Association Rules.

    Science.gov (United States)

    García, Elena Gervilla; Blasco, Berta Cajal; López, Rafael Jiménez; Pol, Alfonso Palmer

    2010-01-01

    The aim of this study is to analyse the factors related to the use of addictive substances in adolescence using association rules, descriptive tools included in Data Mining. Thus, we have a database referring to the consumption of addictive substances in adolescence, and use the free distribution program in the R arules package (version 2.10.0). The sample was made up of 9,300 students between the ages of 14 and 18 (47.1% boys and 52.9% girls) with an average age of 15.6 (SE=1.2). The adolescents answered an anonymous questionnaire on personal, family and environmental risk factors related to substance use. The best rules obtained with regard to substance use relate the consumption of alcohol to perceived parenting style and peer consumption (confidence = 0.8528), the use of tobacco (smoking), cannabis and cocaine to perceived parental action and illegal behaviour (confidence = 0.8032, 0.8718 and 1.0000, respectively), and the use of ecstasy to peer consumption (confidence = 1.0000). In general, the association rules show in a simple manner the relationship between certain patterns of perceived parental action, behaviours that deviate from social behavioural norms, peer consumption and the use of different legal and illegal drugs of abuse in adolescence. The implications of the results obtained are described, together with the usefulness of this new methodology of analysis.

  19. Chronic heart failure in Japan: Implications of the CHART studies

    Directory of Open Access Journals (Sweden)

    Nobuyuki Shiba

    2008-02-01

    Full Text Available Nobuyuki Shiba, Hiroaki ShimokawaDepartment of Cardiovascular Medicine, Department of Evidence-Based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai City, JapanAbstract: The prognosis of patients with chronic heart failure (CHF still remains poor, despite the recent advances in medical and surgical treatment. Furthermore, CHF is a major public health problem in most industrialized countries where the elderly population is rapidly increasing. Although the prevalence and mortality of CHF used to be relatively low in Japan, the disorder has been markedly increasing due to the rapid aging of the society and the Westernization of lifestyle that facilitates the development of coronary artery disease. The Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART-1 study was one of the largest cohorts in Japan. The study has clarified the characteristics and prognosis of Japanese patients with CHF, demonstrating that their prognosis was similarly poor compared with those in Western countries. However, we still need evidence for the prevention and treatment of CHF based on the large cohort studies or randomized treatment trials in the Japanese population. Since the strategy for CHF management is now changing from treatment to prevention, a larger-size prospective cohort, called the CHART-2 study, has been initiated to evaluate the risk factors of CHF in Japan. This review summarizes the current status of CHF studies in Japan and discusses their future perspectives.Keywords: heart failure, aging, Japanese

  20. Implications of Early Sociocultural Adaptation for Study Abroad Students

    Science.gov (United States)

    Savicki, Victor

    2010-01-01

    Helping students and others facing the task of adapting to a foreign culture is becoming ever more pressing. The current study delves into sociocultural adaptation in order to clarify that process and provide information useful for educators, trainers, coaches, and others guiding those facing a sojourn in a foreign culture. A question to be…

  1. Research. Homework Experiments in Social Studies: Implications for Teaching.

    Science.gov (United States)

    Foyle, Harvey C.; Bailey, Gerald D.

    1988-01-01

    Reviews research to answer under what conditions, if any, does homework make a difference in student achievement. Provides a brief history of the homework debate. Reviews 84 homework experiments conduced between 1904 and 1984. Concludes that most studies found homework beneficial. (JDH)

  2. Social Constructionism and Ludology: Implications for the Study of Games

    Science.gov (United States)

    Montola, Markus

    2012-01-01

    This article combines the paradigm of social constructionism with the developing field of ludology. As games are intersubjective meaning-making activities, their study requires understanding of the nature of social constructions, and how such constructions are produced and interpreted: The formalist nature of ludological core concepts such as game…

  3. Technological Revolutions: Some Implications for the Social Studies

    Science.gov (United States)

    Kane, Paul W.

    1975-01-01

    The advantages of a social studies program, centered on the various technological revolutions -- human, agricultural, urban, industrial, and humanizing -- are a multi-disciplinary approach, the use of inquiry skills, wide coverage of history and nations through a framework of concepts, and discussion of ethnocentrism. (JH)

  4. Savant Syndrome: Case Studies, Hypotheses, and Implications for Special Education.

    Science.gov (United States)

    Cheatham, Susan Klug; And Others

    1995-01-01

    The concept of savant syndrome, encompassing those individuals historically known as "idiot savants," is reviewed. Case studies demonstrating special abilities in the areas of calendar calculating, musical ability, artistic talent, memorization, mathematical skills, mechanical achievement, and fine sensory discrimination are discussed,…

  5. Ethical implications of using the minipig in regulatory toxicology studies

    DEFF Research Database (Denmark)

    Webster, John; Bollen, Peter; Grimm, Herwig

    2010-01-01

    circumstances in which minipigs can become the species of choice, e.g. in "reproduction toxicology" trials. We also recognise their potential in new studies designed to improve the implementation of the "three R's" and any sound proposals for specific developments in this regard are to be encouraged. 1...

  6. The Implications of Service-Learning for Technology Studies.

    Science.gov (United States)

    Folkestad, James E.; Senior, Bolivar A.; DeMirana, Michael A.

    2002-01-01

    A "toys for tots" service-learning experience integrated into an industrial technology management course required development and planning using a process planning and costing model and work with a variety of stakeholders including an Even-Start learning center. Challenges include the lack of service-learning precedent in technology studies and…

  7. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-05

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

    Directory of Open Access Journals (Sweden)

    Romoser WS

    2011-09-01

    Full Text Available William S Romoser1, Marco Neira Oviedo1, Kriangkrai Lerdthusnee2, Lisa A Patrican3, Michael J Turell4, David J Dohm4, Kenneth J Linthicum5, Charles L Bailey61Department of Biomedical Sciences, College of Osteopathic Medicine, Tropical Disease Institute, Ohio University, Athens, Ohio, USA; 2Department of Entomology, Faculty of Agriculture, Kasetsart University, Bangkok, Thailand; 3Infectious Disease Division, National Center for Medical Intelligence, Fort Detrick, Frederick, Maryland, USA; 4Department of Vector Assessment, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA; 5Center for Medical, Agricultural, and Veterinary Entomology, United States Department of Agriculture – Agricultural Research Service, Gainesville, Florida, USA; 6National Center for Biodefense and Infectious Disease, School of Systems Biology, College of Science, George Mason University, Manassas, Virginia, USABackground: Endemic/enzootic maintenance mechanisms like vertical transmission (pathogen passage from infected adults to their offspring are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV may be maintained by vertical transmission in ground-pool mosquitoes such as Aedes mcintoshi. RVFV can cause serious morbidity and mortality in humans and livestock. Past epidemics/epizootics have occurred in sub-Saharan Africa but, since the late 1970s, RVFV has also appeared in North Africa and the Middle East. Preliminary results revealed RVFV-infected eggs in Ae. mcintoshi after virus injection into the hemocoel after the first of two blood meals, justifying further study.Methods: Mosquitoes were collected from an artificially flooded water-catching depression along a stream in Kenya, shipped live to the USA, and studied using an immunocytochemical method for RVFV-antigen localization in mosquito sections.Results and conclusion: After virus injection into the

  9. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  10. Contrasting movements and connectivity of reef-associated sharks using acoustic telemetry: implications for management.

    Science.gov (United States)

    Espinoza, Mario; Lédée, Elodie J I; Simpfendorfer, Colin A; Tobin, Andrew J; Heupel, Michelle R

    2015-12-01

    Understanding the efficacy of marine protected areas (MPAs) for wide-ranging predators is essential to designing effective management and conservation approaches. The use of acoustic monitoring and network analysis can improve our understanding of the spatial ecology and functional connectivity of reef-associated species, providing a useful approach for reef-based conservation planning. This study compared and contrasted the movement and connectivity of sharks with different degrees of reef association. We examined the residency, dispersal, degree of reef connectivity, and MPA use of grey reef (Carcharhinus amblyrhynchos), silvertip (C. albimarginatus), and bull (C. leucas) sharks monitored in the central Great Barrier Reef (GBR). An array of 56 acoustic receivers was used to monitor shark movements on 17 semi-isolated reefs. Carcharhinus amblyrhynchos and C. albimarginatus were detected most days at or near their tagging reef. However, while C. amblyrhynchos spent 80% of monitoring days in the array, C. albimarginatus was only detected 50% of the time. Despite both species moving similar distances (sharks like C. leucas, a combination of spatial planning and other alternative measures is critical. Our findings demonstrate that acoustic monitoring can serve as a useful platform for designing more effective MPA networks for reef predators displaying a range of movement patterns.

  11. Genetic diversity of Escherichia coli isolates in irrigation water and associated sediments: implications for source tracking.

    Science.gov (United States)

    Lu, Lingeng; Hume, Michael E; Sternes, Keith L; Pillai, Suresh D

    2004-11-01

    Identifying the sources of fecal contaminants in surface water bodies such as rivers and lakes is of significant importance for environmental quality, food safety and regulatory purposes. Current DNA library-based source tracking approaches rely on the comparison of the genetic relatedness among the fecal contaminants. The objective of this study was to determine the genetic relatedness of Escherichia coli isolated from irrigation water and associated sediments using pulse field gel electrophoresis (PFGE) and to evaluate the genetic stability of the E. coli PFGE patterns. The isolates were obtained over a 4-month period from specific locations within irrigation canals and sediments associated with the Rio Grande River along the Texas-Mexico border. Fifty E. coli isolates were genotyped using PFGE. Different E. coli genotypes were identified among samples collected in 11 different locations. Some isolates obtained over successive months showed similar genotypic patterns. In the laboratory experiment, the PFGE pattern of one E. coli strain changed during survival in irrigation water. The genetic relatedness of this strain changed from >95% to <83% over 8-week survival. These results imply that PFGE is of such extreme resolution that it may be a challenging task to rely solely on a PFGE-based source tracking DNA fingerprint library for large watersheds.

  12. Accessibility of humic-associated Fe to a microbial siderophore: implications for bioavailability.

    Science.gov (United States)

    Kuhn, Keshia M; Maurice, Patricia A; Neubauer, Elisabeth; Hofmann, Thilo; von der Kammer, Frank

    2014-01-21

    Microorganisms in aerobic, circum-neutral environments are challenged to acquire sufficient nutrient Fe due to low solubilities of Fe oxides. To overcome this challenge, many aerobic microbes produce low molecular weight (MW) organic ligands, or siderophores, with extremely high Fe-binding affinities. This research expands the existing understanding of siderophore-mediated Fe acquisition from minerals by examining the effects of the siderophore desferrioxamine B (DFOB) on Fe removal from aquatic humic substances (XAD-8-isolated) and other organic matter (OM) isolates (reverse osmosis, RO; and "transphilic", XAD-4) from several rivers including the Suwannee River (GA, USA). Analysis of samples by asymmetrical flow field-flow fractionation (AsFlFFF) with in-line ICP-MS and UV-vis detectors showed that Fe was naturally abundant and primarily associated with intermediate to high MW OM. An excess of DFOB (relative to naturally present Fe) removed ∼ 75% of Fe and shifted the OM MW distribution to lower MWs, perhaps due to removal of "bridging" Fe, although additional mechanistic study of MW shifts is needed. Removal of other OM-associated metals (e.g., Al, Cu, Zn) by DFOB was minimal for all but a few samples. Fe bound to humic substances and other more "transphilic" organic components therefore should be considered readily bioavailable to aerobic, siderophore-producing microorganisms.

  13. The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications.

    Science.gov (United States)

    Felger, Jennifer C

    Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. Similar relationships between alterations in dopamine-relevant corticostriatal reward circuitry and symptoms of anhedonia and psychomotor slowing have also been observed in patients with major depression who exhibit increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. Of note, these inflammation-associated depressive symptoms are often difficult to treat in patients with medical illnesses or major depression. Furthermore, a wealth of literature suggests that inflammation can decrease dopamine synthesis, packaging, and release, thus sabotaging or circumventing the efficacy of standard antidepressant treatments. Herein, the mechanisms by which inflammation and cytokines affect dopamine neurotransmission are discussed, which may provide novel insights into treatment of inflammation-related behavioral symptoms that contribute to an inflammatory malaise.

  14. Oral implications of the vegan diet: observational study.

    Science.gov (United States)

    Laffranchi, L; Zotti, F; Bonetti, S; Dalessandri, D; Fontana, P

    2010-01-01

    The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.

  15. VHB-JOURQUAL2: Method, Results, and Implications of the German Academic Association for Business Research's Journal Ranking

    Directory of Open Access Journals (Sweden)

    Ulf Schrader

    2009-12-01

    Full Text Available VHB-JOURQUAL represents the official journal ranking of the German Academic Association for Business Research. Since its introduction in 2003, the ranking has become the most influential journal evaluation approach in German-speaking countries, impacting several key managerial decisions of German, Austrian, and Swiss business schools. This article reports the methodological approach of the ranking’s second edition. It also presents the main results and additional analyses on the validity of the rating and the underlying decision processes of the respondents. Selected implications for researchers and higher-education institutions are discussed.

  16. Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation

    NARCIS (Netherlands)

    Huang, Jie; Sabater-Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David; Shin, So-Youn; Ding, Jingzhong; Baumert, Jens; Oudot-Mellakh, Tiphaine; Folkersen, Lasse; Johnson, Andrew D.; Smith, Nicholas L.; Williams, Scott M.; Ikram, Mohammad A.; Kleber, Marcus E.; Becker, Diane M.; Vinh Truong, [No Value; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; Moore, Jason H.; Williams, Frances M. K.; Dehghan, Abbas; Silbernagel, Guenther; Schrijvers, Elisabeth M. C.; Smith, Shelly; Karakas, Mahir; Tofler, Geoffrey H.; Silveira, Angela; Navis, Gerjan J.; Lohman, Kurt; Chen, Ming-Huei; Peters, Annette; Goel, Anuj; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Lundmark, Per; Psaty, Bruce M.; Strawbridge, Rona J.; Boehm, Bernhard O.; Carter, Angela M.; Meisinger, Christa; Peden, John F.; Bis, Joshua C.; McKnight, Barbara; Ohrvik, John; Taylor, Kent; Franzosi, Maria Grazia; Seedorf, Udo; Collins, Rory; Franco-Cereceda, Anders; Syvaenen, Ann-Christine; Goodall, Alison H.; Yanek, Lisa R.; Cushman, Mary; Mueller-Nurasyid, Martina; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Kooner, Jaspal S.; Hofman, Albert; Danesh, John; Clarke, Robert; Meigs, James B.; Kathiresan, Sekar; Reilly, Muredach P.; Klopp, Norman; Harris, Tamara B.; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Watkins, Hugh; Spector, Timothy D.; Becker, Lewis C.; Tracy, Russell P.; Maerz, Winfried; Uitterlinden, Andre G.; Eriksson, Per; Cambien, Francois; Morange, Pierre-Emmanuel; Koenig, Wolfgang; Soranzo, Nicole; van der Harst, Pim; Liu, Yongmei; O'Donnell, Christopher J.; Hamsten, Anders

    2012-01-01

    We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19

  17. Clinical, Diagnostic, and Therapeutic Implications in Psoriasis Associated With Cardiovascular Disease.

    Science.gov (United States)

    Bonanad, C; González-Parra, E; Rivera, R; Carrascosa, J M; Daudén, E; Olveira, A; Botella-Estrada, R

    2017-11-01

    In recent years the concept of psoriasis as a systemic disease has gained acceptance due to its association with numerous comorbid conditions, particularly atherosclerosis and cardiovascular disease. Several studies have shown that patients with psoriasis, especially younger patients and those with more severe forms of psoriasis or with psoriatic arthritis, have a higher prevalence of risk factors and metabolic syndrome, as well as an increased risk of major cardiovascular events such as myocardial infarction, cerebrovascular disease, and peripheral arterial disease. Furthermore, it remains unclear which of the current treatments might be more effective in reducing cardiovascular risk in these patients. It is therefore important for dermatologists to be aware of this increased risk, to be able to detect modifiable risk factors early and, when appropriate, refer patients to other specialists for the prevention of major cardiovascular events. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Close packing effects on clean and dirty snow albedo and associated climatic implications

    Science.gov (United States)

    He, Cenlin; Takano, Yoshi; Liou, Kuo-Nan

    2017-04-01

    Previous modeling of snow albedo, a key climate feedback parameter, follows the independent scattering approximation (ISA) such that snow grains are considered as a number of separate units with distances longer than wavelengths. Here we develop a new snow albedo model for widely observed close-packed snow grains internally mixed with black carbon (BC) and demonstrate that albedo simulations match closer to observations. Close packing results in a stronger light absorption for clean and BC-contaminated snow. Compared with ISA, close packing reduces pure snow albedos by up to 0.05, whereas it enhances BC-induced snow albedo reduction and associated surface radiative forcing by up to 15% (20%) for fresh (old) snow, with larger enhancements for stronger structure packing. Finally, our results suggest that BC-snow albedo forcing and snow albedo feedback (climate sensitivity) are underestimated in previous modeling studies, making snow close packing consideration a necessity in climate modeling and analysis.

  19. Vestibular implants studied in animal models: clinical and scientific implications.

    Science.gov (United States)

    Lewis, Richard F

    2016-12-01

    Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage. Copyright © 2016 the American Physiological Society.

  20. Implication of Powdered Milk in Staphylococcal Intoxication: A Case Study

    Directory of Open Access Journals (Sweden)

    Nicolae Mocuţa

    2015-11-01

    Full Text Available Foodborne diseases are diseases and acute evolution occurs mostly with digestive signs to more consumers of food contaminated with specific pathogens. Staph food poisoning due to consumption of contaminated food is staph enterotoxins enterotoxogeni producing certain temperature conditions. Enterotoxins are 7 types, depending on the type of contaminant stafiloc strain, so enterotoxin detection and diagnosis of the disease is relatively difficult. In the study examined the evolution of an episode of Foodborne staphylococcus in a school unit where 35 children fell ill between 252 consumers of milk reconstituted from milk powder. Duration of evolution was 4-10 hours.

  1. Reassessing the importance of 'lost pleasure' associated with smoking cessation: implications for social welfare and policy.

    Science.gov (United States)

    Pechacek, Terry Frank; Nayak, Pratibha; Slovic, Paul; Weaver, Scott R; Huang, Jidong; Eriksen, Michael P

    2017-11-28

    Benefit-cost analyses of tobacco regulations include estimates of the informed choice of smokers to continue smoking. Few studies have focused on subjective feelings associated with continued smoking. This study estimates how smoker discontent and regret relate to risk perceptions and health concerns. We analysed data from a 2015 nationally representative, online survey of 1284 US adult current smokers. Information was collected on regret, intention to quit, perceived addiction, risk perceptions and health concerns. Multivariate logistic regression adjusting for sociodemographics and health status was used to examine factors associated with smoker discontent. More than 80% of current smokers report high (22.5%) or very high (59.8%) discontent due to inability to quit, perceived addiction and regret about having started to smoke. Higher levels of discontent did not vary significantly by sex, age, race/ethnicity, education or income (adjusted odds ratios (AORs) 0.5-1.2). Compared with the smokers expressing low (5.9%) or very low (3.6%) discontent, those expressing higher levels of discontent perceived their health status as fair/poor (AOR=2.3), worried most of the time about lung cancer (AOR=4.6) and felt they were more likely to develop lung cancer in the future (AOR=5.1). The proportion of smokers who might be characterised as having a preference to continue smoking are greatly outnumbered by addicted, discontent and concerned smokers who want to quit and regret ever having started to smoke. These discontent smokers could have a substantial net welfare gain if new regulations helped them escape their concerns about the health effects from continuing smoking. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Prevalence and associated factors of Schistosomiasis among children in Yemen: implications for an effective control programme.

    Directory of Open Access Journals (Sweden)

    Hany Sady

    Full Text Available Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen.Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤ 10 years (P<0.05. Multivariate analysis confirmed that presence of other infected family member (P<0.001, low household monthly income (P = 0.003, using unsafe sources for drinking water (P = 0.003, living nearby stream/spring (P = 0.006 and living nearby pool/pond (P = 0.002 were the key factors significantly associated with schistosomiasis among these children.This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused by schistosomiasis. Screening and treating other infected

  3. KLHL7 promotes TUT1 ubiquitination associated with nucleolar integrity: Implications for retinitis pigmentosa.

    Science.gov (United States)

    Kim, Jaehyun; Tsuruta, Fuminori; Okajima, Tomomi; Yano, Sarasa; Sato, Ban; Chiba, Tomoki

    2017-12-09

    Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. Recent studies have revealed that mutations in klhl7 gene cause several disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be crucial for regulating the protein homeostasis, little is known about its biological functions. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates a vulnerability of nucleolar integrity, followed by a decrease of TUT1 localization in nucleolus. On the other hand, pathogenic KLHL7 mutants, which causes an onset of RP, have little effect on both nucleolar integrity and TUT1 localization. Finally, KLHL7 increases TUT1 ubiquitination levels. Taken together, these results imply that KLHL7 is a novel regulator of nucleolus associated with TUT1 ubiquitination. Our study may provide a valuable information to elucidate a pathogenic mechanism of RP. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Position of the American Dietetic Association: health implications of dietary fiber.

    Science.gov (United States)

    Slavin, Joanne L

    2008-10-01

    It is the position of the American Dietetic Association that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Populations that consume more dietary fiber have less chronic disease. In addition, intake of dietary fiber has beneficial effects on risk factors for developing several chronic diseases. Dietary Reference Intakes recommend consumption of 14 g dietary fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on epidemiologic studies showing protection against cardiovascular disease. Appropriate kinds and amounts of dietary fiber for children, the critically ill, and the very old are unknown. The Dietary Reference Intakes for fiber are based on recommended energy intake, not clinical fiber studies. Usual intake of dietary fiber in the United States is only 15 g/day. Although solubility of fiber was thought to determine physiological effect, more recent studies suggest other properties of fiber, perhaps fermentability or viscosity are important parameters. High-fiber diets provide bulk, are more satiating, and have been linked to lower body weights. Evidence that fiber decreases cancer is mixed and further research is needed. Healthy children and adults can achieve adequate dietary fiber intakes by increasing variety in daily food patterns. Dietary messages to increase consumption of high-fiber foods such as whole grains, legumes, fruits, and vegetables should be broadly supported by food and nutrition professionals. Consumers are also turning to fiber supplements and bulk laxatives as additional fiber sources. Few fiber supplements have been studied for physiological effectiveness, so the best advice is to consume fiber in foods. Look for physiological studies of effectiveness before selecting functional fibers in dietetics practice.

  5. Periodontal implication of bonded and removable retainers: A comparative study

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    Sonali Mondal

    2017-09-01

    Full Text Available The purpose of this study is to compare the periodontal health of the lower anterior teeth retained with the use of removable and fixed retainers. Fifty four cases receiving comprehensive orthodontic treatment in between 10 to 30 years were randomly selected and divided into 2 groups of 27 each. One group was given removable retainers and other was given fixed retainers. The periodontal status of the patients was accessed with bleeding on probing index, Plaque index and Calculus index. The mean plaque index in case of removable retainers at 1st, 3rd and 6th month were 0.5, 1.0 and 1.7 where as in case of fixed retainers that were 1.8, 3.0 and 4.5. The mean dental calculus index in case of removable retainers at 1st, 3rd and 6th month were 0.0, 0.1 and 0.1 where as in case of fixed retainers that were 0.1, 0.9 and 1.8. In conclusion, removable retainers are superior in oral hygiene maintenance, yet the use of fixed retainers cannot be denied.

  6. Performance Implications of Business Model Change: A Case Study

    Directory of Open Access Journals (Sweden)

    Jana Poláková

    2015-01-01

    Full Text Available The paper deals with changes in performance level introduced by the change of business model. The selected case is a small family business undergoing through substantial changes in reflection of structural changes of its markets. The authors used the concept of business model to describe value creation processes within the selected family business and by contrasting the differences between value creation processes before and after the change introduced they prove the role of business model as the performance differentiator. This is illustrated with the use of business model canvas constructed on the basis interviews, observations and document analysis. The two business model canvases allow for explanation of cause-and-effect relationships within the business leading to change in performance. The change in the performance is assessed by financial analysis of the business conducted over the period of 2006–2012 demonstrates changes in performance (comparing development of ROA, ROE and ROS having their lowest levels before the change of business model was introduced, growing after the introduction of the change, as well as the activity indicators with similar developments of the family business. The described case study contributes to the concept of business modeling with the arguments supporting its value as strategic tool facilitating decisions related to value creation within the business.

  7. REELIN-RELATED DISTURBANCES IN DEPRESSION: IMPLICATIONS FOR TRANSLATIONAL STUDIES

    Directory of Open Access Journals (Sweden)

    Hector J eCaruncho

    2016-02-01

    Full Text Available The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone injections. This methodology produces depression-like symptoms in both rats and mice that are reversed by antidepressant treatment. We have reported that corticosterone causes a decrease in the number of reelin-immunopositive cells in the dentate gyrus subgranular zone, where adult hippocampal neurogenesis takes place; that down-regulation of the number of reelin-positive cells closely parallels the development of a depression-like phenotype during repeated corticosterone treatment; that reelin downregulation alters the co-expression of reelin with neuronal nitric oxide synthase; that deficits in reelin might also create imbalances in glutamatergic and GABAergic circuits within the hippocampus and other limbic structures; and that co-treatment with antidepressant drugs prevents both reelin deficits and the development of a depression-like phenotype. We also observed alterations in the pattern of membrane protein clustering in peripheral lymphocytes in animals with low levels of reelin. Importantly, we found parallel changes in membrane protein clustering in depression patients, which differentiated two subpopulations of naïve depression patients that showed a different therapeutic response to antidepressant treatment. Here we review these findings and develop the hypothesis that restoring reelin-related function could represent a novel approach for antidepressant therapies.

  8. Taphonomy for taxonomists: Implications of predation in small mammal studies

    Science.gov (United States)

    Fernández-Jalvo, Yolanda; Andrews, Peter; Denys, Christiane; Sesé, Carmen; Stoetzel, Emmanuelle; Marin-Monfort, Dolores; Pesquero, Dolores

    2016-05-01

    Predation is one of the most recurrent sources of bone accumulations. The influence of predation is widely studied for large mammal sites where humans, acting as predators, produce bone accumulations similar to carnivore accumulations. Similarly, small mammal fossil sites are mainly occupation levels of predators (nests or dens). In both cases, investigations of past events can be compared with present day equivalents or proxies. Chewing marks are sometimes present on large mammal predator accumulations, but digestion traits are the most direct indication of predation, and evidence for this is always present in small mammal (prey) fossil assemblages. Digestion grades and frequency indicates predator type and this is well established since the publication of Andrews (1990). The identification of the predator provides invaluable information for accurate interpretation of the palaeoenvironment. Traditionally, palaeoenvironmental interpretations are obtained from the taxonomic species identified in the site, but rather than providing direct interpretations of the surrounding palaeoenvironment, this procedure actually describes the dietary preferences of the predators and the type of occupation (nests, marking territory, dens, etc). This paper reviews the identification of traits produced by predators on arvicolins, murins and soricids using a method that may be used equally by taxonomists and taphonomists. It aims to provide the "tools" for taxonomists to identify the predator based on their methodology, which is examining the occlusal surfaces of teeth rather than their lateral aspects. This will greatly benefit both the work of taphonomists and taxonomists to recognize signs of predation and the improvement of subsequent palaeoecological interpretations of past organisms and sites by identifying both the prey and the predator.

