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1. DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes

Author

Thomas Donner, P. Rezaeian, John I. Malone, Sharon B. Schwartz, Xiaoyu Gao, Szilard Kiss, Matthew J. Budoff, David R. Sell, A. Dwoskin, Ronald J. Prineas, C. Pittman, M. Reid, C. McDonald, S. Caulder, M. Szpiech, Oscar B. Crofford, Rachel G. Miller, Louis A. Lobes, M. Patronas, C. Canny, M. E. Lackaye, Sandra R. Montezuma, Richard M. Bergenstal, Patricia Gatcomb, Julie A. Stoner, H. Pan, James L. Kinyoun, J. Mortenson, Osama Hamdy, Connie Fountain, David D. Moore, Kusiel Perlman, R. Trail, David A. Lee, J. Sheindlin, Samuel Dagogo-Jack, Jeffrey L. Mahon, Jill P. Crandall, L. Gill, T. Thompson, Lee M. Jampol, K. Koushan, David S. Schade, J. Brown-Friday, M. Basco, S. Dunnigan, J. Bylsma, R. Birk, L. H. Ketai, J. Hotaling, Stephen W. Scherer, W. Mestrezat, Stephan Villavicencio, R. Lyon, M. Carney, John Kramer, Sunder Mudaliar, David M. Nathan, M. Moran, F. Leandre, James W. Albers, L. Survant, Joseph F. Polak, Manjot K. Gill, Anton Orlin, M. Prince, Pamela A. Silver, Amy K. Saenger, John D. Brunzell, Kathleen E. Bainbridge, L. Babbione, Amisha Wallia, J. Vaccaro-Kish, Bradley D. Jones, M. Hebdon, L. McKenzie, Richard M. Hoffman, S. Chang, C. Siebert, George S. Sharuk, D. Counts, A. Lucas, P. Ramos, N. Burkhart, N. Bakshi, N. Flaherty, D. Kenny, M. Driscoll, Harjit Chahal, Ronald K. Mayfield, S. Hensley, E. Weimann, M. Franz, Martin J. Stevens, N. S. Gregory, Christopher J. O'Donnell, J. Laechelt, Pamela Ossorio, Jerry P. Palmer, Rama Natarajan, G. Ziegler, K. Martin, R. Beaser, C. Beck, L. Zhang, T. J. Declue, David M. Kendall, H. Solc, A. Vella, H. Martinez, Cormac T. Taylor, S. Neill, Douglas A. Greene, P. Lee, D. Norman, Andrew J. Barkmeier, Dean P. Hainsworth, Alka Jain, Sapna Gangaputra, N. Thangthaeng, Lorraine Thomas, Michael H. Brent, M. Bracey, Philip Raskin, Q. Clemens, Barbara H. Braffett, Mark S. Mandelcorn, Lloyd Paul Aiello, John E. Godine, T. Speigelberg, R. Chan, R. Hanna, Shelley B. Bull, William I. Sivitz, R. Sussman, C. Kwong, S. Cercone, P. Hollander, N. Leloudes, Joseph M. Terry, J. Wesche, E. A. Tanaka, D. Rosenberg, Wanjie Sun, L. Sun, Tom Clark, Deborah K. Schlossman, Louis M. Luttrell, R. Dunn, A. Farr, K. McVary, Gayle M. Lorenzi, A. Joseph, Catherine C. Cowie, M. Barr, D. Zimbler, S. Mendley, S. Schussler, N. Grove, Matthew D. Davis, Jong Mu Sun, Sophie Rogers, John P. Bantle, Brandy N. Rutledge, Senda Ajroud-Driss, Vincent M. Monnier, Cladd E. Stevens, Y. G. He, M. Phillips, C. Williams, J. MacIndoe, Kaleigh Farrell, Helen Lambeth, Ayad A. Jaffa, J. Quin, Morey W. Haymond, R. Kirby, D. Steinberg, William H. Herman, M. Mech, Arup Das, Robert Detrano, J. Brown, D. McMillan, Linda Snetselaar, Mark W. Johnson, R. Zeitler, T. Taylor, Peter R. Pavan, Michael H. Goldbaum, Bruce A. Perkins, R. G. Campbell, David A. Nicolle, R. J. van der Geest, Irene Hramiak, D. Freking, Lucy A. Levandoski, S. Colson, Charles Campbell, Victoria R. Trapani, Lawrence J. Singerman, D. Meyer, W. Tang, J. Soule, Anita Harrington, Julie A. Nelson, John A. Colwell, Naji Younes, P. Salemi, K. Hansen, Trevor J. Orchard, S. Huddleston, L. Steranchak, C. Sommer, G. Castle, J. Ginsberg, Paula McGee, V. Gama, John Dupre, Z. Strugula, M. Swenson, N. Wong, David A. Bluemke, M. Nutaitis, Anita Agarwal, M. Lin, K. Nickander, Elsayed Z. Soliman, Joao A. Lima, M. L. Schluter, Fred W. Whitehouse, Lisa Diminick, C. Cornish, M. Spencer, Daniel T. Lackland, Ionut Bebu, Hunter Wessells, S. Yacoub-Wasef, A. Determan, L. Van Ottingham, Howard Wolpert, R. Ehrlich, A. Blevins, L. Jovanovic, D. Finegold, Davida F. Kruger, Jye-Yu C. Backlund, K. Chan, Timothy J. Murtha, R. K. Mayfield, Robert W. Cavicchi, Maria F. Lopes-Virella, Thomas A. Weingeist, K. Lee, Mary E. Larkin, B. Blodi, J. Gott, Timothy J. Lyons, J. Selby, Chris Ryan, J. Harth, P. Pugsley, L. Keasler, John D. Maynard, Paul G. Arrigg, Amy B. Karger, P. Colby, J. Farquhar, Mark H. Schutta, Murk-Hein Heinemann, Kathie L. Hermayer, B. Bosco, C. Lovell, A. Bhan, A. Galprin, M. Cayford, M. Schumer, John E. Chapin, D. Rubinstein, F. Miao, V. Asuquo, Catherine L. Martin, Rodney A. Lorenz, Samuel S. Engel, L. Funk, Cyndi F. Liu, Barbara J. Maschak-Carey, Stephen S. Feman, P. Lindsey, M. Giotta, Philip A. Low, S. Kwon, R. Fahlstrom, A. Iannacone, B. French, H. Remtema, L. Cimino, S. Barron, J. McConnell, Jane L. Lynch, L. Kim, T. Williams, A. Degillio, Blanche M. Chavers, M. Novak, Julio V. Santiago, Ronald P. Danis, P. Gaston, Tae Sup Lee, T. Woodfill, R. Cuddihy, Scott M. Steidl, Alanna C. Morrison, E. Ryan, D. Lawrence, D. Cros, T. Adkins, D. Adelman, L. Dews, Patricia A. Cleary, J. Parker, L. Olmos De Koo, C. Kim, Mark R. Palmert, P. Astelford, Stefan Fritz, B. Olson, Kelvin C. Fong, Alan M. Jacobson, Stanley L. Hazen, D. Hornbeck, K. Folino, M. L. Bernal, Gabriel Virella, William V. Tamborlane, Neil H. White, Daniel L. McGee, Denis Daneman, H. Shamoon, William Dahms, S. Elsing, S. Brink, J. Ahern, Delnaz Roshandel, John M. Pach, N. W. Rodger, E. Cupelli, Dara D. Koozekanani, Abbas E. Kitabchi, K. Stoessel, B. Petty, Jamie R. Wood, J. Seegmiller, T. Strand, Y. Li, Eva L. Feldman, Larry Rand, Robert C. Colligan, T. Smith, A. Carlson, David J. Brillon, Margaret L. Bayless, M. Ong, S. Darabian, W. Hsu, Janet E. Olson, B. Rogness, N. Silvers, M. Pfiefer, B. Schaefer, E. Mendelson, S. Braunstein, Maren Nowicki, R. Reed, James S. Floyd, Z. M. Zhang, T. Sandford, R. B. Avery, A. Pratt, Paolo S. Silva, H. Bode, Alexander J. Brucker, Nikhil D. Patel, Alexander R. Lyon, M. Jenner, N. Wimmergren, L. Tuason, J. Rosenzwieg, D. J. Becker, C. Gauthier-Kelly, M. Richardson, Richard S. Crow, Andrew D. Paterson, Mark E. Molitch, Suzanne M. Strowig, S. Pendegast, M. Burger, Ramzi K. Hemady, J. Dingledine, I. H. de Boer, L. Mayer, F. Perdikaris, Om P. Ganda, F. Thoma, Karen J. Cruickshanks, Abraham Thomas, K. Klumpp, Jerry D. Cavallerano, D. Zheng, Annette Barnie, J. L. Canady, C. Wigley, David G. Miller, Sheila Smith-Brewer, D. Ostrowski, P. Crawford, K. Kelly, Robert G. Devenyi, B. Zimmerman, Susan M. Hitt, C. Johnson, L. Gurry, R. Jarboe, E. Angus, David E. Goldstein, A. Killeen, H. Schrott, Orville G. Kolterman, Mark R. Burge, Michael Rubin, J. Lipps Hagan, Alicia J. Jenkins, Hugh D. Wabers, R. Warhol, Edward Chaum, Karen L. Jones, L. Spillers, C. Miao, J. K. Jones, Angelo J. Canty, Rickey E. Carter, Evrim B. Turkbey, B. Burzuk, R. Woodwick, Evica Simjanoski, Michael W. Steffes, S. Crowell, Suresh D. Shah, H. Ricks, J. D. Carey, Paul A. Edwards, S. Holt, W. F. Schwenk, Ronald J. Oudiz, E. Brown, J. Heier, R. L. Ufret-Vincenty, L. M. Aiello, Robert A. Rizza, Karen L. Anderson, Valerie L. Arends, J. Giangiacomo, R. Liss, Aruna V. Sarma, B. Levy, Ellen J. Anderson, S. Catton, P. Callahan, Rodica Pop-Busui, S. Debrabandere, S. Moser, Bernard H. Doft, A. Malayeri, C. Johannes, R. Ramker, J. Rich, M. Fox, Rukhsana G. Mirza, Katherine A. Morgan, Thomas J. Songer, C. Shah, H. Engel, Saul M. Genuth, S. Ferguson, Anushka Patel, C. Haggan, P. Lou, J. Gordon, M. B. Murphy, D. Sandstrom, Dawn M. Ryan, Daniel H. O'Leary, B. Gloeb, Lois E. Schmidt, H. Zegarra, D. Dalton, W. Brown, Tom G. Sheidow, Margaret E. Stockman, Shyam M. Thomas, Charles McKitrick, Jyotika K. Fernandes, P. A. Bourne, L. Baker, G. Friedenberg, Allan Gordon, Allan L. Drash, S. Yoser, D. Wood, S. Johnsonbaugh, A. De Manbey, L. Kaminski, M. May, L. Bestourous, A. Kowarski, M. Geckle, M. Hartmuller, Michael Bryer-Ash, S. List, F. Goetz, V. Reppucci, D. Etzwiler, Rose A. Gubitosi-Klug, M. Brabham, E. Golden, A. Nayate, J. Hu, M. McLellan, Ronald Klein, N. Rude, B. Vittetoe, John M. Lachin, M. Christofi, Zhuo Chen, Isaac Boniuk, C. Strauch, K. Gunyou, L. Delahanty, W. T. Garvey, Andrew P. Boright, Larry D. Hubbard, D. Weiss, Igor Grant, Jonathan Q. Purnell, Jean M. Bucksa, N. Olson, and B. Zinman

