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1. 'Other People's Money': CSR Goes to the Movies

Author

McArdle, John F. and de Koning, Alice J.

Abstract

We review the film "Other People's Money" as a teaching tool for introducing concepts of corporate social responsibility and board governance. The film's climactic shareholder meeting contains two vivid examples of stakeholder theory and shareholder primacy illustrated through the competing election speeches made by the lead characters. Our article provides step-by-step instructions for how to use the film to explore these concepts and discusses ways to enhance student competency in this area.

Published
2022
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2. Genetic diversity fuels gene discovery for tobacco and alcohol use

Author

Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret I., Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel I., Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Hélène, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tõnu, Faul, Jessica D., Silva, Lilian Fernandes, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I., Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C., Gu, Dongfeng, Gudbjartsson, Daniel F., Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E., Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K., Hickie, Ian, Hidalgo, Bertha, Hokanson, John E., Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J., Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R., Jee, Yon Ho, Johnson, Eric O., Joo, Yoonjung Y., Jorgenson, Eric, Justice, Anne E., Kamatani, Yoichiro, Kaplan, Robert C., Kaprio, Jaakko, Kardia, Sharon L. R., Keller, Matthew C., Kelly, Tanika N., Kooperberg, Charles, Korhonen, Tellervo, Kraft, Peter, Krauter, Kenneth, Kuusisto, Johanna, Laakso, Markku, Lasky-Su, Jessica, Lee, Wen-Jane, Lee, James J., Levy, Daniel, Li, Liming, Li, Kevin, Li, Yuqing, Lin, Kuang, Lind, Penelope A., Liu, Chunyu, Lloyd-Jones, Donald M., Lutz, Sharon M., Ma, Jiantao, Mägi, Reedik, Manichaikul, Ani, Martin, Nicholas G., Mathur, Ravi, Matoba, Nana, McArdle, Patrick F., McGue, Matt, McQueen, Matthew B., Medland, Sarah E., Metspalu, Andres, Meyers, Deborah A., Millwood, Iona Y., Mitchell, Braxton D., Mohlke, Karen L., Moll, Matthew, Montasser, May E., Morrison, Alanna C., Mulas, Antonella, Nielsen, Jonas B., North, Kari E., Oelsner, Elizabeth C., Okada, Yukinori, Orrù, Valeria, Palmer, Nicholette D., Palviainen, Teemu, Pandit, Anita, Park, S. Lani, Peters, Ulrike, Peters, Annette, Peyser, Patricia A., Polderman, Tinca J. C., Rafaels, Nicholas, Redline, Susan, Reed, Robert M., Reiner, Alex P., Rice, John P., Rich, Stephen S., Richmond, Nicole E., Roan, Carol, Rotter, Jerome I., Rueschman, Michael N., Runarsdottir, Valgerdur, Saccone, Nancy L., Schwartz, David A., Shadyab, Aladdin H., Shi, Jingchunzi, Shringarpure, Suyash S., Sicinski, Kamil, Skogholt, Anne Heidi, Smith, Jennifer A., Smith, Nicholas L., Sotoodehnia, Nona, Stallings, Michael C., Stefansson, Hreinn, Stefansson, Kari, Stitzel, Jerry A., Sun, Xiao, Syed, Moin, Tal-Singer, Ruth, Taylor, Amy E., Taylor, Kent D., Telen, Marilyn J., Thai, Khanh K., Tiwari, Hemant, Turman, Constance, Tyrfingsson, Thorarinn, Wall, Tamara L., Walters, Robin G., Weir, David R., Weiss, Scott T., White, Wendy B., Whitfield, John B., Wiggins, Kerri L., Willemsen, Gonneke, Willer, Cristen J., Winsvold, Bendik S., Xu, Huichun, Yanek, Lisa R., Yin, Jie, Young, Kristin L., Young, Kendra A., Yu, Bing, Zhao, Wei, Zhou, Wei, Zöllner, Sebastian, Zuccolo, Luisa, Batini, Chiara, Bergen, Andrew W., Bierut, Laura J., David, Sean P., Gagliano Taliun, Sarah A., Hancock, Dana B., Jiang, Bibo, Munafò, Marcus R., Thorgeirsson, Thorgeir E., Liu, Dajiang J., and Vrieze, Scott