  9. Comparative Study of University and Polytechnic Graduates in Finland: Implications of Higher Education on Earnings

    Science.gov (United States)

    Xia, Belle Selene; Liitiainen, Elia; Rekola, Mika

    2012-01-01

    This study explores the implications of higher education on earnings in Finland. The challenges as well as opportunities of obtaining a university degree as compared to graduating from polytechnics are evaluated using the REFLEX (The Flexible Professional in the Knowledge Society) data. As a Nordic country, Finland is known for its educated…

  10. Vertical Cities of the Future: Implications for the Study and Teaching of Urban Geography

    Science.gov (United States)

    Berger, Michael L.

    1974-01-01

    The implications of a vertical city, of which the John Hancock Center in Chicago is a prototype, should be considered by teachers of urban studies. Questions clustering around nine discussion areas indicate the kinds of expanded, critical, and interdisciplinary thinking that planning and teaching for the future require. (JH)

  11. Theoretical and Policy Implications of Case Study Findings About Federal Efforts to Improve Public Schools

    Science.gov (United States)

    Gross, Neal

    1977-01-01

    Impediments to educational change were identified in six case studies of major innovative efforts in school systems. Their theoretical and policy implications are examined. The findings suggest the need for a reformulation of the theoretical scheme most frequently used to account for the fate of organizational innovations: overcoming resistance to…

  12. An Invitation to the Ethnographic Study of University Examination Behavior: Concepts, Methodology, and Implications.

    Science.gov (United States)

    Albas, Cheryl; Albas, Dan

    1996-01-01

    Reports a series of ethnographic studies of student behavior concerning examinations, conducted in a Canadian university since the mid-1980s. Describes techniques of data gathering and the link between methodology and theory. Examines implications for higher education, including dealing with students' exam-related stress, factors influencing…

  13. The Use of Postcolonial Theory in Social Studies Education Some Implications

    Science.gov (United States)

    Saada, Najwan Lleeb

    2014-01-01

    In this essay I explain the basic tenets of postcolonial theory and its possible implications for teaching social studies and global issues in American high schools. The use of this theory is becoming increasingly significant, given the growing Islamophobia and Orientalism in the United States, the ongoing uprisings in the Middle East, and the…

  14. Public health implications of environmental noise associated with unconventional oil and gas development.

    Science.gov (United States)

    Hays, Jake; McCawley, Michael; Shonkoff, Seth B C

    2017-02-15

    Modern oil and gas development frequently occurs in close proximity to human populations and increased levels of ambient noise have been documented throughout some phases of development. Numerous studies have evaluated air and water quality degradation and human exposure pathways, but few have evaluated potential health risks and impacts from environmental noise exposure. We reviewed the scientific literature on environmental noise exposure to determine the potential concerns, if any, that noise from oil and gas development activities present to public health. Data on noise levels associated with oil and gas development are limited, but measurements can be evaluated amidst the large body of epidemiology assessing the non-auditory effects of environmental noise exposure and established public health guidelines for community noise. There are a large number of noise dependent and subjective factors that make the determination of a dose response relationship between noise and health outcomes difficult. However, the literature indicates that oil and gas activities produce noise at levels that may increase the risk of adverse health outcomes, including annoyance, sleep disturbance, and cardiovascular disease. More studies that investigate the relationships between noise exposure and human health risks from unconventional oil and gas development are warranted. Finally, policies and mitigation techniques that limit human exposure to noise from oil and gas operations should be considered to reduce health risks. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Studying risk factors associated with Human Leptospirosis

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    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

  16. Satisfaction with Life in Orofacial Pain Disorders: Associations and Theoretical Implications.

    Science.gov (United States)

    Boggero, Ian A; Rojas-Ramirez, Marcia V; de Leeuw, Reny; Carlson, Charles R

    2016-01-01

    To test if patients with masticatory myofascial pain, local myalgia, centrally mediated myalgia, disc displacement, capsulitis/synovitis, or continuous neuropathic pain differed in self-reported satisfaction with life. The study also tested if satisfaction with life was similarly predicted by measures of physical, emotional, and social functioning across disorders. Satisfaction with life, fatigue, affective distress, social support, and pain data were extracted from the medical records of 343 patients seeking treatment for chronic orofacial pain. Patients were grouped by primary diagnosis assigned following their initial appointment. Satisfaction with life was compared between disorders, with and without pain intensity entered as a covariate. Disorder-specific linear regression models using physical, emotional, and social predictors of satisfaction with life were computed. Patients with centrally mediated myalgia reported significantly lower satisfaction with life than did patients with any of the other five disorders. Inclusion of pain intensity as a covariate weakened but did not eliminate the effect. Satisfaction with life was predicted by measures of physical, emotional, and social functioning, but these associations were not consistent across disorders. Results suggest that reduced satisfaction with life in patients with centrally mediated myalgia is not due only to pain intensity. There may be other factors that predispose people to both reduced satisfaction with life and centrally mediated myalgia. Furthermore, the results suggest that satisfaction with life is differentially influenced by physical, emotional, and social functioning in different orofacial pain disorders.

  17. Optimal use of video for teaching the practical implications of studying business information systems

    DEFF Research Database (Denmark)

    Fog, Benedikte; Ulfkjær, Jacob Kanneworff Stigsen; Schlichter, Bjarne Rerup

    not sufficiently reflect the theoretical recommendations of using video optimally in a management education. It did not comply with the video learning sequence as introduced by Marx and Frost (1998). However, it questions if the level of cognitive orientation activities can become too extensive. It finds......The study of business information systems has become increasingly important in the Digital Economy. However, it has been found that students have difficulties understanding the practical implications thereof and this leads to a motivational decreases. This study aims to investigate how to optimize...... the use of video to increase comprehension of the practical implications of studying business information systems. This qualitative study is based on observations and focus group interviews with first semester business students. The findings suggest that the video examined in the case study did...

  18. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials – catheters, ventilator-associated pneumonia, urinary tract infections

    Science.gov (United States)

    Guggenbichler, Josef Peter; Assadian, Ojan; Boeswald, Michael; Kramer, Axel

    2012-01-01

    Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices. Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of up to 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria. The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use

  19. Hierarchical Naive Bayes for genetic association studies.

    Science.gov (United States)

    Malovini, Alberto; Barbarini, Nicola; Bellazzi, Riccardo; de Michelis, Francesca

    2012-01-01

    Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability.

  20. Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs

    Science.gov (United States)

    Mackenzie, Amelia C.L.; Kyle, Diane D.; McGinnis, Lauren A.; Lee, Hyo J.; Aldana, Nathalia; Robinson, Douglas N.; Evans, Janice P.

    2016-01-01

    STUDY HYPOTHESIS Cellular aging of the egg following ovulation, also known as post-ovulatory aging, is associated with aberrant cortical mechanics and actomyosin cytoskeleton functions. STUDY FINDING Post-ovulatory aging is associated with dysfunction of non-muscle myosin-II, and pharmacologically induced myosin-II dysfunction produces some of the same deficiencies observed in aged eggs. WHAT IS KNOWN ALREADY Reproductive success is reduced with delayed fertilization and when copulation or insemination occurs at increased times after ovulation. Post-ovulatory aged eggs have several abnormalities in the plasma membrane and cortex, including reduced egg membrane receptivity to sperm, aberrant sperm-induced cortical remodeling and formation of fertilization cones at the site of sperm entry, and reduced ability to establish a membrane block to prevent polyspermic fertilization. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Ovulated mouse eggs were collected at 21–22 h post-human chorionic gonadotrophin (hCG) (aged eggs) or at 13–14 h post-hCG (young eggs), or young eggs were treated with the myosin light chain kinase (MLCK) inhibitor ML-7, to test the hypothesis that disruption of myosin-II function could mimic some of the effects of post-ovulatory aging. Eggs were subjected to various analyses. Cytoskeletal proteins in eggs and parthenogenesis were assessed using fluorescence microscopy, with further analysis of cytoskeletal proteins in immunoblotting experiments. Cortical tension was measured through micropipette aspiration assays. Egg membrane receptivity to sperm was assessed in in vitro fertilization (IVF) assays. Membrane topography was examined by low-vacuum scanning electron microscopy (SEM). MAIN RESULTS AND THE ROLE OF CHANCE Aged eggs have decreased levels and abnormal localizations of phosphorylated myosin-II regulatory light chain (pMRLC; P = 0.0062). Cortical tension, which is mediated in part by myosin-II, is reduced in aged mouse eggs when compared with

  1. CLINICAL IMPLICATION OF FATTY ACID CHANGES IN PATIENTS WITH PRIMARY GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2015-12-01

    Full Text Available Aim. To study blood levels of non-esterified fatty acids (NEFAs and adenyl nucleotides, and fatty acids levels in lipids of erythrocyte membranes in patients with primary gout associated with arterial hypertension (HT. Material and methods. 175 male patients with primary gout were included in the study. According to 24-hour blood pressure (BP monitoring results patients were split into two groups: 74 patients with normal BP (group 1 and 101 patients with HT (group 2. 29 healthy age-comparable subjects were included into control group. Uric acid, total NEFAs and glycerol blood levels were studied in all patients. Adenyl nucleotides (ATP , ADP and AMP levels were determined in erythrocytes. Higher fatty acid levels were specified in lipids of erythrocyte membranes, including the following acids: myristinic (С14:0, palmitinic (С16:0, stearic (С18:0, pentadecanic (С15:0, heptadecanic (С17:0, pentadecenic (С15:1, heptadecenic (С17:1, palmitooleic (С16:1, oleic (С18:1, linoleic (С18:2ω6, α-linolenic (С18:3ω3, γ-linolenic (С18:3ω6, dihomo-γ-linolenic (С20:3ω6, arachidonic (С20:4ω6, eicosapentaenoic (С20:5ω3, and docosapentaenoic (С22:5ω3. Results and discussion. Hypertensive patients with gout demonstrated higher NEFAs blood level and greater changes in ATP-ADP-AMP system than normotensive gout patients and healthy subjects as well as 2.2 and 3.7 times higher NEFAs/ATP ratio, respectively. In hypertensive patients with primary gout the composition of fatty acids in erythrocyte membranes lipids changed due to increase in saturated fatty acids amount and decrease in unsaturated fatty acids amount, at that monoenic acid levels increased while polyenic acid levels decreased in unsaturated acids composition. Hypertensive patients with gout shown 1.3 and 2.5 times less levels of ω-3 poly-unsaturated fatty acids (PUFA than normotensive gout patients and healthy subjects, respectively. At the same time ω-6 PUFA levels changed in

  2. Restoring Wisconsin Art Therapy Association in Art Therapy History: Implications for Professional Definition and Inclusivity

    Science.gov (United States)

    Potash, Jordan; Burnie, Michele; Pearson, Rosemary; Ramirez, Wayne

    2016-01-01

    The Wisconsin Art Therapy Association (WATA), formally established in 1969, was the first incorporated organization of art therapists in the United States. Under the leadership of Wayne Ramirez, WATA lobbied the national association for an inclusive definition of art therapy that aimed to foster respect for psychiatric, educational, and community…

  3. Infant mortality in South Africa--distribution, associations and policy implications, 2007: an ecological spatial analysis.

    Science.gov (United States)

    Sartorius, Benn K D; Sartorius, Kurt; Chirwa, Tobias F; Fonn, Sharon

    2011-11-18

    Many sub-Saharan countries are confronted with persistently high levels of infant mortality because of the impact of a range of biological and social determinants. In particular, infant mortality has increased in sub-Saharan Africa in recent decades due to the HIV/AIDS epidemic. The geographic distribution of health problems and their relationship to potential risk factors can be invaluable for cost effective intervention planning. The objective of this paper is to determine and map the spatial nature of infant mortality in South Africa at a sub district level in order to inform policy intervention. In particular, the paper identifies and maps high risk clusters of infant mortality, as well as examines the impact of a range of determinants on infant mortality. A Bayesian approach is used to quantify the spatial risk of infant mortality, as well as significant associations (given spatial correlation between neighbouring areas) between infant mortality and a range of determinants. The most attributable determinants in each sub-district are calculated based on a combination of prevalence and model risk factor coefficient estimates. This integrated small area approach can be adapted and applied in other high burden settings to assist intervention planning and targeting. Infant mortality remains high in South Africa with seemingly little reduction since previous estimates in the early 2000's. Results showed marked geographical differences in infant mortality risk between provinces as well as within provinces as well as significantly higher risk in specific sub-districts and provinces. A number of determinants were found to have a significant adverse influence on infant mortality at the sub-district level. Following multivariable adjustment increasing maternal mortality, antenatal HIV prevalence, previous sibling mortality and male infant gender remained significantly associated with increased infant mortality risk. Of these antenatal HIV sero-prevalence, previous

  4. '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.

  5. Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases.

    Science.gov (United States)

    Mosa, Rasha Mofeed Habeeb; Zhang, Zhen; Shao, Renfu; Deng, Chao; Chen, Jiezhong; Chen, Chen

    2015-06-01

    Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulin-producing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases.

  6. Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5(+ cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5(+ cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5(+ cells at the basal glands of the gastric antrum. Notably, the number of Lgr5(+ cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5(+ cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5(+ cells were often restricted to the base of the tumor glands, and such Lgr5(+ restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5(+ cells are present at the base of the antral glands in the human stomach and that this cell population significantly expands in intestinal metaplasias. Furthermore, Lgr5(+ cells are seen in a large number of gastric tumors ; their frequent basal arrangements and coexpression of ISC markers support the idea that Lgr5(+ cells act as stem cells during the early stage of intestinal-type gastric tumorigenesis.

  7. Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains.

    Science.gov (United States)

    Messika, Jonathan; Magdoud, Fatma; Clermont, Olivier; Margetis, Dimitri; Gaudry, Stéphane; Roux, Damien; Branger, Catherine; Dreyfuss, Didier; Denamur, Erick; Ricard, Jean-Damien

    2012-12-01

    To characterize Escherichia coli ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients by determining antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP or lung colonization, by comparing them with their oropharyngeal and rectal counterparts and by assessing representative isolates' virulence in a pneumonia mouse model. Patients under mechanical ventilation for more than 72 h were screened for simultaneous presence of E. coli in rectal, oropharyngeal, and respiratory samples (colonization or VAP). If present, E. coli isolates were characterized by antimicrobial susceptibility, phylogenetic grouping, and virulence factor (VF) gene content determination. BALB/c mice were challenged intranasally with 3.6 × 10(8) colony-forming units (CFU) of patients' E. coli isolates. Multisite E. coli colonization was observed in 19 % of patients (25 patients, 12 with E. coli VAP). One hundred fifteen distinct E. coli isolates were analyzed. B2 phylogenetic group was predominant, with high VF gene content and low antimicrobial resistance. Antimicrobial resistance diversity was observed in four patients with VAP. E. coli isolates from VAP patients were more frequently B2 isolates, with significantly greater VF gene content than lung colonization isolates. Among screened VF genes, iroN and sfa appeared important for lung infection. A very strong correlation (R (2) = 0.99) was found between VF gene content and mortality in the mouse model. This is the first study establishing antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP in adult ICU patients. These isolates are highly virulent specific extraintestinal pathogenic E. coli strains expressing virulence factors, representing potential targets for new therapies.

  8. Digital mammography in a screening programme and its implications for pathology: a comparative study.

    LENUS (Irish Health Repository)

    Feeley, Linda

    2011-03-01

    Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.

  9. Certified Health Education Specialists' Participation in Professional Associations: Implications for Marketing and Membership

    Science.gov (United States)

    Thackeray, Rosemary; Neiger, Brad L.; Roe, Kathleen M.

    2005-01-01

    A number of health education professional associations exist to advance the profession through research, practice, and professional development. Benefits of individual membership may include continuing education, networking, leadership, professional recognition, advocacy, professional mobility, access to research findings, advances in the…

  10. Disentangling pooled triad genotypes for association studies.

    Science.gov (United States)

    Shi, Min; Umbach, David M; Weinberg, Clarice R

    2014-09-01

    Association studies that genotype affected offspring and their parents (triads) offer robustness to genetic population structure while enabling assessments of maternal effects, parent-of-origin effects, and gene-by-environment interaction. We propose case-parents designs that use pooled DNA specimens to make economical use of limited available specimens. One can markedly reduce the number of genotyping assays required by randomly partitioning the case-parent triads into pooling sets of h triads each and creating three pools from every pooling set, one pool each for mothers, fathers, and offspring. Maximum-likelihood estimation of relative risk parameters proceeds via log-linear modeling using the expectation-maximization algorithm. The approach can assess offspring and maternal genetic effects and accommodate genotyping errors and missing genotypes. We compare the power of our proposed analysis for testing offspring and maternal genetic effects to that based on a difference approach and that of the gold standard based on individual genotypes, under a range of allele frequencies, missing parent proportions, and genotyping error rates. Power calculations show that the pooling strategies cause only modest reductions in power if genotyping errors are low, while reducing genotyping costs and conserving limited specimens. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  11. Intimate Partner Violence Victimization and Associated Implications for Health and Functioning Among Male and Female Post-9/11 Veterans.

    Science.gov (United States)

    Iverson, Katherine M; Vogt, Dawne; Maskin, Rachel M; Smith, Brian N

    2017-09-01

    There is increased emphasis on identifying patients who experience intimate partner violence (IPV) in Department of Veterans Affairs and other health care settings. A better understanding of IPV's implications for health and functioning is needed among post-911 Veterans, and especially male Veterans, to inform IPV screening and response. To identify past 6-month IPV experienced among partnered post-9/11 Veterans and examine sex-based associations between IPV and health. A national sample of Veterans completed a survey that included measures of IPV victimization and health. Types of IPV and relationships with health and functioning were examined separately for male and female Veterans. In total, 407 post-9/11 Veterans (52% women) in intimate relationships. IPV victimization was assessed with the Conflict Tactics Scales-Revised. Health and functioning indicators included posttraumatic stress disorder (PCL-5) and depression (Beck Depression Inventory-Primary Care) symptoms, physical health-related quality of life (Short-Form 12-item Health Survey), and occupational functioning (Inventory of Psychosocial Functioning). Nearly two thirds of both men and women reported past 6-month IPV, with greatest endorsement of psychological aggression (65% of men, 59% of women). A total of 8% of men and 7% of women reported physical IPV and 4% of men and 7% of women reported sexual IPV. Psychological aggression was strongly linked with mental health for both sexes and greater occupational impairment for men. Physical and sexual IPV were associated with more severe mental health symptoms for women while physical IPV was negatively associated with physical health-related quality of life for men. Recent IPV victimization, especially psychological aggression, is a key health issue for partnered male and female post-9/11 Veterans. Practice and research implications are discussed.

  12. Current and future greenhouse gas emissions associated with electricity generation in China: implications for electric vehicles.

    Science.gov (United States)

    Shen, Wei; Han, Weijian; Wallington, Timothy J

    2014-06-17

    China's oil imports and greenhouse gas (GHG) emissions have grown rapidly over the past decade. Addressing energy security and GHG emissions is a national priority. Replacing conventional vehicles with electric vehicles (EVs) offers a potential solution to both issues. While the reduction in petroleum use and hence the energy security benefits of switching to EVs are obvious, the GHG benefits are less obvious. We examine the current Chinese electric grid and its evolution and discuss the implications for EVs. China's electric grid will be dominated by coal for the next few decades. In 2015 in Beijing, Shanghai, and Guangzhou, EVs will need to use less than 14, 19, and 23 kWh/100 km, respectively, to match the 183 gCO2/km WTW emissions for energy saving vehicles. In 2020, in Beijing, Shanghai, and Guangzhou EVs will need to use less than 13, 18, and 20 kWh/100 km, respectively, to match the 137 gCO2/km WTW emissions for energy saving vehicles. EVs currently demonstrated in China use 24-32 kWh/100 km. Electrification will reduce petroleum imports; however, it will be very challenging for EVs to contribute to government targets for GHGs emissions reduction.

  13. Time perception among the youth and its implication for industry: An exploratory study

    Directory of Open Access Journals (Sweden)

    GG Rousseau

    2015-04-01

    Full Text Available The main objective of this exploratory study was to investigate perceived cultural differences in the perception of time among the youth and its implications for time management and productivity regarding future employment in industry. The study further sought to develop a reliable instrument for measuring time perception across cultures.  A non-probability convenience sample (N=467 was drawn from English, Afrikaans and Xhosa speaking respondents, aged 13 to 18 years.  Results confirmed four factors: time allocation, time economy, time attitudes and scheduling of tasks.  Significant differences between age, language and gender groups on time perception were observed.  These findings have implications for time management training among the youth as well as for industry seeking employees who can perform tasks with speed and efficiency.  Further refinement of the instrument in follow-up studies is essential.

  14. Coaches' implicit associations between size and giftedness: implications for the relative age effect.

    Science.gov (United States)

    Furley, Philip; Memmert, Daniel

    2016-01-01

    The relative age effect (RAE) is a well-established phenomenon in education and sports. Coaches have been assumed to be important social agents of RAE via biased selection decisions in favour of children with maturation advantages. In the present research, we used the Implicit Association Test to investigate automatic associations between body size and a player's domain-specific giftedness amongst youth baseball (N = 18) and youth soccer coaches (N = 34). We found medium to strong automatic associations between body size and player giftedness (baseball: MD = 0.62; soccer: MD = 0.51). Specifically, taller players were associated with positive performance-related attributes, whereas smaller players were associated with negative attributes. The results are in line with theories of grounded cognition by showing that the abstract concept of "sport giftedness" is partly grounded in the perception of physical height amongst youth sports coaches. We argue that this grounded cognition has the potential to influence coaches' selection decisions and in turn account for RAE as coaches are biased towards physically more matured players, even when no apparent performance advantage is evident.

  15. Experimental evidence for friction-enhancing integumentary modifications of chameleons and associated functional and evolutionary implications

    Science.gov (United States)

    Khannoon, Eraqi R.; Endlein, Thomas; Russell, Anthony P.; Autumn, Kellar

    2014-01-01

    The striking morphological convergence of hair-like integumentary derivatives of lizards and arthropods (spiders and insects) demonstrates the importance of such features for enhancing purchase on the locomotor substrate. These pilose structures are responsible for the unique tractive abilities of these groups of animals, enabling them to move with seeming ease on overhanging and inverted surfaces, and to traverse inclined smooth substrates. Three groups of lizards are well known for bearing adhesion-promoting setae on their digits: geckos, anoles and skinks. Similar features are also found on the ventral subdigital and distal caudal skin of chameleons. These have only recently been described in any detail, and structurally and functionally are much less well understood than are the setae of geckos and anoles. The seta-like structures of chameleons are not branched (a characteristic of many geckos), nor do they terminate in spatulate tips (which is characteristic of geckos, anoles and skinks). They are densely packed and have attenuated blunt, globose tips or broad, blade-like shafts that are flattened for much of their length. Using a force transducer, we tested the hypothesis that these structures enhance friction and demonstrate that the pilose skin has a greater frictional coefficient than does the smooth skin of these animals. Our results are consistent with friction being generated as a result of side contact of the integumentary filaments. We discuss the evolutionary and functional implications of these seta-like structures in comparison with those typical of other lizard groups and with the properties of seta-mimicking synthetic structures. PMID:24285195

  16. Association between depression and development of coronary artery disease: pathophysiologic and diagnostic implications

    Directory of Open Access Journals (Sweden)

    Sakamoto

    2011-03-01

    Full Text Available Carlos V Serrano Jr1, Karina Tiemi Setani2, Erica Sakamoto2, Anna Maria Andrei3, Renério Fraguas41Heart Institute (InCor, 2Medical School, University of São Paulo, Brazil; 3Albert Einstein Hospital, São Paulo, Brazil; 4Department and Institute of Psychiatry, Medical School, University of São Paulo, BrazilAbstract: Depression and coronary artery disease (CAD are both extremely prevalent diseases. In addition, compromised quality of life and life expectancy are characteristics of both situations. There are several conditions that aggravate depression and facilitate the development of CAD, as well as provoke a worse prognosis in patients with already established CAD: inferior adherence to medical orientations (medications and life style modifications, greater platelet activation and aggregation, endothelial dysfunction, and impaired autonomic dysfunction (lowered heart rate variability. Recent literature has shown that depression alone is becoming an independent risk factor for cardiac events both in primary and secondary prevention. As the diagnosis of depression in patients with heart disease is difficult, due to similarities of symptoms, the health professional should perform a careful evaluation to differentiate the clinical signs of depression from those related with general heart diseases. After a myocardial infarction, depression is an independent risk factor for mortality. Successful therapy of depression has been shown to improve patients’ quality of life and cardiovascular outcome. However, multicentric clinical trials are needed to support this inference. A practical liaison between qualified professionals is necessary for the better management of depressed patients with excess risk in developing CAD. Accordingly, pathophysiological and clinical implications between depression and CAD are discussed in this article.Keywords: depression, coronary artery disease, behavioral disorders, prognosis

  17. Naturalising Ethics: The Implications of Darwinism for the Study of Moral Philosophy

    Science.gov (United States)

    Cartwright, John

    2010-05-01

    The nature of moral values has occupied philosophers and educationalists for centuries and a variety of claims have been made about their origin and status. One tradition suggests they may be thoughts in the mind of God; another that they are eternal truths to be reached by rational reflection (much like the truths of mathematics) or alternatively through intuition; another that they are social conventions; and another (from the logical positivists) that they are not verifiable facts but simply the expression of emotional likes and dislikes. Standard introductory texts (e.g., Bowie 2004; Vardy and Grosch 1999) on the subject of ethics rarely mention Darwin or Darwinism (Mepham 2005 is a useful exception) possibly mindful of the fact that the relationship of evolutionary biology to moral questions has had a troublesome history. The effect of this has been that whole generations of moral philosophers have given the biological sciences a wide berth and consequently often remain poorly informed about recent advances in evolutionary thought and the neurosciences. On the other hand, scientists have developed interesting models of the evolution of the moral sentiments and are using new imaging techniques to explore the centres of the brain associated with emotion and motivation, but many have been fearful of committing the naturalistic fallacy and so have steered clear of extrapolating their findings to ethical questions. No one after all wants to be seen to be committing an elementary logical blunder. But in the last 20 years, evolutionary biologists have regained the confidence to explore the implications of evolution for the study of ethics (de Waal 1996; Wilson 1998; Wright 1994; Greene 2003). This paper is designed to encourage those entrusted with the teaching of ethics to be open to the potential of Darwinism as a source of ideas on the origins and status of ethical thought and behaviour. It is also hoped that it will illustrate for science educators the enormous

  18. Association studies in late onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Goate, A.M.; Lendon, C.; Talbot, C. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  19. Neutralizing antibodies against adeno-associated viruses in inflammatory bowel disease patients: implications for gene therapy

    NARCIS (Netherlands)

    van der Marel, Sander; Comijn, Elisabeth M.; Verspaget, Hein W.; van Deventer, Sander; van den Brink, Gijs R.; Petry, Harald; Hommes, Daniel W.; Ferreira, Valerie

    2011-01-01

    Inflammatory bowel diseases (IBDs) are comprised of two major disorders: Crohn's disease (CD) and ulcerative colitis (UC). No curative treatment options are available, but gene therapy may offer an alternative therapeutic approach. For this a safe and reliable vector is needed. The adeno-associated

  20. Implications of differential age distribution of disease-associated meningococcal lineages for vaccine development

    NARCIS (Netherlands)

    Brehony, Carina; Trotter, Caroline L.; Ramsay, Mary E.; Chandra, Manosree; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F.; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.