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Diabetic neuropathy, Adolescent, 030209 endocrinology & metabolism, Gastroenterology, Nephropathy, Epigenesis, Genetic, Diabetic complications, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Diabetic Neuropathies, Internal medicine, Diabetes mellitus, Albumins, Genetics, Medicine, Humans, Molecular Biology, Genetics (clinical), Whole blood, Oligonucleotide Array Sequence Analysis, Type 1 diabetes, business.industry, Research, dNaM, DNA methylation age, DNA Methylation, medicine.disease, 030104 developmental biology, Blood pressure, Peripheral neuropathy, Diabetes Mellitus, Type 1, CpG Islands, Female, business, Developmental Biology, Genome-Wide Association Study
Abstract

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Published
2020

2. Practical Cancer Genetics and Genomics in Women's Health

Author

Susan C. Modesitt, Royce T. Adkins, and Holly J. Pederson

Subjects
medicine.medical_specialty, Genital Neoplasms, Female, Genes, BRCA2, Genes, BRCA1, Genomics, Risk Assessment, Obstetrics and gynaecology, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Selection (genetic algorithm), Genetic testing, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Precision medicine, Obstetrics, Gynecology, Family medicine, Cancer genetics, Women's Health, Hereditary Cancer, Human genome, Female, business
Abstract

There have been rapid advances in precision medicine since the Human Genome Project was completed in 2003, including several noteworthy advances in Women's Health. This includes significant advances in predicting individualized cancer risk based on hereditary cancer genetic testing, with the number of known cancer-predisposition genes extending well beyond BRCA1 and BRCA2. This has been coupled with gene-specific management guidelines for several gynecologic cancers. In addition, genetic testing can also inform therapy selection for women with gynecologic cancers. Here we address hereditary cancer and practical cancer genetics as it relates to the practicing Obstetrician/Gynecologist.