Published
2022
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4. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Jr, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M., Lin, Wei-Yu, Lindgren, Arne G., Lorentzen, Erik, Magnusson, Patrik K., Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F., Meschia, James F., Mitchell, Braxton D., Mosley, Thomas H., Nalls, Michael A., Ninomiya, Toshiharu, O’Donnell, Martin J., Psaty, Bruce M., Pulit, Sara L., Rannikmäe, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Sakaue, Saori, Sale, Michele M., Salomaa, Veikko, Sapkota, Bishwa R., Schmidt, Reinhold, Schmidt, Carsten O., Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Björkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Trégouët, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, Jr, W. T., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2018
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5. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Jr, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M., Lin, Wei-Yu, Lindgren, Arne G., Lorentzen, Erik, Magnusson, Patrik K., Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F., Meschia, James F., Mitchell, Braxton D., Mosley, Thomas H., Nalls, Michael A., Ninomiya, Toshiharu, O’Donnell, Martin J., Psaty, Bruce M., Pulit, Sara L., Rannikmäe, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Sakaue, Saori, Sale, Michele M., Salomaa, Veikko, Sapkota, Bishwa R., Schmidt, Reinhold, Schmidt, Carsten O., Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Björkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Trégouët, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium (ISGC), METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network (SiGN), UK Young Lacunar DNA Study, MEGASTROKE Consortium, Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, Jr, W. T., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2019
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7. Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults.

Author

Aradine, Elizabeth M. DO, Ryan, Kathleen A., Cronin, Carolyn A., Wozniak, Marcella A., Cole, John W. MS, Chaturvedi, Seemant, Dutta, Tara L.M., Hou, Yan, Mehndiratta, Prachi, Motta, Melissa, Phipps, Michael S. MHS, Yarbrough, Karen L. DNP, ACNP-BC, CP, McArdle, Patrick F., Kittner, Steven J., Aradine, Elizabeth M, Cole, John W, Phipps, Michael S, and Yarbrough, Karen L

Published
2022
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11. Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference

Author

McArdle Patrick F, Whitcomb Brian W, Tanner Keith, Mitchell Braxton D, Shuldiner Alan R, and Parsa Afshin

Subjects
Bilirubin, Mendelian randomization, Cardiovascular disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. Methods Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. Results Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p = 0.003), LDL (p = 0.0005) and total cholesterol (p = 0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p = 0.003) and cold pressor reactivity (p = 0.01). Conclusions Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity.

Published
2012
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12. Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

Author

Ott Sandy, Ramachandran Vasan, Wang Ying, Damcott Coleen M, Mitchell Braxton D, Rutherford Sue, McArdle Patrick F, Chang Yen-Pei C, Levy Daniel, and Steinle Nanette

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure. Methods We sequenced CHRNA1, CHRND and CHRNG in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS). Results The minor allele of a synonymous coding SNP, rs2099489 in CHRNG, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations). Conclusion CHRNG is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.

Published
2008
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13. Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture

Author

McArdle Patrick F, Dytch Harvey, O'Connell Jeffery R, Shuldiner Alan R, Mitchell Braxton D, and Abney Mark

Subjects
Genetics, QH426-470
Abstract

Abstract Background High blood pressure is a well established risk factor for morbidity and mortality acting through heart disease, stroke and cardiovascular disease. Genome wide scans have linked regions of nearly every human chromosome to blood pressure related traits. We have capitalized on beneficial qualities of the Old Order Amish of Lancaster, PA, a closed founder population with a relatively small number of founders, to perform a genome wide homozygosity by descent mapping scan. Each individual in the study has a non zero probability of consanguinity. Systolic and diastolic blood pressures are shown to have appreciable dominance variance components. Results Areas of two chromosomes were identified as suggestive of linkage to SBP and 5 areas to DBP in either the overall or sex specific analyses. The strongest evidence for linkage in the overall sample was to Chromosome 18q12 (LOD = 2.6 DBP). Sex specific analyses identified a linkage on Chromosome 4p12-14 (LOD in men only = 3.4 SBP). At Chromosome 2q32-33, an area where we previously reported significant evidence for linkage to DBP using a conventional identity by descent approach, the LOD was 1.4; however an appreciable sex effect was observed with men accounting for most of the linkage (LOD in men only = 2.6). Conclusion These results add evidence to a sex specific genetic architecture to blood pressure related traits, particularly in regions of linkage on chromosome 2, 4 and 18.

Published
2007
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14. Exome Array Analysis of Early-Onset Ischemic Stroke.

