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2. Treatment of male stress urinary incontinence at time of inflatable penile prosthesis placement a review of contemporary literature.

Author

Elbakry, Amr, OConnor, Luke, Yafi, Faysal, and Barnard, John

Subjects
Erectile dysfunction (ED), climacturia, dual implant, stress urinary incontinence (SUI)
Abstract

BACKGROUND AND OBJECTIVE: Male stress urinary incontinence (SUI) and erectile dysfunction (ED) are well established diagnoses within Mens Health, often more specifically within the prostate cancer survivorship cohort. Taken individually, well defined treatment algorithms exist with which many surgeons are comfortable; however, treatment of both in a single setting or staged fashion introduces complexity. Emerging treatment options also exist, and there is immature or minimal data when these are combined with inflatable penile prosthesis (IPP) insertion, radiation history, and/or variable degrees of incontinence. Our objective was to describe and summarize the currently available treatment options for SUI particularly at the time of IPP insertion. METHODS: A literature review was performed to summarize contemporary treatment of SUI at time of IPP placement. Anecdotal experience was added from high volume, subspecialty trained Mens Health and Reconstructive Urologists. KEY CONTENT AND FINDINGS: Non-invasive approaches such as pelvic floor muscle training (PFMT), behavioral modification, and external compression devices play some limited role in treatment and/or management of SUI, particularly in the early post operative period, or for those unwilling or unable to undergo more definitive intervention. More invasive options such as artificial urinary sphincter (AUS) implantation, male sling, or other implantable devices are more appropriate for good surgical candidates with higher bother and/or more severe incontinence. These options can be concomitant or staged relative to IPP placement. Climacturia, particularly with mild or no bothersome SUI, can successfully be addressed at the time of penile prosthesis placement with the utilization of the Mini-Jupette suburethral sling. CONCLUSIONS: A variety of treatment options exist for concomitant treatment of SUI at time of IPP, and both safety and efficacy have been demonstrated for many in the same operative setting. As with treatment of ED or SUI in isolation, patient selection, careful counseling, and management of expectations can lead to high patient satisfaction.

Published
2024

3. Multidisciplinary lifestyle interventions for neurological disorders during the Silent phase (MINDS) study: a multi-omics randomized controlled trial protocol

Author

Taylor, Sara, Sachdeva, Seerat, Darling, Sandra, Arrotta, Kayela, Gallagher, Lisa, Supan, Alexis, Shipta, Gabrielle, Perko, Jim, Bar, Judi, James, Joe, Petschek, Iris, Lioi, Anthony, Kundu, Suman, Ellison, Lisa, Bekris, Lynn M., Willard, Belinda, Sangwan, Naseer, Mata, Ignacio, Fernandez, Hubert, Katzan, Irene, Conway, Devon, Pillai, Jagan, Leverenz, James, Busch, Robyn M., Floden, Darlene, Saper, Robert, Barnard, John, Machado, Andre, Najm, Imad, and Punia, Vineet

Published
2024
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4. Abstract 4146592: Device-Recorded Physical Activity and Atrial Fibrillation Burden: A Natural History Experiment from the COVID-19 Pandemic in the TRIM-AF Clinical Trial

Author

Kim, Hyun Su, Sun, Han, Wass, Sojin, Telfer, William, Schilling, Taylor, Lissemore, Frances, Bibidakis, Dimitra, Lin, Cheryl, Yang, Lucy, Sullivan, Erin, Jin, Alison, Guo, Lydia, Foster, Parker, McHale, Meghan, Crookshanks, Michael, Cantlay, Catherine, Cantlay, Paul, Hussein, Ayman, Cho, Leslie, Nissen, Steven, kashyap, sangeeta, Van Iterson, Erik, Bruemmer, Dennis, Mehra, Reena, Smith, Jonathan, Varma, Niraj, Van Wagoner, David, Barnard, John, and Chung, Mina

Published
2024
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6. Collective Effects and Intense Beam-Plasma Interactions in Ion-Beam-Driven High Energy Density Matter and Inertial Fusion Energy

Author

Kaganovich, Igor D., Startsev, Edward A., Qin, Hong, Gilson, Erik, Schenkel, Thomas, Vay, Jean-Luc, Lee, Ed P., Waldron, William, Bangerter, Roger, Persaud, Arun, Seidl, Peter, Ji, Qing, Friedman, Alex, Grote, Dave P., and Barnard, John

Subjects
Physics - Plasma Physics, High Energy Physics - Experiment, Physics - Accelerator Physics
Abstract