Published
2019

3. Hereditary Cancer Risk Assessment and Genetic Testing in the Community-Practice Setting

Author

Lindsey Alico, Mark S DeFrancesco, Richard Waldman, Ryan Bernhisel, Royce T. Adkins, Jennifer Logan, Dana Karanik, and Melissa M Pearlstone

Subjects
medicine.medical_specialty, Referral, Attitude of Health Personnel, Genetic counseling, Genes, BRCA2, Genes, BRCA1, Genetic Counseling, Risk Assessment, Workflow, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Obstetrics and gynaecology, Patient Education as Topic, Neoplasms, Health care, medicine, Humans, 030212 general & internal medicine, Genetic Testing, Prospective Studies, Prospective cohort study, Genetic testing, medicine.diagnostic_test, business.industry, Process Assessment, Health Care, Obstetrics and Gynecology, DNA-Binding Proteins, Obstetrics, Checkpoint Kinase 2, Gynecology, Patient Satisfaction, 030220 oncology & carcinogenesis, Family medicine, Feasibility Studies, Female, business, Risk assessment, Fanconi Anemia Complementation Group N Protein
Abstract

Objective To evaluate the feasibility and results of incorporating routine hereditary cancer risk assessment, counseling, and follow-up genetic testing in the community obstetrics and gynecology practice setting without referral to a genetic counselor. Methods This prospective process intervention study was conducted with two obstetrics and gynecology practice groups (five sites). The intervention included baseline process assessment, refinement of clinic-specific patient screening workflows and tools, and training in hereditary cancer risk screening and follow-up. Outcomes related to hereditary cancer assessment and testing were measured during an 8-week postintervention period. Patients and health care providers were surveyed about satisfaction with the process. Data also were collected during the 8 weeks before the intervention to assess the effects of screening process improvements. Results A total of 4,107 patients were seen during the postintervention period, and 92.8% (3,811) were assessed for hereditary cancer risk. Among those assessed, 906 of 3,811 (23.8%) women met National Comprehensive Cancer Network guidelines for genetic testing, and 813 of 906 (89.7%) eligible patients were offered genetic testing. A total of 165 of 4,107 (4.0%) women completed genetic testing and received a final test result. This represents a fourfold increase over genetic testing immediately before the intervention (1.1%) and an eightfold increase over the previous year (0.5%). Testing identified pathogenic variants in 9 of 165 (5.5%) tested women. All health care providers (15/15) reported that they will continue to use the established hereditary cancer risk assessment process. In addition, 98.8% (167/169) of patients who submitted a sample for genetic testing and completed a patient satisfaction survey stated that they were able to understand the information provided, and 97.6% (165/169) expressed satisfaction with the overall process. Conclusion It is feasible to incorporate hereditary cancer risk assessment, education, and testing into community obstetrics and gynecology practices. As a result, multigene panel testing identified significant cancer risks that otherwise would not have been recognized.

Published
2018

4. Quality Control Measures over 30 Years in a Multicenter Clinical Study: Results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Author

M. Bracey, B. French, Brandy N. Rutledge, Sharon B. Schwartz, D. Steinberg, Peter R. Pavan, Xiaoyu Gao, Alan M. Jacobson, David A. Nicolle, C. Canny, Maria F. Lopes-Virella, A. Kitabchi, K. Hansen, M. E. Lackaye, Denis Daneman, Kandace A. Klumpp, David A. Lee, H. Engel, L. Survant, C. Haggan, K. Lee, G. Ziegler, Dawn M. Ryan, Lloyd Paul Aiello, Tom G. Sheidow, Allan Gordon, Allan L. Drash, S. Johnsonbaugh, L. Kaminski, S. Yoser, David J. Brillon, Osama Hamdy, Connie Fountain, N. Silvers, Kusiel Perlman, S. Caulder, M. Szpiech, D. Freking, Paula McGee, George S. Sharuk, D. Counts, H. Solc, David E. Goldstein, L. Bestourous, W. F. Schwenk, E. Brown, S. Cercone, M. Patronas, James L. Kinyoun, G. Castle, Mark H. Schutta, M. L. Schluter, Anton Orlin, E. Chaum, Daniel P. Joseph, F. Goetz, V. Reppucci, D. Etzwiler, E. Golden, A. Iannacone, R. Kirby, Lucy A. Levandoski, Lawrence J. Singerman, P. Salemi, A. Morrison, G. Vagstad, J. Laechelt, Pamela Ossorio, Tae Sup Lee, R. Cuddihy, S. Hitt, Fred W. Whitehouse, Michael H. Brent, Gayle M. Lorenzi, Anthony D. Morrison, B. Zinman, Szilard Kiss, D. Norman, N. Olson, Thomas Donner, John Dupre, M. Swenson, M. Spencer, Jerry P. Palmer, Scott M. Steidl, M. Franz, R. Beaser, H. Martinez, Samuel S. Engel, L. Diminick, J. Mortenson, David