Author

Jaworek, Thomas, Ryan, Kathleen A., Gaynor, Brady J., McArdle, Patrick F., Stine, Oscar C., OConnor, Timothy D., Lopez, Haley, Aparicio, Hugo J., Gao, Yan, Lin, Xiaochen, Groves, Megan L., Flaherty, Matthew L., Liu, Simin, Yang, Qiong, Wilson, James, Seshadri, Sudha, Kittner, Steven J., Mitchell, Braxton D., Xu, Huichun, and Cole, John W.

Published
2020
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15. Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

Author

Frid, Petrea, Drake, Mattias, Giese, A. K., Wasselius, J., Schirmer, M. D., Donahue, K. L., Cloonan, L., Irie, R., Bouts, M. J. R. J., McIntosh, E. C., Mocking, S. J. T., Dalca, A. V., Sridharan, R., Xu, H., Giralt-Steinhauer, E., Holmegaard, L., Jood, K., Roquer, J., Cole, J. W., and McArdle, P. F.

Subjects
STROKE, INJURY risk factors, MAGNETIC resonance imaging, NEUROLOGICAL disorders, CEREBRAL infarction, POSTERIOR cerebral artery
Abstract

Objective: Posterior circulation ischemic stroke (PCiS) constitutes 20–30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. Methods: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. Results: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04–1.61; male sex, OR = 1.46; 95% CI 1.21–1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. Conclusion: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS. [ABSTRACT FROM AUTHOR]

Published
2020
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18. For Amusement Only: The Availability and Distribution of Simulated Slot Machines in an Urban Center.

Author

McArdle, Patrick F., Kathleen Tracy, J., and Levy, Lauren

Subjects
SLOT machines, CROSS-cultural differences
Abstract

Copyright of Journal of Gambling Issues is the property of Centre for Addiction & Mental Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2015
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19. Genetic variation at 16q24.2 is associated with small vessel stroke

Author

Traylor, Matthew, Malik, Rainer, Nalls, Mike A., Cotlarciuc, Ioana, Radmanesh, Farid, Thorleifsson, Gudmar, Hanscombe, Ken B., Langefeld, Carl, Saleheen, Danish, Rost, Natalia S., Yet, Idil, Spector, Tim D., Bell, Jordana T., Hannon, Eilis, Mill, Jonathan, Chauhan, Ganesh, Debette, Stephanie, Bis, Joshua C., Longstreth, W.T., Ikram, M. Arfan, Launer, Lenore J., Seshadri, Sudha, Hamilton‐Bruce, Monica Anne, Jimenez‐Conde, Jordi, Cole, John W., Schmidt, Reinhold, Słowik, Agnieszka, Lemmens, Robin, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Sacco, Ralph L., Rundek, Tatjana, Rexrode, Kathryn, Arnett, Donna K., Johnson, Julie A., Benavente, Oscar R., Wasssertheil‐Smoller, Sylvia, Lee, Jin‐Moo, Pulit, Sara L., Wong, Quenna, Rich, Stephen S., de Bakker, Paul I.W., McArdle, Patrick F., Woo, Daniel, Anderson, Christopher D., Xu, Huichun, Heitsch, Laura, Fornage, Myriam, Jern, Christina, Stefansson, Kari, Thorsteinsdottir, Unnur, Gretarsdottir, Solveig, Lewis, Cathryn M., Sharma, Pankaj, Sudlow, Cathie L.M., Rothwell, Peter M., Boncoraglio, Giorgio B., Thijs, Vincent, Levi, Chris, Meschia, James F., Rosand, Jonathan, Kittner, Steven J., Mitchell, Braxton D., Dichgans, Martin, Worrall, Bradford B., and Markus, Hugh S.

Abstract

Objective: Genome‐wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger‐onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age‐at‐onset informed GWAS meta‐analysis, including a large younger‐onset SVS population, to identify novel associations with stroke. Methods: We used a three‐stage age‐at‐onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10–1.22]; p = 3.2 × 10−9). The lead single‐nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05–1.16]; p = 5.3 × 10−5; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84–1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10−7) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10−6). Interpretation 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. Ann Neurol 2017;81:383–394

Published
2017
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21. Agreement between TOAST and CCS ischemic stroke classification: the NINDS SiGN study.