For the successful generation of ion-beam-driven high energy density matter and heavy ion fusion energy, intense ion beams must be transported and focused onto a target with small spot size. One of the successful approaches to achieve this goal is to accelerate and transport intense ion charge bunches in an accelerator and then focus the charge bunches ballistically in a section of the accelerator that contains a neutralizing background plasma. This requires the ability to control space-charge effects during un-neutralized (non-neutral) beam transport in the accelerator and transport sections, and the ability to effectively neutralize the space charge and current by propagating the beam through background plasma. As the beam intensity and energy are increased in future heavy ion fusion (HIF) drivers and Fast Ignition (FI) approaches, it is expected that nonlinear processes and collective effects will become much more pronounced than in previous experiments. Making use of 3D electromagnetic particle-in-cell simulation (PIC) codes (BEST, WARP-X, and LTP-PIC, etc.), the theory and modelling studies will be validated by comparing with experimental data on the 100kV Princeton Advanced Test Stand, and future experiments at the FAIR facility. The theoretical predictions that are developed will be scaled to the beam and plasma parameters relevant to heavy ion fusion drivers and Fast Ignition scenarios. Therefore, the theoretical results will also contribute significantly toward the long-term goal of fusion energy production by ion-beam-driven inertial confinement fusion., Comment: White paper submitted to the IFE Science & Technology Community Strategic Planning Workshop https://lasers.llnl.gov/nif-workshops/ife-workshop-2022/white-papers (2022)

Published
2022

9. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Lewis, Joshua P., Rodriguez, Benjamin A. T., Polasek, Ozren, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Davies, Gail, Delgado, Graciela E., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Beswick, Andrew, Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Rich, Stephen S., Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Brody, Lawrence C., Auer, Paul L., Ben-Shlomo, Yoav, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Desch, Karl C., Sabater-Lleal, Maria, Lowenstein, Charles J., and Morrison, Alanna C.

Published
2024
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10. Biomarker Signatures in Cancer Patients With and Without Venous Thromboembolism Events: A Substudy of CASSINI

Author

Khorana, Alok A, Barnard, John, Wun, Ted, Vijapurkar, Ujjwala, Damaraju, CV, Moore, Kenneth Todd, Wildgoose, Peter, and McCrae, Keith R

Subjects
Clinical Research, Cancer, Hematology, Aetiology, 2.1 Biological and endogenous factors, Bayes Theorem, Biomarkers, Female, Humans, Male, Neoplasms, Prospective Studies, Thyrotropin, Venous Thromboembolism
Abstract

Cancer is associated with an increased risk of venous thromboembolism (VTE). In the CASSINI study, ambulatory cancer patients with a Khorana risk score ≥2 had a reduced risk of VTE while receiving rivaroxaban. This analysis used blood samples from CASSINI to compare biomarker levels between patients with and without VTE. VTE occurred in 62 patients during the 6 months of CASSINI (cases), and they were matched by age, sex, cancer type, tumor stage, and Khorana score to 62 controls. Baseline blood samples were analyzed for 280 biomarkers, and biomarker distribution was compared using the Wilcoxon rank-sum test between groups defined by VTE occurrence and vital status. Sparse Bayesian regression modeling was used to select a joint panel of potential VTE biomarkers. Biomarkers with the largest differences in baseline distribution among cancer patients with and without VTE included decreases in stromal cell-derived factor-1 (SDF-1), thyroid-stimulating hormone (TSH), and monocyte chemotactic protein 4 and increases in growth hormone (GH) and interleukin-1 receptor type 1 (IL-1R1). Between survivors and those who died, significantly different biomarkers included ST2, IL-8, and C-reactive protein. Regression analyses also identified decreases in SDF-1 and TSH. Pathway analysis indicated enrichment of cytokine and chemokine activity with IL-1R1, SDF-1, and GH, which are the strongest predictors of VTE or death. Our analyses highlight the interactions between hemostatic and inflammatory processes and identify candidate biomarkers of cancer-associated VTE. Prospective studies will determine clinical relevance of these biomarkers. This trial was registered at www.ClinicalTrials.gov as #NCT02555878.

Published
2022

11. Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

Author

Katz, Daniel H, Tahir, Usman A, Bick, Alexander G, Pampana, Akhil, Ngo, Debby, Benson, Mark D, Yu, Zhi, Robbins, Jeremy M, Chen, Zsu-Zsu, Cruz, Daniel E, Deng, Shuliang, Farrell, Laurie, Sinha, Sumita, Schmaier, Alec A, Shen, Dongxiao, Gao, Yan, Hall, Michael E, Correa, Adolfo, Tracy, Russell P, Durda, Peter, Taylor, Kent D, Liu, Yongmei, Johnson, W Craig, Guo, Xiuqing, Yao, Jie, Ida Chen, Yii-Der, Manichaikul, Ani W, Jain, Deepti, Bouchard, Claude, Sarzynski, Mark A, Rich, Stephen S, Rotter, Jerome I, Wang, Thomas J, Wilson, James G, Natarajan, Pradeep, Gerszten, Robert E, Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April, Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, and Chavan, Sameer