S. Schade, S. Yacoub-Wasef, Misty Good, John E. Chapin, Paolo S. Silva, J. Ginsberg, A. Dwoskin, John P. Bantle, J. D. Carey, D. McMillan, R. G. Campbell, Lisa Diminick, C. Cornish, Ramzi K. Hemady, P. Hollander, A. Farr, D. Zimbler, M. Mech, A. Lucas, Jye-Yu C. Backlund, K. Chan, Timothy J. Murtha, V. Asuquo, A. Bhan, A. Galprin, F. Perdikaris, Michael D. Larsen, L. Gill, Pamela A. Silver, S. Brink, Louis M. Luttrell, Sheila Smith-Brewer, D. Ostrowski, M. Bratkowksi, P. Crawford, M. Bryer-Ash, E. Angus, S. Braunstein, John I. Malone, R. Conwit, C. Pittman, Louis A. Lobes, Rodney A. Lorenz, J. Rosenzwieg, Neil H. White, William I. Sivitz, D. J. Becker, Stephen S. Feman, M. Zaucha, M. Reid, M. Jenner, L. Tuason, C. Gauthier-Kelly, C. McDonald, William H. Herman, John Kramer, Jeffrey L. Mahon, A. Campbell, J. L. Canady, A. Degillio, T. Adkins, P. W. Conrad, Senda Ajroud-Driss, L. Dews, Stephan Villavicencio, David G. Miller, Manjot K. Gill, D. Curtin, J. Brown-Friday, M. Basco, Elsayed Z. Soliman, J. Selby, Bradley D. Jones, M. Hebdon, B. Olson, John M. Pach, N. W. Rodger, K. Stoessel, N. Leloudes, J. Floyd, H. Lambeth, G. Lorenzi, Richard M. Hoffman, S. Chang, M. Guiliani, H. Zegarra, N. Bakshi, Dean P. Hainsworth, Murk-Hein Heinemann, S. Dagogo-Jack, Wanjie Sun, J. Warnicki, Dean B. Burgess, D. Kenny, L. McKenzie, B. Rogness, Martin J. Stevens, M. Nutaitis, William V. Tamborlane, L. Schmidt, Deborah K. Schlossman, J. Giangiacomo, C. Williams, R. Liss, Barbara J. Maschak-Carey, Barbara H. Braffett, Stefan Fritz, J. MacIndoe, Tom Clark, M. Novak, Michael H. Goldbaum, A. DeManbey, J. Ahern, L. Jovanovic, D. Finegold, Davida F. Kruger, Mary E. Larkin, M. Johnson, S. Shah, M. Ong, Catherine L. Martin, M. Giotta, R. Reed, B. Levy, Evica Simjanoski, L. Cimino, P. Callahan, S. Crowell, Rodica Pop-Busui, Howard Wolpert, Bernard H. Doft, J. Arch, C. Shipe, Mark R. Palmert, Philip Raskin, B. Schaefer, P. Astelford, Dara D. Koozekanani, R. B. Avery, Michael W. Steffes, Robert A. Rizza, Karen L. Anderson, Charles McKitrick, P. A. Bourne, L. Baker, G. Friedenberg, D. Wood, J. Wesche, M. Phillips, Gaurav K. Shah, John M. Lachin, M. Christofi, Kevin J. Blinder, R. Ehrlich, J. Rinkoff, Morey W. Haymond, Irene Hramiak, Z. Strugula, A. Blevins, R. Hyre, M. Richardson, Mark E. Molitch, I. H. de Boer, Annette Barnie, Mark R. Burge, M. Prince, P. Ramos, R. Chan, R. Hanna, Jong Mu Sun, Suzanne M. Strowig, C. Wigley, Om P. Ganda, R. Harris, Abraham Thomas, K. Klumpp, K. Kelly, David D. Moore, J. Sheindlin, T. J. Declue, Cormac T. Taylor, C. Kwong, Rose Gubitosi-Klug, T. Sandford, Isaac Boniuk, B. Zimmerman, R. Zeitler, S. Rogers, Joseph M. Terry, C. Johnson, Linda Snetselaar, Naji Younes, Ionut Bebu, N. Wimmergren, Rukhsana G. Mirza, K. Gunyou, Karl R. Olsen, H. Bode, J. Fruit, Michael Rubin, G. Grand, Trevor J. Orchard, Douglas A. Greene, J. Quin, R. Birk, W. Mestrezat, P. Pugsley, Anupam Agarwal, L. Mayer, C. Palmer, Timothy J. Lyons, C. Johannes, A. Determan, L. Van Ottingham, J. Gott, Jerry D. Cavallerano, D. Cros, J. Parker, M. May, Robert Bergren, A. Kowarski, L. Delahanty, Katherine A. Morgan, E. A. Tanaka, Robert W. Cavicchi, Thomas J. Songer, Robert G. Devenyi, J. Harth, Jill P. Crandall, T. Thompson, Lee M. Jampol, H. Schrott, Paul G. Arrigg, Orville G. Kolterman, R. Warhol, L. Thomas, S. Kwon, Jane L. Lynch, Arup Das, Theresa M. Williams, Thomas A. Weingeist, Patricia A. Cleary, Matthew A. Thomas, L. Babbione, Amisha Wallia, J. Lipps Hagan, D. Meyer, D. Rubinstein, P. Lindsey, Mark S. Mandelcorn, R. Fahlstrom, John E. Godine, Kathie L. Hermayer, B. Bosco, J. Rich, K. Folino, M. L. Bernal, S. Yalamanchi, S. Barron, J. McConnell, J. K. Jones, J. Vaccaro-Kish, R. Woodwick, P. Colby, Kelvin C. Fong, Ronald K. Mayfield, L. H. Ketai, Julio V. Santiago, M. B. Murphy, S. Schussler, N. Grove, Larry Rand, Robert C. Colligan, Ronald P. Danis, Valerie L. Arends, S. Ferguson, B. Petty, Christine Stevens, P. Ostrosaka, Margaret L. Bayless, S. Moser, Paul A. Edwards, R. Lyon, M. Carney, Katrina Jones, T. Strand, W. Hsu, Alexander J. Brucker, H. Shamoon, Alice T. Lyon, T. Smith, David M. Nathan, P. Lou, Bruce A. Perkins, Janet E. Olson, D. Rosenberg, H. Ricks, J. Gordon, D. Hornbeck, Nikhil D. Patel, Shelly Olson, Ellen J. Anderson, William Dahms, P. Paczan Rath, S. Elsing, L. Steranchak, L. M. Aiello, Saul Genuth, S. Catton, Sandra R. Montezuma, S. Pendegast, Richard M. Bergenstal, Patricia Gatcomb, Igor Grant, B. Braffett, W. Brown, Margaret E. Stockman, N. Burkhart, David M. Kendall, Jyotika K. Fernandes, S. List, J. Soule, Julie A. Nelson, John A. Colwell, M. McLellan, Silva A. Arslanian, N. Rude, B. Vittetoe, M. Driscoll, and E. Weimann