Author

McArdle, Patrick F, Kittner, Steven J, Ay, Hakan, Brown Jr, Robert D, Meschia, James F, Rundek, Tatjana, Wassertheil-Smoller, Sylvia, Woo, Daniel, Andsberg, Gunnar, Biffi, Alessandro, Brenner, David A, Cole, John W, Corriveau, Roderick, de Bakker, Paul I W, Delavaran, Hossein, Dichgans, Martin, Grewal, Raji P, Gwinn, Katrina, Huq, Mohammed, and Jern, Christina

Published
2014
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22. Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis.

Author

Baijia Jiang, Ryan, Kathleen A., Hamedani, Ali, Yuching Cheng, Sparks, Mary J., Koontz, Deborah, Bean, Christopher J., Gallagher, Margaret, Craig Hooper, W., McArdle, Patrick F., O'Connell, Jeffrey R., Colin Stine, O., Wozniak, Marcella A., Stern, Barney J., Mitchell, Braxton D., Kittner, Steven J., and Cole, John W.

Published
2014
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23. Association of Single Nucleotide Polymorphisms on Chromosome 9p21.3 With Platelet Reactivity.

Author

Musunuru, Kiran, Post, Wendy S., Herzog, William, Shen, Haiqing, O'Connell, Jeffrey R., McArdle, Patrick F., Ryan, Kathleen A., Gibson, Quince, Cheng, Yu-Ching, Clearfield, Elizabeth, Johnson, Andrew D., Toiler, Geoffrey, Yang, Qiong, O'Connell, Christopher J., Becker, Diane M., Yanek, Lisa R., Becker, Lewis C., Faraday, Nauder, Bielak, Lawrence F., and Peyser, Patricia A.

Subjects
GENETIC polymorphism research, BLOOD platelets, CALCIFICATION, HEART disease risk factors, CORONARY heart disease risk factors, MYOCARDIAL infarction risk factors
Abstract

The article discusses a study which hypothesized that single nucleotide polymorphisms (SNPs) is associated with platelet reactivity across multiple population. The study included 1,402 asymptomatic Amish adults whose platelet reactivity and coronary artery calcification (CAC) were measured. It found 12 correlated SNPs in the locus that are associated with platelet reactivity. Study authors claim that their findings suggest a role for risk alleles at 9p21.3 locus in the risks for myocardial infarction/coronary disease and stroke.

Published
2010
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24. Genome-Wide Association Scan Identifies Variants near Matrix Metalloproteinase (MMP) Genes on Chromosome 11q21-22 Strongly Associated With Serum MMP-1 Levels.

Author

Yu-Ching Cheng, Kao, Wen-Hong L., Mitchell, Braxton D., O'Connell, Jeffrey R., Haiqing Shen, McArdle, Patrick F., Gibson, Quince, Ryan, Kathleen A., Shuldiner, Alan R., and Pollin, Toni I.

Subjects
METALLOPROTEINASES, METALLOENZYMES, PROTEINASES, ASTACINS, AMISH
Abstract

The article examines the association of matrix metalloproteinease (MMP) with serum MMP-1 levels in 776 healthy Amish adults to determine the role of MMP1 in cardiovascular disease susceptibility. The method involved a genome wide association analysis of circulating MMP1 levels using 500 K single nucleotide polymorphisms (SNP) to identify genes influencing variation in serum MMP 1 levels. The study suggests strong evidence that the serum MMP1 level is highly heritable and that SNP near MMP on chromosome 11q explains variation in MMP1 levels.

Published
2009
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25. The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study.

Author

Mitchell, Braxton D., McArdle, Patrick F., Shen, Haiqing, Rampersaud, Evadnie, Pollin, Toni I., Bielak, Lawrence F., Jaquish, Cashell, Douglas, Julie A., Roy-Gagnon, Marie-Hélène, Sack, Paul, Naglieri, Rosalie, Hines, Scott, Horenstein, Richard B., Chang, Yen-Pei C., Post, Wendy, Ryan, Kathleen A., Brereton, Nga Hong, Pakyz, Ruth E., Sorkin, John, and Damcott, Coleen M.