Subjects
Epidemiology, Health Sciences, Aging, Heart Disease - Coronary Heart Disease, Human Genome, Genetics, Prevention, Cardiovascular, Heart Disease, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Black People, Cardiovascular Diseases, Female, Genome-Wide Association Study, Humans, Male, Proteome, cardiovascular disease, genetics, proteomics, race and ethnicity, National Heart, Lung, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundPlasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants.MethodsProteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics).ResultsWe identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10-11. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P=3.27×10-30) and MMP-3 (β=-0.60±0.05, P=1.67×10-32), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P=1.34×10-17) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure.ConclusionsTaken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Published
2022

12. Robust, flexible, and scalable tests for Hardy-Weinberg Equilibrium across diverse ancestries

Author

Kwong, Alan M, Blackwell, Thomas W, LeFaive, Jonathon, de Andrade, Mariza, Barnard, John, Barnes, Kathleen C, Blangero, John, Boerwinkle, Eric, Burchard, Esteban G, Cade, Brian E, Chasman, Daniel I, Chen, Han, Conomos, Matthew P, Cupples, L Adrienne, Ellinor, Patrick T, Eng, Celeste, Gao, Yan, Guo, Xiuqing, Irvin, Marguerite Ryan, Kelly, Tanika N, Kim, Wonji, Kooperberg, Charles, Lubitz, Steven A, Mak, Angel CY, Manichaikul, Ani W, Mathias, Rasika A, Montasser, May E, Montgomery, Courtney G, Musani, Solomon, Palmer, Nicholette D, Peloso, Gina M, Qiao, Dandi, Reiner, Alexander P, Roden, Dan M, Shoemaker, M Benjamin, Smith, Jennifer A, Smith, Nicholas L, Su, Jessica Lasky, Tiwari, Hemant K, Weeks, Daniel E, Weiss, Scott T, Consortium, TOPMed Analysis Working Group NHLBI Trans-Omics for Precision Medicine, Scott, Laura J, Smith, Albert V, Abecasis, Gonçalo R, Boehnke, Michael, and Kang, Hyun Min

Subjects
Genetics, Alleles, Gene Frequency, Genetics, Population, Genotype, Humans, Linkage Disequilibrium, Models, Genetic, Models, Statistical, Phenotype, Software, population structure, principal components analysis, next-generation sequencing, genotype likelihoods, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Analysis Working Group, Developmental Biology
Abstract

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.

Published
2021

14. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Author

Taliun, Daniel, Harris, Daniel N, Kessler, Michael D, Carlson, Jedidiah, Szpiech, Zachary A, Torres, Raul, Taliun, Sarah A Gagliano, Corvelo, André, Gogarten, Stephanie M, Kang, Hyun Min, Pitsillides, Achilleas N, LeFaive, Jonathon, Lee, Seung-been, Tian, Xiaowen, Browning, Brian L, Das, Sayantan, Emde, Anne-Katrin, Clarke, Wayne E, Loesch, Douglas P, Shetty, Amol C, Blackwell, Thomas W, Smith, Albert V, Wong, Quenna, Liu, Xiaoming, Conomos, Matthew P, Bobo, Dean M, Aguet, François, Albert, Christine, Alonso, Alvaro, Ardlie, Kristin G, Arking, Dan E, Aslibekyan, Stella, Auer, Paul L, Barnard, John, Barr, R Graham, Barwick, Lucas, Becker, Lewis C, Beer, Rebecca L, Benjamin, Emelia J, Bielak, Lawrence F, Blangero, John, Boehnke, Michael, Bowden, Donald W, Brody, Jennifer A, Burchard, Esteban G, Cade, Brian E, Casella, James F, Chalazan, Brandon, Chasman, Daniel I, Chen, Yii-Der Ida, Cho, Michael H, Choi, Seung Hoan, Chung, Mina K, Clish, Clary B, Correa, Adolfo, Curran, Joanne E, Custer, Brian, Darbar, Dawood, Daya, Michelle, de Andrade, Mariza, DeMeo, Dawn L, Dutcher, Susan K, Ellinor, Patrick T, Emery, Leslie S, Eng, Celeste, Fatkin, Diane, Fingerlin, Tasha, Forer, Lukas, Fornage, Myriam, Franceschini, Nora, Fuchsberger, Christian, Fullerton, Stephanie M, Germer, Soren, Gladwin, Mark T, Gottlieb, Daniel J, Guo, Xiuqing, Hall, Michael E, He, Jiang, Heard-Costa, Nancy L, Heckbert, Susan R, Irvin, Marguerite R, Johnsen, Jill M, Johnson, Andrew D, Kaplan, Robert, Kardia, Sharon LR, Kelly, Tanika, Kelly, Shannon, Kenny, Eimear E, Kiel, Douglas P, Klemmer, Robert, Konkle, Barbara A, Kooperberg, Charles, Köttgen, Anna, Lange, Leslie A, Lasky-Su, Jessica, Levy, Daniel, Lin, Xihong, Lin, Keng-Han, Liu, Chunyu, and Loos, Ruth JF