Subjects
Adult, Male, 030213 general clinical medicine, medicine.medical_specialty, Adolescent, Quality Assurance, Health Care, Psychological intervention, lcsh:Medicine, law.invention, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Health care, medicine, Humans, Medical physics, lcsh:Science, Multidisciplinary, Data collection, business.industry, lcsh:R, Quality control, 3. Good health, Surgery, Data quality, Cohort, 030221 ophthalmology & optometry, Female, lcsh:Q, business, Quality assurance, Follow-Up Studies, Research Article
Abstract

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented.

Published
2015

5. Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

Author

Mario Pirastu, G. E. Munn, L. H. Ketai, K. Taylor, Angela Döring, R. Chan, Jeffrey L. Mahon, Bradley D. Jones, M. Hebdon, Williams L. Dews, Douglas A. Greene, Michael D. Weiss, Sapna Gangaputra, E. A. Tanaka, J. Ginsberg, Ben A. Oostra, Alka Jain, D. Singer, M. Burger, Szilard Kiss, David A. Bluemke, Barbara H. Braffett, Jugnoo S Rahi, L. Sun, C. Clark, Richard M. Bergenstal, Patricia Gatcomb, Paul Mitchell, R. Trail, D. Ryan, Robert Bergren, D. D. Joseph, G. Grand, Blanche M. Chavers, J. M.Verhoeven Virginie, David S. Schade, C. Cowie, Sharon B. Schwartz, G. Ziegler, Lloyd Paul Aiello, Michael H. Brent, John I. Malone, C. Pittman, M. Reid, Stephen S. Feman, Maurizio Fossarello, Kathie L. Hermayer, J. Parker, M. N. Iyer, Hamid Mojibian, Rose Gubitosi-Klug, P. W. Conrad, Daniel T. Lackland, Michael Brändle, C. Canny, Alan F. Wright, M. E. Lackaye, David A. Lee, Rickey E. Carter, J. Brown-Friday, J. K. Jones, J. Distad, A. Thomas, Gordon C. Weir, S. Caulder, M. Szpiech, R. Gstalder, D. Rubinstein, Fred W. Whitehouse, T. Adkins, Gayle M. Lorenzi, L. Survant, Naji Younes, Robert Detrano, Lucy A. Levandoski, Charles Campbell, Lawrence J. Singerman, Johannes R. Vingerling, Joao A.C. Lima, D. Counts, V. Gama, D. M. Nathan, John Dupre, Cornelia M. van Duijn, N. Wong, Anita Harrington, Caroline Hayward, Shelley B. Bull, R. Hackel, William I. Sivitz, Enrico Cagliero, M. Spencer, Albert Hofman, Samuel S. Engel, John E. Hokanson, Julio V. Santiago, David M. Kendall, O. Crofford, T. Thompson, Lee M. Jampol, Kevin Morgan, R. Sussman, James W. Albers, Anita Agarwal, Kevin J. Blinder, Anthony D. Morrison, Nikhil D. Patel, R. Prusak, S. Hitt, Alexander R. Lyon, Saul Genuth, J. Sheindlin, J. Vaccaro-Kish, Goran Benčić, P. Titus, Lisa Diminick, N. Wimmergren, Shelly Olson, Z. Strugula, L. Goings, Lennart C. Karssen, A. Blevins, Harjit Chahal, Ronald K. Mayfield, S. Pendegast, T. J. Lyons, Ozren Polasek, Matthew A. Thomas, Annette Barnie, P. Lindsey, L. Funk, James L. Kinyoun, Neil H. White, L. Mayer, Rodney A. Lorenz, Susan G. Elner, R. L. Pate, E. Simjanoski, R. Beaser, J. Gothrup, Tien Yin Wong, Thomas Bettecken, Jae-Ho Lee, Elsayed Z. Soliman, Ronald P. Danis, Phillippa M. Cumberland, J. Selby, Pamela Rath, H. Martinez, S. Neill, D. Rosenberg, D. Zheng, R. Devenyi, Murk-Hein Heinemann, Albert V. Smith, Alicia J. Jenkins, Rukhsana G. Mirza, Konrad Oexle, Osama Hamdy, John D. Brunzell, Trevor J. Orchard, Daniel Cornfeld, K. Nickander, Igor Rudan, L. Kim, T. Williams, Christopher M. Ryan, William Dahms, P. Paczan Rath, S. Elsing, Matthew J. Budoff, Orville G. Kolterman, Seang-Mei Saw, Lisa A. Prosser, A. Determan, M. Espeland, L. Van Ottingham, B. Petty, A. Farr, Brandy N. Rutledge, Patricia A. Cleary, Margaret L. Bayless, E. Cupelli, Ronald J. Prineas, Jonathan Goldstein, Stefan Fritz, J. Harth, K. Stoessel, Jerry P. Palmer, J. Soule, John A. Colwell, Stephen W. Scherer, Cyndi F. Liu, M. Phillips, Alexander J. Brucker, B. Rogness, Caroline C W Klaver, Joan E. Bailey-Wilson, Claire L. Simpson, Gaurav K. Shah, Louis A. Lobes, S. Mohsen Hosseini, Veronique Vitart, Dwight Stambolian, Mark S. Mandelcorn, John E. Godine, Gabriel Virella, A. Cochrane, David A. Nicolle, Timothy J. Lyons, S. Schussler, Abbas E. Kitabchi, N. Grove, Matthew D. Davis, Andrew K. Vine, Joseph F. Polak, Helen Lambeth, Ayad A. Jaffa, S. Rogers, Samuel Dagogo-Jack, C. Siebert, K. Hansen, H. Shamoon, David J. Brillon, D. Schlossman, H. Ricks, Toby A. Gardner, Mary Frances Cotch, J. Quin, Om P. Ganda, Fernando Rivadeneira, F. Thoma, Brian Fleck, K. Klumpp, Manjot K. Gill, R. J. van der Geest, Hunter Wessells, P. Salemi, P. Gaston, Tae Sup Lee, T. Woodfill, Scott M. Steidl, Thomas Meitinger, Laura Portas, John E. Chapin, Robert Wojciechowski, Martin J. Stevens, Z. M. Zhang, John D. Maynard, Paul G. Arrigg, S. Yacoub-Wasef, Andrew D. Paterson, Barbara J. Maschak-Carey, Ramzi K. Hemady, J. Dingledine, Sheila Smith-Brewer, D. Ostrowski, D. Kenny, Leslie J. Raffel, R. Jarboe, E. Angus, G. Sharuk, Jie Jin Wang, Jye-Yu C. Backlund, K. Chan, R. K. Mayfield, M. Nutaitis, William V. Tamborlane, Emily Y. Chew, Michael H. Goldbaum, S. Kwon, Davida F. Kruger, Mary E. Larkin, Catherine L. Martin, M. Novak, David E. Goldstein, J. Rosenzwieg, D. J. Becker, A. E. Boulton, Jean M. Bucksa, Richard S. Crow, Thomas Donner, Philip A. Low, J. Fradkin, K. Folino, M. L. Bernal, Daniel L. McGee, R. D′Agostino, David G. Miller, Evrim B. Turkbey, Eva L. Feldman, Larry Rand, Harry Campbell, Mark R. Palmert, N. Silvers, M. Driscoll, M. Bracey, Mark E. Molitch, Boniuk Burgess, John P. Bantle, J. D. Carey, Edward Chaum, Philip Raskin, I. H. de Boer, Peter R. Pavan, C. Wigley, Maria F. Lopes-Virella, Pirro G. Hysi, C. Sommer, R. Eastman, B. Schaefer, Maren Nowicki, K. Lee, S. Braunstein, Hugh D. Wabers, A. F. Burrows, M. Johnson, B. Zinman, M. Ong, Samir S. Deeb, C. Gauthier-Kelly, S. Novella, C. Miao, S. Strowig, S. Crowell, Teri A. Manolio, S. Yalamanchi, Christian Gieger, D. Meyer, Louis M. Luttrell, Janie Lipps, William H. Herman, Michael W. Steffes, A. Galprin, A. Iannacone, Federico Murgia, E. Steuer, KyungMann Kim, James F. Wilson, S. Genuth, André G. Uitterlinden, Dean P. Hainsworth, J. Giangiacomo, Wanjie Sun, Aruna V. Sarma, R. Liss, S. Catton, Rodica Pop-Busui, S. Moser, Bernard H. Doft, A. Malayeri, B. Gloeb, W. T. Garvey, Andrew P. Boright, Alan M. Jacobson, Larry D. Hubbard, Barbara E.K. Klein, Shyam M. Thomas, Allan Gordon, Allan L. Drash, S. Yoser, S. Johnsonbaugh, L. Kaminski, G. Meekins, Jonathan Q. Purnell, B. Burzuk, John M. Lachin, M. Geckle, Ronald J. Oudiz, Isaac Boniuk, Xiaohui Li, V. Reppucci, H. Wolpert, D. Etzwiler, M. Brabham, Maria Schache, E. Golden, M. Fox, Jyotika K. Fernandes, Jerome I. Rotter, Paul N. Baird, Michael Bryer-Ash, M. Stern, H. Engel, M. Hawkins, Najaf Amin, C. O′Donnell, M. McLellan, G. Comer, Ronald Klein, D. Sandstrom, H. Zegarra, J. Gordon, M. B. Murphy, P. A. Bourne, L. Baker, Cristina Venturini, D. Wood, H.-Erich Wichmann, M. May, A. Kowarski, Timothy W. Olsen, Thomas J. Songer, Christopher J Hammond, P. Lou, Jill P. Crandall, Miao, Xiaoping, Ophthalmology, Obstetrics & Gynecology, Epidemiology, Clinical Genetics, and Internal Medicine