Subjects
CARDIOVASCULAR diseases, GENETICS, BLOOD pressure, TRIGLYCERIDES
Abstract

Background: The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions.Methods: The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy.Results: The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes.Conclusions: Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals. [ABSTRACT FROM AUTHOR]

Published
2008
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26. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Author

Day, Felix R., Ruth, Katherine S., Thompson, Deborah J., Lunetta, Kathryn L., Pervjakova, Natalia, Chasman, Daniel I., Stolk, Lisette, Finucane, Hilary K., Sulem, Patrick, Bulik-Sullivan, Brendan, Esko, Tõnu, Johnson, Andrew D., Elks, Cathy E., Franceschini, Nora, He, Chunyan, Altmaier, Elisabeth, Brody, Jennifer A., Franke, Lude L., Huffman, Jennifer E., Keller, Margaux F., McArdle, Patrick F., Nutile, Teresa, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Smith, Jennifer A., Teumer, Alexander, Traglia, Michela, Vuckovic, Dragana, Yao, Jie, Zhao, Wei, Albrecht, Eva, Amin, Najaf, Corre, Tanguy, Hottenga, Jouke-Jan, Mangino, Massimo, Smith, Albert V., Tanaka, Toshiko, Abecasis, Goncalo, Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Arndt, Volker, Arnold, Alice M., Barbieri, Caterina, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bielinski, Suzette J., Blomqvist, Carl, Boerwinkle, Eric, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Borresen-Dale, Anne-Lise, Boutin, Thibaud S, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Campbell, Archie, Campbell, Harry, Chanock, Stephen J., Chapman, J. Ross, Chen, Yii-Der Ida, Chenevix-Trench, Georgia, Couch, Fergus J., Coviello, Andrea D., Cox, Angela, Czene, Kamila, Darabi, Hatef, De Vivo, Immaculata, Demerath, Ellen W., Dennis, Joe, Devilee, Peter, Dörk, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Eicher, John D., Fasching, Peter A., Faul, Jessica D., Figueroa, Jonine, Flesch-Janys, Dieter, Gandin, Ilaria, Garcia, Melissa E., García-Closas, Montserrat, Giles, Graham G., Girotto, Giorgia G., Goldberg, Mark S., González-Neira, Anna, Goodarzi, Mark O., Grove, Megan L., Gudbjartsson, Daniel F., Guénel, Pascal, Guo, Xiuqing, Haiman, Christopher A., Hall, Per, Hamann, Ute, Henderson, Brian E., Hocking, Lynne J., Hofman, Albert, Homuth, Georg, Hooning, Maartje J., Hopper, John L., Hu, Frank B., Huang, Jinyan, Humphreys, Keith, Hunter, David J., Jakubowska, Anna, Jones, Samuel E., Kabisch, Maria, Karasik, David, Knight, Julia A., Kolcic, Ivana, Kooperberg, Charles, Kosma, Veli-Matti, Kriebel, Jennifer, Kristensen, Vessela, Lambrechts, Diether, Langenberg, Claudia, Li, Jingmei, Li, Xin, Lindström, Sara, Liu, Yongmei, Luan, Jian’an, Lubinski, Jan, Mägi, Reedik, Mannermaa, Arto, Manz, Judith, Margolin, Sara, Marten, Jonathan, Martin, Nicholas G., Masciullo, Corrado, Meindl, Alfons, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L., Müller-Nurasyid, Martina, Nalls, Michael, Neale, Ben M., Nevanlinna, Heli, Neven, Patrick, Newman, Anne B., Nordestgaard, Børge G., Olson, Janet E., Padmanabhan, Sandosh, Peterlongo, Paolo, Peters, Ulrike, Petersmann, Astrid, Peto, Julian, Pharoah, Paul D.P., Pirastu, Nicola N., Pirie, Ailith, Pistis, Giorgio, Polasek, Ozren, Porteous, David, Psaty, Bruce M., Pylkäs, Katri, Radice, Paolo, Raffel, Leslie J., Rivadeneira, Fernando, Rudan, Igor, Rudolph, Anja, Ruggiero, Daniela, Sala, Cinzia F., Sanna, Serena, Sawyer, Elinor J., Schlessinger, David, Schmidt, Marjanka K., Schmidt, Frank, Schmutzler, Rita K., Schoemaker, Minouk J., Scott, Robert A., Seynaeve, Caroline M., Simard, Jacques, Sorice, Rossella, Southey, Melissa C., Stöckl, Doris, Strauch, Konstantin, Swerdlow, Anthony, Taylor, Kent D., Thorsteinsdottir, Unnur, Toland, Amanda E., Tomlinson, Ian, Truong, Thérèse, Tryggvadottir, Laufey, Turner, Stephen T., Vozzi, Diego, Wang, Qin, Wellons, Melissa, Willemsen, Gonneke, Wilson, James F., Winqvist, Robert, Wolffenbuttel, Bruce B.H.R., Wright, Alan F., Yannoukakos, Drakoulis, Zemunik, Tatijana, Zheng, Wei, Zygmunt, Marek, Bergmann, Sven, Boomsma, Dorret I., Buring, Julie E., Ferrucci, Luigi, Montgomery, Grant W., Gudnason, Vilmundur, Spector, Tim D., van Duijn, Cornelia M, Alizadeh, Behrooz Z., Ciullo, Marina, Crisponi, Laura, Easton, Douglas F., Gasparini, Paolo P., Gieger, Christian, Harris, Tamara B., Hayward, Caroline, Kardia, Sharon L.R., Kraft, Peter, McKnight, Barbara, Metspalu, Andres, Morrison, Alanna C., Reiner, Alex P., Ridker, Paul M., Rotter, Jerome I., Toniolo, Daniela, Uitterlinden, André G., Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Weir, David R., Yerges-Armstrong, Laura M., Price, Alkes L., Stefansson, Kari, Visser, Jenny A., Ong, Ken K., Chang-Claude, Jenny, Murabito, Joanne M., Perry, John R.B., and Murray, Anna