Subjects
Genetics, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, Cytochrome P-450 CYP2D6, Genetic Variation, Genome, Human, Genomics, Haplotypes, Heterozygote, Humans, INDEL Mutation, Loss of Function Mutation, Mutagenesis, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Polymorphism, Single Nucleotide, Population Density, Precision Medicine, Quality Control, Sample Size, United States, Whole Genome Sequencing, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, General Science & Technology
Abstract

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

Published
2021

15. From Simulation to Implementation: Two CAT Case Studies

Author

Barnard, John J.

Abstract

Measurement specialists strive to shorten assessment time without compromising precision of scores. Computerized Adaptive Testing (CAT) has rapidly gained ground over the past decades to fulfill this goal. However, parameters for implementation of CATs need to be explored in simulations before implementation so that it can be determined whether expectations can be met. CATs can become costly if trial-and-error strategies are followed and especially if constraints are included in the algorithms, simulations can save time and money. In this study it was found that for both a multiple-choice question test and a rating scale questionnaire, simulations not only predicted outcomes for CATs very well, but also illustrated the efficiency of CATs when compared to fixed length tests.

Published
2018

16. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P., Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Daniel, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J.F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Powers Becker, Julia, Preethi Boorgula, Meher, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T., Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Williams, Scott, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Baojun, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Lee, Gha Young, Bui, Helena, Lee, Dong Heon, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, O’Connor, George T., and DeMeo, Dawn L.

Published
2023
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18. De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

Author

Kessler, Michael D, Loesch, Douglas P, Perry, James A, Heard-Costa, Nancy L, Taliun, Daniel, Cade, Brian E, Wang, Heming, Daya, Michelle, Ziniti, John, Datta, Soma, Celedón, Juan C, Soto-Quiros, Manuel E, Avila, Lydiana, Weiss, Scott T, Barnes, Kathleen, Redline, Susan S, Vasan, Ramachandran S, Johnson, Andrew D, Mathias, Rasika A, Hernandez, Ryan, Wilson, James G, Nickerson, Deborah A, Abecasis, Goncalo, Browning, Sharon R, Zöllner, Sebastian, O’Connell, Jeffrey R, Mitchell, Braxton D, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium National Heart, Group, TOPMed Population Genetics Working, O’Connor, Timothy D, Aalbers, Sanne, Abdalla, Moustafa, Abdul-Rahman, Omar, Abecasis, Gonçalo, Abhyankar, Avinash, Adrianto, Indra, Aguet, Francois, Akers, Rachel, Al-Tobasei, Rafet, Albert, Christine, Aldred, Micheala, Almasy, Laura, Almeida, Marcio, Alonso, Alvaro, Ament, Seth, Ampleford, Elizabeth, An, Ping, Anderson, Christopher D, Andersson, Charlotte, Anugu, Pramod, Appelbaum, Elizabeth, Ardlie, Kristin, Arking, Dan, Armasu, Sebastian M, Arnett, Donna K, Arruda, Heather, Arvanitis, Marios, Ashley-Koch, Allison, Ashrani, Aneel, Aslibekyan, Stella, Assimes, Tim, Atkinson, Elizabeth, Auer, Paul, Austin, Thomas R, Avery, Christy, Avila-Pacheco, Julian, Avillach, Paul, Aviv, Abraham, Avramopoulos, Dimitrios, Ballantyne, Christie, Balte, Pallavi, Bamshad, Michael, Bancks, Mike, Barnard, John, Barr, R Graham, Barron-Casella, Emily, Bartz, Traci, Barwick, Lucas, Basu, Saonli, Battle, Alexis, Baumann, Michael, Beame, David, Beaty, Terri, Beck, Gerald, Becker, Lewis, Becker, Diane, Beer, Rebecca, Begum, Ferdouse, Beiser, Alexa, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Berk-Rauch, Hanna, Besich, Zachary M, Bezerra, Marcos, Bhatt, Surya, Bi, Wenjian, Bick, Alexander, and Bielak, Larry

Subjects
Biological Sciences, Genetics, Human Genome, Precision Medicine, Biotechnology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Amish, Cohort Studies, DNA Mutational Analysis, Female, Genetics, Population, Genome, Human, Heterozygote, Humans, Male, Mutation, Pedigree, Whole Genome Sequencing, Young Adult, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, de novo mutations, diversity, mutation rate, recombination
Abstract