Subjects
Male, Linkage disequilibrium, Refractive error, genetic structures, Epidemiology, Genome-wide association study, Plant Science, Eye, Linkage Disequilibrium, ASSOCIATION SCANS, MULTIPLE, Medicine and Health Sciences, Myopia, 80 and over, 2.1 Biological and endogenous factors, Aetiology, Age of Onset, FAMILIAL AGGREGATION, Genetics, Aged, 80 and over, Multidisciplinary, AUSTRALIAN SCHOOL-CHILDREN, COMMON VARIANTS, Single Nucleotide, Middle Aged, RETINAL-PIGMENT EPITHELIUM, OUTDOOR ACTIVITY, Hyperopia, Phenotype, Genetic Epidemiology, Medicine, Female, Research Article, Genetic Markers, Adult, General Science & Technology, Science, DCCT/EDIC Research Group, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, and over, Biology, Disease Surveillance, Polymorphism, Single Nucleotide, White People, medicine, Genome-Wide Association Studies, Humans, Inherited Eye Disorders, Genetic Predisposition to Disease, Allele, Polymorphism, Eye Disease and Disorders of Vision, Alleles, Genetic Association Studies, Aged, Whites, Human Genome, Biology and Life Sciences, Computational Biology, Human Genetics, Heritability, Plant Pathology, medicine.disease, Genome Analysis, GENE, eye diseases, Ophthalmology, REFRACTIVE ERROR, Genetics of Disease, LINKAGE-DISEQUILIBRIUM, Age of onset
Abstract

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10-11) and 8q12 (minimum p value 1.82×10-11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Published
2014
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6. Large Scale Structural Rearrangement of a Serine Hydrolase from Francisella tularensis Facilitates Catalysis*

Author

Chinessa T. Adkins, R. Jeremy Johnson, I. Dubrovska, Daniel P. Becker, Alexandra M. Gehring, James Winsor, George Minasov, Luke D. Lavis, Ekaterina V. Filippova, Brett Geissler, Leigh A. Weston, Ludmilla Shuvalova, Wayne F. Anderson, Nicola Armoush, Karla J. F. Satchell, and Misty L. Kuhn

Subjects
Protein family, Cell Membrane, Serine Endopeptidases, Serine hydrolase, Cell Biology, Biology, Ligand (biochemistry), biology.organism_classification, Biochemistry, Enzyme structure, Enzyme catalysis, Structure-Activity Relationship, Protein structure, Thioesterase, Bacterial Proteins, Structural Homology, Protein, Protein Structure and Folding, Mutagenesis, Site-Directed, Humans, lipids (amino acids, peptides, and proteins), Thiolester Hydrolases, Francisella tularensis, Molecular Biology
Abstract

Tularemia is a deadly, febrile disease caused by infection by the Gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding pocket suggest that the observed structural changes are essential to the biological function and catalytic activity of FTT258. Using diverse substrate libraries, site-directed mutagenesis, and liposome binding assays, we determined the importance of these structural changes to the catalytic activity and membrane binding activity of FTT258. Residues within the newly exposed hydrophobic binding pocket and within the peripheral flexible loop proved essential to the hydrolytic activity of FTT258, indicating that structural rearrangement is required for catalytic activity. Both FTT258 and hAPT1 also showed significant association with liposomes designed to mimic bacterial or human membranes, respectively, even though similar structural rearrangements for hAPT1 have not been reported. The necessity for acyl protein thioesterases to have maximal catalytic activity near the membrane surface suggests that these conformational changes in the protein may dually regulate catalytic activity and membrane association in bacterial and human homologues.

Published
2013

7. Radiofrequency endometrial ablation in patients with a history of low transverse cesarean delivery

Author

Royce T. Adkins, Phillip L. Bressman, Theresa L. Lucas, and Patricia B. Bressman

Subjects
Adult, medicine.medical_specialty, business.industry, Vaginal delivery, Cesarean Section, medicine.medical_treatment, Uterine perforation, Obstetrics and Gynecology, Retrospective cohort study, Middle Aged, medicine.disease, Ablation, Surgery, Endometrial ablation, medicine, Catheter Ablation, Humans, In patient, Female, Radiofrequency endometrial ablation, Adverse effect, business, Menorrhagia, Endometrial Ablation Techniques, Retrospective Studies
Abstract

Study Objective To assess adverse events associated with radiofrequency endometrial ablation in treatment of heavy menstrual bleeding in patients with a history of low transverse cesarean delivery (C-section group) and patients who delivered vaginally (vaginal delivery group). Design Retrospective cohort study (Canadian Task Force classification II-2). Setting Community-based gynecology practice in the United States. Patients The study included 194 patients (100 in the C-section group and 94 in the vaginal delivery group), aged 21 to 55 years, with a history of heavy menstrual bleeding. Interventions NovaSure endometrial ablation procedures were performed from April 2004 through December 2010. Measurements and Main Results Demographic characteristics, gynecologic and pregnancy history, and procedure setting were compared between groups. Intraoperative and postoperative adverse events that occurred within 72 hours of the procedure were summarized. The C-section and vaginal delivery groups were similar for demographic characteristics with the exception of age (mean [SD], 40.6 [5.0] years vs 42.5 [5.3] years, respectively; p = .01). Parity was significantly higher in the C-section group compared with the vaginal delivery group (2.4 [0.9] vs 2.1 [0.7]; p = .006). Adverse events commonly associated with endometrial ablation occurred in 3 patients in the C-section group and 5 patients in the vaginal delivery group (p = .68). In addition, 1 patient failed the pre-ablation cavity integrity assessment; therefore, ablation was not performed. All events resolved without sequelae. No uterine perforation or bowel or bladder injury occurred in any patient. Conclusion Radiofrequency endometrial ablation performed in a community practice was well tolerated in patients with a history of low transverse cesarean delivery.

Published
2013

8. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabetes Control and Complications Trial