Abstract

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms.

Published
2015
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28. Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche

Author

Perry, John RB, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, McMahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke-Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges-Armstrong, Laura M, Zhao, Jing Hua, Andrulis, Irene L, Anton-Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang-Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix-Trench, Georgia, Collée, J. Margriet, Couch, Fergus J, Couper, David, Coveillo, Andrea D, Cox, Angela, Czene, Kamila, D’adamo, Adamo Pio, Smith, George Davey, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch-Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García-Closas, Montserrat, Geller, Frank, de Geus, Eco EJ, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, Kiel, Douglas P, Knight, Julia A, Kosma, Veli-Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Mägi, Reedik, Magnusson, Patrik K, Mannermaa, Arto, Martin, Nicholas G, Masson, Gisli, McArdle, Patrick F, McArdle, Wendy L, Melbye, Mads, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A, Oldehinkel, Albertine J, Oostra, Ben A, Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul DP, Postma, Dirkje S, Pouta, Anneli, Pylkäs, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M, Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K, Southey, Mellissa C, Sovio, Ulla, Stampfer, Meir J, Stöckl, Doris, Storniolo, Anna M, Timpson, Nicholas J, Tyrer, Jonathan, Visser, Jenny A, Vollenweider, Peter, Völzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce HR, Wright, Margaret J, Boomsma, Dorret I, Econs, Michael J, Khaw, Kay-Tee, Loos, Ruth JF, McCarthy, Mark I, Montgomery, Grant W, Rice, John P, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A, Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andres, Pennell, Craig E, Ridker, Paul M, Snieder, Harold, Sørensen, Thorkild IA, Spector, Tim D, Strachan, David P, Uitterlinden, André G, Wareham, Nicholas J, Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F, Stefansson, Kari, Murabito, Joanne M, and Ong, Ken K

Abstract

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality1. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation2,3, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P<5×10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25, MKRN3/MAGEL2 and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signaling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Published
2014
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29. HEALTH LAW.

Author

McArdle, Edward F. and Lerch, Kirsten A.

Subjects
MEDICAL care, FEDERAL laws, MEDICAL care laws, HEALTH care reform, PRISONERS' health
Abstract

The article focuses on federal health legislation reform in the U.S. Topics include the U.S. Family Health Care Decisions Act (FHCDA), New York state case law regarding health legislation, and the right to adequate and reasonable medical treatment. Information is provided on the health care rights of prisoners.

Published
2011

30. Restoring a Long-Edentulous Maxillary Ridge Segment with Adjacent Implants.

Author

McArdle, Barry F.

Subjects
DENTAL implants, GINGIVAL diseases, DENTISTRY, DENTAL crown contours, DENTAL materials
Abstract

Using dental implants for restoration of long-edentulous sites on the maxilla in the esthetic zone can be a challenge with regard to soft-tissue architecture. This article discusses a case report in which natural gingival contours were achieved at a decades-old edentulous site on the maxilla through proper treatment planning along with the use of an appropriately selected implant system, custom abutment design, and restorative material. [ABSTRACT FROM AUTHOR]

Published
2014

33. The Immediate Smile.

Author

McArdle, Barry F., Spivey, James D., and Avery, David R.