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains

Published
2020

22. Abstract 17865: Machine Learning With Multimodal Pre Ablation Imaging for Predicting Recurrence in Atrial Fibrillation Patients

Author

Midya, Abhishek, Asaeikheybari, Golnoush, Hiremath, Amogh, Viswanathan, Vidya Sankar, Sun, Han, Harwood, Samuel, Kim, Hyun Su, Schilling, Taylor, Telfer, William, Jin, Alison, Baraboo, Justin, Pradella, Maurice, Markl, Michael, Passman, Rod S, El-Harasis, Majd, Shoemaker, Ben B, Tandon, Animesh A, Barnard, John, Chung, Mina K, and Madabhushi, Anant

Published
2023
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26. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Asthma, Genetics, Pediatric, Biotechnology, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

28. Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease

Author

Hemnes, Anna R., Leopold, Jane A., Radeva, Milena K., Beck, Gerald J., Abidov, Aiden, Aldred, Micheala A., Barnard, John, Rosenzweig, Erika B., Borlaug, Barry A., Chung, Wendy K., Comhair, Suzy A.A., Desai, Ankit A., Dubrock, Hilary M., Erzurum, Serpil C., Finet, J. Emanuel, Frantz, Robert P., Garcia, Joe G.N., Geraci, Mark W., Gray, Michael P., Grunig, Gabriele, Hassoun, Paul M., Highland, Kristin B., Hill, Nicholas S., Hu, Bo, Kwon, Deborah H., Jacob, Miriam S., Jellis, Christine L., Larive, A. Brett, Lempel, Jason K., Maron, Bradley A., Mathai, Stephen C., McCarthy, Kevin, Mehra, Reena, Nawabit, Rawan, Newman, John H., Olman, Mitchell A., Park, Margaret M., Ramos, Jose A., Renapurkar, Rahul D., Rischard, Franz P., Sherer, Susan G., Tang, W.H. Wilson, Thomas, James D., Vanderpool, Rebecca R., Waxman, Aaron B., Wilcox, Jennifer D., Yuan, Jason X.-J., and Horn, Evelyn M.

Published
2022
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30. Current practices regarding corporotomy localization during penoscrotal inflatable penile implant surgery: a multicenter cohort study

Author

van Renterghem, Koenraad, Jacobs, Brecht, Yafi, Faysal, Osmonov, Daniar, Ralph, David, Venturino, Luca, Barnard, John Taylor, Ziegelmann, Matthew, Wang, Run, Kannady, Chris, Lentz, Aaron, Garcia, Enrique Lledo, Andrianne, Robert, Bettochi, Carlo, Hatzichristodoulou, George, Gross, Martin, Faix, Antoine, Otero, Javier Romero, Salamanca, Juan Ignacio Martinez, Sedigh, Omidreza, Albersen, Maarten, Dinkelman-Smit, Marij, and Mykoniatis, Ioannis

Published
2022
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31. Optimizing Beam Transport in Rapidly Compressing Beams on the Neutralized Drift Compression Experiment - II

Author

Stepanov, Anton D., Gilson, Erik P., Kaganovich, Igor D., Seidl, Peter A., Persaud, Arun, Ji, Qing, Schenkel, Thomas, Friedman, Alex, Barnard, John J., and Grote, David P.

Subjects
Physics - Accelerator Physics, Physics - Plasma Physics
Abstract

The Neutralized Drift Compression Experiment-II (NDCX-II) is an induction linac that generates intense pulses of 1.2 MeV helium ions for heating matter to extreme conditions. Here, we present recent results on optimizing beam transport. The NDCX-II beamline includes a 1-meter-long drift section downstream of the last transport solenoid, which is filled with charge-neutralizing plasma that enables rapid longitudinal compression of an intense ion beam against space-charge forces. The transport section on NDCX-II consists of 28 solenoids. Finding optimal field settings for a group of solenoids requires knowledge of the envelope parameters of the beam. Imaging the beam on scintillator gives the radius of the beam, but the envelope angle dr/dz is not measured directly. We demonstrate how the parameters of the beam envelope (r, dr/dz, and emittance) can be reconstructed from a series of images taken at varying B-field strengths of a solenoid upstream of the scintillator. We use this technique to evaluate emittance at several points in the NDCX-II beamline and for optimizing the trajectory of the beam at the entry of the plasma-filled drift section.