Author

Timothy W. Olsen, S. Hitt, Thomas J. Songer, Alan M. Jacobson, A. Burwood, R. Beaser, M. Szpiech, H. Martinez, Gayle M. Lorenzi, Anthony D. Morrison, C. Hannon, A. Farr, M. Hebdon, R. Colligan, T. Manolio, C. Wilson, Kathie L. Hermayer, John I. Malone, B. Burzuk, Kathy Glander, N. Silvers, B. Jones, A. Galpirn, M. Reid, David E. Goldstein, L. Sun, J. Giangiacom, P. Lou, Dean P. Hainsworth, Shalamar D. Sibley, Ronald J. Prineas, Louis A. Lobes, H. Wolpert, Mark E. Molitch, J. Sheindlin, Senda Ajroud-Driss, L. Dews, Kate Edwards, John M. Pach, Wanjie Sun, E. Cupelli, K. Stoessel, Samuel Dagogo-Jack, K. Harvey, J. Gordon, M. B. Murphy, John P. Bantle, J. D. Carey, Inger Burnett-Zeigler, Andrew M. Paterson, Henry Ferreyra, Manjot K. Gill, Barbara H. Waberski, B. Rogness, Fred W. Whitehouse, R. Ufret, Gordon C. Weir, Daniel H. O'Leary, S. Thomas, Barbara E. K. Klein, G. Ziegler, C. Wigley, L. Kastorff, C. Siebert, M. Palmert, C. Clark, J. Brown-Friday, S. Braunstein, Martin J. Stevens, M. Nutaitis, S. Catton, Samir S. Deeb, William V. Tamborlane, J. Alappatt, Robert Bergren, R. Eastman, Samuel S. Engel, K. Gehres, John M. Lachin, Davida F. Kruger, Jill P. Crandall, P. Geithman, Blanche M. Chavers, Stephen S. Feman, Mary E. Larkin, Thomas C. Lee, Catherine L. Martin, J. Parker, C. West, A. Gordon, Hugh D. Wabers, Sharon B. Schwartz, B. Zinman, M. Espeland, Neil H. White, M. N. Iyer, Rose Gubitosi-Klug, C. Canny, Robert Detrano, S. MacLean, Alice T. Lyon, M. E. Lackaye, Oscar B. Crofford, David A. Lee, M. Brent, Mark S. Mandelcorn, D. Badal, Lucy A. Levandoski, Barbara J. Maschak-Carey, John E. Godine, M. Hawkins, R. Gstalder, L. Survant, Charles Campbell, Matthew D. Davis, Anupam Agarwal, Lawrence J. Singerman, Brandy N. Rutledge, Anita Harrington, M. Novak, David A. Nicolle, P. Gaston, Isaac Boniuk, William H. Herman, S. Park, D. Counts, J. Quin, Nancy L. Robinson, Enrico Cagliero, T. Adkins, T. Woodfill, Scott M. Steidl, John Dupre, P. A. Bourne, L. Baker, D. Sandstrom, K. Miner, L. Mayer, S. Schussler, N. Grove, N. Wong, A. Iannacone, D. Wood, Lisa Diminick, D. Meyer, Barbara Esser, T. Thompson, David M. Nathan, A. Edwards, Lee M. Jampol, David S. Schade, M. Croswell, Joseph F. Polak, M. Spencer, Helen Lambeth, Paul G. Arrigg, Janie Lipps, H. Zegarra, Rodney A. Lorenz, Ayad A. Jaffa, James W. Albers, P. Astlesford, Thomas A. Weingeist, J. Vaccaro-Kish, Alicia J. Jenkins, Ronald K. Mayfield, M. May, A. Kowarski, Michael W. Steffes, W. T. Garvey, Saul Genuth, D. Zheng, Andrew P. Boright, J. Ginsberg, M. L. Bernal, Daniel L. McGee, Eva L. Feldman, Larry Rand, P. Low, J. Rosenzweig, L. Funk, Larry D. Hubbard, Orville G. Kolterman, D. Blackburn, E. Steuer, D. Rosenberg, Rodica Pop-Busui, S. Moser, John E. Hokanson, Julio V. Santiago, Daniel T. Lackland, James L. Kinyoun, Kevin J. Blinder, K. Taylor, D. Hornbeck, C. O'Donnell, Bernard H. Doft, Susan G. Elner, Dean B. Burgess, D. Kenny, Jeffrey M. Joyce, John D. Brunzell, O. Hamdy, Jerry P. Palmer, Jonathan Q. Purnell, R. Zeither, Douglas A. Greene, E. A. Tanaka, Yu-Guang He, Ramzi K. Hemady, Arup Das, Michael Bryer-Ash, Sheila Smith-Brewer, D. Ostrowski, M. Stern, C. Williams, Andrew K. Vine, M. McLellan, Ronald Klein, Annette Barnie, Michael H. Goldbaum, E. Angus, S. Scherer, R. D'Agostino, Philip Raskin, Santica M. Marcovina, B. Schaefer, A. F. Burrows, K. Morgan, David J. Brillon, H. Ricks, S. Strowig, R. Oudiz, S. Yacoub-Wasef, Jye-Yu C. Backlund, K. Chan, B. Gloeb, M. Johnson, Stephen R. Russell, D. J. Becker, Richard S. Crow, J. L. Canady, David G. Miller, O. Stone, Allan L. Drash, S. Yoser, S. Johnsonbaugh, Edward Chaum, L. Kaminski, M. Fox, J. Kramer, M. Bracey, H. Engel, Peter R. Pavan, Maria F. Lopes-Virella, C. Sommer, Daniel P. Joseph, M. Geckle, V. Reppucci, D. Etzwiler, M. Brabham, J. Fradkin, K. Lee, Jean M. Bucksa, E. Golden, Thomas Donner, Edwin M. Stone, Shelley B. Bull, William I. Sivitz, J. Selby, Pamela Rath, Murk-Hein Heinemann, L. Kim, T. Williams, D. Noller, D. Singer, J. Long, G. Grand, R. Devenyi, J. M. Schluter, B. Petty, Margaret L. Bayless, Alexander J. Brucker, S. Fritz, C. Cowie, Om P. Ganda, F. Thoma, K. Klumpp, Z. Strugula, Timothy J. Lyons, Patricia A. Cleary, A. Blevins, H. Shamoon, J. Soule, John A. Colwell, M. Phillips, Gaurav K. Shah, C. Hurtenbach, S. Rogers, Richard M. Bergenstal, Patricia Gatcomb, R. Trail, H. Culver Boldt, J. Bayless, Jonathan Shankle, David M. Kendall, Matthew A. Thomas, P. G. Sharuk, P. Lindsey, Ronald P. Danis, Christopher M. Ryan, William Dahms, P. Paczan Rath, S. Elsing, Gabriel Virella, Abbas E. Kitabchi, D. Moore, S. Pendegras, Trevor J. Orchard, K. Nickander, A. Determan, L. Van Ottingham, J. Harth, Michael W. Neider, and Shelly Olson

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Adolescent, Article, law.invention, chemistry.chemical_compound, Young Adult, Randomized controlled trial, law, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Prevalence, Humans, Hypoglycemic Agents, Insulin, Risk factor, Infusion Pumps, Glycated Hemoglobin, Type 1 diabetes, Diabetic Retinopathy, medicine.diagnostic_test, business.industry, Incidence, Fundus photography, Diabetic retinopathy, medicine.disease, Surgery, Ophthalmology, Diabetes Mellitus, Type 1, chemistry, Disease Progression, Female, Glycated hemoglobin, business, Retinopathy, Follow-Up Studies
Abstract

OBJECTIVE To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. METHODS Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. RESULTS After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P < .001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P < .001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. CONCLUSION The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning. TRIAL REGISTRATION (clinicaltrials.gov) Identifiers: NCT00360815 and NCT00360893.