Abstract

The article presents a case study of a 33-year-old North African male presented with a complaint of partial edentulism at the number 11 canine tooth position. Topics discussed include implant placement without soft-tissue augmentation, use of ANKYLOS implant system from DENTSPLY, and the benefits of advances in implant dentistry from the digital technology.

Published
2015

34. Unique Attachment System for Implant-Supported Dentures.

Author

McArdle, Barry F.

Abstract

A case study is presented of a 58-year-old male with maxillary denture and a partial denture in lower dentition. Topics discussed include the patient having discomfort while mastication which was due to the periodontal disease of the mandibular teeth, five dental implants planned for the patient, and the stability of the prostheses placed through dental implantation.

Published
2015

35. NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium

Author

Heard-Costa, Nancy L., Zillikens, M. Carola, Monda, Keri L., Harris, Tamara B., Fu, Mao, Haritunians, Talin, Feitosa, Mary F., Aspelund, Thor, Eiriksdottir, Gudny, Garcia, Melissa, Launer, Lenore J., Smith, Albert V., Mitchell, Braxton D., McArdle, Patrick F., Shuldiner, Alan R., Bielinski, Suzette J., Boerwinkle, Eric, Brancati, Fred, Demerath, Ellen W., Pankow, James S., Arnold, Alice M., Chen, Yii-Der Ida, Glazer, Nicole L., McKnight, Barbara, Psaty, Bruce M., Rotter, Jerome I., Amin, Najaf, Campbell, Harry, Gyllensten, Ulf, Pattaro, Cristian, Pramstaller, Peter P., Rudan, Igor, Struchalin, Maksim, Vitart, Veronique, Gao, Xiaoyi, Kraja, Aldi, Province, Michael A., Zhang, Qunyuan, Atwood, Larry D., Dupuis, Josée, Jaquish, Cashell E., Vasan, Ramachandran S., White, Charles C., Aulchenko, Yurii S., Estrada, Karol, Rivadeneira, Fernando, Uitterlinden, André G., Witteman, Jacqueline C. M., Oostra, Ben A., Gudnason, Vilmundur, O'Connell, Jeffrey R., Borecki, Ingrid B., van Duijn, Cornelia M., Cupples, L. Adrienne, North, Kari E., Hirschhorn, Joel Naom, O'Donnell, Christopher Joseph, Hofman, Albert, Kaplan, Robert C., Fox, Caroline, and Johansson, Asa

Subjects
genetics and genomics, complex traits, nutrition, obesity
Abstract

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10^−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10^−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10^−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10^−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.

Published
2009
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37. Aesthetic Implications of Restorative Material Choice. Considering Soft-Tissue Factors.

Author

McArdle, Barry F.

Abstract

The article presents a case study of a 46-year-old woman who has developed soft-tissue discrepancy related to right central incisor teeth due to the trauma from the treatment of her central incisors. Topics discussed include the findings on the presence of incipient caries at the gingival and palatal margins of her dental veneers, the consideration of crown lengthening surgery to aid soft-tissue configuration, and the selection on the type of restorations for the patient.

Published
2016

38. Abstract WP204: Genetic Variant in VCAM1 Mediates Acute Infarct Size in Ischemic Stroke Patients.

Author

Giese, Anne-Katrin, Musolino, Patricia, Xu, Huichun, Ryan, Kathleen, Schirmer, Markus D, Dalca, Adrian V, Cole, John W, McArdle, Patrick F, Broderick, Joseph P, Jimenez-Conde, Jordi, Jern, Christina, Kissela, Brett M, Kleindorfer, Dawn O, Lemmens, Robin, Lindgren, Arne, Meschia, James F, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Reinhold, and Sharma, Pankaj

Published
2017
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39. Abstract TMP58: Determinants of White Matter Hyperintensity in Acute Ischemic Stroke Patients: The MRI-GENIE Study.

Author

Giese, Anne-Katrin, Schirmer, Markus D, Dalca, Adrian V, Sridharan, Ramesh, Cloonan, Lisa, Xu, Huichun, Cole, John W, McArdle, Patrick F, Broderick, Joseph P, Jimenez-Conde, Jordi, Jern, Christina, Kissela, Brett M, Kleindorfer, Dawn O, Lemmens, Robin, Lindgren, Arne, Meschia, James F, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Reinhold, and Sharma, Pankaj

Published
2017
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40. Abstract 136: Genetics of White Matter Hyperintensity Burden in Patients With Ischemic Stroke: The MRI-GENIE Study.