Published
2017

32. Materials processing with intense pulsed ion beams and masked targets

Author

Barnard, John J. and Schenkel, Thomas

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce materials modifications and phase transitions. Materials properties can potentially be stabilized by rapid quenching. Pulsed ion beams with (sub-) ns pulse lengths have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired materials properties fast enough before the target is altered or damaged by e. g. hydrodynamic expansion. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. The model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters., Comment: 16 pages, 11 figures

Published
2017

33. Transcriptomic Insights into the Atrial Fibrillation Susceptibility Locus near the MYOZ1 and SYNPO2L Genes.

Author

Wass, Sojin Y., Sun, Han, Tchou, Gregory, Liu, Nana, Van Wagoner, David R., Chung, Mina K., Barnard, John, and Smith, Jonathan D.

Subjects
GENE expression, REPORTER genes, GENE transfection, LINKAGE disequilibrium, GENOME-wide association studies
Abstract

Genome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 (MYOZ1) and synaptopodin 2-like (SYNPO2L) transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels. Chromatin marks were used to suggest candidate regulatory SNPs in this region. Protein amino acid changes were examined for predicted functional consequences. Transfection of MYOZ1 and two SYNPO2L isoforms were performed to localize their encoded proteins in cardiomyocytes derived from stem cells. We identified one MYOZ1 transcript isoform and four SYNPO2L transcript isoforms, two of which encode proteins, while the other two encode long noncoding RNAs (lncRNAs). The risk allele of the strongest AF susceptibility SNP on chromosome 10q22 is associated with decreased MYOZ1 expression and increased expression of the two SNYPO2L lncRNA isoforms. There are many SNPs co-inherited with the top AF-associated SNP due to linkage disequilibrium (LD), including rs11000728, which we propose as the MYOZ1 regulatory SNP, confirmed by reporter gene transfection. In addition, this LD block includes three missense SNPs in the SYNPO2L gene, with the minor protective haplotype predicted to be detrimental to protein function. MYOZ1 and both protein isoforms of SYNPO2L were localized to the sarcomere. This is a complex locus with the potential for several SNPs in a haplotype to alter AF susceptibility by opposing effects on MYOZ1 and SYNPO2L lncRNA expression, along with effects on SYNPO2L protein function. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D, Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M, Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D, Aragam, Krishna G, Arking, Dan E, Barnard, John, Bartz, Traci M, Benjamin, Emelia J, Bihlmeyer, Nathan A, Bis, Joshua C, Bloom, Heather L, Boerwinkle, Eric, Bottinger, Erwin B, Brody, Jennifer A, Calkins, Hugh, Campbell, Archie, Cappola, Thomas P, Carlquist, John, Chasman, Daniel I, Chen, Lin Y, Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E, Chung, Mina K, Cole, John W, Conen, David, Cook, James, Crijns, Harry J, Cutler, Michael J, Damrauer, Scott M, Daniels, Brian R, Darbar, Dawood, Delgado, Graciela, Denny, Joshua C, Dichgans, Martin, Dörr, Marcus, Dudink, Elton A, Dudley, Samuel C, Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B, Ford, Ian, Franco, Oscar H, Geelhoed, Bastiaan, Grewal, Raji P, Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Hernesniemi, Jussi, Hocking, Lynne J, Hofman, Albert, Horimoto, Andrea RVR, Huang, Jie, Huang, Paul L, Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kamatani, Yoichiro, Kane, John P, Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L, Kirchhof, Paulus, Kleber, Marcus E, Knight, Stacey, Krieger, Jose E, Kubo, Michiaki, Launer, Lenore J, Laurikka, Jari, Lehtimäki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N, Li, Man, Lim, Hong Euy, Lin, Henry J, and Lin, Honghuang

Subjects
Biological Sciences, Genetics, Heart Disease, Cardiovascular, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Atrial Fibrillation, Case-Control Studies, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Quantitative Trait Loci, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Published
2018

35. Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction

Author

Macri, Vincenzo, Brody, Jennifer A, Arking, Dan E, Hucker, William J, Yin, Xiaoyan, Lin, Honghuang, Mills, Robert W, Sinner, Moritz F, Lubitz, Steven A, Liu, Ching-Ti, Morrison, Alanna C, Alonso, Alvaro, Li, Ning, Fedorov, Vadim V, Janssen, Paul M, Bis, Joshua C, Heckbert, Susan R, Dolmatova, Elena V, Lumley, Thomas, Sitlani, Colleen M, Cupples, L Adrienne, Pulit, Sara L, Newton-Cheh, Christopher, Barnard, John, Smith, Jonathan D, Van Wagoner, David R, Chung, Mina K, Vlahakes, Gus J, O'Donnell, Christopher J, Rotter, Jerome I, Margulies, Kenneth B, Morley, Michael P, Cappola, Thomas P, Benjamin, Emelia J, Muzny, Donna, Gibbs, Richard A, Jackson, Rebecca D, Magnani, Jared W, Herndon, Caroline N, Rich, Stephen S, Psaty, Bruce M, Milan, David J, Boerwinkle, Eric, Mohler, Peter J, Sotoodehnia, Nona, and Ellinor, Patrick T