    2014-01-01

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account

  1. A Case Study with an Identified Bully: Policy and Practice Implications

    OpenAIRE

    Huddleston, Lillie; Varjas, Kris; Meyers, Joel; Cadenhead, Catherine

    2011-01-01

    Objective: Bullying is a serious public health problem that may include verbal or physical injury as well as social isolation or exclusion. As a result, research is needed to establish a database for policies and interventions designed to prevent bullying and its negative effects. This paper presented a case study that contributed to the literature by describing an intervention for bullies that has implications for research, practice and related policies regarding bullying.Methods: An individ...

  2. 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.

  3. HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis

    Directory of Open Access Journals (Sweden)

    Regina Medvedev

    2016-01-01

    Full Text Available HCV (hepatitis C virus is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy.

  4. Courtesy stigma: the social implications of associating with a gay person.

    Science.gov (United States)

    Sigelman, C K; Howell, J L; Cornell, D P; Cutright, J D; Dewey, J C

    1991-02-01

    We investigated the operation of courtesy stigma with American male college students who reacted to a fictitious male student described as gay, rooming by choice with a gay male student, involuntarily assigned to room with a gay, or rooming with a male heterosexual. Among respondents who expressed strong intolerance of gays, the voluntary associate of a gay was perceived as having homosexual tendencies and as possessing the same stereotyped personality traits attributed to a gay. No such courtesy stigma was attached to the involuntary associate of a gay by these respondents. Relatively tolerant respondents engaged in no courtesy stigmatization at all. Thus, courtesy stigmatization occurred only under circumscribed conditions and appeared to depend more on the tendency of highly intolerant individuals to infer that a male student who apparently liked a gay individual was himself gay than on a motivation to maintain cognitive consistency.

  5. Sleep Restriction Therapy for Insomnia is Associated with Reduced Objective Total Sleep Time, Increased Daytime Somnolence, and Objectively Impaired Vigilance: Implications for the Clinical Management of Insomnia Disorder

    Science.gov (United States)

    Kyle, Simon D.; Miller, Christopher B.; Rogers, Zoe; Siriwardena, A. Niroshan; MacMahon, Kenneth M.; Espie, Colin A.

    2014-01-01

    Study Objectives: To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Design: Within-subject, noncontrolled treatment investigation. Setting: Sleep research laboratory. Participants: Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. Interventions: Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Measurement and results: Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P treatment (at four of five assessment points, all P sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia. Citation: Kyle SD; Miller CB; Rogers Z; Siriwardena AN; MacMahon KM; Espie CA. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. SLEEP 2014;37(2):229-237. PMID:24497651

  6. Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.

    Science.gov (United States)

    Wang, Cheng; Qin, Na; Zhu, Meng; Chen, Minjian; Xie, Kaipeng; Cheng, Yang; Dai, Juncheng; Liu, Jia; Xia, Yankai; Ma, Hongxia; Jin, Guangfu; Amos, Christopher I; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing

    2017-10-26

    Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Generic information can retrieve known biological associations: implications for biomedical knowledge discovery.

    Directory of Open Access Journals (Sweden)

    Herman H H B M van Haagen

    Full Text Available MOTIVATION: Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins others generic (e.g., 'Homo sapiens'. Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI by filtering generic concepts (node filtering or links to generic concepts (edge filtering from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering, and assessed the retrieval performance of networks composed of generic information alone. RESULTS: Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept "binding" is indicative for PPI retrieval and the concept "mutation abnormality" is

  8. Ambivalent implications of health care information systems: a study in the Brazilian public health care system

    Directory of Open Access Journals (Sweden)

    João Porto de Albuquerque

    2011-01-01

    Full Text Available This article evaluates social implications of the "SIGA" Health Care Information System (HIS in a public health care organization in the city of São Paulo. The evaluation was performed by means of an in-depth case study with patients and staff of a public health care organization, using qualitative and quantitative data. On the one hand, the system had consequences perceived as positive such as improved convenience and democratization of specialized treatment for patients and improvements in work organization. On the other hand, negative outcomes were reported, like difficulties faced by employees due to little familiarity with IT and an increase in the time needed to schedule appointments. Results show the ambiguity of the implications of HIS in developing countries, emphasizing the need for a more nuanced view of the evaluation of failures and successes and the importance of social contextual factors.

  9. Reference group theory with implications for information studies: a theoretical essay

    Directory of Open Access Journals (Sweden)

    E. Murell Dawson

    2001-01-01

    Full Text Available This article explores the role and implications of reference group theory in relation to the field of library and information science. Reference group theory is based upon the principle that people take the standards of significant others as a basis for making self-appraisals, comparisons, and choices regarding need and use of information. Research that applies concepts of reference group theory to various sectors of library and information studies can provide data useful in enhancing areas such as information-seeking research, special populations, and uses of information. Implications are promising that knowledge gained from like research can be beneficial in helping information professionals better understand the role theory plays in examining ways in which people manage their information and social worlds.

  10. Research studies and their implications for social work practice in a multidisciplinary center for lupus care.

    Science.gov (United States)

    Kim, Su Jin; Persad, Pretima; Erkan, Doruk; Kirou, Kyriakos; Horton, Roberta; Salmon, Jane E

    2012-01-01

    The complexity of systemic lupus erythematosus (SLE) and its psychosocial impact creates management challenges that require a multidisciplinary team approach for optimal patient care and outcomes. This article provides a brief report on current lupus-related research studies at the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery. Studies and their social work implications highlight a comprehensive, integrated model for research, education, and patient care emphasizing interdisciplinary collaboration. Both basic science and clinical research are discussed, with a focus on the role of social workers as an integral part of the health care team in providing assessments and interventions and as support for patients in research studies.

  11. Foraging Strategies of Laysan Albatross Inferred from Stable Isotopes: Implications for Association with Fisheries.

    Science.gov (United States)

    Edwards, Ann E; Fitzgerald, Shannon M; Parrish, Julia K; Klavitter, John L; Romano, Marc D

    2015-01-01

    Fatal entanglement in fishing gear is the leading cause of population decline for albatross globally, a consequence of attraction to bait and fishery discards of commercial fishing operations. We investigated foraging strategies of Laysan albatross (Phoebastria immutabilis), as inferred from nitrogen and carbon isotope values of primary feathers, to determine breeding-related, seasonal, and historic factors that may affect the likelihood of association with Alaskan or Hawaiian longline fisheries. Feather samples were collected from live birds monitored for breeding status and breeding success on Midway Atoll in the northwestern Hawaiian Islands, birds salvaged as fisheries-bycatch, and birds added to museum collections before 1924. During the chick-rearing season (sampled April-May), means and variances of stable isotope values of birds with the highest, most consistent reproductive success were distinct from less productive conspecifics and completely different from birds caught in Hawaiian or Alaskan longline fisheries, suggesting birds with higher multi-annual reproductive success were less likely to associate with these fisheries. Contemporary birds with the highest reproductive success had mean values most similar to historic birds. Values of colony-bound, courting prebreeders were similar to active breeders but distinct from prebreeders caught in Alaskan longline fisheries. During the breeding season, δ15N values were highly variable for both contemporary and historic birds. Although some historic birds exhibited extremely low δ15N values unmatched by contemporary birds (fisheries.

  12. Habitat fragmentation is associated to gut microbiota diversity of an endangered primate: implications for conservation.

    Science.gov (United States)

    Barelli, Claudia; Albanese, Davide; Donati, Claudio; Pindo, Massimo; Dallago, Chiara; Rovero, Francesco; Cavalieri, Duccio; Tuohy, Kieran Michael; Hauffe, Heidi Christine; De Filippo, Carlotta

    2015-10-07

    The expansion of agriculture is shrinking pristine forest areas worldwide, jeopardizing the persistence of their wild inhabitants. The Udzungwa red colobus monkey (Procolobus gordonorum) is among the most threatened primate species in Africa. Primarily arboreal and highly sensitive to hunting and habitat destruction, they provide a critical model to understanding whether anthropogenic disturbance impacts gut microbiota diversity. We sampled seven social groups inhabiting two forests (disturbed vs. undisturbed) in the Udzungwa Mountains of Tanzania. While Ruminococcaceae and Lachnospiraceae dominated in all individuals, reflecting their role in extracting energy from folivorous diets, analysis of genus composition showed a marked diversification across habitats, with gut microbiota α-diversity significantly higher in the undisturbed forest. Functional analysis suggests that such variation may be associated with food plant diversity in natural versus human-modified habitats, requiring metabolic pathways to digest xenobiotics. Thus, the effects of changes in gut microbiota should not be ignored to conserve endangered populations.

  13. The American Heart Association's recent scientific statement on cardiac critical care: implications for pediatric practice.

    Science.gov (United States)

    Penny, Daniel J; Shekerdemian, Lara S

    2013-01-01

    A writing group sponsored by the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, the Council on Clinical Cardiology, the Council on Cardiovascular Nursing, and the Council on Quality of Care and Outcomes Research of The American Heart Association has recently formulated a roadmap to meet the changing needs of the patient with cardiovascular disease requiring critical care. Although this roadmap has been formulated primarily to address the care needs of the adult with critical cardiovascular disease, it contains useful lessons pertinent to the care of the patient with pediatric and congenital cardiovascular disease. In this document, we have examined The Statement and applied its framework to the evolving field of pediatric cardiac critical care. © 2012 Wiley Periodicals, Inc.

  14. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  15. Soil metal concentrations and toxicity: Associations with distances to industrial facilities and implications for human health

    Energy Technology Data Exchange (ETDEWEB)

    Aelion, C. Marjorie [Department of Environmental Health Sciences, University of South Carolina, 921 Assembly Street, Columbia, SC 29208 (United States); Department of Public Health, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003 (United States)], E-mail: maelion@schoolph.umass.edu; Davis, Harley T. [Department of Environmental Health Sciences, University of South Carolina, 921 Assembly Street, Columbia, SC 29208 (United States); McDermott, Suzanne [Department of Family and Preventive Medicine, University of South Carolina, 3209 Colonial Drive, Columbia, SC 29203 (United States); Lawson, Andrew B. [Department of Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, 135 Cannon Street, Charleston, SC 29425 (United States)

    2009-03-15

    Urban and rural areas may have different levels of environmental contamination and different potential sources of exposure. Many metals, i.e., arsenic (As), lead (Pb), and mercury (Hg), have well-documented negative neurological effects, and the developing fetus and young children are particularly at risk. Using a database of mother and child pairs, three areas were identified: a rural area with no increased prevalence of mental retardation and developmental delay (MR/DD) (Area A), and a rural area (Area B) and an urban area (Area C) with significantly higher prevalence of MR/DD in children as compared to the state-wide average. Areas were mapped and surface soil samples were collected from nodes of a uniform grid. Samples were analyzed for As, barium (Ba), beryllium (Be), chromium (Cr), copper (Cu), Pb, manganese (Mn), nickel (Ni), and Hg concentrations and for soil toxicity, and correlated to identify potential common sources. ArcGIS was used to determine distances between sample locations and industrial facilities, which were correlated with both metal concentrations and soil toxicity. Results indicated that all metal concentrations (except Be and Hg) in Area C were significantly greater than those in Areas A and B (p {<=} 0.0001) and that Area C had fewer correlations between metals suggesting more varied sources of metals than in rural areas. Area C also had a large number of facilities whose distances were significantly correlated with metals, particularly Cr (maximum r = 0.33; p = 0.0002), and with soil toxicity (maximum r = 0.25; p = 0.007) over a large spatial scale. Arsenic was not associated with distance to any facility and may have a different anthropogenic, or natural source. In contrast to Area C, both rural areas had lower concentrations of metals, lower soil toxicity, and a small number of facilities with significant associations between distance and soil metals.

  16. Macrofauna associated with an introduced oyster, Pinctada radiata: Spatial scale implications of community differences

    Science.gov (United States)

    Tlig-Zouari, Sabiha; Rabaoui, Lotfi; Cosentino, Andrea; Irathni, Ikram; Ghrairi, Hafedh; Hassine, Oum Kalthoum Ben

    2011-01-01

    The macrozoobenthos associated with the introduced pearl oyster Pinctada radiata has been sampled at two different spatial scales of three sectors (order of hundreds of kilometres) and of eight localities (order of tens of kilometres). Moreover, the NW sector was selected to compare three localities with the presence of P. radiata (low density) and one locality where it was totally absent. The first design was hierarchical, with random localities nested within sectors; the second one was an asymmetrical factorial design, in which the presence/absence of Pinctada and hydrodynamism were considered. Similarity relationships were investigated by means of multivariate clustering, similarity percentage analysis and nm-MDS ordination; the two experimental designs have been tested by permutational MANOVA and analysis of dispersion (PERMDISP). Most of the variability of the associated zoobenthic community appeared to be mainly captured by local environmental factors; the meso-scale variability was more discriminating than differences at larger spatial scale. Large scale NW-SE biogeographic gradient may also have some effects in the assemblage composition. Although the whole arrangement of samples in the MDS plane showed a clear Bray-Curtis distance between the locality without Pinctada and all the remaining sites, pair-wise contrasts were not all significant. The factor "presence/absence" was not significant in this design, whereas the exposure was more indicative of differences in the local assemblage composition. These results may not confirm that the community structure variability is due to the impact of Pincata invasion because the potential and subtle community shift may be masked by the overwhelming influence of just the local environmental gradients. In spite of this, the introduced oyster may play the role of an engineer species at high densities, contributing to the complexity of the benthic habitat and influencing the trophic pattern of its fauna.

  17. 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....

  18. Genome-wide association study of sporadic brain arteriovenous malformations

    NARCIS (Netherlands)

    Weinsheimer, S.; Bendjilali, N.; Nelson, J.; Guo, D.E.; Zaroff, J.G.; Sidney, S.; McCulloch, C.E.; Salman, R. Al-Shahi; Berg, J.N.; Koeleman, B.P.C.; Simon, M.; Bostroem, A.; Fontanella, M.; Sturiale, C.L.; Pola, R.; Puca, A.; Lawton, M.T.; Young, W.L.; Pawlikowska, L.; Klijn, C.J.M.; Kim, H.

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide

  19. 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, ...

  20. The role of associative and non-associative learning in the training of horses and implications for the welfare (a review

    Directory of Open Access Journals (Sweden)

    Paolo Baragli

    2015-03-01

    Full Text Available Horses were domesticated 6000 years ago and since then different types of approaches have been developed to enhance the horse's wellbeing and the human-horse relationship. Even though horse training is an increasingly important research area and many articles have been published on the subject, equitation is still the sport with the highest rate of human injuries, and a significant percentage of horses are sold or slaughtered due to behavioral problems. One explanation for this data is that the human-horse relationship is complex and the communication between humans and horses has not yet been accurately developed. Thus, this review addresses correct horse training based on scientific knowledge in animal learning and psychology. Specifically, it starts from the basic communication between humans and horses and then focuses on associative and non-associative learning, with many practical outcomes in horse management from the ground and under saddle. Finally, it highlights the common mistakes in the use of negative reinforcement, as well as all the implications that improper training could have on horse welfare. Increased levels of competence in horse training could be useful for equine technicians, owners, breeders, veterinarians, and scientists, in order to safeguard horse welfare, and also to reduce the number of human injuries and economic loss for civil society and the public health system.

  1. Learning from the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study: summary of 5-year findings and implications.

    Science.gov (United States)

    Ching, Teresa Y C; Dillon, Harvey; Leigh, Greg; Cupples, Linda

    2017-10-12

    This article summarises findings of the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study, and discusses implications of the findings for research and clinical practice. A population-based study on outcomes of children with hearing loss. Evaluations were conducted at five years of age. Participants were 470 children born with hearing loss between 2002 and 2007 in New South Wales, Victoria and Queensland in Australia, and who first received amplification or cochlear implantation by three years of age. The earlier hearing aids or cochlear implants were fitted, the better the speech, language and functional performance outcomes. Better speech perception was also associated with better language and higher cognitive abilities. Better psychosocial development was associated with better language and functional performance. Higher maternal education level was also associated with better outcomes. Qualitative analyses of parental perspectives revealed the multiple facets of their involvement in intervention. The LOCHI study has shown that early fitting of hearing devices is key to achieving better speech, language and functional performance outcomes for children with hearing loss. The findings are discussed in relation to changes in clinical practice and directions for future research.

  2. Exploring the implications of critical complexity for the study of social-ecological systems.

    Directory of Open Access Journals (Sweden)

    Michelle Audouin

    2013-09-01

    Full Text Available The complexity of social-ecological systems is well recognized (Berkes et al. 2003, Norberg and Cumming 2008. However, in the study of such systems, it is often the uncertainty that results from nonlinear interactions that forms the focus of discussion. Here, the normative implications of complexity for our knowledge of such systems are emphasised, by drawing largely on the work of Cilliers (1998, 2005a, who introduced the term "critical complexity." This perspective on complexity is distinct in bringing the value-based choices that frame our knowledge generation strategies to the fore. It is from this view that we investigate the implications of complexity for social-ecological systems research. Based on these implications, we propose a set of five key questions to guide the incorporation of insights from critical complexity into such research. We end with a brief application of the questions proposed to the National Freshwater Ecosystem Priority Areas (NFEPA project in South Africa, to illustrate their potential use in the context of resource management.

  3. [Possible public health implications regarding associations between the degree of urbanisation and electronic media exposure amongst Colombian children].

    Science.gov (United States)

    Gómez, Luis F; Lucumí, Diego I; Parra, Diana C; Lobelo, Felipe

    2008-01-01

    Determining the association between the degree of urbanisation and excessive television-viewing and video-game use amongst children aged 5 to 12 years old. Data from the Colombian National Nutritional Survey 2005 was used in the analysis. Television viewing and video-game use was determined through parental reports for 13,090 children and classified as being excessive (e' 2 hours/day) or suitable (probability of TV or videogames being used for 2 hours or more as the degree of urbanisation increased. This association was statistically significant for urbanisation level 3 and higher (urbanisation level 2, OR=1,33: 0,89-1,99 95 %CI; urbanisation level 3, 1,35=OR: 1,00-1,80 95 %CI; urbanisation level 4, 1,61=OR: 1,16-2,23 95 %CI and urbanisation level 5, 1,7=OR: 1,17-2,46 95 %CI). Colombian children living in areas of high-to-moderate urbanisation and population density are at a higher risk of excessive exposure to electronic media entertainment. Due to its multiple health implications (in particular obesity and cardio-metabolic health), such sedentary behaviour should be monitored and its determinants in the Colombian paediatric population must be understand for making effective public health interventions.

  4. A cross-sectional study of the effects of load carriage on running characteristics and tibial mechanical stress: implications for stress fracture injuries in women

    Science.gov (United States)

    2017-03-23

    effects of load carriage on running characteristics and tibial mechanical stress : implications for stress -fracture injuries in women Chun Xu1, Amy Silder2...Ju Zhang3, Jaques Reifman1* and Ginu Unnikrishnan1Abstract Background: Load carriage is associated with musculoskeletal injuries, such as stress ...kinematics and kinetics of the body, as well as the tibial mechanical stress during running. We also compared the biomechanics of walking (studied

  5. Increased drinking following social isolation rearing: implications for polydipsia associated with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Emily R Hawken

    Full Text Available Primary polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the effects on schedule-induced polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to polydipsia is a schizophrenia-like behavioral effect of post-weaning social isolation.

  6. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications

    Science.gov (United States)

    Garrido, Daniel; Dallas, David C.

    2013-01-01

    Human milk is a rich source of nutrients and energy, shaped by mammalian evolution to provide all the nutritive requirements of the newborn. In addition, several molecules in breast milk act as bioactive agents, playing an important role in infant protection and guiding a proper development. While major breast milk nutrients such as lactose, lipids and proteins are readily digested and consumed by the infant, other molecules, such as human milk oligosaccharides and glycosylated proteins and lipids, can escape intestinal digestion and transit through the gastrointestinal tract. In this environment, these molecules guide the composition of the developing infant intestinal microbiota by preventing the colonization of enteric pathogens and providing carbon and nitrogen sources for other colonic commensals. Only a few bacteria, in particular Bifidobacterium species, can gain access to the energetic content of milk as it is displayed in the colon, probably contributing to their predominance in the intestinal microbiota in the first year of life. Bifidobacteria deploy exquisite molecular mechanisms to utilize human milk oligosaccharides, and recent evidence indicates that their activities also target other human milk glycoconjugates. Here, we review advances in our understanding of how these microbes have been shaped by breast milk components and the strategies associated with their consumption of milk glycoconjugates. PMID:23460033

  7. A Collapsar Model with Disk Wind: Implications for Supernovae Associated with Gamma-Ray Bursts

    Science.gov (United States)

    Hayakawa, Tomoyasu; Maeda, Keiichi

    2018-02-01

    We construct a simple but self-consistent collapsar model for gamma-ray bursts (GRBs) and SNe associated with GRBs (GRB-SNe). Our model includes a black hole, an accretion disk, and the envelope surrounding the central system. The evolutions of the different components are connected by the transfer of the mass and angular momentum. To address properties of the jet and the wind-driven SNe, we consider competition of the ram pressure from the infalling envelope and those from the jet and wind. The expected properties of the GRB jet and the wind-driven SN are investigated as a function of the progenitor mass and angular momentum. We find two conditions that should be satisfied if the wind-driven explosion is to explain the properties of the observed GRB-SNe: (1) the wind should be collimated at its base, and (2) it should not prevent further accretion even after the launch of the SN explosion. Under these conditions, some relations seen in the properties of the GRB-SNe could be reproduced by a sequence of different angular momentum in the progenitors. Only the model with the largest angular momentum could explain the observed (energetic) GRB-SNe, and we expect that the collapsar model can result in a wide variety of observational counterparts, mainly depending on the angular momentum of the progenitor star.

  8. Evolution of AF6-RAS association and its implications in mixed-lineage leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Matthew J.; Ottoni, Elizabeth; Ishiyama, Noboru; Goudreault, Marilyn; Haman, André; Meyer, Claus; Tucholska, Monika; Gasmi-Seabrook, Genevieve; Menezes, Serena; Laister, Rob C.; Minden, Mark D.; Marschalek, Rolf; Gingras, Anne-Claude; Hoang, Trang; Ikura, Mitsuhiko

    2017-10-23

    Elucidation of activation mechanisms governing protein fusions is essential for therapeutic development. MLL undergoes rearrangement with numerous partners, including a recurrent translocation fusing the epigenetic regulator to a cytoplasmic RAS effector, AF6/afadin. We show here that AF6 employs a non-canonical, evolutionarily conserved α-helix to bind RAS, unique to AF6 and the classical RASSF effectors. Further, all patients with MLL-AF6 translocations express fusion proteins missing only this helix from AF6, resulting in exposure of hydrophobic residues that induce dimerization. We provide evidence that oligomerization is the dominant mechanism driving oncogenesis from rare MLL translocation partners and employ our mechanistic understanding of MLL-AF6 to examine how dimers induce leukemia. Proteomic data resolve association of dimerized MLL with gene expression modulators, and inhibiting dimerization disrupts formation of these complexes while completely abrogating leukemogenesis in mice. Oncogenic gene translocations are thus selected under pressure from protein structure/function, underscoring the complex nature of chromosomal rearrangements.

  9. Nesfatin-1; Implication in Stress and Stress-associated Anxiety and Depression.

    NARCIS (Netherlands)

    Emmerzaal, T.L.; Kozicz, T.L.

    2013-01-01

    Nesfatin-1, derived from an 82-amino-acid peptide precursor protein nucleobindin-2 (NUCB2), is a highly conserved peptide across mammalian species. Initial functional and neuroanatomical studies on NUCB2/nesfatin-1 in the central nervous system have supported a role for NUCB2/nesfatin-1 as a novel

  10. Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2008-01-01

    Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

  11. Trends and Group Differences in the Association between Educational Attainment and U.S. Adult Mortality: Implications for Understanding Education’s Causal Influence*

    Science.gov (United States)

    Hayward, Mark D.; Hummer, Robert A.; Sasson, Isaac

    2014-01-01

    Has the shape of the association between educational attainment and U.S. adult mortality changed in recent decades? If so, is it changing consistently across demographic groups? What can changes in the shape of the association tell us about the possible mechanisms in play for improving health and lowering mortality risk over the adult life course? This paper develops the argument that societal technological change may have had profound effects on the importance of educational attainment – particularly advanced education – in the U.S. adult population for garnering health advantages and that these changes should be reflected in changes in the functional form of the association between educational attainment and mortality. We review the historical evidence on the changing functional form of the association, drawing on studies based in the United States, to assess whether these changes are consistent with our argument about the role of technological change. We also provide an updated analysis of these functional form patterns and trends, contrasting data from the early 21st Century with data from the late 20th Century. This updated evidence suggests that the shape of the association between educational attainment and U.S. adult mortality appears to be reflecting lower and lower adult mortality for very highly educated Americans compared to their low-educated counterparts in the 21st Century. We draw on this review and updated evidence to reflect on the question whether education’s association with adult mortality has become increasingly causal in recent decades, why, and the potential research, policy, and global implications of these changes. PMID:25440841

  12. Indicators to measure risk of disaster associated with drought: Implications for the health sector.

    Science.gov (United States)

    Sena, Aderita; Ebi, Kristie L; Freitas, Carlos; Corvalan, Carlos; Barcellos, Christovam

    2017-01-01

    Brazil has a large semiarid region, which covers part of 9 states, over 20% of the 5565 municipalities in the country and at 22.5 million persons, 12% of the country's population. This region experiences recurrent and extended droughts and is characterized by low economic development, scarcity of natural resources including water, and difficult agricultural and livestock production. Local governments and communities need easily obtainable tools to aid their decision making process in managing risks associated with drought. To inform decision-making at the level of municipalities, we investigated factors contributing to the health risks of drought. We used education and poverty indicators to measure vulnerability, number of drought damage evaluations and historical drought occurrences as indicators of hazard, and access to water as an indicator of exposure, to derive a drought disaster risk index. Indicators such as access to piped water, illiteracy and poverty show marked differences in most states and, in nearly all states, the living conditions of communities in the semiarid region are worse than in the rest of each state. There are municipalities at high drought disaster risk in every state and there are a larger number of municipalities at higher risks from the center to the north of the semiarid region. Understanding local hazards, exposures and vulnerabilities provides the means to understand local communities' risks and develop interventions to reduce them. In addition, communities in these regions need to be empowered to add their traditional knowledge to scientific tools, and to identify the actions most relevant to their needs and realities.