Published
2008

11. Case records of the Department of Medicine University of Mississippi Medical Center. Moderately differentiated adenocarcinoma of the colon with extension through the musculature into the pericolonic fat and metastasis to one of six lymph nodes and the liver

Author

T, Adkins, M, Rees, F, Simeone, S W, Chapman, M, Saif, and N, Pinkard

Subjects
Aged, 80 and over, Diagnosis, Differential, Male, Lymphatic Metastasis, Sepsis, Colonic Neoplasms, Liver Neoplasms, Clostridium Infections, Humans, Adenocarcinoma, Aged
Published
1993

14. Prevention of preterm birth: early detection and aggressive treatment with terbutaline

Author

R T, Adkins, J E, Van Hooydonk, P L, Bressman, J H, Growdon, P R, Bolen, J C, Varin, and B R, Thompson

Subjects
Adult, Male, Gestational Age, Cervix Uteri, Comorbidity, Self Medication, Magnesium Sulfate, Obstetric Labor, Premature, Patient Education as Topic, Pregnancy, Risk Factors, Intensive Care Units, Neonatal, Terbutaline, Birth Weight, Humans, Mass Screening, Infusions, Parenteral, Physical Examination, Pregnancy Outcome, Length of Stay, Home Care Services, Patient Compliance, Drug Therapy, Combination, Female, Follow-Up Studies, Program Evaluation
Abstract

We evaluated a program for prevention of preterm birth involving early detection and aggressive intervention with subcutaneous terbutaline pump therapy in a high-risk, private patient population. Risk factor screening, frequent cervical examinations, and intensive patient education were used to detect preterm labor before it progressed to an advanced stage. Home terbutaline pump therapy was prescribed for patients with uterine contractions associated with progressive cervical change, after stabilization with IV magnesium sulfate. In this study of 51 patients, home terbutaline pump therapy was successful in 98% of the cases, prolonging pregnancy an average of 6.6 weeks. Mean gestational age at delivery was 37 +/- 1.4 weeks, and infant birth weight averaged 3 kg. Only 22% of infants required admission to the neonatal intensive care unit, with a mean length of stay of 7.25 days. Population factors in this compliant, well-educated patient group may have contributed to the positive outcomes achieved.

Published
1993

15. Development of a vital-sign/fluid-balance flow sheet

Author

L A, Ozuna and A T, Adkins

Subjects
Quality Assurance, Health Care, Heart Rate, Nursing Records, Respiration, Oncology Nursing, Humans, Blood Pressure, Forms and Records Control, Water-Electrolyte Balance, Body Temperature
Abstract

An improved flow sheet for recording vital signs and fluid balance on a medical oncology unit was developed and tested using quality-assurance techniques. The new form, which replaced three separate forms, measurably improved documentation on all quality-assurance monitors tested. Additional benefits include cost-savings and decreased time expenditures by nursing staff.

Published
1993

16. Postnatal development of T lymphocytes in a novel X-linked immunodeficiency disease

Author

Leonard E. Swischuk, Armond S. Goldman, Frank C. Schmalstieg, Daniel P. Wirt, Edward G. Brooks, Linda T. Adkins, and Susan D. Stansberry

Subjects
X Chromosome, T cell, T-Lymphocytes, Immunology, Immunoglobulins, Disease, Thymus Gland, Biology, Lymphocyte Activation, Pathology and Forensic Medicine, Leukocyte Count, Immune system, Immunopathology, medicine, Immunology and Allergy, Humans, X chromosome, Cell growth, Immunologic Deficiency Syndromes, Infant, Newborn, Infant, T lymphocyte, Antibodies, Bacterial, Lymphocyte Subsets, medicine.anatomical_structure, CD8
Abstract

We previously reported an X-linked combined immunode-ficiency disease (CID) characterized by immune deficiencies and complicating infections that were more moderate than those found in severe CID (SCID). Since other unstudied males in the family died in infancy, we questioned whether this T cell defect was more profound in early life. Subsequently, the development of blood T cells in an affected new-born male was examined. T cells were virtually undetectable at 48 hr. Over the next several months, CD4+ T cells (principally CD45RO+) rose to levels similar to those found in older affected males, but CD8+ T cells developed more slowly and never attained levels found in other affected males. Thus, this disease in early life mimics SCID and may pose a higher risk of fatal infections to affected individuals during that period. Finally, we speculate that the genetic defect may disrupt intrathymic development or selection of T cells.

Published
1992

17. Cholesterol screening in pediatric practice

Author

D C, Goff, G A, Donker, J D, Ragan, A T, Adkins, R P, Killinger, J W, Caudill, and D R, Labarthe

Subjects
Hyperlipoproteinemia Type II, Male, Aging, Cholesterol, Adolescent, Reference Values, Child, Preschool, Data Collection, Hypercholesterolemia, Humans, Female, Child, Retrospective Studies
Abstract

Four pediatricians introduced a portable cholesterol analyzer into their group practice. Their experience is described on the basis of 12 months of screening in 1665 children and adolescents. The overall 50th and 90th percentile values for a subgroup of 1406 routinely screened children were 156 and 197 mg/dL, respectively, but there was marked variation in these values among specific age and sex groups. Cholesterol levels decreased by age group during the early teenage years and increased thereafter, these changes occurring at ages approximately 2 years younger for girls than for boys. Further analysis of screening results for 398 sibling pairs demonstrated significant concordance between paired cholesterol levels when classified by the respective age- and sex-specific 90th percentile values for each member of the pair. Sibling pairs in which both members' cholesterol values exceeded their 90th percentile value were identified 2.4 times as frequently as expected (confidence interval 1.1 to 4.5, P = .029). The observations reported here indicate that office-based cholesterol screening in a pediatric practice may be both practical and useful, although further consideration of screening criteria is needed. Age- and sex-specific reference values for cholesterol levels during childhood could improve screening results. Special emphasis should be directed toward screening siblings of children in whom high cholesterol levels have been detected.

Published
1991

18. A novel X-linked combined immunodeficiency disease

Author

Frank C. Schmalstieg, Armond S. Goldman, Linda T. Adkins, Edward G. Brooks, Howard M. Rosenblatt, Tamara A. Rakusan, Helen E. Rudloff, Daniel P. Wirt, and Donald P. Lookingbill

Subjects
Adult, Male, X Chromosome, Adolescent, Genetic Linkage, T-Lymphocytes, Immunoglobulins, Biology, Interleukin 21, Leukocyte Count, Antigen, medicine, Humans, X-linked severe combined immunodeficiency, Child, Immunodeficiency, Immunologic Deficiency Syndromes, General Medicine, T lymphocyte, medicine.disease, Pedigree, Lymphatic system, Phenotype, Child, Preschool, Immunology, biology.protein, Female, Antibody, CD8, Research Article
Abstract

A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders.

Published
1990

19. THROMBOCYTOPENIC PURPURA FOLLOWING RUBELLA

Author

A T Adkins and D J Fernbach

Subjects
medicine.medical_specialty, Pediatrics, Adolescent, Rubella, Measles, hemic and lymphatic diseases, medicine, Humans, Child, Exanthem, Purpura, Subclinical infection, business.industry, virus diseases, Infant, General Medicine, medicine.disease, Thrombocytopenic purpura, Thrombocytopenia, Surgery, Purpura, Thrombocytopenic, medicine.symptom, Complication, business
Abstract

NINE CASES of thrombocytopenic purpura associated with rubella were seen on the Hematology Service at Texas Children's Hospital, Houston, from April to July 1964. During this time a particularly virulent rubella epidemic occurred over most of the state. Despite the ubiquity of rubella, we have found only 30 cases complicated by thrombocytopenic purpura in the medical literature.1,2Undoubtedly the frequency is higher than this, but thrombocytopenia is rarely mentioned as a complication of this exanthem. Twelve other cases of thrombocytopenic purpura were seen during this same four-month period. A history of exposure to rubella prior to the onset of purpura was obtained in most cases. Though it is possible that some of these patients had subclinical rubella, only those cases with typical rubella (German measles) were included in this report. The occurrence of purpura associated with rubella appears to have no relationship to the severity of the primary rubella

Published
1965

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