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Biophysical Phenomena, Electrocardiography, Genetic Association Studies, Haplotypes, Heart Conduction System, Humans, Ion Channel Gating, Mutation, Missense, NAV1.8 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Quantitative Trait Loci, atrial fibrillation, electrocardiography, haplotypes, Na plus channels, population genetics, Na+ channels, genetics, population, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BACKGROUND:Genetic variants at the SCN5A/SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. METHODS:We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. RESULTS:We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (r  2=0.86) with each other to be the strongest signals for PR (rs10428132, β=-4.74, P=1.52×10-14) and QRS intervals (rs6599251, QRS β=-0.73; P=1.2×10-4), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium (r  2≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P=0.03, and I962V+V1073A, 22.4±0.8%, P=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P=0.03). CONCLUSIONS:Our findings suggest an association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction.

Published
2018

36. Optimizing beam transport in rapidly compressing beams on the neutralized drift compression experiment-II

Author

Stepanov, Anton D, Barnard, John J, Friedman, Alex, Gilson, Erik P, Grote, David P, Ji, Qing, Kaganovich, Igor D, Persaud, Arun, Seidl, Peter A, and Schenkel, Thomas

Subjects
Nuclear and Plasma Physics, Synchrotrons and Accelerators, Physical Sciences, Charged-particle beams, Induction accelerators, Beam dynamics, Beam emittance, Ion beam diagnostics
Abstract

The Neutralized Drift Compression Experiment-II (NDCX-II) is an induction linac that generates intense pulses of 1.2 MeV helium ions for heating matter to extreme conditions. Here, we present recent results on optimizing beam transport. The NDCX-II beamline includes a 1-m-long drift section downstream of the last transport solenoid, which is filled with charge-neutralizing plasma that enables rapid longitudinal compression of an intense ion beam against space-charge forces. The transport section on NDCX-II consists of 28 solenoids. Finding optimal field settings for a group of solenoids requires knowledge of the envelope parameters of the beam. Imaging the beam on the scintillator gives the radius of the beam, but the envelope angle is not measured directly. We demonstrate how the parameters of the beam envelope (radius, envelop angle, and emittance) can be reconstructed from a series of images taken by varying the B-field strengths of a solenoid upstream of the scintillator. We use this technique to evaluate emittance at several points in the NDCX-II beamline and for optimizing the trajectory of the beam at the entry of the plasma-filled drift section.

Published
2018

37. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author

van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, and Ferrucci, Luigi

Subjects
Biological Sciences, Genetics, Human Genome, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Atrial Function, Atrioventricular Node, Electrocardiography, Electrophysiological Phenomena, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Risk Factors
Abstract

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

Published
2018

40. Pediatric Ureteroscopy

Author

Barnard, John, Crigger, Chad, Hajiran, Ali, Al-Omar, Osama, Ost, Michael, F. Schwartz, Bradley, editor, and D. Denstedt, John, editor

Published
2020
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41. Pyeloplasty

Author

Crigger, Chad, Barnard, John, McClelland, Daniel J., Ost, Michael, and Gargollo, Patricio C., editor

Published
2020
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43. Short-Pulse, Compressed Ion Beams at the Neutralized Drift Compression Experiment

Author

Seidl, Peter A, Barnard, John J, Davidson, Ronald C, Friedman, Alex, Gilson, Erik P, Grote, David, Ji, Qing, Kaganovich, I D, Persaud, Arun, Waldron, William L, and Schenkel, Thomas

Subjects
Physics - Accelerator Physics
Abstract

We have commenced experiments with intense short pulses of ion beams on the Neutralized Drift Compression Experiment (NDCX-II) at Lawrence Berkeley National Laboratory, with 1-mm beam spot size within 2.5 ns full-width at half maximum. The ion kinetic energy is 1.2 MeV. To enable the short pulse duration and mm-scale focal spot radius, the beam is neutralized in a 1.5-meter-long drift compression section following the last accelerator cell. A short-focal-length solenoid focuses the beam in the presence of the volumetric plasma that is near the target. In the accelerator, the line-charge density increases due to the velocity ramp imparted on the beam bunch. The scientific topics to be explored are warm dense matter, the dynamics of radiation damage in materials, and intense beam and beam-plasma physics including select topics of relevance to the development of heavy-ion drivers for inertial fusion energy. Below the transition to melting, the short beam pulses offer an opportunity to study the multi-scale dynamics of radiation-induced damage in materials with pump-probe experiments, and to stabilize novel metastable phases of materials when short-pulse heating is followed by rapid quenching. First experiments used a lithium ion source; a new plasma-based helium ion source shows much greater charge delivered to the target., Comment: 4 pages, 2 figures, 1 table. Submitted to the proceedings for the Ninth International Conference on Inertial Fusion Sciences and Applications, IFSA 2015