  13. Indicators to measure risk of disaster associated with drought: Implications for the health sector.

    Directory of Open Access Journals (Sweden)

    Aderita Sena

    Full Text Available Brazil has a large semiarid region, which covers part of 9 states, over 20% of the 5565 municipalities in the country and at 22.5 million persons, 12% of the country's population. This region experiences recurrent and extended droughts and is characterized by low economic development, scarcity of natural resources including water, and difficult agricultural and livestock production. Local governments and communities need easily obtainable tools to aid their decision making process in managing risks associated with drought.To inform decision-making at the level of municipalities, we investigated factors contributing to the health risks of drought. We used education and poverty indicators to measure vulnerability, number of drought damage evaluations and historical drought occurrences as indicators of hazard, and access to water as an indicator of exposure, to derive a drought disaster risk index.Indicators such as access to piped water, illiteracy and poverty show marked differences in most states and, in nearly all states, the living conditions of communities in the semiarid region are worse than in the rest of each state. There are municipalities at high drought disaster risk in every state and there are a larger number of municipalities at higher risks from the center to the north of the semiarid region.Understanding local hazards, exposures and vulnerabilities provides the means to understand local communities' risks and develop interventions to reduce them. In addition, communities in these regions need to be empowered to add their traditional knowledge to scientific tools, and to identify the actions most relevant to their needs and realities.

  14. Endocrine disruptors and dental materials: health implications associated with their use in Brazil

    Directory of Open Access Journals (Sweden)

    Coelho Antonio Jorge Molinário

    2002-01-01

    Full Text Available This study analyzes international historical trends in the use of different types of materials in dental practice. The author describes the chemical properties of their ingredients and the potential and observed adverse effects in patients and dental technicians resulting from clinical or occupational exposure to various metals like beryllium, used to produce metal alloys. The growing use of various products (resin cements, ionomer cements, aesthetic restorative materials, resins, endodontal cements, and others based on the compound bisphenol-A, whose chemical structure is similar to that of estrogen. Considering the demographic and contemporary work force characteristics of those involved in dental practice in the Brazil, the study highlights the possible effect of the use of these materials in both male and female patients and all age strata, as well as in health professionals with occupational exposure to products containing bisphenol-A.

  15. Meth/amphetamine use and associated HIV: Implications for global policy and public health.

    Science.gov (United States)

    Degenhardt, Louisa; Mathers, Bradley; Guarinieri, Mauro; Panda, Samiran; Phillips, Benjamin; Strathdee, Steffanie A; Tyndall, Mark; Wiessing, Lucas; Wodak, Alex; Howard, John

    2010-09-01

    Amphetamine type stimulants (ATS) have become the focus of increasing attention worldwide. There are understandable concerns over potential harms including the transmission of HIV. However, there have been no previous global reviews of the extent to which these drugs are injected or levels of HIV among users. A comprehensive search of the international peer-reviewed and grey literature was undertaken. Multiple electronic databases were searched and documents and datasets were provided by UN agencies and key experts from around the world in response to requests for information on the epidemiology of use. Amphetamine or methamphetamine (meth/amphetamine, M/A) use was documented in 110 countries, and injection in 60 of those. Use may be more prevalent in East and South East Asia, North America, South Africa, New Zealand, Australia and a number of European countries. In countries where the crystalline form is available, evidence suggests users are more likely to smoke or inject the drug; in such countries, higher levels of dependence may be occurring. Equivocal evidence exists as to whether people who inject M/A are at differing risk of HIV infection than other drug injectors; few countries document HIV prevalence/incidence among M/A injectors. High risk sexual behaviour among M/A users may contribute to increased risk of HIV infection, but available evidence is not sufficient to determine if the association is causal. A range of possible responses to M/A use and harm are discussed, ranging from supply and precursor control, to demand and harm reduction. Evidence suggests that complex issues surround M/A, requiring novel and sophisticated approaches, which have not yet been met with sufficient investment of time or resources to address them. Significant levels of M/A in many countries require a response to reduce harms that in many cases remain poorly understood. More active models of engagement with M/A users and provision of services that meet their specific needs

  16. Changes in heart rate variability associated with acute alcohol consumption: current knowledge and implications for practice and research.

    Science.gov (United States)

    Romanowicz, Magdalena; Schmidt, John E; Bostwick, John M; Mrazek, David A; Karpyak, Victor M

    2011-06-01

    Alcohol consumption is associated with a broad array of physiologic and behavioral effects including changes in heart rate. However, the physiologic mechanisms of alcohol effects and the reasons for individual differences in the cardiac response remain unknown. Measuring changes in resting heart rate (measured as beats/min) has not been found to be as sensitive to alcohol's effects as changes in heart rate variability (HRV). HRV is defined as fluctuations in interbeat interval length which reflect the heart's response to extracardiac factors that affect heart rate. HRV allows simultaneous assessment of both sympathetic and parasympathetic activity and the interplay between them. Increased HRV has been associated with exercise and aerobic fitness, while decreased HRV has been associated with aging, chronic stress, and a wide variety of medical and psychiatric disorders. Decreased HRV has predictive value for mortality in general population samples and patients with myocardial infarction and used as an indicator of altered autonomic function. A significant inverse correlation was found between HRV and both the severity of depression and the duration of the depressive episode. HRV analysis provides insights into mechanisms of autonomic regulation and is extensively used to clarify relationships between depression and cardiovascular disease. This article will review the methodology of HRV measurements and contemporary knowledge about effects of acute alcohol consumption on HRV. Potential implications of this research include HRV response to alcohol that could serve as a marker for susceptibility to alcoholism. At present however there is almost no research data supporting this hypothesis. Copyright © 2011 by the Research Society on Alcoholism.

  17. Male Undergraduates' HPV Vaccination Behavior: Implications for Achieving HPV-Associated Cancer Equity.

    Science.gov (United States)

    Lee, Hee Yun; Lust, Katherine; Vang, Suzanne; Desai, Jay

    2018-02-22

    Despite the availability of the human papillomavirus (HPV) vaccine for males, uptake of the vaccine has been low, particularly among young adult males. This study aimed to investigate the levels of HPV vaccination and predictors of HPV vaccine completion in college men ages 18-26. We analyzed data from the 2015 College Student Health Survey, which was administered at 17 post-secondary institutions in Midwest areas. We included only responses from male participants who were ages 18-26 years old, resulting in a sample size of 2516. We used Andersen's Behavioral Model of Health Services Utilization to guide our study design. Multivariate logistic regression was used to examine predictors of HPV vaccine receipt. College-aged males in our sample had a HPV vaccine completion rate of 50.0%. Male students who were younger, had at least one parent who held a graduate degree, had initiated sex, and were enrolled at a private 4-year institution were more likely to have been vaccinated. These findings suggest that HPV vaccination in college-aged men are low. Efforts are needed to increase HPV vaccination in male students who are older, from lower socioeconomic statuses, have not initiated sex, and enrolled at public institutions. Findings also indicate important gender disparities in vaccine uptake that must be addressed in order to achieve optimal vaccine uptake in college-aged males.

  18. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

    Science.gov (United States)

    Castelli, Erick C.; Arnaiz-Villena, Antonio; Roger, Michel; Rey, Diego; Moreau, Philippe

    2010-01-01

    The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes. PMID:21107637

  19. Genome-wide association study of autistic-like traits in a general population study of young adults

    Directory of Open Access Journals (Sweden)

    Rachel Maree Jones

    2013-10-01

    Full Text Available Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A genome-wide association study using 2,462,046 single nucleotide polymorphisms (SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine Study. No SNP associations reached genome-wide significance (p < 5.0 x 10-8. However, investigations into nominal observed SNP associations (p < 1.0 x 10-5 add support to two positional candidate genes previously implicated in ASD aetiology, PRKCB1 and CBLN1.The rs198198 SNP (p = 9.587 x 10-6, is located within an intron of the protein kinase C, beta 1 (PRKCB1 gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p = 1.78 x 10-6 is located in a region flanking the Cerebellin 1 (CBLN1 gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD.

  20. Identification of aerosol types over Indo-Gangetic Basin: implications to optical properties and associated radiative forcing.

    Science.gov (United States)

    Tiwari, S; Srivastava, A K; Singh, A K; Singh, Sachchidanand

    2015-08-01

    The aerosols in the Indo-Gangetic Basin (IGB) are a mixture of sulfate, dust, black carbon, and other soluble and insoluble components. It is a challenge not only to identify these various aerosol types, but also to assess the optical and radiative implications of these components. In the present study, appropriate thresholds for fine-mode fraction and single-scattering albedo have been used to first identify the aerosol types over IGB. Four major aerosol types may be identified as polluted dust (PD), polluted continental (PC), black carbon-enriched (BCE), and organic carbon-enriched (OCE). Further, the implications of these different types of aerosols on optical properties and radiative forcing have been studied. The aerosol products derived from CIMEL sun/sky radiometer measurements, deployed under Aerosol Robotic Network program of NASA, USA were used from four different sites Karachi, Lahore, Jaipur, and Kanpur, spread over Pakistan and Northern India. PD is the most dominant aerosol type at Karachi and Jaipur, contributing more than 50% of all the aerosol types. OCE, on the other hand, contributes only about 12-15% at all the stations except at Kanpur where its contribution is ∼38%. The spectral dependence of AOD was relatively low for PD aerosol type, with the lowest AE values (aerosol types, with the highest AE values (>1.0). SSA was found to be the highest for OCE (>0.9) and the lowest for BCE (aerosols, with drastically different spectral variability. The direct aerosol radiative forcing at the surface and in the atmosphere was found to be the maximum at Lahore among all the four stations in the IGB.

  1. The implications of sex role identity and psychological capital for organisations: A South African study

    Directory of Open Access Journals (Sweden)

    Colleen Bernstein

    2016-04-01

    Full Text Available Orientation: A large body of research evidence indicates that both sex role identity (SRI and psychological capital (PsyCap may have critical implications for individual and organisational well-being. As SRI is constituted of sex-based personality traits it is possible that SRI may have implications for individuals’ PsyCap.Research purpose: The purpose of this study was to investigate the relationship between SRI and the positive psychological construct of PsyCap.Motivation for the study: Research on SRI and PsyCap has been explored independently of one another with a lack of research exploring the relationship between these two constructs. In addition, much of the previous research on SRI and organisational outcomes has only examined positive sex role identities, focusing almost exclusively on ‘positive’ or ‘socially desirable’ sex role identities. More recently, researchers have noted that this approach is theoretically and methodologically flawed, as it fails to account for negative traits or socially undesirable traits that may be contained within individuals’ SRI and which may have a number of deleterious implications for organisational outcome variables. Furthermore, there is a paucity of research within the South African context, which explores the adoption of positive and negative sexbased behavioural traits and their implications for PsyCap.Research design, approach and method: A quantitative study was conducted using a crosssectional design and a convenience sampling method to explore the relationship between SRI and PsyCap. Four hundred and seventy-eight respondents, all currently working in South African organisations, participated in this research. The composite questionnaire utilised for this research included a demographic questionnaire, The Extended Personal Attribute Questionnaire-Revised (EPAQ-R, and the PCQ-24 which measures PsyCap in terms of self-efficacy, hope, resilience and optimism.Main findings

  2. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    The aim of this study was to identify the genetic risk factors which include alcohol metabolizing genes and neurotransmitter related genes for alcoholism in Yunnan Han population. Eight allelic variants of five genes were genotyped from 332 Yunnan Han individuals (including 118 alcohol-dependent patients (DSM-IV ...

  3. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  4. Pickup ion processes associated with spacecraft thrusters: Implications for solar probe plus

    Energy Technology Data Exchange (ETDEWEB)

    Clemens, Adam, E-mail: a.j.clemens@qmul.ac.uk; Burgess, David [School of Physics and Astronomy, Queen Mary University of London, London (United Kingdom)

    2016-03-15

    Chemical thrusters are widely used in spacecraft for attitude control and orbital manoeuvres. They create an exhaust plume of neutral gas which produces ions via photoionization and charge exchange. Measurements of local plasma properties will be affected by perturbations caused by the coupling between the newborn ions and the plasma. A model of neutral expansion has been used in conjunction with a fully three-dimensional hybrid code to study the evolution and ionization over time of the neutral cloud produced by the firing of a mono-propellant hydrazine thruster as well as the interactions of the resulting ion cloud with the ambient solar wind. Results are presented which show that the plasma in the region near to the spacecraft will be perturbed for an extended period of time with the formation of an interaction region around the spacecraft, a moderate amplitude density bow wave bounding the interaction region and evidence of an instability at the forefront of the interaction region which causes clumps of ions to be ejected from the main ion cloud quasi-periodically.

  5. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations.

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Martin, J.E.; Broen, J.; Gorlova, O.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Callejas, J.L.; Castellvi, I.; Carreira, P.; Garcia-Hernandez, F.J.; Fernandez Castro, M.; Coenen, M.J.H.; Riemekasten, G.; Witte, T.; Hunzelmann, N.; Kreuter, A.; Distler, J.H.; Koeleman, B.P.; Voskuyl, A.E.; Schuerwegh, A.J.; Palm, O.; Hesselstrand, R.; Nordin, A.; Airo, P.; Lunardi, C.; Scorza, R.; Shiels, P.; Laar, J.M. van; Herrick, A.; Worthington, J.; Denton, C.; Tan, F.K.; Arnett, F.C.; Agarwal, S.K.; Assassi, S.; Fonseca, C.; Mayes, M.D.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this

  6. Implications of welfare reform on the elderly: a case study of provider, advocate, and consumer perspectives.

    Science.gov (United States)

    Estes, Carroll L; Goldberg, Sheryl; Wellin, Chris; Linkins, Karen W; Shostak, Sara; Beard, Renée L

    2006-01-01

    Whereas many studies of welfare reform have focused on effects on children and families, little research has examined the implications of welfare reform for the elderly. This case study incorporates interviews with service providers for the aging, members of advocacy organizations, and two focus groups of older consumers conducted in the multi-ethnic urban community of San Francisco. Study findings suggest that welfare reform has had both direct and indirect effects on the elderly and their services in the study community. Direct effects derive primarily from changes in the welfare reform legislation that had the effect of undermining both immigrants' eligibility for and claiming of public assistance benefits. Indirect effects on older persons include increased child-care demands upon grandparents. The case study data bear on a significant policy change within the broader trend of devolution at a historical point when anti-immigrant sentiment in the United States was running high.

  7. A study of diabetes associated oral manifestations

    Directory of Open Access Journals (Sweden)

    T Shanmugam Kathiresan

    2017-01-01

    Full Text Available Aim: The aim of this work was to determine the frequency of oral changes in diabetic patients and to study the relationship between periodontal disease and diabetes mellitus. Materials and Methods: The study sample consisted of 440 known diabetic patients between the age group of 20–80 years, of which 212 were males and 228 were females. One hundred and six patients were below 40 years, 138 patients between 41 and 50 years, 97 in 51–60 years, and 99 above 60 years of age. Data were statistically analyzed by Student's t-test. Results: Nearly 57% of the patients showed a Russell's Periodontal Index score of 2–4.9, which suggested an established periodontal disease. Risk factors for the people above the age of 40 years to develop diabetes were 76%. Conclusion: The frequency of oral manifestations in diabetic patients was significantly high, hence showing a relationship of gingival and periodontal diseases with diabetes mellitus.

  8. Habitat association and conservation implications of endangered Francois' langur (Trachypithecus francoisi.

    Directory of Open Access Journals (Sweden)

    Yajie Zeng

    Full Text Available Francois' langur (Trachypithecus francoisi is an endangered primate and endemic to the limestone forests of the tropical and subtropical zone of northern Vietnam and South-west China with a population of about 2,000 individuals. Conservation efforts are hampered by limited knowledge of habitat preference in its main distribution area. We surveyed the distribution of Francois' langur and modeled the relationship between the probability of use and habitat features in Mayanghe National Nature Reserve, Guizhou, China. The main objectives of this study were to provide quantitative information on habitat preference, estimating the availability of suitable habitat, and providing management guidelines for the effective conservation of this species. By comparing 92 used locations with habitat available in the reserve, we found that Francois' langur was mainly distributed along valleys and proportionally, used bamboo forests and mixed conifer-broadleaf forests more than their availability, whereas they tended to avoid shrubby areas and coniferous forests. The langur tended to occur at sites with lower elevation, steeper slope, higher tree canopy density, and a close distance to roads and water. The habitat occupancy probability was best modeled by vegetation type, vegetation coverage, elevation, slope degree, distances to nearest water, paved road, and farmland edge. The suitable habitat in this reserve concentrated in valleys and accounted for about 25% of the total reserve area. Our results showed that Francois' langur was not only restricted at the landscapes level at the regions with karst topography, limestone cliffs, and caves, but it also showed habitat preference at the local scale. Therefore, the protection and restoration of the langur preferred habitats such as mixed conifer-broadleaf forests are important and urgent for the conservation of this declining species.

  9. The MS Risk Allele of CD40 Is Associated with Reduced Cell-Membrane Bound Expression in Antigen Presenting Cells: Implications for Gene Function.

    Directory of Open Access Journals (Sweden)

    Judith Field

    Full Text Available Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS. We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS.

  10. Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly.

    Science.gov (United States)

    Meier, J; Georgatos, S D

    1994-04-15

    p58 (also referred to as the lamin B receptor) is an integral membrane protein of the nuclear envelope known to form a multimeric complex with the lamins and other nuclear proteins during interphase. To examine the fate of this complex during mitosis, we have investigated the partitioning and the molecular interactions of p58 in dividing chicken hepatoma (DU249) cells. Using confocal microscopy and double immunolabelling, we show here that lamins B1 and B2 co-localize with p58 during all phases of mitosis and co-assemble around reforming nuclei. A close juxtaposition of p58/lamin B-containing vesicles and chromosomes is already detectable in metaphase; however, p58 and lamin reassembly proceeds slowly and is completed in late telophase--G1. Flotation of mitotic membranes in sucrose density gradients and analysis of mitotic vesicles by immunoelectron microscopy confirms that p58 and most of the type B lamins reside in the same compartment. Co-immunoprecipitation of both proteins by affinity-purified anti-p58 antibodies shows that they are physically associated in the context of a mitotic p58 'sub-complex'. This sub-assembly does not include the type A lamins which are fully solubilized during mitosis. Our data provide direct, in vivo and in vitro evidence that the majority of type B lamins remain connected to nuclear membrane 'receptors' during mitosis. The implications of these findings in nuclear envelope reassembly are discussed below.

  11. 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

  12. An investigation of NFXL1, a gene implicated in a study of specific language impairment.

    Science.gov (United States)

    Nudel, Ron

    2016-01-01

    A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus.

  13. Leadership preparation in engineering: A study of perceptions of leadership attributes, preparedness, and policy implications

    Science.gov (United States)

    Latorre, Julia Talarico

    Perceptions of engineers and leaders in the field of engineering regarding leadership preparation for engineers were evaluated in this dissertation. More specifically, engineers' and leaders' perceptions of leadership preparation and the necessary skills of leaders in technical fields were studied. The design and analyses of the study were divided into two parts: (1) Data for employment and college enrollment for engineers in New York State (NYS) were plotted using Geographic Information Systems (GIS) in order to evaluate recent data regarding employment and college enrollment for engineers in order to better understand the relevance of leadership preparation in engineering, (2) Perceptions regarding engineering leadership preparedness were analyzed using descriptive statistical methods and inferential statistical methods and engineers' perceptions regarding the importance of chosen leadership attributes were analyzed using inferential statistics and Generalizability Theory (G-theory). Responses to open-ended questions regarding the importance of leadership or management training for engineers, and responses discussing possible implications of increasing leadership or management training for engineers were also examined. Possible implications of the study, and suggestions for future research, were also included.

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

    Science.gov (United States)

    Tizaoui, Kalthoum

    2017-11-02

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

  15. 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)....

  16. Association studies of lung function in mice.

    Science.gov (United States)

    Ganguly, K; Schulz, H

    2008-07-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and an accelerating decline of lung function is the earliest and a major indicator of the onset of COPD. Therefore it has become necessary to understand the genetic basis of this complex physiological trait in order to determine the potential susceptibility factors of this disease. REINHARD et al (2005) performed the genome wide linkage analysis study with inbred mice having extremely divergent lung function (C3H/HeJ versus JF1/Msf) and identified multiple Quantitative Trait Loci (QTLs) on mouse chromosomes (mCh) 5, 15, 17, and 19 with Logarithm of odd (LOD) scores > or = 4. Significant linkages to total lung capacity (TLC) were detected on mCh 15 and 17, to dead space volume (VD) and lung compliance (C(L)) on mCh 5 and 15, to C(L) on mCh 19, and to diffusing capacity for CO (D(co)) on mCh 15 and 17. Several of the mouse chromosomal regions identified were syntenic to human chromosomal regions identified with linkage to FEV1 (forced expiratory volume-1 second), FVC (forced vital capacity), or FEV1/FVC in separate studies. Using a systematic approach of expression QTL (e-QTL) strategy and exon-wise sequencing of suggested candidate genes followed by predicted protein structure and property, GANGULY et al (2007) recently proposed four candidate genes for lung function in mice. They are superoxide dismutase 3, extracellular [SOD3; mCh 5: V(D)], trefoil factor 2 (TFF2; mCh 17: TLC and D(co)), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2; mCh 15:TLC and C(L)), and relaxin 1 (RLN1; mCh 19; CL and CL/TLC). As a part of functional validation, gene-targeted Sod3-/- mice were detected with increased conducting airway volume (V(D)/TLC) compared with strain-matched control Sod3+/+ mice, consistent with the QTL on mCh 5. Findings with gene-targeted mice suggested that SOD3 is a contributing factor defining the complex trait of conducting airway volume. The human variation in

  17. The GW170817/GRB 170817A/AT 2017gfo Association: Some Implications for Physics and Astrophysics

    Science.gov (United States)

    Wang, Hao; Zhang, Fu-Wen; Wang, Yuan-Zhu; Shen, Zhao-Qiang; Liang, Yun-Feng; Li, Xiang; Liao, Neng-Hui; Jin, Zhi-Ping; Yuan, Qiang; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

    2017-12-01

    On 2017 August 17, a gravitational-wave event (GW170817) and an associated short gamma-ray burst (GRB 170817A) from a binary neutron star merger had been detected. The follow-up optical/infrared observations also identified the macronova/kilonova emission (AT 2017gfo). In this work, we discuss some implications of the remarkable GW170817/GRB 170817A/AT 2017gfo association. We show that the ∼1.7 s time delay between the gravitational-wave (GW) and GRB signals imposes very tight constraints on the superluminal movement of gravitational waves (i.e., the relative departure of GW velocity from the speed of light is ≤slant 4.3× {10}-16) or the possible violation of the weak equivalence principle (i.e., the difference of the gamma-ray and GW trajectories in the gravitational field of the galaxy and the local universe should be within a factor of ∼ 3.4× {10}-9). The so-called Dark Matter Emulators and a class of contender models for cosmic acceleration (“Covariant Galileon”) are ruled out as well. The successful identification of lanthanide elements in the macronova/kilonova spectrum also excludes the possibility that the progenitors of GRB 170817A are a binary strange star system. The high neutron star merger rate (inferred from both the local sGRB data and the gravitational-wave data) together with the significant ejected mass strongly suggest that such mergers are the prime sites of heavy r-process nucleosynthesis.

  18. Dissociation From a Cross-Cultural Perspective: Implications of Studies in Brazil.

    Science.gov (United States)

    Maraldi, Everton de Oliveira; Krippner, Stanley; Barros, Maria Cristina Monteiro; Cunha, Alexandre

    2017-07-01

    A major issue in the study of dissociation concerns the cross-cultural validity of definitions and measurements used to identify and classify dissociative disorders. There is also extensive debate on the etiological factors underlying dissociative experiences. Cross-cultural research is essential to elucidate these issues, particularly regarding evidence obtained from countries in which the study of dissociation is still in its infancy. The aim of this article was to discuss Brazilian research on the topic of dissociation, highlighting its contributions for the understanding of dissociative experiences in nonclinical populations and for the validity and relevance of dissociative disorders in the contexts of psychiatry, psychology, and psychotherapy. We also consider the ways in which dissociative experiences are assimilated by Brazilian culture and religious expressions, and the implications of Brazilian studies for the sociocultural investigation of dissociation. We conclude by addressing the limitations of these studies and potential areas for future research.

  19. U.S. Latina Age of Sexual Debut: Long-term Associations and Implications for HIV and Drug Abuse Prevention

    OpenAIRE

    Dillon, Frank R; DE LA ROSA, MARIO; Schwartz, Seth J; Rojas, Patria; Duan, Rui; Robert M. Malow

    2010-01-01

    This cross-sectional study explored associations among (a) age of sexual debut, (b) drug abuse, and (c) sexual risk behaviors among an urban community based sample of 158 predominantly immigrant, Latina adults. Time in the United States and having a mother who used drugs during the participants' childhood or adolescence were significantly related to age of sexual debut. In turn, younger ages of sexual debut were associated with drug abuse and more sexual risk behaviors (greater number of sexu...

  20. From Mental Game to Cultural Praxis: A Cultural Studies Model's Implications for the Future of Sport Psychology

    Science.gov (United States)

    Ryba, Tatiana V.; Wright, Handel Kashope

    2005-01-01

    This paper explores the implications of a cultural studies as praxis heuristic "model: for transforming sport psychology". It provides a brief introduction to both cultural studies and sport psychology and discusses a cultural studies intersection with sport studies and sport psychology. Cultural studies, it asserts, provides one of several…

  1. Is the Holocaust implicated in posttraumatic growth in second-generation Holocaust survivors? A prospective study.

    Science.gov (United States)

    Dekel, Sharon; Mandl, Christine; Solomon, Zahava

    2013-08-01

    With the growing interest in posttraumatic growth (PTG), and the ongoing debate on the implications of transgenerational transmission of trauma, this longitudinal study examined PTG among Holocaust survivor offspring following their own exposure to trauma. Using self-report questionnaires, we assessed PTG over time in middle aged (age: M = 53 years) Israeli male combat veterans of the 1973 Yom Kippur War whose parents were (n = 43) and were not (n = 156) second-generation survivors of the Nazi Holocaust at 2 time points: 30 and 35 years following the war (in 2003 and 2008). Posttraumatic stress disorder symptoms and trauma exposure were also assessed in 1991. We hypothesized that second-generation survivors would report more PTG than controls. However, repeated measures design revealed that the second-generation veterans reported less PTG than veterans who were not second generation, which was evident in the PTG domains of relations to others, personal strength, and appreciation of life. Our findings suggest that transmission of trauma from one generation to the next is possibly implicated in the offspring's propensity for growth following subsequent trauma. Future research is warranted to examine the link between transmission of trauma and positive outcomes following trauma. Copyright © 2013 International Society for Traumatic Stress Studies.

  2. Musculoskeletal symptoms amongst clinical radiologists and the implications of reporting environment ergonomics--a multicentre questionnaire study.

    Science.gov (United States)

    Rodrigues, Jonathan C L; Morgan, Steven; Augustine, Katharine; Clague, Gavin; Pearce, Tim; Pollentine, Adrian; Wallis, Adam; Wilson, David; McCoubrie, Paul

    2014-04-01

    This multicentre study aimed to assess compliance of the reporting environment with best ergonomic practice and to determine the prevalence of musculoskeletal symptoms related to working as a radiologist. All 148 radiology trainees and consultants in 10 hospitals across the region were invited to complete a musculoskeletal symptoms and reporting ergonomics questionnaire. Best ergonomic reporting practice was defined, following literature review, as being able to alter the following: monitor, desk, chair and armrest height, chair back support, ambient light, and temperature. The frequency that these facilities were available and how often they were used was determined. One hundred and twenty-three out of 148 (83%) radiologists responded, and 38% reported radiology-associated occupational injury. Lower back discomfort was the commonest radiology associated musculoskeletal symptom (41%). Only 13% of those with occupational injury sought the advice of occupational health. No reporting environments conformed completely to best ergonomic practice. Where certain facilities were available, less than a third of radiologists made personal ergonomic adjustments prior to starting a reporting session. Radiologists who had good self-assessed knowledge of best ergonomic practice had significantly less back discomfort than those with poor self-assessed knowledge (P environment with best ergonomic practice, in combination with our other findings of a low level of ergonomic awareness, low rates of making ergonomic adjustments and seeking appropriate help, may be implicated. We hope this study raises awareness of this issue and helps prevent long-term occupational injury amongst radiologists from poor ergonomic practice.