Author

Giese, Anne-Katrin, Xu, Huichun, Ryan, Kathleen, Schirmer, Markus D, Dalca, Adrian V, Dave, Tushar, Cole, John W, McArdle, Patrick F, Broderick, Joseph P, Jimenez-Conde, Jordi, Jern, Christina, Kissela, Brett M, Kleindorfer, Dawn O, Lemmens, Robin, Lindgren, Arne, Meschia, James F, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Reinhold, and Sharma, Pankaj

Published
2017
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41. Enhancing Fixed Partial Denture Gingival Architecture.

Author

McArdle, Barry F.

Abstract

The article focuses on the usage of the fixed partial dentures (FPDs) in gingival architecture. Presented is a case study of a 45-year-old male who had periapical pathology in his tooth, mentioning the potential of an apical fracture. Also discussed is the evaluation of the provisional bridge as well as the aesthetics of the definitive bridge.

Published
2014

43. Abstract W P152.

Author

Mitchell, Andrew B, Cole, John W, Mcardle, Patrick F, Cheng, Yu-Ching, Mitchell, Braxton D, and Kittner, Steven J

Published
2014

44. Abstract 26.

Author

Mcardle, Patrick F, Ay, Hakan, Kittner, Steven J, Brown, Robert D, Meschia, James F, and Worrall, Brad B

Published
2014

46. Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

Author

Frid P, Xu H, Mitchell BD, Drake M, Wasselius J, Gaynor B, Ryan K, Giese AK, Schirmer M, Donahue KL, Irie R, Bouts MJRJ, McIntosh EC, Mocking SJT, Dalca AV, Giralt-Steinhauer E, Holmegaard L, Jood K, Roquer J, Cole JW, McArdle PF, Broderick JP, Jimenez-Conde J, Jern C, Kissela BM, Kleindorfer DO, Lemmens R, Meschia JF, Rosand J, Rundek T, Sacco RL, Schmidt R, Sharma P, Slowik A, Thijs V, Woo D, Worrall BB, Kittner SJ, Petersson J, Golland P, Wu O, Rost NS, and Lindgren A

Subjects
Diffusion Magnetic Resonance Imaging, Humans, Risk Factors, Ischemic Stroke, Migraine with Aura diagnostic imaging, Migraine with Aura genetics, Migraine without Aura diagnostic imaging, Migraine without Aura genetics
Abstract

Objective: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects., Methods: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype., Results: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses., Conclusions: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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47. Improper adjustment for baseline in genetic association studies of change in phenotype.

Author

McArdle PF and Whitcomb BW

Subjects
Bias, Blood Pressure physiology, Computer Simulation, Gene Frequency, Humans, Polymorphism, Single Nucleotide, Regression Analysis, Blood Pressure genetics, Genome-Wide Association Study methods, Models, Genetic, Phenotype
Abstract

Objective: In studies of associations between genetic factors and outcomes where change in phenotype is of interest, proper modeling of the data, particularly the treatment of baseline trait values, is required to draw valid conclusions., Methods: The authors compared models of blood pressure response to a cold pressor test with and without inclusion of baseline blood pressure as a regressor and evaluate the resultant biases., Results: Adjustment for baseline presents a potential source of bias for assessment of genotype-phenotype associations. This bias was observed to occur both under the absence of a true effect, as well when a relation between genotype and change in phenotype was simulated. In simulations that incorporated measurement error, estimates were as great as two fold the true parameter values when unmeasured confounding was a factor., Conclusions: Adjusting for baseline introduces bias in genetic association studies when change in phenotype is the outcome of interest. Model misspecification bias may impact inference and provide one possible source of non-replication of findings in the literature.

Published
2009
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48. Accounting for relatedness in family based genetic association studies.

Author

McArdle PF, O'Connell JR, Pollin TI, Baumgarten M, Shuldiner AR, Peyser PA, and Mitchell BD

Subjects
Humans, Pedigree, Regression Analysis, Family, Genetic Linkage, Inheritance Patterns genetics, Models, Genetic
Abstract

Objective: Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association., Methods: We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families)., Results: Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11., Conclusion: Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration., (Copyright 2007 S. Karger AG, Basel.)

Published
2007
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