Published
2016
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46. NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

Author

Oldham, William M., Hemnes, Anna R., Aldred, Micheala A., Barnard, John, Brittain, Evan L., Chan, Stephen Y., Cheng, Feixiong, Cho, Michael H., Desai, Ankit A., Garcia, Joe G.N., Geraci, Mark W., Ghiassian, Susan D., Hall, Kathryn T., Horn, Evelyn M., Jain, Mohit, Kelly, Rachel S., Leopold, Jane A., Lindstrom, Sara, Modena, Brian D., Nichols, William C., Rhodes, Christopher J., Sun, Wei, Sweatt, Andrew J., Vanderpool, Rebecca R., Wilkins, Martin R., Wilmot, Beth, Zamanian, Roham T., Fessel, Joshua P., Aggarwal, Neil R., Loscalzo, Joseph, and Xiao, Lei

Published
2021
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48. Modeling of intense pulsed ion beam heated masked targets for extreme materials characterization

Author

Barnard, John J and Schenkel, Thomas

Subjects
Mathematical Sciences, Physical Sciences, Engineering, Applied Physics
Abstract

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g., hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. The model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.

Published
2017

49. Surface tension models for a multi-material ALE code with AMR

Author

Liu, Wangyi, Koniges, Alice, Gott, Kevin, Eder, David, Barnard, John, Friedman, Alex, Masters, Nathan, and Fisher, Aaron

Subjects
Fluid Mechanics and Thermal Engineering, Engineering, Surface tension, ALE, AMR, Multi-physics modeling, Interface reconstruction, Lithography, Applied Mathematics, Mechanical Engineering, Interdisciplinary Engineering, Fluid mechanics and thermal engineering
Abstract

A number of surface tension models have been implemented in a 3D multi-physics multi-material code, ALE–AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR). ALE–AMR is unique in its ability to model hot radiating plasmas, cold fragmenting solids, and most recently, the deformation of molten material. The surface tension models implemented include a diffuse interface approach with special numerical techniques to remove parasitic flow and a height function approach in conjunction with a volume-fraction interface reconstruction package. These surface tension models are benchmarked with a variety of test problems. Based on the results, the height function approach using volume fractions was chosen to simulate droplet dynamics associated with extreme ultraviolet (EUV) lithography.

Published
2017

50. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium

Author

Weng, Lu-Chen, Lunetta, Kathryn L, Müller-Nurasyid, Martina, Smith, Albert Vernon, Thériault, Sébastien, Weeke, Peter E, Barnard, John, Bis, Joshua C, Lyytikäinen, Leo-Pekka, Kleber, Marcus E, Martinsson, Andreas, Lin, Henry J, Rienstra, Michiel, Trompet, Stella, Krijthe, Bouwe P, Dörr, Marcus, Klarin, Derek, Chasman, Daniel I, Sinner, Moritz F, Waldenberger, Melanie, Launer, Lenore J, Harris, Tamara B, Soliman, Elsayed Z, Alonso, Alvaro, Paré, Guillaume, Teixeira, Pedro L, Denny, Joshua C, Shoemaker, M Benjamin, Van Wagoner, David R, Smith, Jonathan D, Psaty, Bruce M, Sotoodehnia, Nona, Taylor, Kent D, Kähönen, Mika, Nikus, Kjell, Delgado, Graciela E, Melander, Olle, Engström, Gunnar, Yao, Jie, Guo, Xiuqing, Christophersen, Ingrid E, Ellinor, Patrick T, Geelhoed, Bastiaan, Verweij, Niek, Macfarlane, Peter, Ford, Ian, Heeringa, Jan, Franco, Oscar H, Uitterlinden, André G, Völker, Uwe, Teumer, Alexander, Rose, Lynda M, Kääb, Stefan, Gudnason, Vilmundur, Arking, Dan E, Conen, David, Roden, Dan M, Chung, Mina K, Heckbert, Susan R, Benjamin, Emelia J, Lehtimäki, Terho, März, Winfried, Smith, J Gustav, Rotter, Jerome I, van der Harst, Pim, Jukema, J Wouter, Stricker, Bruno H, Felix, Stephan B, Albert, Christine M, and Lubitz, Steven A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Heart Disease, Cardiovascular, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Age Factors, Aged, Atrial Fibrillation, Body Mass Index, Chromosomes, Human, Pair 4, Epistasis, Genetic, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Sex Characteristics
Abstract

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

Published
2017

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