  3. The cys-loop ligand-gated ion channel gene family of Tetranychus urticae: implications for acaricide toxicology and a novel mutation associated with abamectin resistance.

    Science.gov (United States)

    Dermauw, W; Ilias, A; Riga, M; Tsagkarakou, A; Grbić, M; Tirry, L; Van Leeuwen, T; Vontas, J

    2012-07-01

    The cys-loop ligand-gated ion channel (cysLGIC) super family of Tetranychus urticae, the two-spotted spider mite, represents the largest arthropod cysLGIC super family described to date and the first characterised one within the group of chelicerates. Genome annotation, phylogenetic analysis and comparison of the cysLGIC subunits with their counterparts in insects reveals that the T. urticae genome encodes for a high number of glutamate- and histamine-gated chloride channel genes (GluCl and HisCl) compared to insects. Three orthologues of the insect γ-aminobutyric acid (GABA)-gated chloride channel gene Rdl were detected. Other cysLGIC groups, such as the nAChR subunits, are more conserved and have clear insect orthologues. Members of cysLGIC family mediate endogenous chemical neurotransmission and they are prime targets of insecticides. Implications for toxicology associated with the identity and specific features of T. urticae family members are discussed. We further reveal the accumulation of known and novel mutations in different GluCl channel subunits (Tu_GluCl1 and Tu_GluCl3) associated with abamectin resistance in T. urticae, and provide genetic evidence for their causality. Our study provides useful toxicological insights for the exploration of the T. urticae cysLGIC subunits as putative molecular targets for current and future chemical control strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Signatures of rocky planet engulfment in HAT-P-4. Implications for chemical tagging studies

    Science.gov (United States)

    Saffe, C.; Jofré, E.; Martioli, E.; Flores, M.; Petrucci, R.; Jaque Arancibia, M.

    2017-07-01

    Aims: We aim to explore the possible chemical signature of planet formation in the binary system HAT-P-4 by studying the trends of abundance vs. condensation temperature Tc. The star HAT-P-4 hosts a planet detected by transits, while its stellar companion does not have any detected planet. We also study the lithium content, which might shed light on the problem of Li depletion in exoplanet host stars. Methods: We derived for the first time both stellar parameters and high-precision chemical abundances by applying a line-by-line full differential approach. The stellar parameters were determined by imposing ionization and excitation equilibrium of Fe lines, with an updated version of the FUNDPAR program, together with ATLAS9 model atmospheres and the MOOG code. We derived detailed abundances of different species with equivalent widths and spectral synthesis with the MOOG program. Results: The exoplanet host star HAT-P-4 is found to be 0.1 dex more metal rich than its companion, which is one of the highest differences in metallicity observed in similar systems. This could have important implications for chemical tagging studies. We rule out a possible peculiar composition for each star, such as is the case for λ Boötis and δ Scuti, and neither is this binary a blue straggler. The star HAT-P-4 is enhanced in refractory elements relative to volatile when compared to its stellar companion. Notably, the Li abundance in HAT-P-4 is greater than that of its companion by 0.3 dex, which is contrary to the model that explains the Li depletion by the presence of planets. We propose a scenario where at the time of planet formation, the star HAT-P-4 locked the inner refractory material in planetesimals and rocky planets, and formed the outer gas giant planet at a greater distance. The refractories were then accreted onto the star, possibly as a result of the migration of the giant planet. This explains the higher metallicity, the higher Li content, and the negative Tc trend we

  5. A descriptive study of biological and psychosocial factors associated ...

    African Journals Online (AJOL)

    Conclusion: This study supports previous findings that a significant association exists between maternal and childhood obesity. The association between BMI and psychotropic medication, nutritional intake and eating habits, and level of physical activity could not be confirmed in our study. The study results were limited by ...

  6. Sample size computation for association studies using case–parents ...

    Indian Academy of Sciences (India)

    sample size for case–control association studies is discussed. Materials and methods. Parameter settings. We consider a candidate locus with two alleles A and a where. A is putatively associated with the disease status (increasing. Keywords. sample size; association tests; genotype relative risk; power; autism. Journal of ...

  7. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.Keywords: posttraumatic stress disorder, genetic association study, single nucleotide polymorphism, risk alleles, trauma exposure, neuroticism, childhood adversity

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

    Science.gov (United States)

    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 epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at panalysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the ultimate aim of assisting in disease classification and prognosis. The data suggest that

  9. Environmental implications of electricity purchase from independent power producers: a case study from Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Shrestha, R.; Shrestha, R.M. [Asian Institute of Technology, Pathum Thani (Thailand). School for Environmental Resource & Development

    2003-07-01

    This paper analyses the effect on the environment of electricity purchase from independent power producers (IPPs) in the case of Thailand. The environmental implication is evaluated in terms of the net change in emission of air pollutants with electricity purchase from IPPs by a utility. The main finding of the study is that electricity purchase from a non-dispatchable IPP plant based on coal-fired generation would increase the net emissions compared with that without the purchase from IPPs. The study also shows that the lower plant factor of the IPP plant would also increase the emission of air pollutants. Furthermore, with non-dispatchable IPP plants, the total emission of air pollutants would increase, whereas with dispatchable IPP plants the total emission would decrease with the level of electricity purchases.

  10. Contribution of phytoliths to total biogenic silica volumes in the tropical rivers of Malaysia and associated implications for the marine biogeochemical cycle

    Science.gov (United States)

    Zang, Jiaye; Liu, Sen; Liu, Yanguang; Ma, Yongxing; Ran, Xiangbin

    2016-09-01

    The contribution of phytoliths to total biogenic silica (BSi) volumes in rivers worldwide, and the associated implications for the biogeochemical cycle, require in-depth study. Based on samples from rivers in Peninsular Malaysia, this project investigated the source and characteristics of BSi found in Asian tropical rivers, as well as the process of reverse weathering taking place in these fluvial systems. Results indicated that BSi samples collected in sediments consisted of phytolith, diatom and sponge spicules. Phytoliths, predominantly of the elongate form, comprised 92.8%-98.3% of BSi in the Pahang River. Diatom BSi in this river consisted mainly of pennatae diatoms, but represented a relatively small proportion of the total BSi volume. However, diatom BSi (predominantly of the Centricae form) was more prevalent in the Pontian and Endau Rivers with shares of 68.8% and 79.3% of the total BSi volumes, respectively, than Pahang River. Carbon contents of the BSi particulates ranged from 1.85% to 10.8% with an average of 4.79%. These values are higher than those recorded in other studies to date, and indicate that BSi plays a major role in controlling permanent carbon burial. This study suggests that phytoliths from terrestrial plants are the primary constituents of BSi in the rivers of Peninsular Malaysia, and therefore represent a significant proportion of the coastal silica budget.

  11. The EU-Eastern Partnership Countries: Association Agreements and Transdisciplinarity in Studies, Training and Research

    Directory of Open Access Journals (Sweden)

    Muravska Tatyana

    2014-10-01

    Full Text Available The European Union (EU signed Association Agreements on 27 June 2014 with Georgia, the Republic of Moldova, and Ukraine. The Association Agreement (AA is the EU’s main instrument to bring the countries in the Eastern Partnership (EaP closer to EU standards and norms. For the citizens of the EaP countries to benefit from these agreements, a more in-depth knowledge of the EU and the EU Member States is required to be reflected in a comparative approach to European Union studies. We examine these implications on the need to expand and adapt, the content and approach to research and teaching European Union studies, with the transdisciplinary approach becoming increasingly dominant, becoming a modern tool for research in social sciences. This contribution aims to offer insight into the implementation of transdisciplinarity in the methodology of education and research as it is determined by current increasing global challenges. This approach should serve as a means of integrating a number of main goals as part of learning, teaching and research processes: strengthening employability of young people and preparing them for citizenship. We discuss the need for modernizing European studies in the EU Member States that could serve as an example for the EU Eastern Partnership countries. We conclude that the theoretical approach to European and related studies of other disciplines and their practical implications should always be transdisciplinary in nature and benefit from direct in-situ exposure and should be fully integrated in university curricula

  12. Continuing medical education revisited: theoretical assumptions and practical implications: a qualitative study.

    Science.gov (United States)

    Dionyssopoulos, Alexander; Karalis, Thanassis; Panitsides, Eugenia A

    2014-12-31

    Recent research has evidenced that although investment in Continuing Medical Education (CME), both in terms of participation as well as financial resources allocated to it, has been steadily increasing to catch up with accelerating advances in health information and technology, effectiveness of CME is reported to be rather limited. Poor and disproportional returns can be attributed to failure of CME courses to address and stimulate an adult audience. The present study initially drew on research findings and adult learning theories, providing the basis for comprehending adult learning, while entailing practical implications on fostering effectiveness in the design and delivery of CME. On a second level, a qualitative study was conducted with the aim to elucidate parameters accounting for effectiveness in educational interventions. Qualitative data was retrieved through 12 in-depth interviews, conducted with a random sample of participants in the 26th European Workshop of Advanced Plastic Surgery (EWAPS). The data underwent a three level qualitative analysis, following the "grounded theory" methodology, comprising 'open coding', 'axial coding' and 'selective coding'. Findings from the EWAPS study come in line with relevant literature, entailing significant implications for the necessity to apply a more effective and efficient paradigm in the design and delivery of educational interventions, advocating for implementing learner-centered schemata in CME and benefiting from a model that draws on the learning environment and social aspects of learning. What emerged as a pivotal parameter in designing educational interventions is to focus on small group educational events which could provide a supportive friendly context, enhance motivation through learner-centered approaches and allow interaction, experimentation and critical reflection. It should be outlined however that further research is required as the present study is limited in scope, having dealt with a limited

  13. Associations between the peer support relationship, service satisfaction and recovery-oriented outcomes: a correlational study.

    Science.gov (United States)

    Thomas, Elizabeth C; Salzer, Mark S

    2017-12-18

    The working alliance between non-peer providers and mental health consumers is associated with positive outcomes. It is hypothesized that this factor, in addition to other active support elements, is also positively related to peer support service outcomes. This study evaluates correlates of the peer-to-peer relationship and its unique association with service satisfaction and recovery-oriented outcomes. Participants were 46 adults with serious mental illnesses taking part in a peer-brokered self-directed care intervention. Pearson correlation analyses examined associations among peer relationship factors, services-related variables and recovery-oriented outcomes (i.e. empowerment, recovery and quality of life). Hierarchical multiple regression analyses evaluated associations between relationship factors and outcomes over time, controlling for other possible intervention effects. The peer relationship was not related to number of contacts. There were robust associations between the peer relationship and service satisfaction and some recovery-oriented outcomes at 24-months, but not at 12-months. These associations were not explained by other possible intervention effects. This study contributes to a better understanding of the positive, unique association between the peer-to-peer relationship and outcomes, similar to what is found in non-peer-delivered interventions. Implications for program administrators and policymakers seeking to integrate peer specialists into mental health service systems are discussed.

  14. Association of Breast Feeding and Birth Weight with Anthropometric Measures and Blood Pressure in Children and Adolescents: The CASPIAN-IV Study

    Directory of Open Access Journals (Sweden)

    Shirin Djalalinia

    2015-10-01

    Conclusion: BW was associated with a higher prevalence in general obesity and a lower prevalence of being underweight. Duration of BF had no significant association with anthropometric measures and BP. Future longitudinal studies are necessary to determine the clinical implications of these findings.

  15. Association of religion with delusions and hallucinations in the context of schizophrenia: implications for engagement and adherence.

    Science.gov (United States)

    Gearing, Robin Edward; Alonzo, Dana; Smolak, Alex; McHugh, Katie; Harmon, Sherelle; Baldwin, Susanna

    2011-03-01

    The relationship of religion and schizophrenia is widely acknowledged, but often minimized by practitioners and under investigated by researchers. In striving to help fill this gap, this paper focuses on examining four aims: 1) how research has investigated the association between religiosity and schizophrenia; 2) how is religiosity associated with delusions and hallucinations; 3) what are the risk and protective factors associated with religiosity and schizophrenia; and 4) does religion influence treatment adherence with individuals diagnosed with schizophrenia. A systematic literature search of PsycINFO and MEDLINE databases from January 1, 1980 through January 1, 2010 was conducted using the terms schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified (NOS) and religion, religiosity, spirituality, or faith. Seventy (n=70) original research studies were identified. Religion can act as both a risk and protective factor as it interacts with the schizophrenia symptoms of hallucination and delusions. Cultural influences tend to confound the association of religion and schizophrenia. Adherence to treatment has a mixed association with religiosity. The relationship between religion and schizophrenia may be of benefit to both clinicians and researchers through enhancing adherence to treatment, and enhancement of the protective aspects while minimizing associated risk. The relationship of religion and schizophrenia needs further research that is more nuanced and methodologically rigorous, specifically concerning its influence on engagement and adherence to treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Moving beyond Alcohol: A Review of Other Issues Associated with Fraternity Membership with Implications for Practice and Research

    Science.gov (United States)

    Biddix, J. Patrick

    2016-01-01

    This review of research synthesizes more than a decade of published studies on problems associated with fraternity membership beyond alcohol misuse. Topics include sex-related issues, drug use, hazing, and other issues such as gambling, academic dishonesty, campus civility, and fake identification use. Recommendations suggest the need for a role…

  17. Relational antecedents and social implications of the emotion of empathy: Evidence from three studies.

    Science.gov (United States)

    Kim, Sanghag; Kochanska, Grazyna

    2017-09-01

    Despite emotion researchers' strong interest in empathy and its implications for prosocial functioning, surprisingly few studies have examined parent-child attachment as a context for early origins of empathy in young children. Consequently, empirical evidence on links among children's attachment, empathy, and prosociality is thin and inconsistent. We examined such links in 2 longitudinal studies of community families (Family Study, N = 101 mothers, fathers, and children, 14 to 80 months; Parent-Child Study, mothers and children, N = 108, 15 to 45 months) and a study of low-income, diverse mothers and toddlers (Play Study, N = 186, 30 months). Children's security was assessed in Strange Situation in infancy and rated by observers and mothers using Attachment Q-Set at toddler age. Children's empathy was observed in scripted probes that involved parental simulated distress. Children's prosociality was rated by parents (Family Study, Play Study). Security with mothers related to higher empathy. For mother- and father-child dyads, security moderated the path from empathy to prosociality. For insecure children, but not secure ones, variations in empathy related to prosociality. Insecure and unempathic children were particularly low in prosociality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Do emotional eating urges regulate affect? Concurrent and prospective associations and implications for risk models of binge eating.

    Science.gov (United States)

    Haedt-Matt, Alissa A; Keel, Pamela K; Racine, Sarah E; Burt, S Alexandra; Hu, Jean Yueqin; Boker, Steven; Neale, Michael; Klump, Kelly L

    2014-12-01

    Emotional eating (EE) reflects an urge to eat in response to emotional rather than physical cues and is a risk factor for the development of binge eating. EE has been conceptualized as an attempt to regulate negative affect (NA), a posited maintenance factor for binge eating. However, no study has examined whether EE urges regulate affect. Further, no studies have examined longitudinal associations between EE urges and positive affect (PA). We examined within-subject longitudinal associations between affect and EE urges in a community-based sample of female twins (mean age = 17.8 years). Participants (N = 239) completed ratings of affect and EE urges for 45 consecutive days. Greater NA was concurrently associated with greater EE urges. Additionally, greater EE urges predicted worse NA for both concurrent and prospective (next-day) analyses. Finally, lower PA was associated with greater EE urges in concurrent analyses, but there were no prospective associations between changes in PA and EE urges. EE urges do not appear to effectively regulate affect. EE urges in a community-based sample appear to have the same functional relationship with affect as binge eating in clinical samples, further supporting EE as a useful dimensional construct for examining processes related to binge eating. © 2014 Wiley Periodicals, Inc.

  19. Factors Associated With General and Sexual Alcohol-Related Consequences: An Examination of College Students Studying Abroad

    OpenAIRE

    Hummer, Justin F.; Pedersen, Eric R.; Mirza, Tehniat; LaBrie, Joseph W.

    2010-01-01

    This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), predeparture expectations surrounding alcohol use while abroad, culture-related social anxiety, and perceived disparity between home and host cultures differentially predicted consequences abroad. The findings include important implications for student affa...

  20. The Canadian Association for the Study of International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Canadian Association for the Study of International Development (CASID) was founded in 1989 to provide a forum for Canadian scholars, policymakers, and civil society to meet and exchange views. It is the only Canadian learned society devoted to the study of international development. The Association's journal, the ...

  1. 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 ...

  2. The Tuskegee Syphilis Study, 1932 to 1972: Implications for HIV Education and AIDS Risk Education Programs in the Black Community.

    Science.gov (United States)

    Thomas, Stephen B.; Quinn, Sandra Crouse

    1991-01-01

    The Tuskegee study of untreated syphilis in black males caused distrust by blacks of the public health system that has implications for Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) studies. AIDS prevention among blacks may require openness about the Tuskegee study to allay fears of repetition. (SLD)

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Sleep Quality and Associated Factors in Older Turkish Adults With Hypertension: A Pilot Study.

    Science.gov (United States)

    Kara, Belgüzar; Tenekeci, Elif Gökçe

    2017-05-01

    The purpose of this study was to evaluate sleep quality and to explore its associations with participant characteristics, anemia, excessive daytime sleepiness, and physical activity in older Turkish adults with hypertension. This cross-sectional study included 128 adults aged 60 years or older with hypertension. Data were collected by using a personal information form, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the International Physical Activity Questionnaire. Anemia was assessed by hemoglobin levels. Eighty-one patients (63.3%) reported poor sleep quality. Anemia was present in 35.2% of the patients (defined as hemoglobin sleep quality. Conclusion/Implication: The majority of the participants had poor sleep quality. Better understanding of risk factors associated with poor sleep quality may contribute to more effective interventions to improve health and well-being.

  5. The Experimental Study of Bacterial Evolution and Its Implications for the Modern Synthesis of Evolutionary Biology.

    Science.gov (United States)

    O'Malley, Maureen A

    2017-10-04

    Since the 1940s, microbiologists, biochemists and population geneticists have experimented with the genetic mechanisms of microorganisms in order to investigate evolutionary processes. These evolutionary studies of bacteria and other microorganisms gained some recognition from the standard-bearers of the modern synthesis of evolutionary biology, especially Theodosius Dobzhansky and Ledyard Stebbins. A further period of post-synthesis bacterial evolutionary research occurred between the 1950s and 1980s. These experimental analyses focused on the evolution of population and genetic structure, the adaptive gain of new functions, and the evolutionary consequences of competition dynamics. This large body of research aimed to make evolutionary theory testable and predictive, by giving it mechanistic underpinnings. Although evolutionary microbiologists promoted bacterial experiments as methodologically advantageous and a source of general insight into evolution, they also acknowledged the biological differences of bacteria. My historical overview concludes with reflections on what bacterial evolutionary research achieved in this period, and its implications for the still-developing modern synthesis.

  6. Crystallographic studies of drug--nucleic acid crystalline complexes and their biological implications

    Energy Technology Data Exchange (ETDEWEB)

    Sobell, H.M.; Jain, S.C.; Sakore, T.D.; Reddy, B.S.; Bhandary, K.K.; Seshadri, T.P.

    1978-01-01

    It is now over a decade since Lerman proposed his intercalation hypothesis to explain the strong binding mode of the aminoacridines to DNA. A large body of evidence now supports this concept, and it has become increasingly apparent that (in addition to the aminoacridines) a large number of additional drugs and dyes bind to DNA by intercalation. The technique of molecular cocrystallization as developed in our laboratory has provided an opportunity to obtain detailed stereochemical information about interactions between many of these drugs and nucleic acid components and this has led to unifying structural concepts in understanding a large number of drug-DNA interactions. This paper will summarize the results of our crystallographic studies of drug-nucleic acid crystalline complexes done in recent years. It also discusses their broader biological implications in further detail.

  7. Statistical trends in the Journal of the American Medical Association and implications for training across the continuum of medical education.

    Science.gov (United States)

    Arnold, Lauren D; Braganza, Melissa; Salih, Rondek; Colditz, Graham A

    2013-01-01

    Statistical training across the continuum of medical education may not have advanced at the pace of statistical reporting in the medical literature, yet a comprehensive understanding of statistical concepts most commonly presented in current research is critical to the effective practice of Evidence Based Medicine. The objective of this content analysis was to describe statistical techniques used in a leading medical journal, JAMA, across a 20-year period, with a focus on implications for medical education. Two issues of JAMA published each month in 1990, 2000, and 2010 were randomly selected; from these, 361 articles were reviewed. Primary focus, study design, and statistical components were abstracted and examined by year of publication. The number of published RCTs and cohort studies differed significantly across years of interest, with an increasing trend of publication. The most commonly reported statistics over the 20-year period of interest included measures of morbidity and mortality, descriptive statistics, and epidemiologic outcomes. However, between 1990 and 2010, there was an increase in reporting of more advanced methods, such as multivariable regression, multilevel modeling, survival analysis, and sensitivity analysis. While this study is limited by a focus on one specific journal, a strength is that the journal examined is widely read by a range of clinical specialties and is considered a leading journal in the medical field, setting standards for published research. The increases in frequency and complexity of statistical reporting in the literature over the past two decades may suggest that moving beyond basic statistical concepts to a more comprehensive understanding of statistical methods is an important component of clinicians' ability to effectively read and use the medical research. These findings provide information to consider as medical schools and graduate medical education training programs review and revise their statistical training

  8. Statistical trends in the Journal of the American Medical Association and implications for training across the continuum of medical education.

    Directory of Open Access Journals (Sweden)

    Lauren D Arnold

    Full Text Available BACKGROUND: Statistical training across the continuum of medical education may not have advanced at the pace of statistical reporting in the medical literature, yet a comprehensive understanding of statistical concepts most commonly presented in current research is critical to the effective practice of Evidence Based Medicine. The objective of this content analysis was to describe statistical techniques used in a leading medical journal, JAMA, across a 20-year period, with a focus on implications for medical education. METHODS AND FINDINGS: Two issues of JAMA published each month in 1990, 2000, and 2010 were randomly selected; from these, 361 articles were reviewed. Primary focus, study design, and statistical components were abstracted and examined by year of publication. The number of published RCTs and cohort studies differed significantly across years of interest, with an increasing trend of publication. The most commonly reported statistics over the 20-year period of interest included measures of morbidity and mortality, descriptive statistics, and epidemiologic outcomes. However, between 1990 and 2010, there was an increase in reporting of more advanced methods, such as multivariable regression, multilevel modeling, survival analysis, and sensitivity analysis. While this study is limited by a focus on one specific journal, a strength is that the journal examined is widely read by a range of clinical specialties and is considered a leading journal in the medical field, setting standards for published research. CONCLUSIONS: The increases in frequency and complexity of statistical reporting in the literature over the past two decades may suggest that moving beyond basic statistical concepts to a more comprehensive understanding of statistical methods is an important component of clinicians' ability to effectively read and use the medical research. These findings provide information to consider as medical schools and graduate medical education

  9. Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.

    Directory of Open Access Journals (Sweden)

    Azhari Aziz

    Full Text Available Autism spectrum disorders (ASDs are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1 and cXorf36 or Deleted in Autism-1 Related (DIA1R are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L, lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental

  10. Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1937360 people in England: lifetime risks and implications for risk prediction.

    Science.gov (United States)

    Pujades-Rodriguez, Mar; George, Julie; Shah, Anoop Dinesh; Rapsomaniki, Eleni; Denaxas, Spiros; West, Robert; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

    2015-02-01

    It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation. Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997-2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme). During 11.6 million person-years of follow-up, 114859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers' lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR)=1.04, 95% confidence interval (CI) 0.91-1.19).The strength of association differed markedly according to disease type: stable angina (HR=1.08, 95% CI 1.01-1.15),transient ischaemic attack (HR=1.41, 95% CI 1.28-1.55), unstable angina (HR=1.54, 95% CI 1.38-1.72), intracerebral haemorrhage (HR=1.61, 95% CI 1.37-1.89), heart failure (HR=1.62, 95% CI 1.47-1.79), ischaemic stroke (HR=1.90, 95% CI 1.72-2.10), MI (HR=2.32, 95% CI 2.20-2.45), SAH (HR= 2.70, 95% CI 2.27-3.21), PAD (HR=5.16, 95% CI 4.80-5.54) and abdominal aortic aneurysm (AAA) (HR=5.18, 95% CI 4.61-5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR=1.36, 1.47 and 2.74, respectively). The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important

  11. Free Associations Mirroring Self- and World-Related Concepts: Implications for Personal Construct Theory, Psycholinguistics and Philosophical Psychology.

    Science.gov (United States)

    Kuška, Martin; Trnka, Radek; Kuběna, Aleš A; Růžička, Jiří

    2016-01-01

    People construe reality by using words as basic units of meaningful categorization. The present theory-driven study applied the method of a free association task to explore how people express the concepts of the world and the self in words. The respondents were asked to recall any five words relating with the word world. Afterward they were asked to recall any five words relating with the word self. The method of free association provided the respondents with absolute freedom to choose any words they wanted. Such free recall task is suggested as being a relatively direct approach to the respondents' self- and world-related conceptual categories, without enormous rational processing. The results provide us, first, with associative ranges for constructs of the world and the self, where some associative dimensions are defined by semantic polarities in the meanings of peripheral categories (e.g., Nature vs. Culture). Second, our analysis showed that some groups of verbal categories that were associated with the words world and self are central, while others are peripheral with respect to the central position. Third, the analysis of category networks revealed that some categories play the role of a transmitter, mediating the pathway between other categories in the network.

  12. An Empirical Study on User-oriented Association Analysis of Library Classification Schemes

    Directory of Open Access Journals (Sweden)

    Hsiao-Tieh Pu

    2002-12-01

    Full Text Available Library classification schemes are mostly organized based on disciplines with a hierarchical structure. From the user point of view, some highly related yet non-hierarchical classes may not be easy to perceive in these schemes. This paper is to discover hidden associations between classes by analyzing users’ usage of library collections. The proposed approach employs collaborative filtering techniques to discover associated classes based on the circulation patterns of similar users. Many associated classes scattered across different subject hierarchies could be discovered from the circulation patterns of similar users. The obtained association norms between classes were found to be useful in understanding users' subject preferences for a given class. Classification schemes can, therefore, be made more adaptable to changes of users and the uses of different library collections. There are implications for applications in information organization and retrieval as well. For example, catalogers could refer to the ranked associated classes when they perform multi-classification, and users could also browse the associated classes for related subjects in an enhanced OPAC system. In future research, more empirical studies will be needed to validate the findings, and methods for obtaining user-oriented associations can still be improved.[Article content in Chinese

  13. Dentists' restorative decision-making and implications for an 'amalgamless' profession. Part 2: a qualitative study.

    Science.gov (United States)

    Alexander, G; Hopcraft, M S; Tyas, M J; Wong, R H K

    2014-12-01

    In some countries the use of amalgam has been restricted, and the dental profession may be forced into using alternatives to amalgam by a combination of public opinion and legislation, including the proposal that the material be 'phased-down'. The limited research that exists as to restorative decision-making is quantitative in nature and focuses on 'when' a restoration is placed. There is little qualitative research exploring 'why' a material is chosen. Purposive sampling of a representative group of dentists registered in Australia was carried out in two phases; initially six interviews followed by a focus group of six different participants who were audio-recorded. Qualitative data were analysed using computer aided qualitative data analysis software. The findings suggest that dentists' restorative decision-making is a complex interplay of factors. These may be categorized as 'clinical', 'knowledge', 'patient', 'practice type', 'biological' and 'environmental'. Use of amalgam is influenced by each of these to varying degrees. Quantitative analysis of the influences on restorative decision-making is recommended. While the potential future 'phase-down' of amalgam as a restorative material was of concern, there was a general sense of resignation or apathy to the matter. The implications for public health authorities, dental organizations and educators are noted. © 2014 Australian Dental Association.

  14. A Multilevel Study of Students' Motivations of Studying Accounting: Implications for Employers

    Science.gov (United States)

    Law, Philip; Yuen, Desmond

    2012-01-01

    Purpose: The purpose of this study is to examine the influence of factors affecting students' choice of accounting as a study major in Hong Kong. Design/methodology/approach: Multinomial logistic regression and Hierarchical Generalized Linear Modeling (HGLM) are used to analyze the survey data for the level one and level two data, which is the…

  15. Universal design of workplaces through the use of Poka-Yokes: Case study and implications

    Directory of Open Access Journals (Sweden)

    Cristóbal Miralles

    2011-10-01

    Full Text Available Purpose: Employment plays an important part in many people’s lives beyond merely providing income, since continued participation in work can have many therapeutic benefits for workers defined as disabled. However, disabled workers face a range of barriers to employment, despite legislation intended to improve workplace accessibility emphasizing adaptations to the workplace, which many employers often find difficult and expensive. The Poka-Yoke approach was developed in the manufacturing industry as a way of improving productivity by reducing errors using often very simple adaptations. This paper argues that, as Poka-Yokes are designed to make life easier and improve the performance of workers without impairments, they are closer to the philosophy of Universal Design than to Accessible Design, and offer an easy and inclusive way of making work more accessible for all kind of workers. Design/methodology/approach: This paper provides a case study demonstrating the use of the Poka-Yoke approach in a sheltered work centre for disabled; highlighting how they served to improve accessibility to work by fulfilling Universal Design principles. Findings: Our research allows us to demonstrate the great potential of Poka-yokes for gaining accessibility to the workplace. The real application of this approach, both in sheltered work centres and ordinary companies, can contribute to improve the high unemployment rates of disabled people. Research limitations/implications: The proposal is innovative and was applied in one specific company. Thus, a range of customized Poka-yokes would be desirable for different industrial sectors. Practical implications: Managers of sheltered work centres, and also of ordinary companies, can realize about the great potential of Poka-Yokes as an easy means of gaining flexibility and accessibility. Originality/value: There are very few papers relating lean manufacturing tools and disability. Our approach analyzes the benefits of

  16. What is the probability of replicating a statistically significant association in genome-wide association studies?

    Science.gov (United States)

    Jiang, Wei; Xue, Jing-Hao; Yu, Weichuan

    2017-11-01

    The goal of genome-wide association studies (GWASs) is to discover genetic variants associated with diseases/traits. Replication is a common validation method in GWASs. We regard an association as true finding when it shows significance in both primary and replication studies. A question worth pondering is what is the probability of a primary association (i.e. a statistically significant association in the primary study) being validated in the replication study? This article systematically reviews the answers to this question from different points of view. As Bayesian methods can help us integrate out the uncertainty about the underlying effect of the primary association, we will mainly focus on the Bayesian view in this article. We refer the Bayesian replication probability as the replication rate (RR). We further describe an estimation method for RR, which makes use of the summary statistics from the primary study. We can use the estimated RR to determine the sample size of the replication study and to check the consistency between the results of the primary study and those of the replication study. We describe an R-package to estimate and apply RR in GWASs. Simulation and real data experiments show that the estimated RR has good prediction and calibration performance. We also use these data to demonstrate the usefulness of RR. The R-package is available at http://bioinformatics.ust.hk/RRate.html. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Association between restless legs syndrome and migraine: a population-based study.

    Science.gov (United States)

    Zanigni, Stefano; Giannini, Giulia; Melotti, Roberto; Pattaro, Cristian; Provini, Federica; Cevoli, Sabina; Facheris, Maurizio F; Cortelli, Pietro; Pramstaller, Peter P

    2014-09-01

    A higher prevalence of restless legs syndrome (RLS) in migraineurs has been reported in clinical samples and in two large-scale clinical trials performed on healthcare workers but general population-based studies on this topic are lacking. The aim of this study was to assess the association between migraine and RLS in an Italian rural adult population-based setting. The presence of migraine and RLS was assessed via a computer-assisted personal interview and self-administered questionnaires according to current diagnostic criteria in 1567 participants of a preliminary phase of an adult population-based study performed in South Tyrol, Italy. Migraineurs had an increased risk of having RLS also after adjustment for confounding factors such as age, sex, major depression, anxiety and sleep quality (odds ratio 1.79; confidence interval 1.00-3.19; P = 0.049). This association was not modified by aura status and possible causes of secondary RLS. RLS was not significantly associated with tension-type headache. Restless legs syndrome and migraine were associated in our rural adult population. This association could be explained by a possible shared pathogenic pathway which would implicate new management strategies of these two disorders. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

  18. Genome-wide association implicates numerous genes and pleiotropy underlying ecological trait variation in natural populations of Populus trichocarpa

    Energy Technology Data Exchange (ETDEWEB)

    McKown, Athena [University of British Columbia, Vancouver; Klapste, Jaroslav [University of British Columbia, Vancouver; Guy, Robert [University of British Columbia, Vancouver; Geraldes, Armando [University of British Columbia, Vancouver; Porth, Ilga [University of British Columbia, Vancouver; Hannemann, Jan [University of Victoria, Canada; Friedmann, Michael [University of British Columbia, Vancouver; Muchero, Wellington [ORNL; Tuskan, Gerald A [ORNL; Ehlting, Juergen [University of Victoria, Canada; Cronk, Quentin [University of British Columbia, Vancouver; El-Kassaby, Yousry [University of British Columbia, Vancouver; Mansfield, Shawn [University of British Columbia, Vancouver; Douglas, Carl [University of British Columbia, Vancouver

    2014-01-01

    To uncover the genetic basis of phenotypic trait variation, we used 448 unrelated wild accessions of black cottonwood (Populus trichocarpa Torr. & Gray) from natural populations throughout western North America. Extensive information from large-scale trait phenotyping (with spatial and temporal replications within a common garden) and genotyping (with a 34K Populus SNP array) of all accessions were used for gene discovery in a genome-wide association study (GWAS).

  19. Black Families' Lay Views on Health and the Implications for Health Promotion: A Community-Based Study in the UK

    Science.gov (United States)

    Ochieng, Bertha

    2012-01-01

    Many studies focusing on beliefs about health and health promotion have paid little attention to the life experiences of Black and other visible minority ethnic families in western societies. This paper is a report of a study exploring Black families' beliefs about health and the implications of such beliefs for health promotion. Ten Black…

  20. Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.

    Science.gov (United States)

    Ebbert, Mark T W; Ross, Christian A; Pregent, Luc J; Lank, Rebecca J; Zhang, Cheng; Katzman, Rebecca B; Jansen-West, Karen; Song, Yuping; da Rocha, Edroaldo Lummertz; Palmucci, Carla; Desaro, Pamela; Robertson, Amelia E; Caputo, Ana M; Dickson, Dennis W; Boylan, Kevin B; Rademakers, Rosa; Ordog, Tamas; Li, Hu; Belzil, Veronique V

    2017-11-01

    We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease. Our results strongly implicate SERPINA1 in both C9orf72 repeat expansion carriers and non-carriers, where expression levels are greatly increased in both patient groups across the frontal cortex and cerebellum. SERPINA1 expression is particularly pronounced in C9orf72 repeat expansion carriers for both brain regions, where SERPINA1 levels are strictly down regulated across most human tissues, including the brain, except liver and blood, and are not measurable in E18 mouse brain. The altered biological networks we identified contain critical molecular players known to contribute to ALS pathology, which also interact with SERPINA1. Our comprehensive combined methylation and transcription study identifies new genes and highlights that direct genetic and epigenetic changes contribute to c9ALS and sALS pathogenesis.

  1. Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study

    Science.gov (United States)

    Gottlieb, Daniel J.; Hek, Karin; Chen, Ting-hsu; Watson, Nathaniel F.; Eiriksdottir, Gudny; Byrne, Enda M.; Cornelis, Marilyn; Warby, Simon C.; Bandinelli, Stefania; Cherkas, Lynn; Evans, Daniel S.; Grabe, Hans J.; Lahti, Jari; Li, Man; Lehtimäki, Terho; Lumley, Thomas; Marciante, Kristin D.; Pérusse, Louis; Psaty, Bruce M.; Robbins, John; Tranah, Gregory J.; Vink, Jacqueline M.; Wilk, Jemma B.; Stafford, Jeanette M.; Bellis, Claire; Biffar, Reiner; Bouchard, Claude; Cade, Brian; Curhan, Gary C.; Eriksson, Johan G.; Ewert, Ralf; Ferrucci, Luigi; Fülöp, Tibor; Gehrman, Philip R.; Goodloe, Robert; Harris, Tamara B.; Heath, Andrew C.; Hernandez, Dena; Hofman, Albert; Hottenga, Jouke-Jan; Hunter, David J.; Jensen, Majken K.; Johnson, Andrew D.; Kähönen, Mika; Kao, Linda; Kraft, Peter; Larkin, Emma K.; Lauderdale, Diane S.; Luik, Annemarie I.; Medici, Marco; Montgomery, Grant W.; Palotie, Aarno; Patel, Sanjay R.; Pistis, Giorgio; Porcu, Eleonora; Quaye, Lydia; Raitakari, Olli; Redline, Susan; Rimm, Eric B.; Rotter, Jerome I.; Smith, Albert V.; Spector, Tim D.; Teumer, Alexander; Uitterlinden, André G.; Vohl, Marie-Claude; Widen, Elisabeth; Willemsen, Gonneke; Young, Terry; Zhang, Xiaoling; Liu, Yongmei; Blangero, John; Boomsma, Dorret I.; Gudnason, Vilmundur; Hu, Frank; Mangino, Massimo; Martin, Nicholas G.; O’Connor, George T.; Stone, Katie L.; Tanaka, Toshiko; Viikari, Jorma; Gharib, Sina A.; Punjabi, Naresh M.; Räikkönen, Katri; Völzke, Henry; Mignot, Emmanuel; Tiemeier, Henning

    2015-01-01

    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 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 35–80 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 minutes longer per night. The alleles associated with longer sleep duration were associated in previous genome-wide association studies 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

  2. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    However, in Australia, Finland, Spain, Sweden and U.S., there is no significant association between CASP8 D302H and breast cancer risk (Figure 3). No heterogeneity was found between groups or between studies. Hence, the association between CASP8 D302H and breast cancer risk may be country variable. Previously ...

  3. A Discovery Genome-Wide Association Study of Entrepreneurship

    Science.gov (United States)

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

    2012-01-01

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

  4. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects

    National Research Council Canada - National Science Library

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-01-01

    .... We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242...

  5. Robust ranks of true associations in genome-wide case-control association studies.

    Science.gov (United States)

    Zheng, Gang; Joo, Jungnam; Lin, Jing-Ping; Stylianou, Mario; Waclawiw, Myron A; Geller, Nancy L

    2007-01-01

    In whole-genome association studies, at the first stage, all markers are tested for association and their test statistics or p-values are ranked. At the second stage, some most significant markers are further analyzed by more powerful statistical methods. This helps reduce the number of hypotheses to be corrected for in multiple testing. Ranks of true associations in genome-wide scans using a single test statistic have been studied. In a case-control design for association, the trend test has been proposed. However, three different trend tests, optimal for the recessive, additive, and dominant models, respectively, are available for each marker. Because the true genetic model is unknown, we rank markers based on multiple test statistics or test statistics robust to model mis-specification. We studied this problem with application to Problem 3 of Genetic Analysis Workshop 15. An independent simulation study was also conducted to further evaluate the proposed procedure.

  6. Perceptions of Rural Consumers on the Aspects of Meat Quality and Health Implications Associated With Meat Consumption

    Directory of Open Access Journals (Sweden)

    Nomasonto M. Xazela

    2017-05-01

    Full Text Available This study was conducted to determine the perceptions of rural low-income consumers on meat quality and health issues associated with meat consumption. A total of 466 consumers in the Eastern Cape (EC Province (South Africa (SA were randomly sampled, and principal component analyses (PCA were used to analyse the data. With regard to purchasing decisions, correlation analysis was performed to establish the relationships between actual scores and mean scores so as to determine purchase motives and decisions. The major purchase point mentioned by all consumers was the supermarket (65%, and the reasons were that this purchase point was the most hygienic and the meat was fresh (35%. The estimated relationship showed a significant association between products consumed at home and the source of income of consumers. With regard to consumption patterns and health issues, most consumers were aware of nutritional balance issues (64%, and most were aware of the health risks associated with meat consumption (59%. It was concluded that consumer perceptions on the meat quality aspects associated with health and consumption patterns are affected by disposable income and cultural background.

  7. Short-term Exposure to Microgravity and the Associated Risk of Sudden Cardiac Arrest: Implications for Commercial Spaceflight

    Science.gov (United States)

    Laing, Kevin J. C.; Russamono, Thais

    2013-02-01

    The likelihood of trained astronauts developing a life threatening cardiac event during spaceflight is relatively rare, whilst the incidence in untrained individuals is unknown. Space tourists who live a sedentary lifestyle have reduced cardiovascular function, but the associated danger of sudden cardiac arrest (SCA) during a suborbital spaceflight (SOSF) is unclear. Risk during SOSF was examined by reviewing several microgravity studies and methods of determining poor cardiovascular condition. Accurately assessing cardiovascular function and improving baroreceptor sensitivity through exercise is suggested to reduce the incidence of SCA during future SOSFs. Future studies will benefit from past participants sharing medical history; allowing creation of risk profiles and suitable guidelines.

  8. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Directory of Open Access Journals (Sweden)

    Jiali Han

    2008-05-01

    Full Text Available We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62 and p = 7.46x10(-127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14, eye color (p = 6.1x10(-13, and skin tanning response to sunlight (p = 3.9x10(-89. A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52. One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

  9. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Science.gov (United States)

    Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E; Hu, Frank B; Duffy, David L; Zhao, Zhen Zhen; Martin, Nicholas G; Montgomery, Grant W; Hayward, Nicholas K; Thomas, Gilles; Hoover, Robert N; Chanock, Stephen; Hunter, David J

    2008-05-16

    We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62) and p = 7.46x10(-127), respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14)), eye color (p = 6.1x10(-13)), and skin tanning response to sunlight (p = 3.9x10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

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

    OpenAIRE

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

    2015-01-01

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

  11. Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

    DEFF Research Database (Denmark)

    Starnawska, Anna; Tan, Qihua; McGue, Matt

    2017-01-01

    As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance......, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS) in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1) and correlated their blood DNA methylation to their level (cross-sectional analysis) and change in cognitive...... abilities over 10 years (longitudinal analysis). We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10-7), and TAF12 (p = 4.91 × 10-7). KEGG's enrichment analyses of the most...

  12. Progress of genome-wide association studies of ankylosing spondylitis

    Science.gov (United States)

    Li, Zhixiu; Brown, Matthew A

    2017-01-01

    Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily affects the spine and sacroiliac joints. Significant progress has been made in discovery of genetic associations with AS by genome-wide association studies (GWAS) over past decade. These findings have uncovered novel pathways involved pathogenesis of the disease and have led to introduction of novel therapeutic treatments for AS. In this Review, we discuss the genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS-associated variations and critical cell types involved in AS development. PMID:29333268

  13. Trends in participation rates for wildlife-associated outdoor recreation activities by age and race/ethnicity: implications for cohort-component projection models

    Science.gov (United States)

    John F. Dwyer; Allan Marsinko

    1998-01-01

    Cohort-component projection models have been used to explore the implications of increased aging and growth of racial/ethnic minority groups on number of participants in outdoor recreation activities in the years ahead. Projections usually assume that participation rates by age and race/ethnicity remain constant over time. This study looks at trends in activity...

  14. Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

    Directory of Open Access Journals (Sweden)

    Anna Starnawska

    2017-12-01

    Full Text Available As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1 and correlated their blood DNA methylation to their level (cross-sectional analysis and change in cognitive abilities over 10 years (longitudinal analysis. We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10−7, and TAF12 (p = 4.91 × 10−7. KEGG's enrichment analyses of the most associated findings identified “Neuroactive ligand-receptor interaction” as the most enriched pathway (p = 0.0098. Change in cognitive functioning over 10 years was associated with DNA methylation levels in AGBL4 (p = 9.01 × 10−7 and SORBS1 (p = 5.28 × 10−6, with the first gene playing an important role in neuronal survival and the latter gene implicated before in Alzheimer's disease and ischemic stroke. Our findings point to an association between changes in DNA methylation of genes related to neuronal survival and change of cognitive functioning in aging individuals.

  15. Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.

    Science.gov (United States)

    Sano, Motoaki; Kamitsuji, Shigeo; Kamatani, Naoyuki; Hong, Kyung-Won; Han, Bok-Ghee; Kim, Yeonjung; Kim, Jong Wook; Aizawa, Yoshiyasu; Fukuda, Keiichi

    2014-12-15

    Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Genome-Wide Association Studies of Multiple Keratinocyte Cancers

    Science.gov (United States)

    Verkouteren, Joris A. C.; Hofman, Albert; Uitterlinden, André G.; Kraft, Peter; Turman, Constance; Han, Jiali; Cho, Eunyoung; Murabito, Joanne M.; Levy, Daniel; Qureshi, Abrar A.; Nijsten, Tamar

    2017-01-01

    There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene. PMID:28081215

  17. Genome-Wide Association Studies of Multiple Keratinocyte Cancers.

    Directory of Open Access Journals (Sweden)

    Luba M Pardo

    Full Text Available There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs, but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs are associated with susceptibility for mKCs. A genome-wide association study (GWAS of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1. We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6 in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6 were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7. In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis, and found that rs1805007 (MC1R locus was significantly associated with risk of mKCs (p-value = 2.80x10-4. Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007 located at the MC1R gene.

  18. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Science.gov (United States)

    Wendler, Jason P; Okombo, John; Amato, Roberto; Miotto, Olivo; Kiara, Steven M; Mwai, Leah; Pole, Lewa; O'Brien, John; Manske, Magnus; Alcock, Dan; Drury, Eleanor; Sanders, Mandy; Oyola, Samuel O; Malangone, Cinzia; Jyothi, Dushyanth; Miles, Alistair; Rockett, Kirk A; MacInnis, Bronwyn L; Marsh, Kevin; Bejon, Philip; Nzila, Alexis; Kwiatkowski, Dominic P

    2014-01-01

    Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs) and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ) activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ) overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

  19. Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese

    Directory of Open Access Journals (Sweden)

    Li Sheng-Bin

    2011-10-01

    Full Text Available Abstract Background Monoamine oxidases (MAOs catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population. Methods Two functional single nucleotide polymorphisms (SNPs, rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. Results No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001. The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002, but the frequency difference was not significant among male groups. Conclusions Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia.

  20. The relationship between GPs and hospital consultants and the implications for patient care: a qualitative study.

    Science.gov (United States)

    Sampson, Rod; Barbour, Rosaline; Wilson, Philip

    2016-04-14

    Improving the quality of care of at the medical primary-secondary care interface is both a national and a wider concern. In a qualitative exploration of clinicians' relationship at the interface, we want to study how both GPs and hospital specialists regard and behave towards each other and how this may influence patient care. A qualitative interview study was carried out in primary and secondary care centres in NHS Highland health board area, Scotland. Eligible clinicians (general practitioners and hospital specialists) were invited to take part in a semi-structured interview to explore the implications of interface relationships upon patient care. A standard thematic analysis was used, involving an iterative process based on grounded theory. Key themes that emerged for clinicians included communication (the importance of accessing and listening to one another, and the transfer of soft intelligence), conduct (referring to perceived inappropriate transfer of workload at the interface, and resistance to this transfer), relationships (between interface clinicians and between clinicians and their patients), and unrealistic expectations (clinicians expressing idealistic hopes of what their colleagues at the other interface could achieve). The relationship between primary and secondary care clinicians, and, in particular, difficulties and misunderstandings can have an influence upon patient care. Addressing key areas identified in the study may help to improve interface relationships and benefit patient care.

  1. Strontium isotopes in otoliths of a non-migratory fish (slimy sculpin): Implications for provenance studies

    Science.gov (United States)

    Brennan, Sean R.; Fernandez, Diego P.; Zimmerman, Christian E.; Cerling, Thure E.; Brown, Randy J.; Wooller, Matthew J.

    2015-01-01

    Heterogeneity in 87Sr/86Sr ratios of river-dissolved strontium (Sr) across geologically diverse environments provides a useful tool for investigating provenance, connectivity and movement patterns of various organisms and materials. Evaluation of site-specific 87Sr/86Sr temporal variability throughout study regions is a prerequisite for provenance research, but the dynamics driving temporal variability are generally system-dependent and not accurately predictable. We used the time-keeping properties of otoliths from non-migratory slimy sculpin (Cottus cognatus) to evaluate multi-scale 87Sr/86Sr temporal variability of river waters throughout the Nushagak River, a large (34,700 km2) remote watershed in Alaska, USA. Slimy sculpin otoliths incorporated site-specific temporal variation at sub-annual resolution and were able to record on the order of 0.0001 changes in the 87Sr/86Sr ratio. 87Sr/86Sr profiles of slimy sculpin collected in tributaries and main-stem channels of the upper watershed indicated that these regions were temporally stable, whereas the Lower Nushagak River exhibited some spatio-teporal variability. This study illustrates how the behavioral ecology of a non-migratory organism can be used to evaluate sub-annual 87Sr/86Sr temporal variability and has broad implications for provenance studies employing this tracer.

  2. Computational Glycobiology: Mechanistic Studies of Carbohydrate-Active Enzymes and Implication for Inhibitor Design.

    Science.gov (United States)

    Montgomery, Andrew P; Xiao, Kela; Wang, Xingyong; Skropeta, Danielle; Yu, Haibo

    2017-01-01

    Carbohydrate-active enzymes (CAZymes) are families of essential and structurally related enzymes, which catalyze the creation, modification, and degradation of glycosidic bonds in carbohydrates to maintain essentially all kingdoms of life. CAZymes play a key role in many biological processes underpinning human health and diseases (e.g., cancer, diabetes, Alzheimer's diseases, AIDS) and have thus emerged as important drug targets in the fight against pathogenesis. The realization of the full potential of CAZymes remains a significant challenge, relying on a deeper understanding of the molecular mechanisms of catalysis. Considering numerous unsettled questions in the literature, while with a large amount of structural, kinetic, and mutagenesis data available for CAZymes, there is a pressing need and an abundant opportunity for collaborative computational and experimental investigations with the aim to unlock the secrets of CAZyme catalysis at an atomic level. In this review, we briefly survey key methodology development in computational studies of CAZyme catalysis. This is complemented by selected case studies highlighting mechanistic insights provided by computational glycobiology. Implication for inhibitor design by mimicking the transition state is also illustrated for both glycoside hydrolases and glycosyltransferases. The challenges for such studies will be noted and finally an outlook for future directions will be provided. © 2017 Elsevier Inc. All rights reserved.

  3. Association between Helicobacter pylori seropositivity and mild to moderate COPD: clinical implications in an Asian country with a high prevalence of H. pylori.

    Science.gov (United States)

    Lee, Ha Youn; Kim, Ji Won; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Keom

    2016-01-01

    Helicobacter pylori infection is a major cause of gastric diseases. The clinical implications of H. pylori infection in various diseases outside the gastrointestinal system have also been reported, including in some respiratory disorders. In this study, we investigated the seroprevalence of H. pylori in patients with mild to moderate COPD in an Asian country with a high prevalence of H. pylori infection. Also, we aimed to elucidate the association between the seroprevalence of H. pylori and the decline of lung function in patients with COPD. Participants who underwent a medical checkup for H. pylori at a referral hospital in Korea were recruited for this study. All participants were tested for H. pylori infection using an immunoassay of the H. pylori-specific immunoglobulin G (IgG) concentration and a rapid urease test at the time of endoscopy with a gastric mucosal specimen. We assessed the decline in lung function using the spirometric data of those who underwent spirometry more than three times. In total, 603 participants (201 patients with COPD and 402 controls) were analyzed. The seroprevalence of H. pylori IgG in the patients and controls was 45.8% and 52.2%, respectively (P=0.134). The H. pylori IgG level in patients with COPD was not significantly different from that of the controls (114.8 and 109.6 units/mL, respectively; P=0.549). In addition, there were no significant differences in the annual forced expiratory volume in 1 second or forced vital capacity between the participants with H. pylori seropositivity and seronegativity. This study showed no relationship between H. pylori infection and COPD in a country with a high burden of H. pylori infection. Furthermore, H. pylori infection did not affect the rate of lung function decline in this study population.

  4. Association between erectile dysfunction and chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ranjit Singh Uppal

    2014-01-01

    Conclusion: It may be concluded that chronic periodontitis and ED are associated with each other. However, further large scale studies with confounder analysis and longitudinal follow-up are warranted to explore the link between these two diseases.

  5. Family history of diabetes is associated with enhanced adipose lipolysis: Evidence for the implication of epigenetic factors.

    Science.gov (United States)

    Dahlman, I; Ryden, M; Arner, P

    2017-11-11

    Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes. Abdominal subcutaneous fat biopsies were obtained from 581 subjects in a cross-sectional study. Fat cells were isolated, and the difference between measured and expected fat-cell volume was used to determine adipose morphology (degree of hypertrophy or hyperplasia). Spontaneous lipolytic activity was determined in explants of adipose tissue by measuring glycerol release. Insulin-stimulated lipogenesis was assessed by measuring the incorporation of radiolabelled glucose into fat-cell lipids. Information on parental history of diabetes was gathered by a questionnaire. Adipose morphology correlated positively with lipolysis (P<0.0001) and inversely with insulin-stimulated lipogenesis (P<0.008). Also, 24% of probands had a family history of diabetes, which was associated with higher body mass index (BMI) scores, and more insulin resistance (HOMAIR) and adipose hypertrophy. Lipolytic activity was increased, and insulin-stimulated lipogenesis decreased, in probands with a parental history of diabetes. The results for HOMAIR, lipolysis and adipose morphology remained significant after adjusting for proband BMI. A maternal history of diabetes was associated with increased adipose lipolytic activity in probands. A family history of diabetes is independent of proband BMI, but associated with adipocyte hypertrophy and enhanced lipolysis, which suggests that these factors are genetically linked to diabetes. Moreover, the influence on lipolysis was only observed in probands with a maternal history of diabetes, thereby supporting an epigenetic impact. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.

    Science.gov (United States)

    Hedman, Åsa K; Mendelson, Michael M; Marioni, Riccardo E; Gustafsson, Stefan; Joehanes, Roby; Irvin, Marguerite R; Zhi, Degui; Sandling, Johanna K; Yao, Chen; Liu, Chunyu; Liang, Liming; Huan, Tianxiao; McRae, Allan F; Demissie, Serkalem; Shah, Sonia; Starr, John M; Cupples, L Adrienne; Deloukas, Panos; Spector, Timothy D; Sundström, Johan; Krauss, Ronald M; Arnett, Donna K; Deary, Ian J; Lind, Lars; Levy, Daniel; Ingelsson, Erik

    2017-01-01

    Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage ( P disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P =0.0007). We found significant cis -methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels ( P TC =0.004, P HDL-C =0.008 and P triglycerides =0.00003) and coronary heart disease ( P =0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis -methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events. © 2017 The Authors.

  7. Genome-wide association study of pancreatic cancer in Japanese population.

    Directory of Open Access Journals (Sweden)

    Siew-Kee Low

    Full Text Available Pancreatic cancer shows very poor prognosis and is the fifth leading cause of cancer death in Japan. Previous studies indicated some genetic factors contributing to the development and progression of pancreatic cancer; however, there are limited reports for common genetic variants to be associated with this disease, especially in the Asian population. We have conducted a genome-wide association study (GWAS using 991 invasive pancreatic ductal adenocarcinoma cases and 5,209 controls, and identified three loci showing significant association (P-value<5x10(-7 with susceptibility to pancreatic cancer. The SNPs that showed significant association carried estimated odds ratios of 1.29, 1.32, and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P-value of 3.30x10(-7, 3.30x10(-7, and 4.41x10(-7; located on chromosomes 6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located within linkage disequilibrium blocks containing genes that have been implicated some roles in the oncogenesis of pancreatic cancer.

  8. A Case Study with an Identified Bully: Policy and Practice Implications

    Directory of Open Access Journals (Sweden)

    Huddleston, Lillie

    2011-07-01

    Full Text Available Objective: Bullying is a serious public health problem that may include verbal or physical injury as well as social isolation or exclusion. As a result, research is needed to establish a database for policies and interventions designed to prevent bullying and its negative effects. This paper presented a case study that contributed to the literature by describing an intervention for bullies that has implications for research, practice and related policies regarding bullying.Methods: An individualized intervention for an identified bully was implemented using the Participatory Culture-Specific Intervention Model (PCSIM; Nastasi, Moore, & Varjas, 2004 with a seventh-grade middle school student. Ecological and culture-specific perspectives were used to develop and implement the intervention that included psychoeducational sessions with the student and consultation with the parent and school personnel. A mixed methods intervention design was used with the following informants: the target student, the mother of the student, a teacher and the school counselor. Qualitative data included semi-structured interviews with the parent, teacher and student, narrative classroom observations and evaluation/feedback forms filled out by the student and interventionist. Quantitative data included the following quantitative surveys (i.e., Child Posttraumatic Stress Reaction Index [CPTS-RI] and the Behavior Assessment Scale for Children, 2nd Edition. Both qualitative and quantitative data were used to evaluate the acceptability, integrity and efficacy of this intervention.Results: The process of intervention design, implementation and evaluation are described through an illustrative case study. Qualitative and quantitative findings indicated a decrease in internalizing, externalizing and bullying behaviors as reported by the teacher and the mother, and a high degree of acceptability and treatment integrity as reported by multiple stakeholders.Conclusion: This case

  9. Rh factor is associated with individual radiosensitivity: A cytogenetic study

    OpenAIRE

    Khosravifarsani, Meysam; Monfared, Ali Shabestani; Borzoueisileh, Sajad

    2016-01-01

    Introduction Radiosensitivity is an inherent trait, associated with a raised reaction to ionizing radiation on the human body. In radiotherapy and radiation protection fields, individualization of the patient?s treatment is one of the main topics. With the goal of determining biomarkers capable of anticipating normal tissue side reactions, we studied the association between the Rh factor and radiosensitivity. Methods This experimental study was carried out from January to June 2014 among 50 n...

  10. 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.......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....

  11. Genome-wide association study of sporadic brain arteriovenous malformations

    OpenAIRE

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G.; Sidney, Stephen; McCulloch, Charles E.; Al-Shahi Salman, Rustam; Berg, Jonathan N; Bobby P. C. Koeleman; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium.METHODS: The Caucasian discovery cohort included 515 BAVM c...

  12. Self-injury and aggression in adults with tuberous sclerosis complex: Frequency, associated person characteristics, and implications for assessment.

    Science.gov (United States)

    Wilde, Lucy; Eden, Kate; de Vries, Petrus; Moss, Jo; Welham, Alice; Oliver, Chris

    2017-05-01

    Even though self-injury and aggression are common in tuberous sclerosis complex (TSC), understanding of these behaviours in adults with TSC and intellectual disability (ID) is limited. Little is known about their frequency in comparison to other ID-related genetic disorders or their association with other TSC-Associated Neuropsychiatric Disorders (TAND). This study determined the caregiver-reported frequency of self-injury and aggression in adults with TSC plus ID in comparison to Down syndrome (DS) and Angelman syndrome (AS), and assessed demographic and behavioural characteristics associated with the occurrence of each behaviour in TSC. Rates of self-injury and aggression in adults with TSC plus ID were 31% and 37.9% respectively. The odds of self-injury for adults with TSC were nearly twice as high as the odds for adults with DS, and the odds of aggression were over 2.5 times higher for adults with TSC than for adults with DS. When compared to adults with AS, odds of self-injury in TSC were around half those of the AS group, and odds of aggression were less than a third of those for adults with AS. These differences were not statistically significant. In adults with TSC, poorer communication and socialisation skills, gastric health problems and impulsivity were associated with self-injury; compulsive behaviour and impulsivity were associated with aggression. Caregivers and professionals should be alert to the likelihood of these behaviours in adults with TSC plus ID, and to characteristics associated with increased risk for their occurrence. We suggest assessment strategies to identify those at elevated risk. This paper adds specific examination of behavioural difficulties in adults with tuberous sclerosis complex who also have intellectual disability, a population at heightened risk of adverse behavioural outcomes which has received limited focussed examination to date. Findings support existing suggestions that there is relatively high risk for both self

  13. Association Between Heart Rate Variability Measures and Blood Glucose Levels: Implications for Noninvasive Glucose Monitoring for Diabetes.

    Science.gov (United States)

    Rothberg, Leon J; Lees, Ty; Clifton-Bligh, Roderick; Lal, Sara

    2016-06-01

    Diabetes mellitus (DM) is a global metabolic epidemic associated with numerous adverse complications. Invasive finger prick tests or invasive monitors are currently the most common means of monitoring and controlling blood glucose levels (BGLs). Heart rate variability (HRV) is a noninvasive measure of the autonomic nervous system, and its dynamic physiological nature may provide an alternative means of blood glucose monitoring. However, the relationship between BGL and HRV parameters remains relatively unknown. Thirty-two participants with diabetes (39.97 ± 17.21 years of age) and 31 without diabetes (27.87 ± 10.55 years of age) participated in the current study. Fasting preceded a 10-min three-lead electrocardiogram (ECG), which was followed by a finger prick blood glucose assessment. Following this, a regular meal was consumed, and 30 min after ingestion, a second postprandial 10-min ECG was obtained, and blood glucose assessment was conducted. Low-frequency (LF) power, high-frequency (HF) power, and total power (TP) of HRV were negatively associated with BGL in participants with DM. Additionally, the ratio of LF to HF was positively correlated with BGL. Duration of DM was also associated with multiple HRV parameters, with negative associations to both LF and HF parameters as well as TP. This study demonstrates links between specific HRV variables and BGL. In the future the dynamic nature of HRV could provide a unique and real-time method for monitoring BGL, for continuous noninvasive prediction and/or management of DM.

  14. Leveraging the HapMap Correlation Structure in Association Studies

    OpenAIRE

    Zaitlen, Noah; Kang, Hyun Min; Eskin, Eleazar; Halperin, Eran

    2007-01-01

    Recent high-throughput genotyping technologies, such as the Affymetrix 500k array and the Illumina HumanHap 550 beadchip, have driven down the costs of association studies and have enabled the measurement of single-nucleotide polymorphism (SNP) allele frequency differences between case and control populations on a genomewide scale. A key aspect in the efficiency of association studies is the notion of “indirect association,” where only a subset of SNPs are collected to serve as proxies for th...

  15. Kinesiophobia is Strongly Associated with Altered Loading after an ACL Reconstruction: Implications for Re-injury Risk

    Science.gov (United States)

    Noehren, Brian; Kline, Paul; Ireland, Mary Lloyd; Johnson, Darren L.

    2017-01-01

    Objectives: The effect of kinesiophobia (fear of movement) following an anterior cruciate ligament (ACL) reconstruction has recently received greater attention. Elevated kinesiophobia as measured on the Tampa Scale of Kinesiophobia (TSK) has been previously found to be associated with poorer outcomes. However, the effect of kinesiophobia in ACL reconstructed patients on high impact and challenging tasks associated with re injury risk such as jumping has not been investigated. Establishing the relationship between kinesiophobia and jump landing mechanics could result in the development of specific treatments to reduce fear of movement and improve jump landing mechanics after ACL reconstruction, resulting in a diminished re-injury risk. Therefore, the purpose of this study is to define the relationship between landing mechanics (axial loading rates and impact forces) with the TSK score in patients 6 months after ACL reconstruction. Methods: Twenty subjects, 6 months post ACL reconstruction, who had completed post-operative physical therapy, and were cleared by their physician to begin return to sport drills participated in the study. Subjects completed an instrumented drop vertical landing assessment with the ground reaction forces recorded while the subjects performed a drop vertical jump task off a 30.48 cm high box. Three trials were taken and the data were analyzed using custom Labview code and Visual 3D software during the period of time from foot contact until initial impact peak. The average loading rate was defined as the linear portion of the vertical ground reaction curve between 20-80% of foot contact to initial impact peak. Subjects also completed the TSK questionnaire. Associations between loading rate and vertical impact peak to the TSK scale were made with Pearson correlation coefficients with significant relationships defined as pkinesiophobia to be associated with a lower weight-bearing in the ACL reconstructed limb. Potentially, subjects who are

  16. Reorganization of the injured brain: Implications for studies of the neural substrate of cognition

    Directory of Open Access Journals (Sweden)

    Jesper eMogensen

    2011-01-01

    Full Text Available In the search for a neural substrate of cognitive processes, a frequently utilized method is the scrutiny of posttraumatic symptoms exhibited by individuals suffering focal injury to the brain. For instance, the presence or absence of conscious awareness within a particular domain may, combined with knowledge of which regions of the brain have been injured, provide important data in the search for neural correlates of consciousness. Like all studies addressing the consequences of brain injury, however, such research has to face the fact that in most cases, posttraumatic impairments are accompanied by a functional recovery during which symptoms are reduced or eliminated. The apparent contradiction between localization and recovery, respectively, of functions constitutes a problem to almost all aspects of cognitive neuroscience. Several lines of investigation indicate that although the brain remains highly plastic throughout life, the posttraumatic plasticity does not recreate a copy of the neural mechanisms lost to injury. Instead, the uninjured parts of the brain are functionally reorganized in a manner which – in spite of not recreating the basic information processing lost to injury – is able to allow a more or less complete return of the surface phenomena (including manifestations of consciousness originally impaired by the trauma. A novel model (the REF-model of these processes is presented – and some of its implications discussed relative to studies of the neural substrates of cognition and consciousness.

  17. A comprehensive genetic association study of Alzheimer disease in African Americans.

    Science.gov (United States)

    Logue, Mark W; Schu, Matthew; Vardarajan, Badri N; Buros, Jacki; Green, Robert C; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O; Shatz, Rhonna; Borenstein, Amy; Cupples, L Adrienne; Lunetta, Kathryn L; Fallin, M Daniele; Baldwin, Clinton T; Farrer, Lindsay A

    2011-12-01

    To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites. We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population. Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects. Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study. Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P = .0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes. Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific.

  18. Temporomandibular disorders and dental occlusion. A systematic review of association studies: end of an era?

    Science.gov (United States)

    Manfredini, D; Lombardo, L; Siciliani, G

    2017-11-01

    To answer a clinical research question: 'is there any association between features of dental occlusion and temporomandibular disorders (TMD)?' A systematic literature review was performed. Inclusion was based on: (i) the type of study, viz., clinical studies on adults assessing the association between TMD (e.g., signs, symptoms, specific diagnoses) and features of dental occlusion by means of single or multiple variable analysis, and (ii) their internal validity, viz., use of clinical assessment approaches to TMD diagnosis. The search accounted for 25 papers included in the review, 10 of which with multiple variable analysis. Quality assessment showed some possible shortcomings, mainly related with the unspecified representativeness of study populations. Seventeen (N = 17) articles compared TMD patients with non-TMD individuals, whilst eight papers compared the features of dental occlusion in individuals with TMD signs/symptoms and healthy subjects in non-patient populations. Findings are quite consistent towards a lack of clinically relevant association between TMD and dental occlusion. Only two (i.e., centric relation [CR]-maximum intercuspation [MI] slide and mediotrusive interferences) of the almost forty occlusion features evaluated in the various studies were associated with TMD in the majority (e.g., at least 50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses. Such association does not imply a causal relationship and may even have opposite implications than commonly believed (i.e., interferences being the result, and not the cause, of TMD). Findings support the absence of a disease-specific association. Based on that, there seems to lack ground to further hypothesise a role for dental occlusion in the pathophysiology of TMD. Clinicians are encouraged to abandon the old gnathological paradigm in TMD practice. © 2017 John Wiley & Sons Ltd.

  19. Family-based association study of the MTHFR polymorphism C677T in patients with nonsyndromic cleft lip and palate from central Europe.

    NARCIS (Netherlands)

    Reutter, H.; Birnbaum, S.; Lacava, A.D.; Mende, M.; Henschke, H.; Berge, S.; Braumann, B.; Lauster, C.; Schiefke, F.; Wenghoefer, M.H.; Saffar, M.; Reich, R.; Scheer, M.; Kramer, F.J.; Knapp, M.; Mangold, E.

    2008-01-01

    OBJECTIVE: The 677C-->T allele in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the etiology of nonsyndromic cleft lip and palate (CL/P). This study involved a family-based association study of the MTHFR polymorphism. PATIENTS/PARTICIPANTS: We examined 181

  20. Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

    DEFF Research Database (Denmark)

    Vassos, Evangelos; Steinberg, Stacy; Cichon, Sven

    2012-01-01

    Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric...

  1. Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause.

    Science.gov (United States)

    Belo, Najara O; Sairam, M Ram; Dos Reis, Adelina M

    2008-03-01

    Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

  2. Heterogeneity of environments associated with transmission of visceral leishmaniasis in South-Eastern France and implication for control strategies.

    Directory of Open Access Journals (Sweden)

    Benoit Faucher

    Full Text Available BACKGROUND: Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. METHODOLOGY/FINDINGS: We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus, canine reservoir, parasite (L. infantum zymodeme MON-1, and human host. CONCLUSIONS/SIGNIFICANCE: This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They

  3. A genetic association study of DNA methylation levels in the DRD4 gene region finds associations with nearby SNPs.

    Science.gov (United States)

    Docherty, Sophia J; Davis, Oliver Sp; Haworth, Claire Ma; Plomin, Robert; D'Souza, Ursula; Mill, Jonathan

    2012-06-12

    Dopamine receptor D4(DRD4) polymorphisms have been associated with a number of psychiatric disorders, but little is known about the mechanism of these associations. DNA methylation is linked to the regulation of gene expression and plays a vital role in normal cellular function, with abnormal DNA methylation patterns implicated in a range of disorders. Recent evidence suggests DNA methylation can be influenced by cis-acting DNA sequence variation, that is, DNA sequence variation located nearby on the same chromosome. To investigate the potential influence of cis-acting genetic elements within DRD4, we analysed DRD4 promoter DNA methylation levels in the transformed lymphoblastoid cell-line DNA of 89 individuals (from 30 family-trios). Five SNPs located +/- 10kb of the promoter region were interrogated for associations with DNA methylation levels. Four significant SNP associations were found with DNA methylation (rs3758653, rs752306, rs11246228 and rs936465). The associations of rs3758653 and rs936465 with DNA methylation were tested and nominally replicated (p-value associations. DRD4 has been implicated in several psychiatric disease phenotypes and our results shed light upon the possible mode of action of SNP associations in this region.

  4. 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.

  5. Rainfall characteristics and their implications for rain-fed agriculture : a case study in the Upper Zambezi River Basin

    NARCIS (Netherlands)

    Beyer, M.; Wallner, M.; Bahlmann, L.; Thiemig, V.; Dietrich, J.; Billib, M.

    2016-01-01

    This study investigates rainfall characteristics in the Upper Zambezi River Basin and implications for rain-fed agriculture. Seventeen indices describing the character of each rainy season were calculated using a bias-corrected version of TRMM-B42 v6 rainfall estimate for 1998–2010. These were

  6. Genotypic and phenotypic properties of cattle-associated Campylobacter and their implications to public health in the USA.

    Directory of Open Access Journals (Sweden)

    Yasser M Sanad

    Full Text Available Since cattle are a major source of food and the cattle industry engages people from farms to processing plants and meat markets, it is conceivable that beef-products contaminated with Campylobacter spp. would pose a significant public health concern. To better understand the epidemiology of cattle-associated Campylobacter spp. in the USA, we characterized the prevalence, genotypic and phenotypic properties of these pathogens. Campylobacter were detected in 181 (19.2% out of 944 fecal samples. Specifically, 71 C. jejuni, 132 C. coli, and 10 other Campylobacter spp. were identified. The prevalence of Campylobacter varied regionally and was significantly (P<0.05 higher in fecal samples collected from the South (32.8% as compared to those from the North (14.8%, Midwest (15.83%, and East (12%. Pulsed Field Gel Electrophoresis (PFGE analysis showed that C. jejuni and C. coli isolates were genotypically diverse and certain genotypes were shared across two or more of the geographic locations. In addition, 13 new C. jejuni and two C. coli sequence types (STs were detected by Multi Locus Sequence Typing (MLST. C. jejuni associated with clinically human health important sequence type, ST-61 which was not previously reported in the USA, was identified in the present study. Most frequently observed clonal complexes (CC were CC ST-21, CC ST-42, and CC ST-61, which are also common in humans. Further, the cattle associated C. jejuni strains showed varying invasion and intracellular survival capacity; however, C. coli strains showed a lower invasion and intracellular survival potential compared to C. jejuni strains. Furthermore, many cattle associated Campylobacter isolates showed resistance to several antimicrobials including ciprofloxacin, erythromycin, and gentamicin. Taken together, our results highlight the importance of cattle as a potential reservoir for clinically important Campylobacter.

  7. An Emerging Entity: Pancreatic Adenocarcinoma Associated with a Known BRCA Mutation: Clinical Descriptors, Treatment Implications, and Future Directions

    Science.gov (United States)

    Lowery, Maeve A.; Kelsen, David P.; Stadler, Zsofia K.; Yu, Kenneth H.; Janjigian, Yelena Y.; Ludwig, Emmy; D'Adamo, David R.; Salo-Mullen, Erin; Robson, Mark E.; Allen, Peter J.; Kurtz, Robert C.

    2011-01-01

    Background. BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported. Methods. Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center. Results. Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response. Conclusion. BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC. PMID:21934105

  8. 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.

  9. Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study.

    Science.gov (United States)

    Lunetta, Kathryn L; D'Agostino, Ralph B; Karasik, David; Benjamin, Emelia J; Guo, Chao-Yu; Govindaraju, Raju; Kiel, Douglas P; Kelly-Hayes, Margaret; Massaro, Joseph M; Pencina, Michael J; Seshadri, Sudha; Murabito, Joanne M

    2007-09-19

    Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate > or =80%, minor allele frequency > or =10%, Hardy-Weinberg test p > or = 0.001). In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate

  10. Counseling a Student Presenting Borderline Personality Disorder in the Small College Context: Case Study and Implications

    Science.gov (United States)

    Draper, Matthew R.; Faulkner, Ginger E.

    2009-01-01

    This case study examines the dynamics and challenges associated with counseling a client experiencing borderline personality disorder in the small college institutional context. The work of counseling centers at small private institutions has been relatively unexplored in the extant college counseling literature. To help fill this gap, the current…

  11. Isotopic study on the volcanics of the Rooiberg group - age implications and a potential exploration tool

    CSIR Research Space (South Africa)

    Harmer, RE

    1995-04-01

    Full Text Available Many geochronological studies on silicic magmatic rocks associated with the Bushveld Complex (rhyolitic lavas of the Rooiberg Group and granites of the Lebowa Granite Suite) have shown evidence of open-system behaviour of the Rb-Sr and Pb-Pb...

  12. A synthesis of studies searching for school factors : implications for theory and research

    NARCIS (Netherlands)

    Kyriakides, L.; Creemers, B.P.M.; Antoniou, P.; Demetriou, D.

    2010-01-01

    This paper reports the results of a meta-analysis in which the dynamic model of educational effectiveness is used as a framework to search for school factors associated with student achievement. The methods and results of a synthesis of 67 studies are presented. Findings reveal that effective

  13. Inhibitions and implications associated with celebrity participation in social marketing programs focusing on HIV prevention: an exploratory research

    OpenAIRE

    Beatriz Casais; João F. Proença

    2010-01-01

    This paper discusses celebrity participation in social marketing programs focusing on public health, especially on HIV programs. The research identifies the inhibitions of celebrity people and implications that this involvement may have upon their lives. The paper analysis data from in-depth interviews made to twenty-seven Portuguese celebrities from arts, show business and sports. The results show absence of prejudice against HIV. Famous people feel motivated to join public health and HIV ca...

  14. Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

    Science.gov (United States)

    Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

    2009-01-01

    Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

  15. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  16. Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention.

    Directory of Open Access Journals (Sweden)

    Cosmeri Rizzato

    Full Text Available Helicobacter pylori (HP is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes pathogenicity island (cagPAI, a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS. This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous showed statistically significant differences (P<0.05, and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10⁻⁶, and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations.

  17. Associations of specific phobia and its subtypes with physical diseases: an adult community study.

    Science.gov (United States)

    Witthauer, Cornelia; Ajdacic-Gross, Vladeta; Meyer, Andrea Hans; Vollenweider, Peter; Waeber, Gerard; Preisig, Martin; Lieb, Roselind

    2016-05-21

    Specific phobia is the most prevalent anxiety disorder in the community and is associated with substantial impairment. Comorbidity with physical diseases is assumed and has important implications for etiology, treatment, or prevention of the comorbid conditions. However, due to methodological issues data are limited and subtypes of specific phobia have not been investigated yet. We examined the association of specific phobia and its subtypes with physical diseases in a representative community sample with physician-diagnosed physical diseases and diagnostic criteria of specific phobia. Data of the German Mental Health Survey from 4181 subjects aged 18-65 years were used. Specific phobia was diagnosed using M-CIDI/DIA-X interview; physical diseases were assessed through a self-report questionnaire and a medical interview. Logistic regression analyses adjusted for sex were calculated. Specific phobia was associated with cardiac diseases, gastrointestinal diseases, respiratory diseases, arthritic conditions, migraine, and thyroid diseases (odds ratios between 1.49 and 2.53). Among the subtypes, different patterns of associations with physical diseases were established. The findings were partially replicated in the Swiss PsyCoLaus Study. Our analyses show that subjects with specific phobia have an increased probability for specific physical diseases. From these analyses etiological mechanisms of specific phobia and physical disease can be deduced. As subtypes differed in their patterns of associations with physical diseases, different etiological mechanisms may play a role. The findings are highly relevant for public health in terms of prevention and therapy of the comorbid conditions.

  18. A genome-wide association study of copy number variations with umbilical hernia in swine.

    Science.gov (United States)

    Long, Yi; Su, Ying; Ai, Huashui; Zhang, Zhiyan; Yang, Bin; Ruan, Guorong; Xiao, Shijun; Liao, Xinjun; Ren, Jun; Huang, Lusheng; Ding, Nengshui

    2016-06-01

    Umbilical hernia (UH) is one of the most common congenital defects in pigs, leading to considerable economic loss and serious animal welfare problems. To test whether copy number variations (CNVs) contribute to pig UH, we performed a case-control genome-wide CNV association study on 905 pigs from the Duroc, Landrace and Yorkshire breeds using the Porcine SNP60 BeadChip and penncnv algorithm. We first constructed a genomic map comprising 6193 CNVs that pertain to 737 CNV regions. Then, we identified eight CNVs significantly associated with the risk for UH in the three pig breeds. Six of seven significantly associated CNVs were validated using quantitative real-time PCR. Notably, a rare CNV (CNV14:13030843-13059455) encompassing the NUGGC gene was strongly associated with UH (permutation-corrected P = 0.0015) in Duroc pigs. This CNV occurred exclusively in seven Duroc UH-affected individuals. SNPs surrounding the CNV did not show association signals, indicating that rare CNVs may play an important role in complex pig diseases such as UH. The NUGGC gene has been implicated in human omphalocele and inguinal hernia. Our finding supports that CNVs, including the NUGGC CNV, contribute to the pathogenesis of pig UH. © 2016 Stichting International Foundation for Animal Genetics.

  19. Martian sand sheet characterization and implications for formation: A case study

    Science.gov (United States)

    Runyon, Kirby D.; Bridges, Nathan T.; Newman, Claire E.

    2017-12-01

    Windblown sand and dust dominate surface geologic processes in Mars' current environment. Besides sand dune fields, areally extensive sand sheets are common across Mars, blanketing the underlying topography with several meters of rippled sand. Earth's sand sheets commonly form upwind or cross-wind to dunes and both partially trap and source sediment to downwind dunes. In contrast, Mars' sheets are frequently located downwind of active barchan and dome sand dunes, suggesting they cannot be a sediment source for the dunes as on Earth. Here, we characterize a Martian sand sheet and its geologic context, model the regional atmospheric circulation, and more broadly consider the implications for sand sheet formation on Mars. Our case study sand sheet in central Herschel Crater is geologic unit interpreted as outcrops of paleo-sand sheets is adjacent to the active sheets. Our observations and atmospheric modeling-which predict wind shear stresses above the sand suspension threshold-indicate that the upwind dunes may be eroding and their sand deposited downwind in sheets in what may be a cyclical process, possibly related to Mars' axial obliquity cycles.

  20. Comparison of the observed and calculated clear sky greenhouse effect - Implications for climate studies

    Science.gov (United States)

    Kiehl, J. T.; Briegleb, B. P.

    1992-01-01

    The clear sky greenhouse effect is defined in terms of the outgoing longwave clear sky flux at the top of the atmosphere. Recently, interest in the magnitude of the clear sky greenhouse effect has increased due to the archiving of the clear sky flux quantity through the Earth Radiation Budget Experiment (ERBE). The present study investigates to what degree of accuracy this flux can be analyzed by using independent atmospheric and surface data in conjunction with a detailed longwave radiation model. The conclusion from this comparison is that for most regions over oceans the analyzed fluxes agree to within the accuracy of the ERBE-retrieved fluxes (+/- 5 W/sq m). However, in regions where deep convective activity occurs, the ERBE fluxes are significantly higher (10-15 W/sq m) than the calculated fluxes. This bias can arise from either cloud contamination problems or variability in water vapor amount. It is argued that the use of analyzed fluxes may provide a more consistent clear sky flux data set for general circulation modeling validation. Climate implications from the analyzed fluxes are explored. Finally, results for obtaining longwave surface fluxes over the oceans are presented.

  1. Rapid Urban Expansion and Its Implications on Geomorphology: A Remote Sensing and GIS Based Study

    Directory of Open Access Journals (Sweden)

    S. N. Mohapatra

    2014-01-01

    Full Text Available Topography, vegetation, climate, water table, and even the anthropogenic activities all are affected by urban growth through diverse mechanisms. The present study focuses on the implications of urban expansion on geomorphology in the historical city of Gwalior in central India. The expansion of urban area has been quantified by deriving data for four decades (1972–2013 from the Landsat images. The results show that the urban built-up area has increased by 08.48 sq. km during the first eighteen years (1972–1990 which has increased to 16.28 sq. km during the next sixteen years (1990–2006. The built-up area has gone up to 23.19 sq. km in the next seven years (2006–2013. Overall during the last 40 years the growth of the urban built-up is nearly three times of the built-up areas in 1972. The average decadal growth rate of population is 27.28 percent while that of built-up land is 36.29 percent. The construction activities have affected important geomorphic features such pediplain, buried pediplain, residual hills, and denudational hills. It was concluded that, instead of shortsighted urban development, proper measures should be taken in accordance with scientific planning for the urban expansion of the city in the future.

  2. Modelling the black death. A historical case study and implications for the epidemiology of bubonic plague.

    Science.gov (United States)

    Monecke, Stefan; Monecke, Hannelore; Monecke, Jochen

    2009-12-01

    We analysed a plague outbreak in the mining town of Freiberg in Saxony which started in May 1613 and ended in February 1614. This epidemic was selected for study because of the high quality of contemporary sources. It was possible to identify 1400 individual victims meaning that more than 10% of the population of the city perished. The outbreak was modelled by 9 differential equations describing flea, rat, and human populations. This resulted in a close fit to the historical records of this outbreak. An interesting implication of the model is that the introduction of even a small number of immune rats into an otherwise unchanged setting results in an abortive outbreak with very few human victims. Hence, the percentage of immune rats directly influences the magnitude of a human epidemic by diverting search activities of the fleas. Thus, we conclude that the spread of Rattus norvegicus, which might acquire partial herd immunity by exposure to soil- or water-borne Yersinia species due to its preference for wet habitats, contributed to the disappearance of Black Death epidemics from Europe in the 18th century. In order to prove whether or not the parameter values obtained by fitting a given outbreak are also applicable to other cases, we modelled the plague outbreak in Bombay 1905/06 using the same parameter values except for the number of humans as well as of immune and susceptible rats.

  3. Implications of Switching Fossil Fuel Subsidies to Solar: A Case Study for the European Union

    Directory of Open Access Journals (Sweden)

    Jon Sampedro

    2017-12-01

    Full Text Available Fossil fuel subsidies (FFS constitute one of the most obvious barriers to tackling climate change, as they encourage inefficient energy consumption and divert investment away from clean energy sources. According to the International Monetary Fund, FFS amounted globally to $233 billion in 2014, over four times the value of subsidies awarded to promote renewable energy. In this study an integrated assessment model is used to analyse the CO2 implications in the European Union of eliminating FFS and recycling the revenues to promote rooftop PV. It is found that eliminating FFS would give rise to a small reduction in CO2 due to fuel-switching from coal to gas. If the revenues were recycled to promote solar, then the CO2 reduction would increase from 1.8% to 2.2% by 2030. Eliminating FFS is not a panacea from the mitigation point of view, even if the revenues are recycled, but other important objectives, such as those related to renewable energy promotion and the reduction of air pollution, are advanced at zero cost for the government.

  4. Correlates of Cortisol in Human Hair: Implications for Epidemiologic Studies on Health Effects of Chronic Stress

    Science.gov (United States)

    Wosu, Adaeze C.; Valdimarsdóttir, Unnur; Shields, Alexandra E.; Williams, David R.; Williams, Michelle A.

    2013-01-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, “cortisol” “hair” “confounders” “chronic” “stress” and “correlates.” Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., PTSD), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing´s syndrome) and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear to not be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. PMID:24184029

  5. Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression.

    Science.gov (United States)

    Takada, Kazuki; Okamoto, Tatsuro; Tominaga, Masaki; Teraishi, Koji; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Masaki; Oda, Yoshinao; Hoshino, Tomoaki; Maehara, Yoshihiko

    2017-01-01

    Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher's exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.

  6. Power analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Klein Robert J

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  7. 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.

  8. Students’ Understanding of the Concept of Democracy and Implications for Teacher Education in Social Studies

    Directory of Open Access Journals (Sweden)

    Nora Elise Hesby Mathé

    2016-04-01

    be actively encouraged and maintained also in successful democracies. Little is known, however, about how students understand and explain democracy as a subject-specific concept. Such knowledge may be valuable for social studies teachers and teacher educators to fulfil the purpose of the social studies curriculum. The present article investigates 16-year-old students’ understanding of the concept of democracy. In social studies, the concept of democracy is essential not only for disciplinary understanding and discourse, but also for students’ out-of-school democratic participation. To investigate students’ understanding of this concept, semi-structured group interviews were conducted with a total of 23 students at three different Norwegian upper secondary schools. A central finding is that students primarily expressed a liberal understanding of democracy focusing on voting in elections as the main political activity. Students also demonstrated more or less limited or elaborate understanding. In addition to presenting and discussing students’ understandings of the concept of democracy, this article considers implications for teacher education in social studies. One implication is that teacher educators need to engage actively in discussing and defining core concepts with their students. This is related to supporting student teachers’ professional development and in turn developing adolescents’ opportunities for democratic participation. Such a dual focus can provide a knowledge base to help student teachers in their professional development in their first years as practicing teachers.Keywords: democracy, concepts, understanding, teacher education, social studies, democratic theory

  9. Population structure and association mapping studies for important ...

    Indian Academy of Sciences (India)

    Large phenotypic variability was observed for the agronomic traits under study indicating suitability of the genotypes for association studies. The maximum values for plant height, pods per plant, seeds per pod, 100-seed weight and seed yield per plant were approximately two and half to three times more than the minimum ...

  10. A genome-wide association study of aging

    NARCIS (Netherlands)

    S. Walter (Stefan); G. Atzmon (Gil); E.W. Demerath (Ellen); M. Garcia (Melissa); R.C. Kaplan (Robert); M. Kumari (Meena); K.L. Lunetta (Kathryn); Y. Milaneschi (Yuri); T. Tanaka (Toshiko); G.J. Tranah (Gregory); U. Völker (Uwe); L. Yu (Lei); A.M. Arnold (Alice); E.J. Benjamin (Emelia); R. Biffar (Reiner); A.S. Buchman (Aron); E.A. Boerwinkle (Eric); D. Couper (David); P.L. de Jager (Philip); D.A. Evans (Denis); T.B. Harris (Tamara); W. Hoffmann (Wolfgang); A. Hofman (Albert); D. Karasik (David); D.P. Kiel (Douglas); T. Kocher (Thomas); M. Kuningas (Maris); L.J. Launer (Lenore); K. Lohman (Kurt); P.L. Lutsey (Pamela); J.P. Mackenbach (Johan); K. Marciante (Kristin); B.M. Psaty (Bruce); E.M. Reiman (Eric); J.I. Rotter (Jerome); S. Seshadri (Sudha); M.D. Shardell (Michelle); A.V. Smith (Albert Vernon); P. Tikka-Kleemola (Päivi); J. Walston (Jeremy); M.C. Zillikens (Carola); S. Bandinelli (Stefania); S.E. Baumeister (Sebastian); D.A. Bennett (David); L. Ferrucci (Luigi); V. Gudnason (Vilmundur); M. Kivimaki (Mika); Y. Liu (Yongmei); J. Murabito (Joanne); A.B. Newman (Anne); H.W. Tiemeier (Henning); N. Franceschini (Nora)

    2011-01-01

    textabstractHuman longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2)

  11. Update on bacterial meningitis: epidemiology, trials and genetic association studies

    NARCIS (Netherlands)

    Kasanmoentalib, E. Soemirien; Brouwer, Matthijs C.; van de Beek, Diederik

    2013-01-01

    Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of

  12. 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|info:eu-repo/dai/nl/369207084; 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|info:eu-repo/dai/nl/191430129; 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

  13. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    Yamamoto T. 2004 Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res. 27, 903–909. Murabito J. M., Yang Q., Fox C., Wilson P. W. and Cupples L. A.. 2005a Heritability of age at natural menopause in the Framing- ham Heart Study. J. Clin.

  14. Learner, Patient, and Supervisor Features Are Associated With Different Types of Cognitive Load During Procedural Skills Training: Implications for Teaching and Instructional Design.

    Science.gov (United States)

    Sewell, Justin L; Boscardin, Christy K; Young, John Q; Ten Cate, Olle; O'Sullivan, Patricia S

    2017-11-01

    Cognitive load theory, focusing on limits of the working memory, is relevant to medical education; however, factors associated with cognitive load during procedural skills training are not well characterized. The authors sought to determine how features of learners, patients/tasks, settings, and supervisors were associated with three types of cognitive load among learners performing a specific procedure, colonoscopy, to identify implications for procedural teaching. Data were collected through an electronically administered survey sent to 1,061 U.S. gastroenterology fellows during the 2014-2015 academic year; 477 (45.0%) participated. Participants completed the survey immediately following a colonoscopy. Using multivariable linear regression analyses, the authors identified sets of features associated with intrinsic, extraneous, and germane loads. Features associated with intrinsic load included learners (prior experience and year in training negatively associated, fatigue positively associated) and patient/tasks (procedural complexity positively associated, better patient tolerance negatively associated). Features associated with extraneous load included learners (fatigue positively associated), setting (queue order positively associated), and supervisors (supervisor engagement and confidence negatively associated). Only one feature, supervisor engagement, was (positively) associated with germane load. These data support practical recommendations for teaching procedural skills through the lens of cognitive load theory. To optimize intrinsic load, level of experience and competence of learners should be balanced with procedural complexity; part-task approaches and scaffolding may be beneficial. To reduce extraneous load, teachers should remain engaged, and factors within the procedural setting that may interfere with learning should be minimized. To optimize germane load, teachers should remain engaged.

  15. Interchangeability among reference insulin analogues and their biosimilars: regulatory framework, study design and clinical implications.

    Science.gov (United States)

    Dowlat, H A; Kuhlmann, M K; Khatami, H; Ampudia-Blasco, F J

    2016-08-01

    Biosimilars are regulated differently from small-molecule generic, chemically derived medicines. The complexity of biological products means that small changes in manufacturing or formulation may result in changes in efficacy and safety of the final product. In the face of this complexity, the regulatory landscape for biosimilars continues to evolve, and global harmonization regarding requirements is currently lacking. It is essential that clinicians and patients are reassured that biosimilars are equally safe and effective as their reference product, and this is particularly important when interchangeability, defined as 'changing one medicine for another one which is expected to achieve the same clinical effect in a given clinical setting in any one patient', is considered. Although the automatic substitution (i.e. substitution without input from the prescribing healthcare provider) of biosimilars for reference products is currently not permitted by the majority of countries, this may change in the future. In order to demonstrate interchangeability between reference products and a biosimilar, more stringent and specific studies of the safety and efficacy of biosimilars are likely to be needed; however, guidance on the design of and the need for any such studies is currently limited. The present article provides an overview of the current regulatory framework around the demonstration of interchangeability with biosimilars, with a specific focus on biosimilar insulin analogues, and details experiences with other biosimilar products. In addition, designs for studies to evaluate interchangeability with a biosimilar insulin analogue product are proposed and a discussion about the implications of interchangeability in clinical practice is included. © 2016 John Wiley & Sons Ltd.

  16. A qualitative study of recently bereaved people's beliefs about death: implications for bereavement care.

    Science.gov (United States)

    Draper, Peter; Holloway, Margaret; Adamson, Susan

    2014-05-01

    To investigate the beliefs of recently bereaved people about death and to explore the implications of these beliefs for bereavement care. Little is known about recently bereaved people's beliefs about death, although there is evidence that these beliefs may have an impact on health. The funeral provides an opportunity for bereaved people to reflect on their beliefs about death. A qualitative approach. This paper describes one aspect of an interdisciplinary study of the spirituality of contemporary funerals. We obtained access to 46 funerals through funeral directors and other contacts, and interviewed principal mourners to explore their beliefs. Interviews were recorded, transcribed verbatim and analysed thematically. Three themes emerged that reflected the beliefs and experiences of bereaved people. The first theme describes people's understanding of death in terms of five positions: religious, dualist, eco-spiritualist, materialist and death-as-transition. The second theme addresses a range of views about the possibility of life after death: resurrection, reuniting and reincarnation. The third theme describes ways in which people felt that their relationship with the deceased person continues after death: continuity as sense of presence and continuity as memory, legacy and love. Some people were reluctant to express a firm view about death. People express a spectrum of beliefs about death. Their beliefs are infrequently linked to formal religious or spiritual perspectives but seem to have an important role in coping with bereavement. This is a unique study illustrating the complexity of bereaved people's beliefs about death. The study provides a research-based framework within which to understand contemporary beliefs about death, and contributes to our understanding of how health professionals can support recently bereaved people. © 2013 John Wiley & Sons Ltd.

  17. The ISO 14001 EMS Implementation Process and Its Implications: A Case Study of Central Japan.

    Science.gov (United States)

    Mohammed

    2000-02-01

    / This study aims to investigate the ISO 14001 implementation process and its implications for regional environmental management. The region of Central Japan (known as Chubu in Japanese, which literally means center) was chosen for this case study. The study focuses on selected issues such as the: (1) trends and motives of private firms in the implementation of an ISO 14001-based environmental management system (EMS); (2) obstacles during system implementation; (3) role of the system in enhancing environmental performance within the certified organization; and (4) relation between the major stakeholders, local citizens, governments, and firms after adopting the system. To achieve these objectives, a questionnaire survey was mailed to all certified firms in the region. A 58% response was achieved overall. The results show that the main aims behind the adoption of ISO 14001 by firms in the Chubu region are to improve the environmental aspects within the enterprises and to enhance the employees' environmental awareness and capacity. The results have also shown that the ISO 14001-based EMS has had a great effect on a firm's environmental status as certified firms have claimed that natural resources such as fuel, water, and paper consumption have been more efficiently managed after adopting the system. Implementation of the system causes the firms to consider the role of the local people and the government in more effectively involving the local people in the firm's daily environmental activities. It also helps to enhance the environmental awareness among the local people. Adopting the system also promotes a better relation within the enterprises affiliated to the same group, such as more attention given by the parent firms (head offices) towards other firms working for the same group, or branches-mainly small and medium sized enterprises (SMEs)-in the field of EMS. Finally, the results show that firms give serious consideration to their final products' impacts on the

  18. Genetic association studies of copy-number variation: should assignment of copy number states precede testing?

    Directory of Open Access Journals (Sweden)

    Patrick Breheny

    Full Text Available Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array at the level of the individual marker, and then aggregate neighboring test results to identify CNVs associated with the phenotype. Here, we explore the strengths and weaknesses of these two approaches using both simulations and real data from a pharmacogenomic study of the chemotherapeutic agent gemcitabine. Our results indicate that pooled marker-level testing is capable of offering a dramatic increase in power (> 12-fold over CNV-level testing, particularly for small CNVs. However, CNV-level testing is superior when CNVs are large and rare; understanding these tradeoffs is an important consideration in conducting association studies of structural variation.

  19. Genetics of Myasthenia Gravis: A Case-Control Association Study in the Hellenic Population

    Directory of Open Access Journals (Sweden)

    Zoi Zagoriti

    2012-01-01

    Full Text Available Myasthenia gravis (MG is an heterogeneous autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane, in the neuromuscular junction. The contribution of genetic factors to MG susceptibility has been evaluated through family and twin studies however, the precise genetic background of the disease remains elusive. We conducted a case-control association study in 101 unrelated MG patients of Hellenic origin and 101 healthy volunteers in order to assess the involvement of common genetic variants in susceptibility to MG. We focused on three candidate genes which have been clearly associated with several autoimmune diseases, aiming to investigate their potential implication in MG pathogenesis. These are interferon regulatory factor 5 (IRF-5, TNFα-induced protein 3 (TNFAIP3, also known as A20, and interleukin-10 (IL-10, key molecules in the regulation of immune function. A statistical trend of association (P=0.068 between IL-10 promoter single nucleotide polymorphisms (SNPs and the subgroups of early and late-onset MG patients was revealed. No statistically significant differences were observed in the rest of the variants examined. As far as we are aware, this is the first worldwide attempt to address the possible association between IRF-5 and TNFAIP3 common genetic variants and the genetic basis of MG.

  20. Genetic association studies of obesity in Africa: a systematic review.

    Science.gov (United States)

    Yako, Y Y; Echouffo-Tcheugui, J B; Balti, E V; Matsha, T E; Sobngwi, E; Erasmus, R T; Kengne, A P

    2015-03-01

    Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies. © 2015 World Obesity.

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

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    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.

  2. 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

  3. Eating breakfast and dinner together as a family: Associations with sociodemographic characteristics and implications for diet quality and weight status

    Science.gov (United States)

    Larson, Nicole; MacLehose, Rich; Fulkerson, Jayne A.; Berge, Jerica M.; Story, Mary; Neumark-Sztainer, Dianne

    2013-01-01

    Background Research has shown that adolescents who frequently share evening meals with their families experience more positive health outcomes, including diets of higher nutritional quality. However, little is known about families eating together at breakfast. Objectives This study examined sociodemographic differences in family meal frequencies in a population-based adolescent sample. Additionally, this study examined associations of family breakfast meal frequency with dietary quality and weight status. Design Cross-sectional data from EAT 2010 (Eating and Activity in Teens) included anthropometric assessments and classroom-administered surveys completed in 2009-2010. Participants/setting Participants included 2,793 middle and high school students (53.2% girls, mean age=14.4 years) from Minneapolis/St. Paul, MN, public schools. Main outcome measures Usual dietary intake was self-reported on a food frequency questionnaire. Height and weight were measured. Statistical analyses performed Regression models adjusted for sociodemographic characteristics, family dinner frequency, family functioning, and family cohesion were used to examine associations of family breakfast frequency with dietary quality and weight status. Results On average, adolescents reported having family breakfast meals 1.5 times (SD=2.1) and family dinner meals 4.1 times (SD=2.6) in the past week. There were racial/ethnic differences in family breakfast frequency, with the highest frequencies reported by adolescents of Black, Hispanic, Native American, and mixed race/ethnicity. Family breakfast frequency was also positively associated with male sex; younger age; and living in a two-parent household. Family breakfast frequency was associated with several markers of better diet quality (such as higher intake of fruit, whole grains, and fiber) and lower risk for overweight/obesity. For example, adolescents who reported seven family breakfasts in the past week consumed an average of 0.37 additional

  4. The admixture structure and genetic variation of the archipelago of Cape Verde and its implications for admixture mapping studies.

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    Sandra Beleza

    implications for the design of association studies using this population.

  5. The effect of stimulus strength on binocular rivalry rate in healthy individuals: Implications for genetic, clinical and individual differences studies.

    Science.gov (United States)

    Law, Phillip C F; Miller, Steven M; Ngo, Trung T

    2017-11-01

    Binocular rivalry (BR) occurs when conflicting images concurrently presented to corresponding retinal locations of each eye stochastically alternate in perception. Anomalies of BR rate have been examined in a range of clinical psychiatric conditions. In particular, slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) to improve power in large-scale genome-wide association studies. Examining the validity of BR rate as a BD endophenotype however requires large-scale datasets (n=1000s to 10,000s), a standardized testing protocol, and optimization of stimulus parameters to maximize separation between BD and healthy groups. Such requirements are indeed relevant to all clinical psychiatric BR studies. Here we address the issue of stimulus optimization by examining the effect of stimulus parameter variation on BR rate and mixed-percept duration (MPD) in healthy individuals. We aimed to identify the stimulus parameters that induced the fastest BR rates with the least MPD. Employing a repeated-measures within-subjects design, 40 healthy adults completed four BR tasks using orthogonally drifting grating stimuli that varied in drift speed and aperture size. Pairwise comparisons were performed to determine modulation of BR rate and MPD by these stimulus parameters, and individual variation of such modulation was also assessed. From amongst the stimulus parameters examined, we found that 8cycles/s drift speed in a 1.5° aperture induced the fastest BR rate without increasing MPD, but that BR rate with this stimulus configuration was not substantially different to BR rate with stimulus parameters we have used in previous studies (i.e., 4cycles/s drift speed in a 1.5° aperture). In addition to contributing to stimulus optimization issues, the findings have implications for Levelt's Proposition IV of binocular rivalry dynamics and individual differences in such dynamics. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Chronic biofilm infection in breast implants is associated with an increased T-cell lymphocytic infiltrate: implications for breast implant-associated lymphoma.

    Science.gov (United States)

    Hu, Honghua; Jacombs, Anita; Vickery, Karen; Merten, Steven L; Pennington, David G; Deva, Anand K

    2015-02-01

    Biofilm infection of breast implants significantly potentiates capsular contracture. This study investigated whether chronic biofilm infection could promote T-cell hyperplasia. In the pig study, 12 textured and 12 smooth implants were inserted into three adult pigs. Implants were left in situ for a mean period of 8.75 months. In the human study, 57 capsules from patients with Baker grade IV contracture were collected prospectively over a 4-year period. Biofilm and surrounding lymphocytes were analyzed using culture, nucleic acid, and visualization techniques. In the pig study, all samples were positive for bacterial biofilm. There was a significant correlation between the bacterial numbers and grade of capsular contracture (p = 0.04). Quantitative real-time polymerase chain reaction showed that all lymphocytes were significantly more numerous on textured compared with smooth implants (p biofilm. Analysis of lymphocyte numbers showed a T-cell predominance (p biofilm infection around breast prostheses produces an increased T-cell response both in the pig and in humans. A possible link between bacterial biofilm and T-cell hyperplasia is significant in light of breast implant-associated anaplastic large-cell lymphoma. Risk, V.

  7. Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults - The GOYA Study

    DEFF Research Database (Denmark)

    Paternoster, L.; Evans, D. M.; Nohr, E. A.

    2011-01-01

    Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining,similar to 1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched...

  8. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    Science.gov (United States)

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-10-01

    High amylase activity in dogs is associated with a drastic increase in copy numbers of the gene coding for pancreatic amylase, AMY2B, that likely allowed dogs to thrive on a relatively starch-rich diet during early dog domestication. Although most dogs thus probably digest starch more efficiently than do wolves, AMY2B copy numbers vary widely within the dog population, and it is not clear how this variation affects the individual ability to handle starch nor how it affects dog health. In humans, copy numbers of the gene coding for salivary amylase, AMY1, correlate with both salivary amylase levels and enzyme activity, and high amylase activity is related to improved glycemic homeostasis and lower frequencies of metabolic syndrome. Here, we investigate the relationship between AMY2B copy numbers and serum amylase activity in dogs and show that amylase activity correlates with AMY2B copy numbers. We then describe how AMY2B copy numbers vary in individuals from 20 dog breeds and find strong breed-dependent patterns, indicating that the ability to digest starch varies both at the breed and individual level. Finally, to test whether AMY2B copy number is strongly associated with the risk of developing diabetes mellitus, we compare copy numbers in cases and controls as well as in breeds with varying diabetes susceptibility. Although we see no such association here, future studies using larger cohorts are needed before excluding a possible link between AMY2B and diabetes mellitus. © 2014 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  9. 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

  10. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  11. The Essentiality of Reporting Hardy-Weinberg Equilibrium Calculations in Population-Based Genetic Association Studies.

    Science.gov (United States)

    Namipashaki, Atefeh; Razaghi-Moghadam, Zahra; Ansari-Pour, Naser

    2015-01-01

    Population-based genetic association studies have proven to be a powerful tool in identifying genes implicated in many complex human diseases that have a huge impact on public health. An essential quality control step in such studies is to undertake Hardy-Weinberg equilibrium (HWE) calculations. Deviations from HWE in the control group may reflect important problems including selection bias, population stratification and genotyping errors. If HWE is violated, the inferences of these studies may thus be biased. We therefore aimed to examine the extent to which HWE calculations are reported in genetic association studies published in Cell Journal(Yakhteh)(Cell J). Using keywords pertaining to genetic association studies, eleven relevant articles were identified of which ten provided full genotypic data. The genotype distribution of 16 single nucleotide polymorphisms (SNPs) was re-analyzed for HWE by using three different methods where appropriate. HWE was not reported in 60% of all articles investigated. Among those reporting, only one article provided calculations correctly and in detail. Therefore, 90% of articles analyzed failed to provide sufficient HWE data. Interestingly, three articles had significant HWE deviation in their control groups of which one highly deviated from HWE expectations (P= 9.8×10(-12)). We thus show that HWE calculations are under-reported in genetic association studies published in this journal. Furthermore, the conclusions of the three studies showing significant HWE in their control groups should be treated cautiously as they may be potentially misleading. We therefore recommend that reporting of detailed HWE calculations should become mandatory for such studies in the future.

  12. A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability.

    Science.gov (United States)

    Chen, Huan; Gu, Xiao-Hong; Zhou, Yuxi; Ge, Zeng; Wang, Bin; Siok, Wai Ting; Wang, Guoqing; Huen, Michael; Jiang, Yuyang; Tan, Li-Hai; Sun, Yimin

    2017-02-03

    Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10(-10), maximum β -2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.

  13. Power Analysis for Genetic Association Test (PAGEANT) provides insights to challenges for rare variant association studies.

    Science.gov (United States)

    Derkach, Andriy; Zhang, Haoyu; Chatterjee, Nilanjan

    2017-11-28

    Genome-wide association studies are now shifting focus from analysis of common to rare variants. As power for association testing for individual rare variants may often be low, various aggregate level association tests have been proposed to detect genetic loci. Typically, power calculations for such tests require specification of large number of parameters, including effect sizes and allele frequencies of individual variants, making them difficult to use in practice. We propose to approximate power to varying degree of accuracy using a smaller number of key parameters, including the total genetic variance explained by multiple variants within a locus. We perform extensive simulation studies to assess the accuracy of the proposed approximations in realistic settings. Using these simplified power calculations, we develop an analytic framework to obtain bounds on genetic architecture of an underlying trait given results from a genome-wide association studies with rare variants. Finally, we provide insights into the required quality of annotation/functional information for identification of likely causal variants to make meaningful improvement in power. A shiny application that allows a variety of Power Analysis of GEnetic AssociatioN Tests (PAGEANT), in R is made publicly available at https://andrewhaoyu.shinyapps.io/PAGEANT/. nilanjan@jhu.edu. Supplementary data are available at Bioinformatics online.

  14. Psychiatric disorders and obesity: A review of association studies

    Directory of Open Access Journals (Sweden)

    T M Rajan

    2017-01-01

    Full Text Available Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15, obesity and anxiety (four and one each on obesity and personality disorders, eating disorder (ED, attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs were similar for developing depression in obesity (OR: 1.21–5.8 and vice versa (OR: 1.18–3.76 with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40. Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5. Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84. Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric

  15. Psychiatric disorders and obesity: A review of association studies

    Science.gov (United States)

    Rajan, TM; Menon, V

    2017-01-01

    Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evide